Monte Carlo simulations of the secondary neutron ambient and effective dose equivalent rates from surface to suborbital altitudes and low Earth orbit

NASA Astrophysics Data System (ADS)

El-Jaby, Samy; Richardson, Richard B.

2015-07-01

Occupational exposures from ionizing radiation are currently regulated for airline travel (<20 km) and for missions to low-Earth orbit (∼300-400 km). Aircrew typically receive between 1 and 6 mSv of occupational dose annually, while aboard the International Space Station, the area radiation dose equivalent measured over just 168 days was 106 mSv at solar minimum conditions. It is anticipated that space tourism vehicles will reach suborbital altitudes of approximately 100 km and, therefore, the annual occupational dose to flight crew during repeated transits is expected to fall somewhere between those observed for aircrew and astronauts. Unfortunately, measurements of the radiation environment at the high altitudes reached by suborbital vehicles are sparse, and modelling efforts have been similarly limited. In this paper, preliminary MCNPX radiation transport code simulations are developed of the secondary neutron flux profile in air from surface altitudes up to low Earth orbit at solar minimum conditions and excluding the effects of spacecraft shielding. These secondary neutrons are produced by galactic cosmic radiation interacting with Earth's atmosphere and are among the sources of radiation that can pose a health risk. Associated estimates of the operational neutron ambient dose equivalent, used for radiation protection purposes, and the neutron effective dose equivalent that is typically used for estimates of stochastic health risks, are provided in air. Simulations show that the neutron radiation dose rates received at suborbital altitudes are comparable to those experienced by aircrew flying at 7 to 14 km. We also show that the total neutron dose rate tails off beyond the Pfotzer maximum on ascension from surface up to low Earth orbit.

Monte Carlo simulations of the secondary neutron ambient and effective dose equivalent rates from surface to suborbital altitudes and low Earth orbit.

PubMed

El-Jaby, Samy; Richardson, Richard B

2015-07-01

Occupational exposures from ionizing radiation are currently regulated for airline travel (<20 km) and for missions to low-Earth orbit (∼300-400 km). Aircrew typically receive between 1 and 6 mSv of occupational dose annually, while aboard the International Space Station, the area radiation dose equivalent measured over just 168 days was 106 mSv at solar minimum conditions. It is anticipated that space tourism vehicles will reach suborbital altitudes of approximately 100 km and, therefore, the annual occupational dose to flight crew during repeated transits is expected to fall somewhere between those observed for aircrew and astronauts. Unfortunately, measurements of the radiation environment at the high altitudes reached by suborbital vehicles are sparse, and modelling efforts have been similarly limited. In this paper, preliminary MCNPX radiation transport code simulations are developed of the secondary neutron flux profile in air from surface altitudes up to low Earth orbit at solar minimum conditions and excluding the effects of spacecraft shielding. These secondary neutrons are produced by galactic cosmic radiation interacting with Earth's atmosphere and are among the sources of radiation that can pose a health risk. Associated estimates of the operational neutron ambient dose equivalent, used for radiation protection purposes, and the neutron effective dose equivalent that is typically used for estimates of stochastic health risks, are provided in air. Simulations show that the neutron radiation dose rates received at suborbital altitudes are comparable to those experienced by aircrew flying at 7 to 14 km. We also show that the total neutron dose rate tails off beyond the Pfotzer maximum on ascension from surface up to low Earth orbit. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Leisure-time physical activity dose-response effects on obesity among US adults: results from the 1999-2006 National Health and Nutrition Examination Survey.

PubMed

Seo, Dong-Chul; Li, Kaigang

2010-05-01

It is not well established whether total volume of leisure-time physical activity (LTPA) has dose-response effects on obesity. The dose-response relationship was examined using 12 227 non-institutionalised individuals, aged 20-64 years, drawn from the 8 years (1999-2006) of the continuous National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of the US population. The age-adjusted prevalence of women's obesity was 41.4% for those with no LTPA in the past month; 39.1% for those who engaged in LTPA but fell short of the recommended minimum amount of LTPA (ie, <450 metabolic equivalent minutes per week (MET min/week)); 31.0% for those who met the recommended minimum guideline (ie, 450 to < 750); 28.0% for those whose LTPA exceeded the minimum guideline but less than the first quartile among the overachievers (ie, 750 to <1260); 23.4% for the overachievers between the first and third quartile (ie, 1260 to <3556); and 19.5% for the overachievers at or above the third quartile (ie, 3556 MET min/week or above). This association was maintained even after occupational physical activity (OPA) was controlled. However, this pattern was not observed for Mexican and black adults and showed a floor effect as LTPA increased. There is a crude graded inverse dose-response relationship between total volume of LTPA and obesity in US adult women, but not in men. Gender and racial/ethnic differences exist in the relationship of accumulated LTPA with obesity due, in part, to differential ratios of LTPA to OPA.

Quantifying the Combined Effect of Radiation Therapy and Hyperthermia in Terms of Equivalent Dose Distributions

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

Kok, H. Petra, E-mail: H.P.Kok@amc.uva.nl; Crezee, Johannes; Franken, Nicolaas A.P.

2014-03-01

Purpose: To develop a method to quantify the therapeutic effect of radiosensitization by hyperthermia; to this end, a numerical method was proposed to convert radiation therapy dose distributions with hyperthermia to equivalent dose distributions without hyperthermia. Methods and Materials: Clinical intensity modulated radiation therapy plans were created for 15 prostate cancer cases. To simulate a clinically relevant heterogeneous temperature distribution, hyperthermia treatment planning was performed for heating with the AMC-8 system. The temperature-dependent parameters α (Gy{sup −1}) and β (Gy{sup −2}) of the linear–quadratic model for prostate cancer were estimated from the literature. No thermal enhancement was assumed for normalmore » tissue. The intensity modulated radiation therapy plans and temperature distributions were exported to our in-house-developed radiation therapy treatment planning system, APlan, and equivalent dose distributions without hyperthermia were calculated voxel by voxel using the linear–quadratic model. Results: The planned average tumor temperatures T90, T50, and T10 in the planning target volume were 40.5°C, 41.6°C, and 42.4°C, respectively. The planned minimum, mean, and maximum radiation therapy doses were 62.9 Gy, 76.0 Gy, and 81.0 Gy, respectively. Adding hyperthermia yielded an equivalent dose distribution with an extended 95% isodose level. The equivalent minimum, mean, and maximum doses reflecting the radiosensitization by hyperthermia were 70.3 Gy, 86.3 Gy, and 93.6 Gy, respectively, for a linear increase of α with temperature. This can be considered similar to a dose escalation with a substantial increase in tumor control probability for high-risk prostate carcinoma. Conclusion: A model to quantify the effect of combined radiation therapy and hyperthermia in terms of equivalent dose distributions was presented. This model is particularly instructive to estimate the potential effects of interaction from different treatment modalities.« less

Dose-response association of moderate-to-vigorous physical activity with cardiovascular biomarkers and all-cause mortality: Considerations by individual sports, exercise and recreational physical activities.

PubMed

Loprinzi, Paul D

2015-12-01

Previous research demonstrates that moderate-to-vigorous physical activity (MVPA) is associated with reduced all-cause mortality risk. Our understanding of whether individual physical activities are associated with all-cause mortality is less understood. Data from the 1999-2006 NHANES were employed, with follow-up through 2011. 48 different individual physical activities (e.g., swimming, running, bicycling) were assessed, and total MVPA MET-min-month was calculated based on their responses to these 48 individual physical activities. Greater engagement in MVPA was associated with more favorable cardiovascular biomarkers, particularly for men. Even after adjustment for total MVPA, different individual physical activities were associated with cardiovascular biomarkers across gender. When compared to those not meeting guidelines (0-1999 MVPA MET-min-month), a dose-response association between MVPA and mortality was observed, with those engaging in 5 times the guideline level having the lowest risk of all-cause mortality (45% reduced risk). There was no evidence of a harmful effect of very high MVPA (e.g., 20,000+ MVPA MET-min-month). Engaging in MVPA even below the minimum recommendation was associated with survival benefits, and the greatest survival effects occurred at a dose of approximately 5 times the minimum recommendation. Although very high levels (e.g., 10 times the minimum recommendation) of self-reported MVPA did not demonstrate the greatest survival effects, high levels of physical activity did not appear to have harmful effects. Copyright © 2015 Elsevier Inc. All rights reserved.

Fluoroscopically Guided Interventional Procedures: A Review of Radiation Effects on Patients’ Skin and Hair

DTIC Science & Technology

2010-02-01

subsequent research has yielded additional in- sights. This review is a consensus report of current scien- tifi c data. Expected skin reactions for an...table has been cited and reproduced Essentials The minimum radiation dose n causing a specifi c type of reac- tion in the skin or hair is best...expressed in terms of a range of doses, rather than a single threshold dose. The times of onset and resolution n of specifi c radiation injuries

Survey of Occupational Noise Exposure in CF Personnel in Selected High-Risk Trades

DTIC Science & Technology

2003-11-01

peak, maximum level , minimum level , average sound level , time weighted average, dose, projected 8-hour dose, and upper limit time were measured for...10 4.4.2 Maximum Sound Level ...11 4.4.3 Minimum Sound Level

RADIATION STERILIZATION OF COCOA POWDERS. Report No. 2 (Progress) for May 17, 1959-August 17, 1959

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

McComb, C.

1961-10-31

A study was made of the effects of O.l, 0.3, and 0.6 megarad of gamma radiation on microflora, flavor, and vitamin content of chocolate syrup. A dose of 0.3 was found to be the minimum useful dose bacteriologically. Vitamin content was not reduced, and no off-flavor was reported. (T.R.H.)

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

McCulloch, M; Cazoulat, G; Polan, D

Purpose: It is well documented that the delivered dose to patients undergoing radiotherapy (RT) is often different from the planned dose due to geometric variability and uncertainties in patient positioning. Recent work suggests that accumulated dose to the GTV is a better predictor of progression compared to the minimum planned dose to the PTV. The purpose of this study is to evaluate if deviations from the planned dose can contributed to tumor progression. Methods: From 2010 to 2014 an in-house Phase II clinical trial of adaptive stereotactic body RT was completed. Of the 90 patients enrolled, 7 patients had amore » local recurrence defined on contrast enhanced CT or MR imaging 3–21 months after completion of RT. Retrospective dose accumulation was performed using a biomechanical model-based deformable image registration algorithm (DIR) to accumulate the dose based on the kV CBCT acquired prior to each fraction for soft tissue alignment of the patient. The DIR algorithm was previously validated for geometric accuracy in the liver (target registration error = 2.0 mm) and dose accumulation in a homogeneous image, similar to a liver CBCT (gamma index = 91%). Following dose accumulation, the minimum dose to 0.5 cc of the GTV was compared between the planned and accumulated dose. Work is ongoing to evaluate the tumor control probability based on the planned and accumulated dose. Results: DIR and dose accumulation was performed on all fractions for 6 patients with local recurrence. The difference in minimum dose to 0.5 cc of the GTV ranged from −0.3–2.3 Gy over 3–5 fractions. One patient had a potentially significant difference in minimum dose of 2.3 Gy. Conclusion: Dose accumulation can reveal tumor underdosage, improving our ability to understand recurrence and tumor progression patterns, and could aid in adaptive re-planning during therapy to correct for this. This work was supported in part by NIH P01CA059827.« less

Sphinganine to sphingosine ratio and predictive biochemical markers of fumonisin B1 exposure in ducks.

PubMed

Tran, S T; Bailly, J D; Tardieu, D; Durand, S; Benard, G; Guerre, P

2003-07-25

The kinetics of free sphinganine (Sa), sphinganine to sphingosine ratio (Sa/So), proteins, cholesterol, alanine aminotransferase (ALAT) and lactate dehydrogenase (LDH) were investigated in the course of fumonisin B1 (FB1) exposure in ducks (20 growing males divided into four groups of 5 receiving, respectively, a daily dose of 0, 5, 15 or 45 mg/kg FB1 via oral administration over 12 days). Descriptive statistics of these parameters were also studied in a large number of ducks not exposed to mycotoxins and free of known pathology. Although the toxin at the end of the treatment affected all the parameters investigated, only 2 days of treatment appeared necessary to increase free Sa concentrations in serum, whereas 6 days were necessary to detect a significant effect on Sa/So ratio. Significant differences between control and treated ducks were observed after 4 days of treatment for ALAT and LDH and after 6 and 8 days for cholesterol and proteins concentrations. The minimum doses of FB1 required to determine an effect were assessed using three different methods. This approach reveals that FB1 has greater effects when it is ingested at a low dose for a long time than when ingested at a high dose for a short time. Although the minimum toxic dose of FB1 in ducks remains to be determined, this result must be considered in the context of chronic exposure to the toxin, not only in avian populations.

Motion Interplay as a Function of Patient Parameters and Spot Size in Spot Scanning Proton Therapy for Lung Cancer

PubMed Central

Grassberger, Clemens; Dowdell, Stephen; Lomax, Antony; Sharp, Greg; Shackleford, James; Choi, Noah; Willers, Henning; Paganetti, Harald

2013-01-01

Purpose Quantify the impact of respiratory motion on the treatment of lung tumors with spot scanning proton therapy. Methods and Materials 4D Monte Carlo simulations were used to assess the interplay effect, which results from relative motion of the tumor and the proton beam, on the dose distribution in the patient. Ten patients with varying tumor sizes (2.6-82.3cc) and motion amplitudes (3-30mm) were included in the study. We investigated the impact of the spot size, which varies between proton facilities, and studied single fractions and conventionally fractionated treatments. The following metrics were used in the analysis: minimum/maximum/mean dose, target dose homogeneity and 2-year local control rate (2y-LC). Results Respiratory motion reduces the target dose homogeneity, with the largest effects observed for the highest motion amplitudes. Smaller spot sizes (σ≈3mm) are inherently more sensitive to motion, decreasing target dose homogeneity on average by a factor ~2.8 compared to a larger spot size (σ≈13mm). Using a smaller spot size to treat a tumor with 30mm motion amplitude reduces the minimum dose to 44.7% of the prescribed dose, decreasing modeled 2y-LC from 87.0% to 2.7%, assuming a single fraction. Conventional fractionation partly mitigates this reduction, yielding a 2y-LC of 71.6%. For the large spot size, conventional fractionation increases target dose homogeneity and prevents a deterioration of 2y-LC for all patients. No correlation with tumor volume is observed. The effect on the normal lung dose distribution is minimal: observed changes in mean lung dose and lung V20 are <0.6Gy(RBE) and <1.7% respectively. Conclusions For the patients in this study, 2y-LC could be preserved in the presence of interplay using a large spot size and conventional fractionation. For treatments employing smaller spot sizes and/or in the delivery of single fractions, interplay effects can lead to significant deterioration of the dose distribution and lower 2y-LC. PMID:23462423

An estimation of Canadian population exposure to cosmic rays.

PubMed

Chen, Jing; Timmins, Rachel; Verdecchia, Kyle; Sato, Tatsuhiko

2009-08-01

The worldwide average exposure to cosmic rays contributes to about 16% of the annual effective dose from natural radiation sources. At ground level, doses from cosmic ray exposure depend strongly on altitude, and weakly on geographical location and solar activity. With the analytical model PARMA developed by the Japan Atomic Energy Agency, annual effective doses due to cosmic ray exposure at ground level were calculated for more than 1,500 communities across Canada which cover more than 85% of the Canadian population. The annual effective doses from cosmic ray exposure in the year 2000 during solar maximum ranged from 0.27 to 0.72 mSv with the population-weighted national average of 0.30 mSv. For the year 2006 during solar minimum, the doses varied between 0.30 and 0.84 mSv, and the population-weighted national average was 0.33 mSv. Averaged over solar activity, the Canadian population-weighted average annual effective dose due to cosmic ray exposure at ground level is estimated to be 0.31 mSv.

Quantification of interplay and gradient effects for lung stereotactic ablative radiotherapy (SABR) treatments.

PubMed

Tyler, Madelaine K

2016-01-08

This study quantified the interplay and gradient effects on GTV dose coverage for 3D CRT, dMLC IMRT, and VMAT SABR treatments for target amplitudes of 5-30 mm using 3DVH v3.1 software incorporating 4D Respiratory MotionSim (4D RMS) module. For clinically relevant motion periods (5 s), the interplay effect was small, with deviations in the minimum dose covering the target volume (D99%) of less than ± 2.5% for target amplitudes up to 30 mm. Increasing the period to 60 s resulted in interplay effects of up to ± 15.0% on target D99% dose coverage. The gradient effect introduced by target motion resulted in deviations of up to ± 3.5% in D99% target dose coverage. VMAT treatments showed the largest deviation in dose metrics, which was attributed to the long delivery times in comparison to dMLC IMRT. Retrospective patient analysis indicated minimal interplay and gradient effects for patients treated with dMLC IMRT at the NCCI.

Combined effect of gamma-irradiation and conventional cooking on Aeromonas hydrophila in meatball.

PubMed

Ozbaş, Z Y; Vural, H; Aytaç, S A

1996-01-01

Irradiation combined with a conventional cooking procedure was applied to meatball and the effects on bacterial load and inoculated Aeromonas hydrophila were determined. Meatball samples were irradiated by using a 60Co source at the dose levels of 0, 0.30, 0.75, 1.50, 2.50 kGy and cold stored at 4 +/- 1 degrees C for 7 days. Bacterial load and the count of A. hydrophila decreased when the irradiation dose level increased. A minimum inhibition effect was found at the dose of 0.30 kGy. Irradiation in combination with a conventional cooking procedure was found to be more effective in reducing A. hydrophila and the bacterial load in meatball. This study indicated that a dose of 0.75 kGy was sufficient to destroy approximately 10(4) cfu/g of A. hydrophila in meatball.

Hemodialysis patients receiving a greater Kt dose than recommended have reduced mortality and hospitalization risk.

PubMed

Maduell, Francisco; Ramos, Rosa; Varas, Javier; Martin-Malo, Alejandro; Molina, Manuel; Pérez-Garcia, Rafael; Marcelli, Daniele; Moreso, Francesc; Aljama, Pedro; Merello, Jose Ignacio

2016-12-01

Achieving an adequate dialysis dose is one of the key goals for dialysis treatments. Here we assessed whether patients receiving the current cleared plasma volume (Kt), individualized for body surface area per recommendations, had improved survival and reduced hospitalizations at 2 years of follow-up. Additionally, we assessed whether patients receiving a greater dose gained more benefit. This prospective, observational, multicenter study included 6129 patients in 65 Fresenius Medical Care Spanish facilities. Patients were classified monthly into 1 of 10 risk groups based on the difference between achieved and target Kt. Patient groups with a more negative relationship were significantly older with a higher percentage of diabetes mellitus and catheter access. Treatment dialysis time, effective blood flow, and percentage of on-line hemodiafiltration were significantly higher in groups with a higher dose. The mortality risk profile showed a progressive increase when achieved minus target Kt became more negative but was significantly lower in the group with 1 to 3 L clearance above target Kt and in groups with greater increases above target Kt. Additionally, hospitalization risk appeared significantly reduced in groups receiving 9 L or more above the minimum target. Thus, prescribing an additional 3 L or more above the minimum Kt dose could potentially reduce mortality risk, and 9 L or more reduce hospitalization risk. As such, future prospective studies are required to confirm these dose effect findings. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Passive dosimetry aboard the Mir Orbital Station: internal measurements.

PubMed

Benton, E R; Benton, E V; Frank, A L

2002-10-01

Passive radiation dosimeters were exposed aboard the Mir Orbital Station over a substantial portion of the solar cycle in order to measure the change in dose and dose equivalent rates as a function of time. During solar minimum, simultaneous measurements of the radiation environment throughout the habitable volume of the Mir were made using passive dosimeters in order to investigate the effect of localized shielding on dose and dose equivalent. The passive dosimeters consisted of a combination of thermoluminescent detectors to measure absorbed dose and CR-39 PNTDs to measure the linear energy transfer (LET) spectrum from charged particles of LET infinity H2O > or = 5 keV/micrometers. Results from the two detector types were then combined to yield mean total dose rate, mean dose equivalent rate, and average quality factor. Contrary to expectations, both dose and dose equivalent rates measured during May-October 1991 near solar maximum were higher than similar measurements carried out in 1996-1997 during solar minimum. The elevated dose and dose equivalent rates measured in 1991 were probably due to a combination of intense solar activity, including a large solar particle event on 9 June 1991, and the temporary trapped radiation belt created in the slot region by the solar particle event and ensuing magnetic storm of 24 March 1991. During solar minimum, mean dose and dose equivalent rates were found to vary by factors of 1.55 and 1.37, respectively, between different locations through the interior of Mir. More heavily shielded locations tended to yield lower total dose and dose equivalent rates, but higher average quality factor than did more lightly shielding locations. However, other factors such as changes in the immediate shielding environment surrounding a given detector location, changes in the orientation of the Mir relative to its velocity vector, and changes in the altitude of the station also contributed to the variation. Proton and neutron-induced target fragment secondaries, not primary galactic cosmic rays, were found to dominate the LET spectrum above 100 keV/micrometers. This indicates that in low earth orbit, trapped protons in the South Atlantic Anomaly are responsible for the major fraction of the total dose equivalent. c2002 Elsevier Science Ltd. All rights reserved.

[Effectiveness of various dopamine doses in acute myocardial ischemia complicated by cardiogenic shock (an experimental study)].

PubMed

Kipshidze, N N; Korotkov, A A; Marsagishvili, L A; Prigolashvili, T Sh; Bokhua, M R

1981-06-01

The effect of various doses of dopamine on the values of cardiac contractile and hemodynamic function under conditions of acute two-hour ischemia complicated by cardiogenic shock was studied in 27 experiments on dogs. In a dose of 5 microgram/kg/min dopamine caused an optimum increase in cardiac productive capacity, reduction of peripheral resistance, adequate increase in coronary circulation and decrease in ST segment depression on the ECG. Infusion of 10 microgram/kg/min dopamine usually caused myocardial hyperfunction with an increase in total peripheral resistance and cardiac performance. Maximum dopamine doses (10 microgram/kg/min and more) were effective in the areactive form of cardiogenic shock. In longterm dopamine infusion it is necessary to establish continuous control over the hemodynamic parameters and the ECG to prevent aggravation of ischemia and for stage-by-stage reduction of the drug concentration and determination of the minimum maintenance dose.

Acute and subchronic toxicities of QX100626, a 5-HT4 receptor agonist, in rodents and Beagle dogs.

PubMed

Zhang, Xiaofang; Yuan, Bojun; Mao, Yu; Dai, Xiaoyu; Zhang, Xiaodong; Lu, Guocai

2014-10-01

Serotonin 5-hydroxytryptamine 4(5-HT4) receptor agonists have been widely prescribed as a prokinetics drug for patients with gastro-esophageal reflux disease and functional dyspepsia. QX100626, one of the 5-HT4 receptor agonists, has been studied as a promising agent for this clinical use. The objective of the present study was to identify possible target organs of toxicity and propose a non-toxic dose of QX100626 for clinical usage. After single lethal dose oral and intravenous testing in rodents, some signs indicative of adverse CNS effects were observed. The minimum toxic dose of QX100626 for a single oral administration for dogs was 90.0mg/kgb.w., and the severe toxic dose was more than 300mg/kgb.w. The No Observed Adverse Effect Level (NOAEL) of QX100626 by daily oral administration for rats and dogs was 20mg/kg and 10mg/kg, respectively, whereas the minimum toxic dosages were 67 and 30mg/kg, respectively. All of the adverse effects suggested that kidney, digestive tract, as well as nervous, hematological, and respiratory systems might be the target organs of toxicity for humans induced by QX100626. The compound could be a safe alternative to other existing prokinetic agents for the treatment of functional bowel disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

Outcomes of high-dose levofloxacin therapy remain bound to the levofloxacin minimum inhibitory concentration in complicated urinary tract infections.

PubMed

Armstrong, Eliana S; Mikulca, Janelle A; Cloutier, Daniel J; Bliss, Caleb A; Steenbergen, Judith N

2016-11-25

Fluoroquinolones are a guideline-recommended therapy for complicated urinary tract infections, including pyelonephritis. Elevated drug concentrations of fluoroquinolones in the urine and therapy with high-dose levofloxacin are believed to overcome resistance and effectively treat infections caused by resistant bacteria. The ASPECT-cUTI phase 3 clinical trial (ClinicalTrials.gov, NCT01345929 and NCT01345955 , both registered April 28, 2011) provided an opportunity to test this hypothesis by examining the clinical and microbiological outcomes of high-dose levofloxacin treatment by levofloxacin minimum inhibitory concentration. Patients were randomly assigned 1:1 to ceftolozane/tazobactam (1.5 g intravenous every 8 h) or levofloxacin (750 mg intravenous once daily) for 7 days of therapy. The ASPECT-cUTI study provided data on 370 patients with at least one isolate of Enterobacteriaceae at baseline who were treated with levofloxacin. Outcomes were assessed at the test-of-cure (5-9 days after treatment) and late follow-up (21-42 days after treatment) visits in the microbiologically evaluable population (N = 327). Test-of-cure clinical cure rates above 90% were observed at minimum inhibitory concentrations ≤4 μg/mL. Microbiological eradication rates were consistently >90% at levofloxacin minimum inhibitory concentrations ≤0.06 μg/mL. Lack of eradication of causative pathogens at the test-of-cure visit increased the likelihood of relapse by the late follow-up visit. Results from this study do not support levofloxacin therapy for complicated urinary tract infections caused by organisms with levofloxacin minimum inhibitory concentrations ≥4 μg/mL. ClinicalTrials.gov, NCT01345929 and NCT01345955.

Method for the prediction of the effective dose equivalent to the crew of the International Space Station

NASA Astrophysics Data System (ADS)

El-Jaby, Samy; Tomi, Leena; Sihver, Lembit; Sato, Tatsuhiko; Richardson, Richard B.; Lewis, Brent J.

2014-03-01

This paper describes a methodology for assessing the pre-mission exposure of space crew aboard the International Space Station (ISS) in terms of an effective dose equivalent. In this approach, the PHITS Monte Carlo code was used to assess the particle transport of galactic cosmic radiation (GCR) and trapped radiation for solar maximum and minimum conditions through an aluminum shield thickness. From these predicted spectra, and using fluence-to-dose conversion factors, a scaling ratio of the effective dose equivalent rate to the ICRU ambient dose equivalent rate at a 10 mm depth was determined. Only contributions from secondary neutrons, protons, and alpha particles were considered in this analysis. Measurements made with a tissue equivalent proportional counter (TEPC) located at Service Module panel 327, as captured through a semi-empirical correlation in the ISSCREM code, where then scaled using this conversion factor for prediction of the effective dose equivalent. This analysis shows that at this location within the service module, the total effective dose equivalent is 10-30% less than the total TEPC dose equivalent. Approximately 75-85% of the effective dose equivalent is derived from the GCR. This methodology provides an opportunity for pre-flight predictions of the effective dose equivalent and therefore offers a means to assess the health risks of radiation exposure on ISS flight crew.

77 FR 40320 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-09

... irradiation treatment of imported fruits and vegetables including a minimum generic dose for the fruit fly family, the minimum dose of irradiation for some specific fruit fly species, and provides for the use of irradiation as a treatment for cut flowers and foliage. Need and Use of the Information: Certain fruits and...

Аnticonvulsant effects of citicoline and diazepam at their combined application on model of the acute generalized convulsions induced by pentylenetetrazole in Wistar rats.

PubMed

Kuznetsova, L V; Karpova, M N; Zinkovski, K A; Klishina, N Yu

2016-01-01

Studying of efficiency of the combined application of the citicoline possessing nootropic and anticonvulsive action and antiepileptic drug of diazepam on the acute generalized convulsions (AGC) caused by a convulsant pentylentetrazole (PTZ). Experiments are executed on the male Wistar rats (n = 68) weighing 160-190 g on the AGС model caused by of PTZ in a dose of 80 mg/kg, intraperitoneally (i.p.). For studying of efficiency of the combined use of drugs determined the minimum anticonvulsive action of a citicoline (Tserakson, «Nicomed Ferrer Internacional, S.A.») and diazepam (Relanium, Warsaw pharmaceutical plant of Polf AO, Warsaw, Poland). For this citicoline were administered i.p. in doses 500 and 300 mg/kg 1 hour before the PTZ and diazepam - in doses of 0,5 and 0,25 mg/kg 30 min before administration of PTZ. Control animals were injected with saline to the same extent and under the same experimental conditions. It is shown that the combined administration of a citicoline and diazepam in minimum active doses (300 and 0.25 mg/kg respectively), increases anticonvulsive properties of both drugs. The combined administration of citicoline with diazepam in minimally active doses enhances anticonvulsant properties of both drugs, thereby reducing the risk of development of side effects. In addition, the research may serve as experimental justification for the use of drugs in case of convulsions for the purpose beneficial effect on cognitive function and delays of progressing of neurodegenerative processes.

Measurements of the radiation quality factor Q at aviation altitudes during solar minimum (2006-2008)

NASA Astrophysics Data System (ADS)

Meier, Matthias M.; Hubiak, Melina

2010-05-01

In radiation protection, the Q-factor has been defined to describe the biological effectiveness of the energy deposition or absorbed dose to humans in the mixed radiation fields at aviation altitudes. This particular radiation field is generated by the interactions of primary cosmic particles with the atoms of the constituents of the Earth’s atmosphere. Thus the intensity, characterized by the ambient dose equivalent rate H∗(10), depends on the flight altitude and the energy spectra of the particles, mainly protons and alpha particles, impinging on the atmosphere. These charged cosmic projectiles are deflected both by the interplanetary and the Earth’s magnetic field such that the corresponding energy spectra are modulated by these fields. The solar minimum is a time period of particular interest since the interplanetary magnetic field is weakest within the 11-year solar cycle and the dose rates at aviation altitudes reach their maximum due to the reduced shielding of galactic cosmic radiation. For this reason, the German Aerospace Center (DLR) performed repeated dosimetric on-board measurements in cooperation with several German airlines during the past solar minimum from March 2006 to August 2008. The Q-factors measured with a TEPC range from 1.98 at the equator to 2.60 in the polar region.

Inactivation of ascaris lumbricoides eggs by heat, radiation, and thermoradiation

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

Brannen, J. P.; Garst, D. M.; Langley, S.

1975-07-01

It is desirable to eliminate the public health hazards associated with land application of municipal sewage sludge as a fertilizer or soil conditioner. This report describes experimentation to determine the effects of heat, radiation, and thermoradiation on the suppression of embryonation of Ascaris lumbricoides ova, a parasite commonly found in sewage sludge. Heat effects were observed at a minimum temperature of 51°C and radiation effects at doses in excess of 15 krads of ionizing gamma radiation. Thermoradiation at 47°C suppressed embryonation at less than half the total dose required by radiation alone.

Effect of 2',3'-didehydro-3'-deoxythymidine in an in vitro hollow-fiber pharmacodynamic model system correlates with results of dose-ranging clinical studies.

PubMed Central

Bilello, J A; Bauer, G; Dudley, M N; Cole, G A; Drusano, G L

1994-01-01

We sought to validate an in vitro system which could predict the minimal effect dose of antiretroviral agents. Mixtures of uninfected CEM cells and CEM cells chronically infected with human immunodeficiency virus (HIV) type 1 MN were exposed to 2',3'-didehydro-3'-deoxythymidine (D4T) in vitro in a hollow-fiber model which simulates the plasma concentration-time profile of D4T in patients. Drug concentration was adjusted to simulate continuous intravenous infusion, or an intravenous bolus administered twice daily. The effect of the dosing regimen was measured with viral infectivity, p24 antigen, and reverse transcriptase or PCR for unintegrated HIV DNA. Dose deescalation studies on a twice-daily dosing schedule predicted a minimum effect dose of 0.5 mg/kg of body weight per day which correlated with the results of a clinical trial. Antiviral effect was demonstrated to be independent of schedule for every 12-h dosing versus continuous infusion. Finally, at or near the minimal effect dose, efficacy appeared to depend on the viral load. The ability of this in vitro pharmacodynamic model to assess the response of HIV-infected cells to different doses and schedules of antiviral agents may be useful in the design of optimal dosing regimens for clinical trials but requires validation with other types of antiretroviral agents. PMID:8092842

32 CFR 218.1 - Policies.

Code of Federal Regulations, 2011 CFR

2011-07-01

... radiation environment to which the veteran was exposed and shall include inhaled, ingested and neutron doses. In determining the veteran's dose, initial neutron, initial gamma, residual gamma, and internal... dose, neutron dose, and internal dose. The minimum standards for reporting dose estimates are set forth...

32 CFR 218.1 - Policies.

Code of Federal Regulations, 2010 CFR

2010-07-01

... radiation environment to which the veteran was exposed and shall include inhaled, ingested and neutron doses. In determining the veteran's dose, initial neutron, initial gamma, residual gamma, and internal... dose, neutron dose, and internal dose. The minimum standards for reporting dose estimates are set forth...

32 CFR 218.1 - Policies.

Code of Federal Regulations, 2012 CFR

2012-07-01

... radiation environment to which the veteran was exposed and shall include inhaled, ingested and neutron doses. In determining the veteran's dose, initial neutron, initial gamma, residual gamma, and internal... dose, neutron dose, and internal dose. The minimum standards for reporting dose estimates are set forth...

32 CFR 218.1 - Policies.

Code of Federal Regulations, 2014 CFR

2014-07-01

... radiation environment to which the veteran was exposed and shall include inhaled, ingested and neutron doses. In determining the veteran's dose, initial neutron, initial gamma, residual gamma, and internal... dose, neutron dose, and internal dose. The minimum standards for reporting dose estimates are set forth...

32 CFR 218.1 - Policies.

Code of Federal Regulations, 2013 CFR

2013-07-01

... radiation environment to which the veteran was exposed and shall include inhaled, ingested and neutron doses. In determining the veteran's dose, initial neutron, initial gamma, residual gamma, and internal... dose, neutron dose, and internal dose. The minimum standards for reporting dose estimates are set forth...

Radiation Risks From A Weak Field in the Coming Years

NASA Astrophysics Data System (ADS)

Rahmanifard, F.; Schwadron, N.; Smith, C. W.; Joyce, C. J.; Townsend, L.

2017-12-01

Recent solar conditions, including a prolonged solar minimum (2005-2009) and the recent small solar maximum, indicate that we are entering an era of lower solar activity than observed at other times during the space age- possibly similar to the past solar grand minima. During such periods of extremely low activity, the fluxes of galactic cosmic rays (GCRs) increase dramatically and limit the allowable days for human space missions. We use data from the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) on the Lunar Reconnaissance Orbiter (LRO) to examine the correlation between the heliospheric magnetic field at 1AU and the modulation potential of the GCRs. We apply past grand solar minima conditions, including the Maunder minimum (1645-1715) and the Dalton minimum (1790-1830), to predict the modulation potential and the dose rates of the GCRs throughout the next solar cycle. The heliospheric magnetic field can drop to 4.21 (3.72) nT, leading to a modulation potential of 448.51 (235.96) MV and dose rates as high as 11.72 (16.68) cGy/yr for the case of conditions similar to the Dalton minimum (Maunder minimum). We use these results to predict the most conservative estimations of the time to 3% risk of exposure-induced death (REID) and the allowable mission durations in interplanetary space.

Bolus-dependent dosimetric effect of positioning errors for tangential scalp radiotherapy with helical tomotherapy

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

Lobb, Eric, E-mail: eclobb2@gmail.com

2014-04-01

The dosimetric effect of errors in patient position is studied on-phantom as a function of simulated bolus thickness to assess the need for bolus utilization in scalp radiotherapy with tomotherapy. A treatment plan is generated on a cylindrical phantom, mimicking a radiotherapy technique for the scalp utilizing primarily tangential beamlets. A planning target volume with embedded scalplike clinical target volumes (CTVs) is planned to a uniform dose of 200 cGy. Translational errors in phantom position are introduced in 1-mm increments and dose is recomputed from the original sinogram. For each error the maximum dose, minimum dose, clinical target dose homogeneitymore » index (HI), and dose-volume histogram (DVH) are presented for simulated bolus thicknesses from 0 to 10 mm. Baseline HI values for all bolus thicknesses were in the 5.5 to 7.0 range, increasing to a maximum of 18.0 to 30.5 for the largest positioning errors when 0 to 2 mm of bolus is used. Utilizing 5 mm of bolus resulted in a maximum HI value of 9.5 for the largest positioning errors. Using 0 to 2 mm of bolus resulted in minimum and maximum dose values of 85% to 94% and 118% to 125% of the prescription dose, respectively. When using 5 mm of bolus these values were 98.5% and 109.5%. DVHs showed minimal changes in CTV dose coverage when using 5 mm of bolus, even for the largest positioning errors. CTV dose homogeneity becomes increasingly sensitive to errors in patient position as bolus thickness decreases when treating the scalp with primarily tangential beamlets. Performing a radial expansion of the scalp CTV into 5 mm of bolus material minimizes dosimetric sensitivity to errors in patient position as large as 5 mm and is therefore recommended.« less

Quantification of interplay and gradient effects for lung stereotactic ablative radiotherapy (SABR) treatments

PubMed Central

2016-01-01

This study quantified the interplay and gradient effects on GTV dose coverage for 3D CRT, dMLC IMRT, and VMAT SABR treatments for target amplitudes of 5–30 mm using 3DVH v3.1 software incorporating 4D Respiratory MotionSim (4D RMS) module. For clinically relevant motion periods (5 s), the interplay effect was small, with deviations in the minimum dose covering the target volume (D99%) of less than ±2.5% for target amplitudes up to 30 mm. Increasing the period to 60 s resulted in interplay effects of up to ±15.0% on target D99% dose coverage. The gradient effect introduced by target motion resulted in deviations of up to ±3.5% in D99% target dose coverage. VMAT treatments showed the largest deviation in dose metrics, which was attributed to the long delivery times in comparison to dMLC IMRT. Retrospective patient analysis indicated minimal interplay and gradient effects for patients treated with dMLC IMRT at the NCCI. PACS numbers: 87.55.km, 87.56.Fc PMID:26894347

The Effect of Dose-Volume Parameters and Interfraction Interval on Cosmetic Outcome and Toxicity After 3-Dimensional Conformal Accelerated Partial Breast Irradiation

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

Leonard, Kara Lynne, E-mail: karalynne.kerr@gmail.com; Hepel, Jaroslaw T.; Department of Radiation Oncology, Rhode Island Hospital, Warren Alpert School of Medicine of Brown University, Providence, Rhode Island

2013-03-01

Purpose: To evaluate dose-volume parameters and the interfraction interval (IFI) as they relate to cosmetic outcome and normal tissue effects of 3-dimensional conformal radiation therapy (3D-CRT) for accelerated partial breast irradiation (APBI). Methods and Materials: Eighty patients were treated by the use of 3D-CRT to deliver APBI at our institutions from 2003-2010 in strict accordance with the specified dose-volume constraints outlined in the National Surgical Adjuvant Breast and Bowel Project B39/Radiation Therapy Oncology Group 0413 (NSABP-B39/RTOG 0413) protocol. The prescribed dose was 38.5 Gy in 10 fractions delivered twice daily. Patients underwent follow-up with assessment for recurrence, late toxicity, andmore » overall cosmetic outcome. Tests for association between toxicity endpoints and dosimetric parameters were performed with the chi-square test. Univariate logistic regression was used to evaluate the association of interfraction interval (IFI) with these outcomes. Results: At a median follow-up time of 32 months, grade 2-4 and grade 3-4 subcutaneous fibrosis occurred in 31% and 7.5% of patients, respectively. Subcutaneous fibrosis improved in 5 patients (6%) with extended follow-up. Fat necrosis developed in 11% of women, and cosmetic outcome was fair/poor in 19%. The relative volume of breast tissue receiving 5%, 20%, 50%, 80%, and 100% (V5-V100) of the prescribed dose was associated with risk of subcutaneous fibrosis, and the volume receiving 50%, 80%, and 100% (V50-V100) was associated with fair/poor cosmesis. The mean IFI was 6.9 hours, and the minimum IFI was 6.2 hours. The mean and minimum IFI values were not significantly associated with late toxicity. Conclusions: The incidence of moderate to severe late toxicity, particularly subcutaneous fibrosis and fat necrosis and resulting fair/poor cosmesis, remains high with continued follow-up. These toxicity endpoints are associated with several dose-volume parameters. Minimum and mean IFI values were not associated with late toxicity.« less

A systematic study of posterior cervical lymph node irradiation with electrons: Conventional versus customized planning.

PubMed

Jankowska, Petra J; Kong, Christine; Burke, Kevin; Harrington, Kevin J; Nutting, Christopher

2007-10-01

High dose irradiation of the posterior cervical lymph nodes usually employs applied electron fields to treat the target volume and maintain the spinal cord dose within tolerance. In the light of recent advances in elective lymph node localisation we investigated optimization of field shape and electron energy to treat this target volume. In this study, three sequential hypotheses were tested. Firstly, that customization of the electron fields based on the nodal PTV outlined gives better PTV coverage than conventional field delineation. Using the consensus guidelines, customization of the electron field shape was compared to conventional fields based on bony landmarks. Secondly, that selection of electron energy using DVHs for spinal cord and PTV improves the minimum dose to PTV. Electron dose-volume histograms (DVHs) for the PTV, spinal cord and para-vertebral muscles, were generated using the Monte Carlo electron algorithm. These DVHs were used to compare standard vs optimized electron energy calculations. Finally, that combination of field customization and electron energy optimization improves both the minimum and mean doses to PTV compared with current standard practice. Customized electron beam shaping based on the consensus guidelines led to fewer geographical misses than standard field shaping. Customized electron energy calculation led to higher minimum doses to the PTV. Overall, the customization of field shape and energy resulted in an improved mean dose to the PTV (92% vs 83% p=0.02) and a 27% improvement in the minimum dose delivered to the PTV (45% vs 18% p=0.0009). Optimization of electron field shape and beam energy based on current consensus guidelines led to significant improvement in PTV coverage and may reduce recurrence rates.

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.

A retrospective study on annual evaluation of radiation processing for frozen bone allografts complying to quality system requirements.

PubMed

Ramalingam, Saravana; Mohd, Suhaili; Samsuddin, Sharifah Mazni; Min, N G Wuey; Yusof, Norimah; Mansor, Azura

2015-12-01

Bone allografts have been used widely to fill up essential void in orthopaedic surgeries. The benefit of using allografts to replace and reconstruct musculoskeletal injuries, fractures or disease has obtained overwhelming acceptance from orthopaedic surgeons worldwide. However, bacterial infection and disease transmission through bone allograft transplantation have always been a significant issue. Sterilization by radiation is an effective method to eliminate unwanted microorganisms thus assist in preventing life threatening allograft associated infections. Femoral heads procured from living donors and long bones (femur and tibia) procured from cadaveric donors were sterilized at 25 kGy in compliance with international standard ISO 11137. According to quality requirements, all records of bone banking were evaluated annually. This retrospective study was carried out on annual evaluation of radiation records from 1998 until 2012. The minimum doses absorbed by the bones were ranging from 25.3 to 38.2 kGy while the absorbed maximum doses were from 25.4 to 42.3 kGy. All the bones supplied by our UMMC Bone Bank were sterile at the required minimum dose of 25 kGy. Our analysis on dose variation showed that the dose uniformity ratios in 37 irradiated boxes of 31 radiation batches were in the range of 1.003-1.251, which indicated the doses were well distributed.

Lowering the Radiation Dose in Dental Offices.

PubMed

Radan, Elham

2017-04-01

While the use of dental imaging continues to evolve into more advanced modalities such as 3-D cone beam computed tomography, in addition to conventional 2-D imaging (intraoral, panoramic and cephalometric), the public concern for radiation safety is also increasing. This article is a guide for how to reduce patients’ exposure to the minimum with proper selection criteria (as needed only if it benefits the patient) and knowledge of effective doses, exposure parameters and proper collimation.

Experimentally studied dynamic dose interplay does not meaningfully affect target dose in VMAT SBRT lung treatments.

PubMed

Stambaugh, Cassandra; Nelms, Benjamin E; Dilling, Thomas; Stevens, Craig; Latifi, Kujtim; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir

2013-09-01

The effects of respiratory motion on the tumor dose can be divided into the gradient and interplay effects. While the interplay effect is likely to average out over a large number of fractions, it may play a role in hypofractionated [stereotactic body radiation therapy (SBRT)] treatments. This subject has been extensively studied for intensity modulated radiation therapy but less so for volumetric modulated arc therapy (VMAT), particularly in application to hypofractionated regimens. Also, no experimental study has provided full four-dimensional (4D) dose reconstruction in this scenario. The authors demonstrate how a recently described motion perturbation method, with full 4D dose reconstruction, is applied to describe the gradient and interplay effects during VMAT lung SBRT treatments. VMAT dose delivered to a moving target in a patient can be reconstructed by applying perturbations to the treatment planning system-calculated static 3D dose. Ten SBRT patients treated with 6 MV VMAT beams in five fractions were selected. The target motion (motion kernel) was approximated by 3D rigid body translation, with the tumor centroids defined on the ten phases of the 4DCT. The motion was assumed to be periodic, with the period T being an average from the empirical 4DCT respiratory trace. The real observed tumor motion (total displacement ≤ 8 mm) was evaluated first. Then, the motion range was artificially increased to 2 or 3 cm. Finally, T was increased to 60 s. While not realistic, making T comparable to the delivery time elucidates if the interplay effect can be observed. For a single fraction, the authors quantified the interplay effect as the maximum difference in the target dosimetric indices, most importantly the near-minimum dose (D99%), between all possible starting phases. For the three- and five-fractions, statistical simulations were performed when substantial interplay was found. For the motion amplitudes and periods obtained from the 4DCT, the interplay effect is negligible (<0.2%). It is also small (0.9% average, 2.2% maximum) when the target excursion increased to 2-3 cm. Only with large motion and increased period (60 s) was a significant interplay effect observed, with D99% ranging from 16% low to 17% high. The interplay effect was statistically significantly lower for the three- and five-fraction statistical simulations. Overall, the gradient effect dominates the clinical situation. A novel method was used to reconstruct the volumetric dose to a moving tumor during lung SBRT VMAT deliveries. With the studied planning and treatment technique for realistic motion periods, regardless of the amplitude, the interplay has nearly no impact on the near-minimum dose. The interplay effect was observed, for study purposes only, with the period comparable to the VMAT delivery time.

Evaluation of dosimetry and image of very low-dose computed tomography attenuation correction for pediatric positron emission tomography/computed tomography: phantom study

NASA Astrophysics Data System (ADS)

Bahn, Y. K.; Park, H. H.; Lee, C. H.; Kim, H. S.; Lyu, K. Y.; Dong, K. R.; Chung, W. K.; Cho, J. H.

2014-04-01

In this study, phantom was used to evaluate attenuation correction computed tomography (CT) dose and image in case of pediatric positron emission tomography (PET)/CT scan. Three PET/CT scanners were used along with acryl phantom in the size for infant and ion-chamber dosimeter. The CT image acquisition conditions were changed from 10 to 20, 40, 80, 100 and 160 mA and from 80 to 100, 120 and 140 kVp, which aimed at evaluating penetrate dose and computed tomography dose indexvolume (CTDIvol) value. And NEMA PET Phantom™ was used to obtain PET image under the same CT conditions in order to evaluate each attenuation-corrected PET image based on standard uptake value (SUV) value and signal-to-noise ratio (SNR). In general, the penetrate dose was reduced by around 92% under the minimum CT conditions (80 kVp and 10 mA) with the decrease in CTDIvol value by around 88%, compared with the pediatric abdomen CT conditions (100 kVp and 100 mA). The PET image with its attenuation corrected according to each CT condition showed no change in SUV value and no influence on the SNR. In conclusion, if the minimum dose CT that is properly applied to body of pediatric patient is corrected for attenuation to ensure that the effective dose is reduced by around 90% or more compared with that for adult patient, this will be useful to reduce radiation exposure level.

Reconstruction of Absorbed Doses to Fibroglandular Tissue of the Breast of Women undergoing Mammography (1960 to the Present)

PubMed Central

Thierry-Chef, Isabelle; Simon, Steven L.; Weinstock, Robert M.; Kwon, Deukwoo; Linet, Martha S.

2013-01-01

The assessment of potential benefits versus harms from mammographic examinations as described in the controversial breast cancer screening recommendations of the U.S. Preventive Task Force included limited consideration of absorbed dose to the fibroglandular tissue of the breast (glandular tissue dose), the tissue at risk for breast cancer. Epidemiological studies on cancer risks associated with diagnostic radiological examinations often lack accurate information on glandular tissue dose, and there is a clear need for better estimates of these doses. Our objective was to develop a quantitative summary of glandular tissue doses from mammography by considering sources of variation over time in key parameters including imaging protocols, x-ray target materials, voltage, filtration, incident air kerma, compressed breast thickness, and breast composition. We estimated the minimum, maximum, and mean values for glandular tissue dose for populations of exposed women within 5-year periods from 1960 to the present, with the minimum to maximum range likely including 90% to 95% of the entirety of the dose range from mammography in North America and Europe. Glandular tissue dose from a single view in mammography is presently about 2 mGy, about one-sixth the dose in the 1960s. The ratio of our estimates of maximum to minimum glandular tissue doses for average-size breasts was about 100 in the 1960s compared to a ratio of about 5 in recent years. Findings from our analysis provide quantitative information on glandular tissue doses from mammographic examinations which can be used in epidemiologic studies of breast cancer. PMID:21988547

Comparison of dose volume parameters evaluated using three forward planning – optimization techniques in cervical cancer brachytherapy involving two applicators

PubMed Central

Basu-Roy, Somapriya; Kar, Sanjay Kumar; Das, Sounik; Lahiri, Annesha

2017-01-01

Purpose This study is intended to compare dose-volume parameters evaluated using different forward planning- optimization techniques, involving two applicator systems in intracavitary brachytherapy for cervical cancer. It looks for the best applicator-optimization combination to fulfill recommended dose-volume objectives in different high-dose-rate (HDR) fractionation schedules. Material and methods We used tandem-ring and Fletcher-style tandem-ovoid applicator in same patients in two fractions of brachytherapy. Six plans were generated for each patient utilizing 3 forward optimization techniques for each applicator used: equal dwell weight/times (‘no optimization’), ‘manual dwell weight/times’, and ‘graphical’. Plans were normalized to left point A and dose of 8 Gy was prescribed. Dose volume and dose point parameters were compared. Results Without graphical optimization, maximum width and thickness of volume enclosed by 100% isodose line, dose to 90%, and 100% of clinical target volume (CTV); minimum, maximum, median, and average dose to both rectum and bladder are significantly higher with Fletcher applicator. Even if it is done, dose to both points B, minimum dose to CTV, and treatment time; dose to 2 cc (D2cc) rectum and rectal point etc.; D2cc, minimum, maximum, median, and average dose to sigmoid colon; D2cc of bladder remain significantly higher with this applicator. Dose to bladder point is similar (p > 0.05) between two applicators, after all optimization techniques. Conclusions Fletcher applicator generates higher dose to both CTV and organs at risk (2 cc volumes) after all optimization techniques. Dose restriction to rectum is possible using graphical optimization only during selected HDR fractionation schedules. Bladder always receives dose higher than recommended, and 2 cc sigmoid colon always gets permissible dose. Contrarily, graphical optimization with ring applicators fulfills all dose volume objectives in all HDR fractionations practiced. PMID:29204164

SU-E-J-240: The Impact On Clinical Dose-Distributions When Using MR-Images Registered with Stereotactic CT-Images in Gamma Knife Radiosurgery

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

Benmakhlouf, H; Kraepelien, T; Forander, P

2014-06-01

Purpose: Most Gamma knife treatments are based solely on MR-images. However, for fractionated treatments and to implement TPS dose calculations that require electron densities, CT image data is essential. The purpose of this work is to assess the dosimetric effects of using MR-images registered with stereotactic CT-images in Gamma knife treatments. Methods: Twelve patients treated for vestibular schwannoma with Gamma Knife Perfexion (Elekta Instruments, Sweden) were selected for this study. The prescribed doses (12 Gy to periphery) were delivered based on the conventional approach of using stereotactic MR-images only. These plans were imported into stereotactic CT-images (by registering MR-images withmore » stereotactic CT-images using the Leksell gamma plan registration software). The dose plans, for each patient, are identical in both cases except for potential rotations and translations resulting from the registration. The impact of the registrations was assessed by an algorithm written in Matlab. The algorithm compares the dose-distributions voxel-by-voxel between the two plans, calculates the full dose coverage of the target (treated in the conventional approach) achieved by the CT-based plan, and calculates the minimum dose delivered to the target (treated in the conventional approach) achieved by the CT-based plan. Results: The mean dose difference between the plans was 0.2 Gy to 0.4 Gy (max 4.5 Gy) whereas between 89% and 97% of the target (treated in the conventional approach) received the prescribed dose, by the CT-plan. The minimum dose to the target (treated in the conventional approach) given by the CT-based plan was between 7.9 Gy and 10.7 Gy (compared to 12 Gy in the conventional treatment). Conclusion: The impact of using MR-images registered with stereotactic CT-images has successfully been compared to conventionally delivered dose plans showing significant differences between the two. Although CTimages have been implemented clinically; the effect of the registration has not been fully investigated.« less

40 CFR 799.9430 - TSCA combined chronic toxicity/carcinogenicity.

Code of Federal Regulations, 2010 CFR

2010-07-01

... effects and determine dose-response relationships. The design and conduct should allow for the detection... dynamic inhalation equipment designed to sustain a minimum air flow of 10 air changes per hour, an... measurements during the exposures should be sufficient. If pretest measurements are not within 10% of each...

40 CFR 799.9430 - TSCA combined chronic toxicity/carcinogenicity.

Code of Federal Regulations, 2011 CFR

2011-07-01

... effects and determine dose-response relationships. The design and conduct should allow for the detection... dynamic inhalation equipment designed to sustain a minimum air flow of 10 air changes per hour, an... measurements during the exposures should be sufficient. If pretest measurements are not within 10% of each...

40 CFR 799.9430 - TSCA combined chronic toxicity/carcinogenicity.

Code of Federal Regulations, 2013 CFR

2013-07-01

... effects and determine dose-response relationships. The design and conduct should allow for the detection... dynamic inhalation equipment designed to sustain a minimum air flow of 10 air changes per hour, an... measurements during the exposures should be sufficient. If pretest measurements are not within 10% of each...

40 CFR 799.9430 - TSCA combined chronic toxicity/carcinogenicity.

Code of Federal Regulations, 2012 CFR

2012-07-01

... effects and determine dose-response relationships. The design and conduct should allow for the detection... dynamic inhalation equipment designed to sustain a minimum air flow of 10 air changes per hour, an... measurements during the exposures should be sufficient. If pretest measurements are not within 10% of each...

40 CFR 799.9430 - TSCA combined chronic toxicity/carcinogenicity.

Code of Federal Regulations, 2014 CFR

2014-07-01

... effects and determine dose-response relationships. The design and conduct should allow for the detection... dynamic inhalation equipment designed to sustain a minimum air flow of 10 air changes per hour, an... measurements during the exposures should be sufficient. If pretest measurements are not within 10% of each...

[Clinical Investigation of the Effects of Filgrastim BS1 on Neutropenia Following Oral Cancer Chemotherapy (TPF Therapy)].

PubMed

Uchiyama, Kimio; Yamada, Manabu; Tamate, Shusuke; Iwasaki, Konomi; Mitomo, Keisuke; Nakayama, Seiichi

2015-09-01

The time for the neutrophil count to recover after subcutaneous injection of filgrastim BS1 or lenograstim was studied in patients suffering from neutropenia following preoperative combined chemotherapy using docetaxel, nedaplatin, or cisplatin (in divided doses for 5 days)and 5-fluorouracil for oral cancer. 1. There was no significant difference in the minimum leukocyte and neutrophil counts after chemotherapy. 2. There was no significant difference in the maximum leukocyte and neutrophil counts after chemotherapy. 3. Time for leukocytes to recover from their minimum count(>4,000/mm3)or for neutrophils to recover from their minimum count(>2,000/mm3)and the number of days on which treatment was administered tended to be shorter in the filgrastim BS1 group. Thus, it was concluded that filgrastim BS1 is just as effective as other prior G-CSF agents in treating patients suffering from neutropenia following chemotherapy(TPF therapy).

[Classical antihypertensive drugs: diuretics].

PubMed

Nagy, Viktor László

2017-03-01

The diuretics are essential medicaments of antihypertensive therapy. They reduce blood pressure and cardiovascular events optimally. With increasing doses of thiazides and thiazide analogs do not come further powerful effect of reducing blood pressure or cardiovascular mortality and morbidity, but clearly elevate the side effects. Because of it, the minimum effective dose level and the fixed-dose combination therapy should be preferred. The use these drugs leads to especially positive outcome in elder patients, isolated systolic hypertension, heart failure, after stroke and in black population. Loop diuretics as antihypertensive therapy can be used only by renal impairment. The use of aldosterone antagonists can have a good effect not only on heart failure but also on prevention of atrial fibrillation. Furthermore, using it in a combination therapy with thiazides, it reduces the risk of hypokalemia. Therefore, the diuretic treatment in hypertension is flourishing again. Orv. Hetil., 2017, 158(11), 403-408.

Dose-Response Effects of Aerobic Exercise on Quality of Life in Postmenopausal Women: Results from the Breast Cancer and Exercise Trial in Alberta (BETA).

PubMed

Courneya, Kerry S; McNeil, Jessica; O'Reilly, Rachel; Morielli, Andria R; Friedenreich, Christine M

2017-06-01

Exercise generally improves quality of life (QoL) and psychosocial functioning in adult populations but few randomized trials have examined dose-response effects. The purpose of the present study was to report the QoL and psychosocial outcomes from the Breast Cancer and Exercise Trial in Alberta (BETA). Healthy but inactive postmenopausal women at risk for breast cancer were randomized to a year-long aerobic exercise intervention consisting of either 150 min/week (moderate volume group, n = 200) or 300 min/week (high volume group, n = 200). QoL was assessed at baseline and 1 year using the short form-36 health survey. Sleep quality, depression, anxiety, stress, self-esteem, and happiness were also assessed. Participant preference for group assignment (i.e., exercise volume) was assessed at baseline and tested as a moderator. There were no statistically significant dose-response effects of aerobic exercise on any QoL, sleep quality, or psychosocial outcome. Participant preference for group assignment did not moderate any QoL, sleep quality, or psychosocial responses. Marital status was a significant moderator (p for interaction = 0.01) and obesity showed a trend towards being a moderator (p for interaction = 0.08) of the dose-response effects of aerobic exercise on global sleep quality such that unmarried and obese women improved sleep quality with the higher volume of aerobic exercise. A higher volume of aerobic exercise, approximately double the minimum public health guideline, did not provide additional QoL or psychosocial benefits compared to the minimum public health guideline in inactive postmenopausal women, even for women who preferred the higher volume of exercise at baseline. Trial Registration clinicaltrials.gov identifier: NCT1435005.

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.

External-beam Co-60 radiotherapy for canine nasal tumors: a comparison of survival by treatment protocol.

PubMed

Yoon, J H; Feeney, D A; Jessen, C R; Walter, P A

2008-02-01

A retrospective analysis of survival times in dogs with intranasal tumors was performed comparing those treated using hypofractionated or full course Co-60 radiotherapy protocols alone or with surgical adjuvant therapy and those receiving no radiation treatment. One hundred thirty-nine dogs presented to the University of Minnesota Veterinary Medical Center for treatment of histologically-confirmed nasal neoplasia between July 1983 and October 2001 met the criteria for review. Statistically analyzed parameters included age at diagnosis, tumor histologic classification, fractionation schedule (number of treatments, and number of treatment days/week) (classified as hypofractionated if 2 or less treatments/week); calculated minimum tumor dose/fraction; calculated total minimum tumor dose (classified as hypofractionated if less than 37 Gy in six or fewer fractions); number of radiotherapy portals, a treatment gap of more than 7 days in a full course (3-5 treatments/week, 3-3.5 week treatment time) radiotherapy protocol, the influence of eye shields on survival following single portal DV fields, the survey radiographic extent of the disease, and the presence or absence of cytoreductive surgery. There was a significant relationship only between protocols using 3 or more treatments/week and at least 37 Gy cumulative minimum tumor dose and survival. However, there was no significant relationship between either total minimum tumor dose or dose/fraction and survival and there were no significant relationships between survival and any of the other variables analyzed including tumor histologic type.

Thermoluminescence response of flat optical fiber subjected to 9 MeV electron irradiations

NASA Astrophysics Data System (ADS)

Hashim, S.; Omar, S. S. Che; Ibrahim, S. A.; Hassan, W. M. S. Wan; Ung, N. M.; Mahdiraji, G. A.; Bradley, D. A.; Alzimami, K.

2015-01-01

We describe the efforts of finding a new thermoluminescent (TL) media using pure silica flat optical fiber (FF). The present study investigates the dose response, sensitivity, minimum detectable dose and glow curve of FF subjected to 9 MeV electron irradiations with various dose ranges from 0 Gy to 2.5 Gy. The above-mentioned TL properties of the FF are compared with commercially available TLD-100 rods. The TL measurements of the TL media exhibit a linear dose response over the delivered dose using a linear accelerator. We found that the sensitivity of TLD-100 is markedly 6 times greater than that of FF optical fiber. The minimum detectable dose was found to be 0.09 mGy for TLD-100 and 8.22 mGy for FF. Our work may contribute towards the development of a new dosimeter for personal monitoring purposes.

Radon activity concentrations and effective doses in ancient Egyptian tombs of the Valley of the Kings.

PubMed

Hafez, A F; Hussein, A S

2001-09-01

Radon concentrations and equilibrium factors were measured in three pharaonic tombs during the year 1998. The tombs, which are open to the public are located in a limestone wadi on the West Bank of the River Nile at Luxor, 650 km south of Cairo. The radon activity concentration and equilibrium factor were measured monthly by two-integral nuclear track detectors (bare and diffusion detectors). Seasonal variation of radon concentrations, with summer maximum and winter minimum were observed in all tombs investigated. The yearly mean radon activity concentrations insidc the tombs ranged from 540 to 3115 Bq m(-3). The mean equilibrium factor over a year was found to be 0.25 and 0.32 inside and at the entrance, respectively. Estimated annual effective doses to tour guides ranged from 0.33 to 1.90 mSv, visitors receive doses from 0.65 to 3.80 microSv per visit. The effective dose to tomb workers did not exceed the 20 mSv yr(-1) limit.

[Effectiveness of thalidomide for erythema nodosum leprosum (ENL): retrospective study of 20 Japanese cases in National Sanatrium Oku-Komyoen].

PubMed

Matsuki, Takanobu; Okano, Yoshiko; Aoki, Yoshinori; Ishida, Yutaka; Hatano, Kentaro; Kumano, Kimiko

2014-12-01

Thalidomide is a TNF-alpha inhibitor and has been administrated for erythema nodosum leprosum (ENL, Type II leprosy reaction) which is one of leprosy reactions and can cause serious illness to patients oflepromatous pole among the immune spectrum. Twenty live cases (at May, 2011) were identified to whom thalidomide had been administrated since 1978 for their ENL reactions. Data were collected from their clinical records in order to evaluate the usage and effectiveness of thalidomide in National Sanatorium Oku-Komyoen, Okayama, Setouchi-city, Japan. Individual data includes bacillary index (BI), total dose, average daily dose, maximum daily dose, minimum daily dose, methods of thalidomide administration and change of symptoms of ENL. Results: No adverse effect was found among 20 cases. Average daily dose of 20 cases was 19 mg. Regarding to the maximum daily dose, in 3 cases (15%) more than 100 mg, in 3 cases (15%) 50 mg, and in 14 cases (70%) less than 40 mg was administrated. Dose was gradually tapered in most cases. From clinical records, thalidomide was found effective for ENL in 19 cases and clinicians concerned were trying to adjust the proper dose of the drug carefully depending on the current symptoms, because there was no guideline of thalidomide administration for ENL. This data suggests that even less than 50-100 mg as the initial daily dose was still effective, though 50-100 mg daily dose is recommended in the current guideline of Japan (2011) and more dose had been administrated in USA and India.

Correlation of Noncancer Benchmark Doses in Short- and Long-Term Rodent Bioassays.

PubMed

Kratchman, Jessica; Wang, Bing; Fox, John; Gray, George

2018-05-01

This study investigated whether, in the absence of chronic noncancer toxicity data, short-term noncancer toxicity data can be used to predict chronic toxicity effect levels by focusing on the dose-response relationship instead of a critical effect. Data from National Toxicology Program (NTP) technical reports have been extracted and modeled using the Environmental Protection Agency's Benchmark Dose Software. Best-fit, minimum benchmark dose (BMD), and benchmark dose lower limits (BMDLs) have been modeled for all NTP pathologist identified significant nonneoplastic lesions, final mean body weight, and mean organ weight of 41 chemicals tested by NTP between 2000 and 2012. Models were then developed at the chemical level using orthogonal regression techniques to predict chronic (two years) noncancer health effect levels using the results of the short-term (three months) toxicity data. The findings indicate that short-term animal studies may reasonably provide a quantitative estimate of a chronic BMD or BMDL. This can allow for faster development of human health toxicity values for risk assessment for chemicals that lack chronic toxicity data. © 2017 Society for Risk Analysis.

Estimates of galactic cosmic ray shielding requirements during solar minimum

NASA Technical Reports Server (NTRS)

Townsend, Lawrence W.; Nealy, John E.; Wilson, John W.; Simonsen, Lisa C.

1990-01-01

Estimates of radiation risk from galactic cosmic rays are presented for manned interplanetary missions. The calculations use the Naval Research Laboratory cosmic ray spectrum model as input into the Langley Research Center galactic cosmic ray transport code. This transport code, which transports both heavy ions and nucleons, can be used with any number of layers of target material, consisting of up to five different arbitrary constituents per layer. Calculated galactic cosmic ray fluxes, dose and dose equivalents behind various thicknesses of aluminum, water and liquid hydrogen shielding are presented for the solar minimum period. Estimates of risk to the skin and the blood-forming organs (BFO) are made using 0-cm and 5-cm depth dose/dose equivalent values, respectively, for water. These results indicate that at least 3.5 g/sq cm (3.5 cm) of water, or 6.5 g/sq cm (2.4 cm) of aluminum, or 1.0 g/sq cm (14 cm) of liquid hydrogen shielding is required to reduce the annual exposure below the currently recommended BFO limit of 0.5 Sv. Because of large uncertainties in fragmentation parameters and the input cosmic ray spectrum, these exposure estimates may be uncertain by as much as a factor of 2 or more. The effects of these potential exposure uncertainties or shield thickness requirements are analyzed.

Surface dose measurement for helical tomotherapy.

PubMed

Snir, Jonatan A; Mosalaei, Homeira; Jordan, Kevin; Yartsev, Slav

2011-06-01

To compare the surface dose measurements made by different dosimeters for the helical tomotherapy (HT) plan in the case of the target close to the surface. Surface dose measurements in different points for the HT plan to deliver 2 Gy to the planning target volume (PTV) at 5 mm below the surface of the cylindrical phantom were performed by radiochromic films, single use metal oxide semiconductor field-effect transistor (MOSFET) dosimeters, silicon IVD QED diode, and optically stimulated luminescence (OSL) dosimeters. The measured doses by all dosimeters were within 12 +/- 8% difference of each other. Radiochromic films, EBT, and EBT2, provide high spatial resolution, although it is difficult to get accurate measurements of dose. Both the OSL and QED measured similar dose to that of the MOSFET detectors. The QED dosimeter is promising as a reusable on-line wireless dosimeter, while the OSL dosimeters are easier to use, require minimum setup time and are very precise.

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.

Pupillometry as an indicator of L-DOPA dosages in Parkinson's disease patients.

PubMed

Bartošová, O; Bonnet, C; Ulmanová, O; Šíma, M; Perlík, F; Růžička, E; Slanař, O

2018-04-01

Dopamine was shown to induce mydriasis by excitation of alpha-adrenergic receptors at the dilator pupillae muscle. Pupilla diameter may thus serve as an indirect measure of peripheral pharmacokinetics of L-DOPA and dopamine. The aim of this study is to evaluate the effect of L-DOPA dosage on pupillometric parameters in Parkinson's disease (PD) patients. Sixteen PD patients and 14 healthy control subjects (CS) were studied. The statistical analysis revealed significant differences between CS and PD patients for the mean maximum and minimum pupil diameters (p = 0.017, p = 0.028, respectively), with higher values found in PD. Moreover, a significant dose-response relationship was found between the maximum pupil diameter and both the morning L-DOPA dose (R 2  = 0.78) and the total daily L-DOPA dose (R 2  = 0.93). A sigmoid-shaped curve best describes the dose-response relationship, with a ceiling effect at about 400 mg L-DOPA daily dose. In conclusion, measuring pupillometric parameters represents a sensitive tool for non-invasive evaluation of the peripheral effect of L-DOPA, especially with daily doses below 400 mg L-DOPA.

Pi meson radiotherapy for advanced head and neck neoplasms: preliminary results.

PubMed

Khan, K M; Bush, S; Herzon, F; Klingerman, M M

1981-01-01

Under the auspices of the University of New Mexico Cancer Research and Treatment Center, trials are under way at the Los Alamos Meson Physics Facility to evaluate the effects of pi meson irradiation on locally advanced human tumors. This paper summarizes the preliminary results in patients with locally advanced head and neck tumors treated under Phase 1 and Phase II studies. A total of 26 patients were treated between June 1977 and May 1979 with a minimum follow-up of 9 months and a maximum follow-up of 33 months. Sites of disease included the oropharynx in 10 cases (base of tongue in 7, tonsil in 2, and pharyngoepiglottic fold in 1), the supraglottic larynx in 4, the nasopharynx in 5, the oral cavity in 4, the hypopharynx in 2, and the sublingual salivary gland in 1. Twelve of the 26 patients are alive, and 10 survive with no evidence of disease. Doses employed ranged from a minimum of 1,000 peak pion rad in 7 fractions over 9 days to a maximum of 5,4000 peak pion rad in 51 fractions of 89 days. The minimum dose employed for any patients treated with peak pions alone was 3,000 rad. These data are analyzed according to dose, sit, histology, tumor response, local control, and survival. Results from these cases form the basis of the Phase III randomized trials for advanced squamous-cell carcinomas of the head and neck, which are currently in progress.

Delayed match-to-sample early performance decrement in monkeys after $sup 60$Co irradiation

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

Bruner, A.; Bogo, V.; Jones, R.K.

1975-07-01

Sixteen monkeys were trained on a delayed match-to-sample task (DMTS) based on shock avoidance and irradiated with single, whole-body exposures of from 396 to 2000 rad $sup 60$Co (midbody dose) at between 163 and 233 rad/min. Pre- to post-irradiation performance changes were assessed using a penalty-scaling measure which differentially weighted incorrect responses, response omissions, and error-omission sequences. Thirteen of the animals displayed early performance decrement, including five incapacitations, at lower doses (less than 1000 rad) than heretofore found effective. This was considered a function of task complexity, measurement sensitivity, and gamma effectiveness. The minimum effective midbody dose for inducing decrementmore » using the DMTS task was estimated to be on the order of 500 rad. The nature of early, transient performance decrement seems to reflect more of an inability to perform than an inability to perform correctly. (auth)« less

Dexmedetomidine in Attenuation of Haemodynamic Response and Dose Sparing Effect on Opioid and Anaesthetic Agents in Patients undergoing Laparoscopic Cholecystectomy- A Randomized Study

PubMed Central

Bhagat, Nandlal; Karim, Habib Md Reazaul; Hajong, Ranendra; Bhattacharyya, Prithwis; Singh, Manorama

2016-01-01

Introduction Perioperative procedures are stressful and lead to haemodynamic instability with potentially devastating consequences. Dexmedetomidine is found to have many of the desired characteristics that are required in perioperative period. Aim To evaluate the ability of pre and intraoperative dexmedetomidine to attenuate stress induced haemodynamic responses, quantifying the anaesthetic agents sparing as well as its cost-effectiveness in patients undergoing laparoscopic cholecystectomy. Materials and Methods The present single blind randomized study was conducted with 120 ASA I and II consented patients who underwent laparoscopic cholecystectomy. Patients were randomly divided into 2 groups (i.e., group D and group N). Prior to induction, group D received 1 μg/kg of Dexmedetomidine and group N received Normal saline infusion over 20 minutes. Group D also received maintenance Dexmedetomidine intraoperatively. Bispectral index and minimum alveolar concentration monitoring was done in both the groups. Haemodynamic parameters were noted till 100 minutes post laryngoscopy. Opioid and anaesthetic agent consumptions were also noted and cost analysis was done. Medcalc–Version 12.5.0.0 software was used for statistics and p <0.05 was considered significant. Results Dexmedetomidine attenuated the stress induced haemodynamics responses and produced stable, relatively non fluctuating haemodynamics throughout. The Minimum Alveolar Concentration (MAC) requirement and the consumptions of Fentanyl and Isoflurane were significantly less in the Dexmedetomidine group (p<0.0001). However, despite anaesthetic dose sparing effect the anaesthetic technique was not cost-effective. Conclusion Dexmedetomidine is effective in attenuating haemodynamic responses in laparoscopic surgery and having dose sparing effect on Fentanyl, Propofol and Isoflurane. However, overall this technique is not cost-effective. PMID:28050479

Low dose radiotherapy for plantar fasciitis. Treatment outcome of 171 patients.

PubMed

Badakhshi, Harun; Buadch, Volker

2014-12-01

Although the effectiveness of low-dose radiotherapy for chronic degenerative and inflammatory diseases has been documented in previous studies, patient-reported clinical outcomes are rarely available. This study aimed to determine the effect of low-dose radiotherapy on patients with painful plantar fasciitis. From 2002 to 2008, 200 patients older than 65 years of age with painful plantar fasciitis were treated in our hospital. Records from 171 of these patients were available for analysis. All patients were treated with an identical dose of 3Gy using identical equipment and techniques. Response was evaluated with patient-reported questionnaires and clinical visits. Minimum-term follow-up was 18 months, with mean follow-up at 54 months. Three months after receiving low-dose radiotherapy, 67.3% of patients had no or mild pain, and 57.9% had no or discrete mobility restriction. At a mean of 54 months, 61.4% of patients had no or mild pain and 64.9% of patients had no or discrete mobility restriction; 60.8% of patients reported improved quality of life. Low-dose radiotherapy is effective in most patients with painful plantar fasciitis. Due to minimal side effects and low costs, it represents an excellent treatment option compared to conventional therapies or surgery. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparison of Two Different Doses of Intrathecal Levobupivacaine for Transurethral Endoscopic Surgery

PubMed Central

Dizman, Secil; Turker, Gurkan; Gurbet, Alp; Mogol, Elif Basagan; Turkcan, Suat; Karakuzu, Ziyaatin

2011-01-01

Objective: To evaluate the effects of two different spinal isobaric levobupivacaine doses on spinal anesthesia characteristics and to find the minimum effective dose for surgery in patients undergoing transurethral resection (TUR) surgery. Materials and Methods: Fifty male patients undergoing TUR surgery were included in the study and were randomized into two equal groups: Group LB10 (n=25): 10 mg 0.5% isobaric levobupivacaine (2 ml) and Group LB15 (n=25): 15 mg 0.75% isobaric levobupivacaine (2 ml). Spinal anesthesia was administered via a 25G Quincke spinal needle through the L3–4 intervertebral space. Sensorial block levels were evaluated using the ‘pin-prick test’, and motor block levels were evaluated using the ‘Bromage scale’. The sensorial and motor block characteristics of patients during intraoperative and postoperative periods and recovery time from spinal anesthesia were evaluated. Results: In three cases in the Group LB10, sensorial block did not reach the T10 level. Complete motor block (Bromage=3) did not occur in eight cases in the Group LB10 and in five cases in the Group LB15. The highest sensorial dermatomal level detected was higher in Group LB15. In Group LB15, sensorial block initial time and the time of complete motor block occurrence were significantly shorter than Group LB10. Hypotension was observed in one case in Group LB15. No significant difference between groups was detected in two segments of regression times: the time to S2 regression and complete sensorial block regression time. Complete motor block regression time was significantly longer in Group LB15 than in Group LB10 (p<0.01). Conclusion: Our findings showed that the minimum effective spinal isobaric levobupivacaine dose was 10 mg for TUR surgery. PMID:25610173

Benchmarking the minimum Electron Beam (eBeam) dose required for the sterilization of space foods

NASA Astrophysics Data System (ADS)

Bhatia, Sohini S.; Wall, Kayley R.; Kerth, Chris R.; Pillai, Suresh D.

2018-02-01

As manned space missions extend in length, the safety, nutrition, acceptability, and shelf life of space foods are of paramount importance to NASA. Since food and mealtimes play a key role in reducing stress and boredom of prolonged missions, the quality of food in terms of appearance, flavor, texture, and aroma can have significant psychological ramifications on astronaut performance. The FDA, which oversees space foods, currently requires a minimum dose of 44 kGy for irradiated space foods. The underlying hypothesis was that commercial sterility of space foods could be achieved at a significantly lower dose, and this lowered dose would positively affect the shelf life of the product. Electron beam processed beef fajitas were used as an example NASA space food to benchmark the minimum eBeam dose required for sterility. A 15 kGy dose was able to achieve an approximately 10 log reduction in Shiga-toxin-producing Escherichia coli bacteria, and a 5 log reduction in Clostridium sporogenes spores. Furthermore, accelerated shelf life testing (ASLT) to determine sensory and quality characteristics under various conditions was conducted. Using Multidimensional gas-chromatography-olfactometry-mass spectrometry (MDGC-O-MS), numerous volatiles were shown to be dependent on the dose applied to the product. Furthermore, concentrations of off -flavor aroma compounds such as dimethyl sulfide were decreased at the reduced 15 kGy dose. The results suggest that the combination of conventional cooking combined with eBeam processing (15 kGy) can achieve the safety and shelf-life objectives needed for long duration space-foods.

NAIRAS aircraft radiation model development, dose climatology, and initial validation.

PubMed

Mertens, Christopher J; Meier, Matthias M; Brown, Steven; Norman, Ryan B; Xu, Xiaojing

2013-10-01

[1] The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) is a real-time, global, physics-based model used to assess radiation exposure to commercial aircrews and passengers. The model is a free-running physics-based model in the sense that there are no adjustment factors applied to nudge the model into agreement with measurements. The model predicts dosimetric quantities in the atmosphere from both galactic cosmic rays (GCR) and solar energetic particles, including the response of the geomagnetic field to interplanetary dynamical processes and its subsequent influence on atmospheric dose. The focus of this paper is on atmospheric GCR exposure during geomagnetically quiet conditions, with three main objectives. First, provide detailed descriptions of the NAIRAS GCR transport and dosimetry methodologies. Second, present a climatology of effective dose and ambient dose equivalent rates at typical commercial airline altitudes representative of solar cycle maximum and solar cycle minimum conditions and spanning the full range of geomagnetic cutoff rigidities. Third, conduct an initial validation of the NAIRAS model by comparing predictions of ambient dose equivalent rates with tabulated reference measurement data and recent aircraft radiation measurements taken in 2008 during the minimum between solar cycle 23 and solar cycle 24. By applying the criterion of the International Commission on Radiation Units and Measurements (ICRU) on acceptable levels of aircraft radiation dose uncertainty for ambient dose equivalent greater than or equal to an annual dose of 1 mSv, the NAIRAS model is within 25% of the measured data, which fall within the ICRU acceptable uncertainty limit of 30%. The NAIRAS model predictions of ambient dose equivalent rate are generally within 50% of the measured data for any single-point comparison. The largest differences occur at low latitudes and high cutoffs, where the radiation dose level is low. Nevertheless, analysis suggests that these single-point differences will be within 30% when a new deterministic pion-initiated electromagnetic cascade code is integrated into NAIRAS, an effort which is currently underway.

NAIRAS aircraft radiation model development, dose climatology, and initial validation

NASA Astrophysics Data System (ADS)

Mertens, Christopher J.; Meier, Matthias M.; Brown, Steven; Norman, Ryan B.; Xu, Xiaojing

2013-10-01

The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) is a real-time, global, physics-based model used to assess radiation exposure to commercial aircrews and passengers. The model is a free-running physics-based model in the sense that there are no adjustment factors applied to nudge the model into agreement with measurements. The model predicts dosimetric quantities in the atmosphere from both galactic cosmic rays (GCR) and solar energetic particles, including the response of the geomagnetic field to interplanetary dynamical processes and its subsequent influence on atmospheric dose. The focus of this paper is on atmospheric GCR exposure during geomagnetically quiet conditions, with three main objectives. First, provide detailed descriptions of the NAIRAS GCR transport and dosimetry methodologies. Second, present a climatology of effective dose and ambient dose equivalent rates at typical commercial airline altitudes representative of solar cycle maximum and solar cycle minimum conditions and spanning the full range of geomagnetic cutoff rigidities. Third, conduct an initial validation of the NAIRAS model by comparing predictions of ambient dose equivalent rates with tabulated reference measurement data and recent aircraft radiation measurements taken in 2008 during the minimum between solar cycle 23 and solar cycle 24. By applying the criterion of the International Commission on Radiation Units and Measurements (ICRU) on acceptable levels of aircraft radiation dose uncertainty for ambient dose equivalent greater than or equal to an annual dose of 1 mSv, the NAIRAS model is within 25% of the measured data, which fall within the ICRU acceptable uncertainty limit of 30%. The NAIRAS model predictions of ambient dose equivalent rate are generally within 50% of the measured data for any single-point comparison. The largest differences occur at low latitudes and high cutoffs, where the radiation dose level is low. Nevertheless, analysis suggests that these single-point differences will be within 30% when a new deterministic pion-initiated electromagnetic cascade code is integrated into NAIRAS, an effort which is currently underway.

NAIRAS aircraft radiation model development, dose climatology, and initial validation

PubMed Central

Mertens, Christopher J; Meier, Matthias M; Brown, Steven; Norman, Ryan B; Xu, Xiaojing

2013-01-01

[1] The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) is a real-time, global, physics-based model used to assess radiation exposure to commercial aircrews and passengers. The model is a free-running physics-based model in the sense that there are no adjustment factors applied to nudge the model into agreement with measurements. The model predicts dosimetric quantities in the atmosphere from both galactic cosmic rays (GCR) and solar energetic particles, including the response of the geomagnetic field to interplanetary dynamical processes and its subsequent influence on atmospheric dose. The focus of this paper is on atmospheric GCR exposure during geomagnetically quiet conditions, with three main objectives. First, provide detailed descriptions of the NAIRAS GCR transport and dosimetry methodologies. Second, present a climatology of effective dose and ambient dose equivalent rates at typical commercial airline altitudes representative of solar cycle maximum and solar cycle minimum conditions and spanning the full range of geomagnetic cutoff rigidities. Third, conduct an initial validation of the NAIRAS model by comparing predictions of ambient dose equivalent rates with tabulated reference measurement data and recent aircraft radiation measurements taken in 2008 during the minimum between solar cycle 23 and solar cycle 24. By applying the criterion of the International Commission on Radiation Units and Measurements (ICRU) on acceptable levels of aircraft radiation dose uncertainty for ambient dose equivalent greater than or equal to an annual dose of 1 mSv, the NAIRAS model is within 25% of the measured data, which fall within the ICRU acceptable uncertainty limit of 30%. The NAIRAS model predictions of ambient dose equivalent rate are generally within 50% of the measured data for any single-point comparison. The largest differences occur at low latitudes and high cutoffs, where the radiation dose level is low. Nevertheless, analysis suggests that these single-point differences will be within 30% when a new deterministic pion-initiated electromagnetic cascade code is integrated into NAIRAS, an effort which is currently underway. PMID:26213513

Sterility and Sexual Competitiveness of Tapachula-7 Anastrepha ludens Males Irradiated at Different Doses.

PubMed

Orozco-Dávila, Dina; Adriano-Anaya, Maria de Lourdes; Quintero-Fong, Luis; Salvador-Figueroa, Miguel

2015-01-01

A genetic sexing strain of Anastrepha ludens (Loew), Tapachula-7, was developed by the Mexican Program Against Fruit Flies to produce and release only males in programs where the sterile insect technique (SIT) is applied. Currently, breeding are found at a massive scale, and it is necessary to determine the optimum irradiation dose that releases sterile males with minimum damage to their sexual competitiveness. Under laboratory and field conditions, we evaluated the effects of gamma irradiation at doses of 0, 20, 40, 60 and 80 Gy on the sexual competitiveness of males, the induction of sterility in wild females and offspring survivorship. The results of the study indicate that irradiation doses have a significant effect on the sexual behavior of males. A reduction of mating capacity was inversely proportional to the irradiation dose of males. It is estimated that a dose of 60 Gy can induce more than 99% sterility in wild females. In all treatments, the degree of offspring fertility was correlated with the irradiation dose of the parents. In conclusion, the results of the study indicate that a dose of 60 Gy can be applied in sterile insect technique release programs. The application of this dose in the new genetic sexing strain of A. ludens is discussed.

Sterility and Sexual Competitiveness of Tapachula-7 Anastrepha ludens Males Irradiated at Different Doses

PubMed Central

Orozco-Dávila, Dina; Adriano-Anaya, Maria de Lourdes; Quintero-Fong, Luis; Salvador-Figueroa, Miguel

2015-01-01

A genetic sexing strain of Anastrepha ludens (Loew), Tapachula-7, was developed by the Mexican Program Against Fruit Flies to produce and release only males in programs where the sterile insect technique (SIT) is applied. Currently, breeding are found at a massive scale, and it is necessary to determine the optimum irradiation dose that releases sterile males with minimum damage to their sexual competitiveness. Under laboratory and field conditions, we evaluated the effects of gamma irradiation at doses of 0, 20, 40, 60 and 80 Gy on the sexual competitiveness of males, the induction of sterility in wild females and offspring survivorship. The results of the study indicate that irradiation doses have a significant effect on the sexual behavior of males. A reduction of mating capacity was inversely proportional to the irradiation dose of males. It is estimated that a dose of 60 Gy can induce more than 99% sterility in wild females. In all treatments, the degree of offspring fertility was correlated with the irradiation dose of the parents. In conclusion, the results of the study indicate that a dose of 60 Gy can be applied in sterile insect technique release programs. The application of this dose in the new genetic sexing strain of A. ludens is discussed. PMID:26274926

Efficacy of a single dose of milbemycin oxime/praziquantel combination tablets, Milpro(®), against adult Echinococcus multilocularis in dogs and both adult and immature E. multilocularis in young cats.

PubMed

Cvejic, Dejan; Schneider, Claudia; Fourie, Josephus; de Vos, Christa; Bonneau, Stephane; Bernachon, Natalia; Hellmann, Klaus

2016-03-01

Two single-site, laboratory, negatively controlled, masked, randomised dose confirmation studies were performed: one in dogs, the other in cats. After a period of acclimatisation, both the dogs and cats were orally infected with Echinococcus multilocularis protoscoleces. In the dog study, 10 dogs received a single dose of Milpro® tablets at a minimum dose of 0.5 mg/kg milbemycin oxime and 5 mg/kg praziquantel 18 days post-infection and 10 dogs received no treatment. In the cat study, 10 cats received a single dose of Milpro® tablets at a minimum dose of 2 mg/kg milbemycin oxime and 5 mg/kg praziquantel 7 days post-infection, 10 cats received a single dose of the treatment 18 days post-infection and 10 cats remained untreated. In both studies, intestinal worm counts were performed 23 days post-infection at necropsy. No worms were retrieved from any of the 30 treated animals. Nine of 10 control dogs had multiple worms (geometric mean 91, arithmetic mean 304) and all 10 control cats had multiple worms (geometric mean 216, arithmetic mean 481). The difference in worm counts between all three treated groups and their controls was highly significant (ANOVA p values of log transformed data <0.0001). Efficacy of 100 % was demonstrated for the elimination of adult E. multilocularis in dogs and cats as well as for elimination of immature E. multilocularis in cats as evidenced by the effectiveness of treatment 7 days post-infection. The treatments were well accepted and tolerated, and there were no adverse drug reactions observed.

Estimating the dose response relationship for occupational radiation exposure measured with minimum detection level.

PubMed

Xue, Xiaonan; Shore, Roy E; Ye, Xiangyang; Kim, Mimi Y

2004-10-01

Occupational exposures are often recorded as zero when the exposure is below the minimum detection level (BMDL). This can lead to an underestimation of the doses received by individuals and can lead to biased estimates of risk in occupational epidemiologic studies. The extent of the exposure underestimation is increased with the magnitude of the minimum detection level (MDL) and the frequency of monitoring. This paper uses multiple imputation methods to impute values for the missing doses due to BMDL. A Gibbs sampling algorithm is developed to implement the method, which is applied to two distinct scenarios: when dose information is available for each measurement (but BMDL is recorded as zero or some other arbitrary value), or when the dose information available represents the summation of a series of measurements (e.g., only yearly cumulative exposure is available but based on, say, weekly measurements). Then the average of the multiple imputed exposure realizations for each individual is used to obtain an unbiased estimate of the relative risk associated with exposure. Simulation studies are used to evaluate the performance of the estimators. As an illustration, the method is applied to a sample of historical occupational radiation exposure data from the Oak Ridge National Laboratory.

Lidocaine, Dexmedetomidine and Their Combination Reduce Isoflurane Minimum Alveolar Concentration in Dogs

PubMed Central

Acevedo-Arcique, Carlos M.; Ibancovichi, José A.; Chavez, Julio R.; Gutierrez-Blanco, Eduardo; Moran-Muñoz, Rafael; Victoria-Mora, José M.; Tendillo-Cortijo, Francisco; Santos-González, Martín; Sanchez-Aparicio, Pedro

2014-01-01

The effects of intravenous (IV) lidocaine, dexmedetomidine and their combination delivered as a bolus followed by a constant rate infusion (CRI) on the minimum alveolar concentration of isoflurane (MACISO) in dogs were evaluated. Seven healthy adult dogs were included. Anaesthesia was induced with propofol and maintained with isoflurane. For each dog, baseline MAC (MACISO/BASAL) was determined after a 90-minute equilibration period. Thereafter, each dog received one of the following treatments (loading dose, CRI): lidocaine 2 mg kg−1, 100 µg kg−1 minute−1; dexmedetomidine 2 µg kg−1, 2 µg kg−1 hour−1; or their combination. MAC was then determined again after 45- minutes of treatment by CRI. At the doses administered, lidocaine, dexmedetomidine and their combination significantly reduced MACISO by 27.3% (range: 12.5–39.2%), 43.4% (33.3–53.3%) and 60.9% (46.1–78.1%), respectively, when compared to MACISO/BASAL. The combination resulted in a greater MACISO reduction than the two drugs alone. Their use, at the doses studied, provides a clinically important reduction in the concentration of ISO during anaesthesia in dogs. PMID:25232737

Efficacy of afoxolaner plus milbemycin oxime chewable tablets (NexGard Spectra®, Merial) against adult Ancylostoma ceylanicum hookworm, in dogs.

PubMed

Tielemans, E; Lebon, W; Dumont, P; Taweethavonsawat, P; Larsen, D; Rehbein, S

2017-04-30

A fixed-combination chewable tablet incorporating afoxolaner plus milbemycin oxime (NexGard Spectra ® , Merial) was tested in purpose-bred Beagle dogs for efficacy against adult Ancylostoma ceylanicum hookworms. Sixteen dogs were inoculated each by oral administration of approximately 500 infective larvae of A. ceylanicum. Seventeen days after inoculation, the dogs were weighed and allocated randomly to be treated with afoxolaner plus milbemycin oxime chewable tablets or to remain untreated. Commercial chewable tablets of different strength were combined to deliver doses as close as possible to the minimum effective dose of 2.5mg afoxolaner plus 0.5mg milbemycin oxime per kg body weight. Parasites were recovered and counted for determination of efficacy seven days after treatment. All eight dogs that had been left untreated were harboring adult A. ceylanicum (geometric mean, 317.8; range, 210-428) while only one and nine A. ceylanicum were recovered from two of the eight dogs treated with afoxolaner plus milbemycin oxime chewable tablets (geometric mean, 0.5; p<0.0001). Thus, 99.9% efficacy against induced infection of A. ceylanicum was obtained by the use of oral NexGard Spectra ® at the minimum effective dose. Treatment with afoxolaner plus milbemycin oxime chewable tablets was well accepted and safe. Copyright © 2017 Elsevier B.V. All rights reserved.

/sup 125/I interstitial implants in the RIF-1 murine flank tumor: an animal model for brachytherapy

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

Bernstein, M.; Gutin, P.H.; Weaver, D.A.

1982-09-01

The development of a model for interstitial brachytherapy that uses high-activity, removable /sup 125/I sources in the RIF-1 murine flank tumor is reported. Experimental end points are clonogenic cell and tumor regrowth delay assays. For the clonogenic cell assay, interestitial radiation is delivered at total doses of 500-10,000 rad at dose rates of 0.9-2.7 rad/min to cells in annuli of tissue in the tumor. Dose-survival curves are characterized by an initial shoulder followed by a straight (exponential) portion, with D/sub 0/ similar to that of the curve obtained by external irradiation of the RIF-1 tumor in a self-contained cesium irradiatormore » at similar dose rates. Tumor regrowth curves have been obtained for minimum tumor doses of 500-5000 rad; marked tumor regression has been observed with minimum tumor doses as low as 2000 rad, but results are not as reproducible as the results obtained with the clonogenic cell assay.« less

Effects of Solar Particle Event Proton Radiation on Parameters Related to Ferret Emesis

PubMed Central

Sanzari, J. K.; Wan, X. S.; Krigsfeld, G. S.; King, G. L.; Miller, A.; Mick, R.; Gridley, D. S.; Wroe, A. J.; Rightnar, S.; Dolney, D.; Kennedy, A. R.

2013-01-01

The effectiveness of simulated solar particle event (SPE) proton radiation to induce retching and vomiting was evaluated in the ferret experimental animal model. The endpoints measured in the study included: (1) the fraction of animals that retched or vomited, (2) the number of retches or vomits observed, (3) the latency period before the first retch or vomit and (4) the duration between the first and last retching or vomiting events. The results demonstrated that γ ray and proton irradiation delivered at a high dose rate of 0.5 Gy/min induced dose-dependent changes in the endpoints related to retching and vomiting. The minimum radiation doses required to induce statistically significant changes in retching- and vomiting-related endpoints were 0.75 and 1.0 Gy, respectively, and the relative biological effectiveness (RBE) of proton radiation at the high dose rate did not significantly differ from 1. Similar but less consistent and smaller changes in the retching- and vomiting-related endpoints were observed for groups irradiated with γ rays and protons delivered at a low dose rate of 0.5 Gy/h. Since this low dose rate is similar to a radiation dose rate expected during a SPE, these results suggest that the risk of SPE radiation-induced vomiting is low and may reach statistical significance only when the radiation dose reaches 1 Gy or higher. PMID:23883319

Final comprehensive report of overall activities of AEC contract AT(30-1)- 3269 from its initiation

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

None

1973-01-01

Research accomplishments are reported for the following projects: determination of the minimum level of x radiation in rats to alter the taste threshold; determination of the permanency of such alteration; determination of the dose and time dependency of the alteration; changes in hypothalamic function following low doses of ionizing radiation; development of new behavioral technique for determination of taste thresholds; correlation of taste sensitivity changes with alteration in taste bud morphology; effects of olfaction on taste thresholds; properties of taste material that influence x radiation effects on taste; determination of effects of in utero x-irradiation on taste function in themore » adult rat; and effects of ingestion of heavy metals on taste acuity and response of taste sensitivity to x radiation. (HLW)« less

Radiation production and absorption in human spacecraft shielding systems under high charge and energy Galactic Cosmic Rays: Material medium, shielding depth, and byproduct aspects

NASA Astrophysics Data System (ADS)

Barthel, Joseph; Sarigul-Klijn, Nesrin

2018-03-01

Deep space missions such as the planned 2025 mission to asteroids require spacecraft shields to protect electronics and humans from adverse effects caused by the space radiation environment, primarily Galactic Cosmic Rays. This paper first reviews the theory on how these rays of charged particles interact with matter, and then presents a simulation for a 500 day Mars flyby mission using a deterministic based computer code. High density polyethylene and aluminum shielding materials at a solar minimum are considered. Plots of effective dose with varying shield depth, charged particle flux, and dose in silicon and human tissue behind shielding are presented.

Development and evaluation of a technique for in vivo monitoring of 60Co in human lungs

NASA Astrophysics Data System (ADS)

de Mello, J. Q.; Lucena, E. A.; Dantas, A. L. A.; Dantas, B. M.

2016-07-01

60Co is a fission product of 235U and represents a risk of internal exposure of workers in nuclear power plants, especially those involved in the maintenance of potentially contaminated parts and equipment. The control of 60Co intake by inhalation can be performed through in vivo monitoring. This work describes the evaluation of a technique through the minimum detectable activity and the corresponding minimum detectable effective doses, based on biokinetic and dosimetric models of 60Co in the human body. The results allow to state that the technique is suitable either for monitoring of occupational exposures or evaluation of accidental intake.

A chromogranin A ELISA absent of an apparent high-dose hook effect observed in other chromogranin A ELISAs.

PubMed

Erickson, J Alan; Grenache, David G

2016-01-15

Routine testing for chromogranin A (CgA) using an established commercial ELISA revealed an apparent high-dose hook effect in approximately 15% of specimens. Investigations found the same effect in two additional ELISAs. We hypothesized that a CgA derived peptide(s) at high concentrations was responsible but experiments were inconclusive. Here we describe the analytical performance characteristics of the Chromoa™ CgA ELISA that did not display the apparent high-dose hook effect. Performance characteristics of the Chromoa ELISA were assessed. The reference interval was established utilizing healthy volunteers. Specimens producing the apparent high-dose hook effect in other assays were evaluated using the Chromoa ELISA. The limit of detection was 8ng/ml. Linearity was acceptable (slope=1.04, intercept=18.1 and r(2)=0.997). CVs were ≤4.6 and ≤9.3% for repeatability and within-laboratory imprecision, respectively. CgA was stable at ambient and refrigerated temperatures for a minimum of two and 14days, respectively. An upper reference interval limit of 95ng/ml was established. Specimens demonstrating the apparent high-dose hook effect in other ELISAs did not exhibit the phenomenon using the Chromoa ELISA. The Chromoa ELISA demonstrates acceptable performance for quantifying serum CgA. The apparent high-dose hook effect exhibited in other ELISAs was absent using the Chromoa assay. Copyright © 2015 Elsevier B.V. All rights reserved.

32 CFR 218.4 - Dose estimate reporting standards.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) MISCELLANEOUS GUIDANCE FOR THE DETERMINATION AND REPORTING OF NUCLEAR RADIATION DOSE FOR DOD PARTICIPANTS IN THE ATMOSPHERIC NUCLEAR TEST PROGRAM (1945-1962) § 218.4 Dose estimate reporting standards. The following minimum... of the radiation environment to which the veteran was exposed and shall include inhaled, ingested...

32 CFR 218.4 - Dose estimate reporting standards.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) MISCELLANEOUS GUIDANCE FOR THE DETERMINATION AND REPORTING OF NUCLEAR RADIATION DOSE FOR DOD PARTICIPANTS IN THE ATMOSPHERIC NUCLEAR TEST PROGRAM (1945-1962) § 218.4 Dose estimate reporting standards. The following minimum... of the radiation environment to which the veteran was exposed and shall include inhaled, ingested...

32 CFR 218.4 - Dose estimate reporting standards.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) MISCELLANEOUS GUIDANCE FOR THE DETERMINATION AND REPORTING OF NUCLEAR RADIATION DOSE FOR DOD PARTICIPANTS IN THE ATMOSPHERIC NUCLEAR TEST PROGRAM (1945-1962) § 218.4 Dose estimate reporting standards. The following minimum... of the radiation environment to which the veteran was exposed and shall include inhaled, ingested...

32 CFR 218.4 - Dose estimate reporting standards.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) MISCELLANEOUS GUIDANCE FOR THE DETERMINATION AND REPORTING OF NUCLEAR RADIATION DOSE FOR DOD PARTICIPANTS IN THE ATMOSPHERIC NUCLEAR TEST PROGRAM (1945-1962) § 218.4 Dose estimate reporting standards. The following minimum... of the radiation environment to which the veteran was exposed and shall include inhaled, ingested...

32 CFR 218.4 - Dose estimate reporting standards.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) MISCELLANEOUS GUIDANCE FOR THE DETERMINATION AND REPORTING OF NUCLEAR RADIATION DOSE FOR DOD PARTICIPANTS IN THE ATMOSPHERIC NUCLEAR TEST PROGRAM (1945-1962) § 218.4 Dose estimate reporting standards. The following minimum... of the radiation environment to which the veteran was exposed and shall include inhaled, ingested...

SU-E-J-33: Cardiac Movement in Deep Inspiration Breath-Hold for Left-Breast Cancer Radiotherapy

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

Kim, M; Lee, S; Suh, T

Purpose: The present study was designed to investigate the displacement of heart using Deep Inspiration Breath Hold (DIBH) CT data compared to free-breathing (FB) CT data and radiation exposure to heart. Methods: Treatment planning was performed on the computed tomography (CT) datasets of 20 patients who had received lumpectomy treatments. Heart, lung and both breasts were outlined. The prescribed dose was 50 Gy divided into 28 fractions. The dose distributions in all the plans were required to fulfill the International Commission on Radiation Units and Measurement specifications that include 100% coverage of the CTV with ≥ 95% of the prescribedmore » dose and that the volume inside the CTV receiving > 107% of the prescribed dose should be minimized. Displacement of heart was measured by calculating the distance between center of heart and left breast. For the evaluation of radiation dose to heart, minimum, maximum and mean dose to heart were calculated. Results: The maximum and minimum left-right (LR) displacements of heart were 8.9 mm and 3 mm, respectively. The heart moved > 4 mm in the LR direction in 17 of the 20 patients. The distances between the heart and left breast ranged from 8.02–17.68 mm (mean, 12.23 mm) and 7.85–12.98 mm (mean, 8.97 mm) with DIBH CT and FB CT, respectively. The maximum doses to the heart were 3115 cGy and 4652 cGy for the DIBH and FB CT dataset, respectively. Conclusion: The present study has demonstrated that the DIBH technique could help to reduce the risk of radiation dose-induced cardiac toxicity by using movement of cardiac; away from radiation field. The DIBH technique could be used in an actual treatment room for a few minutes and could effectively reduce the cardiac dose when used with a sub-device or image acquisition standard to maintain consistent respiratory motion.« less

Proof of concept and dose estimation with binary responses under model uncertainty.

PubMed

Klingenberg, B

2009-01-30

This article suggests a unified framework for testing Proof of Concept (PoC) and estimating a target dose for the benefit of a more comprehensive, robust and powerful analysis in phase II or similar clinical trials. From a pre-specified set of candidate models, we choose the ones that best describe the observed dose-response. To decide which models, if any, significantly pick up a dose effect, we construct the permutation distribution of the minimum P-value over the candidate set. This allows us to find critical values and multiplicity adjusted P-values that control the familywise error rate of declaring any spurious effect in the candidate set as significant. Model averaging is then used to estimate a target dose. Popular single or multiple contrast tests for PoC, such as the Cochran-Armitage, Dunnett or Williams tests, are only optimal for specific dose-response shapes and do not provide target dose estimates with confidence limits. A thorough evaluation and comparison of our approach to these tests reveal that its power is as good or better in detecting a dose-response under various shapes with many more additional benefits: It incorporates model uncertainty in PoC decisions and target dose estimation, yields confidence intervals for target dose estimates and extends to more complicated data structures. We illustrate our method with the analysis of a Phase II clinical trial. Copyright (c) 2008 John Wiley & Sons, Ltd.

Solar cosmic ray hazard to interplanetary and earth-orbital space travel

NASA Technical Reports Server (NTRS)

Yucker, W. R.

1972-01-01

A statistical treatment of the radiation hazards to astronauts due to solar cosmic ray protons is reported to determine shielding requirements for solar proton events. More recent data are incorporated into the present analysis in order to improve the accuracy of the predicted mission fluence and dose. The effects of the finite data sample are discussed. Mission fluence and dose versus shield thickness data are presented for mission lengths up to 3 years during periods of maximum and minimum solar activity; these correspond to various levels of confidence that the predicted hazard will not be exceeded.

From Earth to Mars, Radiation Intensities in Interplanetary Space

NASA Astrophysics Data System (ADS)

O'Brien, Keran

2007-10-01

The radiation field in interplanetary space between Earth and Mars is rather intense. Using a modified version of the ATROPOS Monte Carlo code combined with a modified version of the deterministic code, PLOTINUS, the effective dose rate to crew members in space craft hull shielded with a shell of 2 g/cm^2 of aluminum and 20 g/cm^2 of polyethylene was calculated to be 51 rem/y. The total dose during the solar-particle event of September 29, 1989, GLE 42, was calculated to be 50 rem. The dose in a ``storm cellar'' of 100 g/cm^2 of polyethylene equivalent during this time was calculated to be 5 rem. The calculations were for conditions corresponding to a recent solar minimum.

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.

SU-E-T-578: On Definition of Minimum and Maximum Dose for Target Volume

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

Gong, Y; Yu, J; Xiao, Y

Purpose: This study aims to investigate the impact of different minimum and maximum dose definitions in radiotherapy treatment plan quality evaluation criteria by using tumor control probability (TCP) models. Methods: Dosimetric criteria used in RTOG 1308 protocol are used in the investigation. RTOG 1308 is a phase III randomized trial comparing overall survival after photon versus proton chemoradiotherapy for inoperable stage II-IIIB NSCLC. The prescription dose for planning target volume (PTV) is 70Gy. Maximum dose (Dmax) should not exceed 84Gy and minimum dose (Dmin) should not go below 59.5Gy in order for the plan to be “per protocol” (satisfactory).A mathematicalmore » model that simulates the characteristics of PTV dose volume histogram (DVH) curve with normalized volume is built. The Dmax and Dmin are noted as percentage volumes Dη% and D(100-δ)%, with η and d ranging from 0 to 3.5. The model includes three straight line sections and goes through four points: D95%= 70Gy, Dη%= 84Gy, D(100-δ)%= 59.5 Gy, and D100%= 0Gy. For each set of η and δ, the TCP value is calculated using the inhomogeneously irradiated tumor logistic model with D50= 74.5Gy and γ50=3.52. Results: TCP varies within 0.9% with η; and δ values between 0 and 1. With η and η varies between 0 and 2, TCP change was up to 2.4%. With η and δ variations from 0 to 3.5, maximum of 8.3% TCP difference is seen. Conclusion: When defined maximum and minimum volume varied more than 2%, significant TCP variations were seen. It is recommended less than 2% volume used in definition of Dmax or Dmin for target dosimetric evaluation criteria. This project was supported by NIH grants U10CA180868, U10CA180822, U24CA180803, U24CA12014 and PA CURE Grant.« less

A motion phantom study on helical tomotherapy: the dosimetric impacts of delivery technique and motion

NASA Astrophysics Data System (ADS)

Kanagaki, Brian; Read, Paul W.; Molloy, Janelle A.; Larner, James M.; Sheng, Ke

2007-01-01

Helical tomotherapy (HT) can potentially be used for lung cancer treatment including stereotactic radiosurgery because of its advanced image guidance and its ability to deliver highly conformal dose distributions. However, previous theoretical and simulation studies reported that the effect of respiratory motion on statically planned tomotherapy treatments may cause substantial differences between the calculated and actual delivered radiation isodose distribution, particularly when the treatment is hypofractionated. In order to determine the dosimetric effects of motion upon actual HT treatment delivery, phantom film dosimetry measurements were performed under static and moving conditions using a clinical HT treatment unit. The motion phantom system was constructed using a programmable motor, a base, a moving platform and a life size lung heterogeneity phantom with wood inserts representing lung tissue with a 3.0 cm diameter spherical tumour density equivalent insert. In order to determine the effects of different motion and tomotherapy delivery parameters, treatment plans were created using jaw sizes of 1.04 cm and 2.47 cm, with incremental gantry rotation periods between the minimum allowed (10 s) and the maximum allowed (60 s). The couch speed varied from 0.009 cm s-1 to 0.049 cm s-1, and delivered to a phantom under static and dynamic conditions with peak-to-peak motion amplitudes of 1.2 cm and 2 cm and periods of 3 and 5 s to simulate human respiratory motion of lung tumours. A cylindrical clinical target volume (CTV) was contoured to tightly enclose the tumour insert. 2.0 Gy was prescribed to 95% of the CTV. Two-dimensional dose was measured by a Kodak EDR2 film. Dynamic phantom doses were then quantitatively compared to static phantom doses in terms of axial dose profiles, cumulative dose volume histograms (DVH), percentage of CTV receiving the prescription dose and the minimum dose received by 95% of the CTV. The larger motion amplitude resulted in more under-dosing at the ends of the CTV in the axis of motion, and this effect was greater for the smaller jaw size plans. Due to the size of the penumbra, the 2.47 cm jaw plans provide adequate coverage for smaller amplitudes of motion, ±0.6 cm in our experiment, without adding any additional margin in the axis of motion to the treatment volume. The periodic heterogeneous patterns described by previous studies were not observed from the single fraction of the phantom measurement. Besides the jaw sizes, CTV dose coverage is not significantly dependent on machine and phantom motion periods. The lack of adverse synchronization patterns from both results validate that HT is a safe technique for treating moving target and hypofractionation.

Killing of Serratia marcescens biofilms with chloramphenicol.

PubMed

Ray, Christopher; Shenoy, Anukul T; Orihuela, Carlos J; González-Juarbe, Norberto

2017-03-29

Serratia marcescens is a Gram-negative bacterium with proven resistance to multiple antibiotics and causative of catheter-associated infections. Bacterial colonization of catheters mainly involves the formation of biofilm. The objectives of this study were to explore the susceptibility of S. marcescens biofilms to high doses of common antibiotics and non-antimicrobial agents. Biofilms formed by a clinical isolate of S. marcescens were treated with ceftriaxone, kanamycin, gentamicin, and chloramphenicol at doses corresponding to 10, 100 and 1000 times their planktonic minimum inhibitory concentration. In addition, biofilms were also treated with chemical compounds such as polysorbate-80 and ursolic acid. S. marcescens demonstrated susceptibility to ceftriaxone, kanamycin, gentamicin, and chloramphenicol in its planktonic form, however, only chloramphenicol reduced both biofilm biomass and biofilm viability. Polysorbate-80 and ursolic acid had minimal to no effect on either planktonic and biofilm grown S. marcescens. Our results suggest that supratherapeutic doses of chloramphenicol can be used effectively against established S. marcescens biofilms.

The mass-action law based algorithms for quantitative econo-green bio-research.

PubMed

Chou, Ting-Chao

2011-05-01

The relationship between dose and effect is not random, but rather governed by the unified theory based on the median-effect equation (MEE) of the mass-action law. Rearrangement of MEE yields the mathematical form of the Michaelis-Menten, Hill, Henderson-Hasselbalch and Scatchard equations of biochemistry and biophysics, and the median-effect plot allows linearization of all dose-effect curves regardless of potency and shape. The "median" is the universal common-link and reference-point for the 1st-order to higher-order dynamics, and from single-entities to multiple-entities and thus, it allows the all for one and one for all unity theory to "integrate" simple and complex systems. Its applications include the construction of a dose-effect curve with a theoretical minimum of only two data points if they are accurately determined; quantification of synergism or antagonism at all dose and effect levels; the low-dose risk assessment for carcinogens, toxic substances or radiation; and the determination of competitiveness and exclusivity for receptor binding. Since the MEE algorithm allows the reduced requirement of the number of data points for small size experimentation, and yields quantitative bioinformatics, it points to the deterministic, efficient, low-cost biomedical research and drug discovery, and ethical planning for clinical trials. It is concluded that the contemporary biomedical sciences would greatly benefit from the mass-action law based "Green Revolution".

Minimum exposure limits and measured relationships between the vitamin D, erythema and international commission on non-ionizing radiation protection solar ultraviolet.

PubMed

Downs, Nathan; Parisi, Alfio; Butler, Harry; Turner, Joanna; Wainwright, Lisa

2015-01-01

The International Commission on Non-Ionizing Radiation Protection (ICNIRP) has established guidelines for exposure to ultraviolet radiation in outdoor occupational settings. Spectrally weighted ICNIRP ultraviolet exposures received by the skin or eye in an 8 h period are limited to 30 J m(-2). In this study, the time required to reach the ICNIRP exposure limit was measured daily in 10 min intervals upon a horizontal plane at a subtropical Australian latitude over a full year and compared with the effective Vitamin D dose received to one-quarter of the available skin surface area for all six Fitzpatrick skin types. The comparison of measured solar ultraviolet exposures for the full range of sky conditions in the 2009 measurement period, including a major September continental dust event, show a clear relationship between the weighted ICNIRP and the effective vitamin D dose. Our results show that the horizontal plane ICNIRP ultraviolet exposure may be used under these conditions to provide minimum guidelines for the healthy moderation of vitamin D, scalable to each of the six Fitzpatrick skin types. © 2014 The American Society of Photobiology.

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

Zhang, J; Li, X; Ding, X

Purpose: We investigate the spot characteristic and dose profiles properties from a compact gantry proton therapy system. This compact design features a dedicated pencil beam scanning nozzle with the scanning magnet located upstream of the final 60 degree bending magnet. Due to the unique beam line design, uncertainty has been raised in the virtual source-to-axis distance (SAD). We investigate its potential clinical impact through measurements and simulation. Methods: A scintillator camera based detector was used to measure spot characteristics and position accuracy. An ion chamber array device was used to measure planar dose profile. Dose profile in-air simulation was performedmore » using in-house built MATLAB program based on additional spot parameters directly from measurements. Spot characteristics such as position and in-air sigma values were used to general simulated 2D elliptical Gaussian spots. The virtual SAD distance changes in the longitudinal direction were also simulated. Planar dose profiles were generated by summation of simulated spots at the isocenter, 15 cm above the isocenter, and 15 cm below the isocenter for evaluation of potential clinical dosimetric impact. Results: We found that the virtual SAD varies depending on the spot location on the longitudinal axis. Measurements have shown that the variable SAD changes from 7 to 12 meters from one end to the other end of the treatment field in the longitudinal direction. The simulation shows that the planer dose profiles differences between the fixed SAD and variable SAD are within 3% from the isocenter profile and the lateral penumbras are within 1 mm difference. Conclusion: Our measurements and simulations show that there are minimum effects on the spot characteristics and dose profiles for this up-stream scanning compact system proton system. Further treatment planning study is needed with the variable virtual SAD accounted for in the planning system to show minimum dosimetric impact.« less

Quantifying the interplay effect in prostate IMRT delivery using a convolution-based method.

PubMed

Li, Haisen S; Chetty, Indrin J; Solberg, Timothy D

2008-05-01

The authors present a segment-based convolution method to account for the interplay effect between intrafraction organ motion and the multileaf collimator position for each particular segment in intensity modulated radiation therapy (IMRT) delivered in a step-and-shoot manner. In this method, the static dose distribution attributed to each segment is convolved with the probability density function (PDF) of motion during delivery of the segment, whereas in the conventional convolution method ("average-based convolution"), the static dose distribution is convolved with the PDF averaged over an entire fraction, an entire treatment course, or even an entire patient population. In the case of IMRT delivered in a step-and-shoot manner, the average-based convolution method assumes that in each segment the target volume experiences the same motion pattern (PDF) as that of population. In the segment-based convolution method, the dose during each segment is calculated by convolving the static dose with the motion PDF specific to that segment, allowing both intrafraction motion and the interplay effect to be accounted for in the dose calculation. Intrafraction prostate motion data from a population of 35 patients tracked using the Calypso system (Calypso Medical Technologies, Inc., Seattle, WA) was used to generate motion PDFs. These were then convolved with dose distributions from clinical prostate IMRT plans. For a single segment with a small number of monitor units, the interplay effect introduced errors of up to 25.9% in the mean CTV dose compared against the planned dose evaluated by using the PDF of the entire fraction. In contrast, the interplay effect reduced the minimum CTV dose by 4.4%, and the CTV generalized equivalent uniform dose by 1.3%, in single fraction plans. For entire treatment courses delivered in either a hypofractionated (five fractions) or conventional (> 30 fractions) regimen, the discrepancy in total dose due to interplay effect was negligible.

SU-E-I-16: Scan Length Dependency of the Radial Dose Distribution in a Long Polyethylene Cylinder

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

Bakalyar, D; McKenney, S; Feng, W

Purpose: The area-averaged dose in the central plane of a long cylinder following a CT scan depends upon the radial dose distribution and the length of the scan. The ICRU/TG200 phantom, a polyethylene cylinder 30 cm in diameter and 60 cm long, was the subject of this study. The purpose was to develop an analytic function that could determine the dose for a scan length L at any point in the central plane of this phantom. Methods: Monte Carlo calculations were performed on a simulated ICRU/TG200 phantom under conditions of cylindrically symmetric conditions of irradiation. Thus, the radial dose distributionmore » function must be an even function that accounts for two competing effects: The direct beam makes its weakest contribution at the center while the scatter begins abruptly at the outer radius and grows as the center is approached. The scatter contribution also increases with scan length with the increase approaching its limiting value at the periphery faster than along the central axis. An analytic function was developed that fit the data and possessed these features. Results: Symmetry and continuity dictate a local extremum at the center which is a minimum for the ICRU/TG200 phantom. The relative depth of the minimum decreases as the scan length grows and an absolute maximum can occur between the center and outer edge of the cylinders. As the scan length grows, the relative dip in the center decreases so that for very long scan lengths, the dose profile is relatively flat. Conclusion: An analytic function characterizes the radial and scan length dependency of dose for long cylindrical phantoms. The function can be integrated with the results expressed in closed form. One use for this is to help determine average dose distribution over the central cylinder plane for any scan length.« less

Dose Equivalents for Second-Generation Antipsychotic Drugs: The Classical Mean Dose Method

PubMed Central

Leucht, Stefan; Samara, Myrto; Heres, Stephan; Patel, Maxine X.; Furukawa, Toshi; Cipriani, Andrea; Geddes, John; Davis, John M.

2015-01-01

Background: The concept of dose equivalence is important for many purposes. The classical approach published by Davis in 1974 subsequently dominated textbooks for several decades. It was based on the assumption that the mean doses found in flexible-dose trials reflect the average optimum dose which can be used for the calculation of dose equivalence. We are the first to apply the method to second-generation antipsychotics. Methods: We searched for randomized, double-blind, flexible-dose trials in acutely ill patients with schizophrenia that examined 13 oral second-generation antipsychotics, haloperidol, and chlorpromazine (last search June 2014). We calculated the mean doses of each drug weighted by sample size and divided them by the weighted mean olanzapine dose to obtain olanzapine equivalents. Results: We included 75 studies with 16 555 participants. The doses equivalent to 1 mg/d olanzapine were: amisulpride 38.3 mg/d, aripiprazole 1.4 mg/d, asenapine 0.9 mg/d, chlorpromazine 38.9 mg/d, clozapine 30.6 mg/d, haloperidol 0.7 mg/d, quetiapine 32.3mg/d, risperidone 0.4mg/d, sertindole 1.1 mg/d, ziprasidone 7.9 mg/d, zotepine 13.2 mg/d. For iloperidone, lurasidone, and paliperidone no data were available. Conclusions: The classical mean dose method is not reliant on the limited availability of fixed-dose data at the lower end of the effective dose range, which is the major limitation of “minimum effective dose methods” and “dose-response curve methods.” In contrast, the mean doses found by the current approach may have in part depended on the dose ranges chosen for the original trials. Ultimate conclusions on dose equivalence of antipsychotics will need to be based on a review of various methods. PMID:25841041

The direct anti-MRSA effect of emodin via damaging cell membrane.

PubMed

Liu, Ming; Peng, Wei; Qin, Rongxin; Yan, Zifei; Cen, Yanyan; Zheng, Xinchuan; Pan, Xichun; Jiang, Weiwei; Li, Bin; Li, Xiaoli; Zhou, Hong

2015-09-01

Methicillin-resistant Staphylococcus aureus (MRSA) has become an important bacterium for nosocomial infection. Only a few antibiotics can be effective against MRSA. Therefore, searching for new drugs against MRSA is important. Herein, anti-MRSA activities of emodin and its mechanisms were investigated. Firstly, in vitro antimicrobial activity was investigated by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and time-growth curve, and multipassage resistance testing was performed. Secondly, protection of emodin on mice survival and blood bacterial load in mice challenged with lethal or sublethal dose of MRSA were investigated. Subsequently, the influences of emodin on the bacterial morphology, messenger RNA (mRNA) expressions related to cell wall synthesis and lysis, β-lactamase activity, drug accumulation, membrane fluidity, and integrity were performed to investigate its mechanisms. Lastly, in vitro cytotoxicity assay were performed using the 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) method. The results showed MICs and MBCs of emodin against MRSA252 and 36 clinical MRSA strains were among 2-8 and 4-32 μg/mL, respectively. There was no MIC increase for emodin during 20 passages. In vivo, emodin dose-dependently protected mice challenged with lethal dose of MRSA and decreased bacterial load in mice challenged with sublethal dose of MRSA. Morphology observation showed emodin might disrupt cell wall and membrane of MRSA. Although emodin had no influence on genes related to cell wall synthesis and lysis as well as β-lactamase activity and drug accumulation, emodin reduced membrane fluidity and disrupted membrane integrity. Based on the fact that emodin had no significant cytotoxicity against mammalian cells, it could be further investigated as a membrane-damage bactericide against MRSA in the future.

Optimal Chemotherapy for Leukemia: A Model-Based Strategy for Individualized Treatment

PubMed Central

Jayachandran, Devaraj; Rundell, Ann E.; Hannemann, Robert E.; Vik, Terry A.; Ramkrishna, Doraiswami

2014-01-01

Acute Lymphoblastic Leukemia, commonly known as ALL, is a predominant form of cancer during childhood. With the advent of modern healthcare support, the 5-year survival rate has been impressive in the recent past. However, long-term ALL survivors embattle several treatment-related medical and socio-economic complications due to excessive and inordinate chemotherapy doses received during treatment. In this work, we present a model-based approach to personalize 6-Mercaptopurine (6-MP) treatment for childhood ALL with a provision for incorporating the pharmacogenomic variations among patients. Semi-mechanistic mathematical models were developed and validated for i) 6-MP metabolism, ii) red blood cell mean corpuscular volume (MCV) dynamics, a surrogate marker for treatment efficacy, and iii) leukopenia, a major side-effect. With the constraint of getting limited data from clinics, a global sensitivity analysis based model reduction technique was employed to reduce the parameter space arising from semi-mechanistic models. The reduced, sensitive parameters were used to individualize the average patient model to a specific patient so as to minimize the model uncertainty. Models fit the data well and mimic diverse behavior observed among patients with minimum parameters. The model was validated with real patient data obtained from literature and Riley Hospital for Children in Indianapolis. Patient models were used to optimize the dose for an individual patient through nonlinear model predictive control. The implementation of our approach in clinical practice is realizable with routinely measured complete blood counts (CBC) and a few additional metabolite measurements. The proposed approach promises to achieve model-based individualized treatment to a specific patient, as opposed to a standard-dose-for-all, and to prescribe an optimal dose for a desired outcome with minimum side-effects. PMID:25310465

Doses of Nearby Nature Simultaneously Associated with Multiple Health Benefits

PubMed Central

Cox, Daniel T. C.; Shanahan, Danielle F.; Hudson, Hannah L.; Fuller, Richard A.; Anderson, Karen; Hancock, Steven; Gaston, Kevin J.

2017-01-01

Exposure to nature provides a wide range of health benefits. A significant proportion of these are delivered close to home, because this offers an immediate and easily accessible opportunity for people to experience nature. However, there is limited information to guide recommendations on its management and appropriate use. We apply a nature dose-response framework to quantify the simultaneous association between exposure to nearby nature and multiple health benefits. We surveyed ca. 1000 respondents in Southern England, UK, to determine relationships between (a) nature dose type, that is the frequency and duration (time spent in private green space) and intensity (quantity of neighbourhood vegetation cover) of nature exposure and (b) health outcomes, including mental, physical and social health, physical behaviour and nature orientation. We then modelled dose-response relationships between dose type and self-reported depression. We demonstrate positive relationships between nature dose and mental and social health, increased physical activity and nature orientation. Dose-response analysis showed that lower levels of depression were associated with minimum thresholds of weekly nature dose. Nearby nature is associated with quantifiable health benefits, with potential for lowering the human and financial costs of ill health. Dose-response analysis has the potential to guide minimum and optimum recommendations on the management and use of nearby nature for preventative healthcare. PMID:28208789

Doses of Nearby Nature Simultaneously Associated with Multiple Health Benefits.

PubMed

Cox, Daniel T C; Shanahan, Danielle F; Hudson, Hannah L; Fuller, Richard A; Anderson, Karen; Hancock, Steven; Gaston, Kevin J

2017-02-09

Exposure to nature provides a wide range of health benefits. A significant proportion of these are delivered close to home, because this offers an immediate and easily accessible opportunity for people to experience nature. However, there is limited information to guide recommendations on its management and appropriate use. We apply a nature dose-response framework to quantify the simultaneous association between exposure to nearby nature and multiple health benefits. We surveyed ca. 1000 respondents in Southern England, UK, to determine relationships between (a) nature dose type, that is the frequency and duration (time spent in private green space) and intensity (quantity of neighbourhood vegetation cover) of nature exposure and (b) health outcomes, including mental, physical and social health, physical behaviour and nature orientation. We then modelled dose-response relationships between dose type and self-reported depression. We demonstrate positive relationships between nature dose and mental and social health, increased physical activity and nature orientation. Dose-response analysis showed that lower levels of depression were associated with minimum thresholds of weekly nature dose. Nearby nature is associated with quantifiable health benefits, with potential for lowering the human and financial costs of ill health. Dose-response analysis has the potential to guide minimum and optimum recommendations on the management and use of nearby nature for preventative healthcare.

Effects of alfaxalone administered intravenously to healthy yearling loggerhead sea turtles (Caretta caretta) at three different doses.

PubMed

Phillips, Brianne E; Posner, Lysa P; Lewbart, Gregory A; Christiansen, Emily F; Harms, Craig A

2017-04-15

OBJECTIVE To compare physiologic and anesthetic effects of alfaxalone administered IV to yearling loggerhead sea turtles (Caretta caretta) at 3 different doses. DESIGN Randomized crossover study. ANIMALS 9 healthy yearling loggerhead sea turtles. PROCEDURES Animals received each of 3 doses of alfaxalone (3 mg/kg [1.4 mg/lb], 5 mg/kg [2.3 mg/lb], or 10 mg/kg [4.5 mg/lb]) administered IV in randomly assigned order, with a minimum 7-day washout period between doses. Endotracheal intubation was attempted following anesthetic induction, and heart rate, sedation depth, cloacal temperature, and respirations were monitored. Times to first effect, induction, first voluntary muscle movement, first respiration, and recovery were recorded. Venous blood gas analysis was performed at 0 and 30 minutes. Assisted ventilation was performed if apnea persisted 30 minutes following induction. RESULTS Median anesthetic induction time for all 3 doses was 2 minutes. Endotracheal intubation was accomplished in all turtles following induction. Heart rate significantly increased after the 3- and 5-mg/kg doses were administered. Median intervals from alfaxalone administration to first spontaneous respiration were 16, 22, and 54 minutes for the 3-, 5-, and 10-mg/kg doses, respectively, and median intervals to recovery were 28, 46, and 90 minutes, respectively. Assisted ventilation was required for 1 turtle after receiving the 5-mg/kg dose and for 5 turtles after receiving the 10-mg/kg dose. The 10-mg/kg dose resulted in respiratory acidosis and marked hypoxemia at 30 minutes. CONCLUSIONS AND CLINICAL RELEVANCE IV alfaxalone administration to loggerhead sea turtles resulted in a rapid anesthetic induction and dose-dependent duration of sedation. Assisted ventilation is recommended if the 10 mg/kg dose is administered.

Exercise and Health: Dose and Response, Considering Both Ends of the Curve.

PubMed

Simon, Harvey B

2015-11-01

Over the past 60 years, an enormous body of data has demonstrated that exercise is good for health. Recently, however, there has been concern that repetitive intense exercise may have deleterious cardiovascular effects. To evaluate this possibility, I have reviewed the health response to exercise, with particular attention to the body's minimum daily requirement and to the maximum amount that is safe and effective. Copyright © 2015 Elsevier Inc. All rights reserved.

Commissioning dosimetry and in situ dose mapping of a semi-industrial Cobalt-60 gamma-irradiation facility using Fricke and Ceric-cerous dosimetry system and comparison with Monte Carlo simulation data

NASA Astrophysics Data System (ADS)

Mortuza, Md Firoz; Lepore, Luigi; Khedkar, Kalpana; Thangam, Saravanan; Nahar, Arifatun; Jamil, Hossen Mohammad; Bandi, Laxminarayan; Alam, Md Khorshed

2018-03-01

Characterization of a 90 kCi (3330 TBq), semi-industrial, cobalt-60 gamma irradiator was performed by commissioning dosimetry and in-situ dose mapping experiments with Ceric-cerous and Fricke dosimetry systems. Commissioning dosimetry was carried out to determine dose distribution pattern of absorbed dose in the irradiation cell and products. To determine maximum and minimum absorbed dose, overdose ratio and dwell time of the tote boxes, homogeneous dummy product (rice husk) with a bulk density of 0.13 g/cm3 were used in the box positions of irradiation chamber. The regions of minimum absorbed dose of the tote boxes were observed in the lower zones of middle plane and maximum absorbed doses were found in the middle position of front plane. Moreover, as a part of dose mapping, dose rates in the wall positions and some selective strategic positions were also measured to carry out multiple irradiation program simultaneously, especially for low dose research irradiation program. In most of the cases, Monte Carlo simulation data, using Monte Carlo N-Particle eXtended code version MCNPX 2.7., were found to be in congruence with experimental values obtained from Ceric-cerous and Fricke dosimetry; however, in close proximity positions from the source, the dose rate variation between chemical dosimetry and MCNP was higher than distant positions.

Gamma Irradiation as a Phytosanitary Treatment of Bactrocera tau (Diptera: Tephritidae) in Pumpkin Fruits.

PubMed

Guoping, Zhan; Lili, Ren; Ying, Shao; Qiaoling, Wang; Daojian, Yu; Yuejin, Wang; Tianxiu, Li

2015-02-01

The fruit fly Bactrocera tau (Walker) is an important quarantine pest that damages fruits and vegetables throughout Asian regions. Host commodities shipped from infested areas should undergo phytosanitary measures to reduce the risk of shipping viable flies. The dose-response tests with 1-d-old eggs and 3-, 5-, 7-, 8-d-old larvae were initiated to determine the most resistant stages in fruits, and the minimum dose for 99.9968% prevention of adult eclosion at 95% confidence level was validated in the confirmatory tests. The results showed that 1) the pupariation rate was not affected by gamma radiation except for eggs and first instars, while the percent of eclosion was reduced significantly in all instars at all radiation dose; 2) the tolerance to radiation increased with increasing age and developmental stage; 3) the estimated dose to 99.9968% preventing adult eclosion from late third instars was 70.9 Gy (95% CL: 65.6-78.2, probit model) and 71.8 Gy (95% CL: 63.0-87.3, logit model); and iv) in total, 107,135 late third instars cage infested in pumpkin fruits were irradiated at the target dose of 70 Gy (62.5-85.0, Gy measured), which resulted in no adult emergence in the two confirmatory tests. Therefore, a minimum dose of 85 and 72 Gy, which could prevent adult emergence at the efficacy of 99.9972 and 99.9938% at the 95% confidence level, respectively, can be recommended as a minimum dose for phytosanitary treatment of B. tau in any host fruits and vegetables under ambient atmospheres. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dosimetric effects of Onyx embolization on Gamma Knife arteriovenous malformation dose distributions.

PubMed

Schlesinger, David J; Nordström, Håkan; Lundin, Anders; Xu, Zhiyuan; Sheehan, Jason P

2016-12-01

OBJECTIVE Patients with arteriovenous malformations (AVMs) treated with Gamma Knife radiosurgery (GKRS) subsequent to embolization suffer from elevated local failure rates and differences in adverse radiation effects. Onyx is a common embolic material for AVMs. Onyx is formulated with tantalum, a high atomic number (Z = 73) element that has been investigated as a source of dosimetric uncertainty contributing to the less favorable clinical results. However, prior studies have not modeled the complicated anatomical and beam geometries characteristic of GKRS. This study investigated the magnitude of dose perturbation that can occur due to Onyx embolization using clinically realistic anatomical and Gamma Knife beam models. METHODS Leksell GammaPlan (LGP) was used to segment the AVM nidus and areas of Onyx from postcontrast stereotactic MRI for 7 patients treated with GKRS postembolization. The resulting contours, skull surface, and clinically selected dose distributions were exported from LGP in DICOM-RT (Digital Imaging and Communications in Medicine-radiotherapy) format. Isocenter locations and dwell times were recorded from the LGP database. Contours were converted into 3D mesh representations using commercial and in-house mesh-editing software. The resulting data were imported into a Monte Carlo (MC) dose calculation engine (Pegasos, Elekta Instruments AB) with a beam geometry for the Gamma Knife Perfexion. The MC-predicted dose distributions were calculated with Onyx assigned manufacturer-reported physical constants (MC-Onyx), and then compared with corresponding distributions in which Onyx was reassigned constants for water (MC-water). Differences in dose metrics were determined, including minimum, maximum, and mean dose to the AVM nidus; selectivity index; and target coverage. Combined differences in dose magnitude and distance to agreement were calculated as 3D Gamma analysis passing rates using tolerance criteria of 0.5%/0.5 mm, 1.0%/1.0 mm, and 3.0%/3.0 mm. RESULTS Overall, the mean percentage differences in dose metrics for MC-Onyx relative to MC-water were as follows; all data are reported as mean (SD): minimum dose to AVM = -0.7% (1.4%), mean dose to AVM = 0.1% (0.2%), maximum dose to AVM = 2.9% (5.0%), selectivity = 0.1% (0.2%), and coverage = -0.0% (0.2%). The mean percentage of voxels passing at each Gamma tolerance were as follows: 99.7% (0.1%) for 3.0%/3.0 mm, 98.2% (0.7%) for 1.0%/1.0 mm, and 52.1% (4.4%) for 0.5%/0.5 mm. CONCLUSIONS Onyx embolization appears to have a detectable effect on the delivered dose distribution. However, the small changes in dose metrics and high Gamma passing rates at 1.0%/1.0 mm tolerance suggest that these changes are unlikely to be clinically significant. Additional sources of delivery and biological uncertainty should be investigated to determine the root cause of the observed less favorable postembolization GKRS outcomes.

Measurement of Individual Doses of Radiation by Personal Dosimeter Is Important for the Return of Residents from Evacuation Order Areas after Nuclear Disaster

PubMed Central

Orita, Makiko; Hayashida, Naomi; Taira, Yasuyuki; Fukushima, Yoshiko; Ide, Juichi; Endo, Yuuko; Kudo, Takashi; Yamashita, Shunichi; Takamura, Noboru

2015-01-01

To confirm the availability of individual dose evaluation for the return of residents after the accident at the Fukushima Dai-ichi Nuclear Power Plant (FNPP), we evaluated individual doses of radiation as measured by personal dosimeters in residents who temporarily stayed in Evacuation Order Areas in Kawauchi village, which is partially located within a 20 km radius of the FNPP. We also compared individual doses with the external radiation doses estimated from the ambient dose rates and with doses estimated from the concentrations of radionuclides in the soil around each individual’s house. Individual doses were significantly correlated with the ambient doses in front of the entrances to the houses (r = 0.90, p<0.01), in the backyards (r = 0.41, p<0.01) and in the nearby fields (r = 0.80, p<0.01). The maximum cumulative ambient doses in the backyards and fields around the houses were 6.38 and 9.27 mSv/y, respectively. The maximum cumulative individual dose was 3.28 mSv/y, and the median and minimum doses were 1.35 and 0.71 mSv/y. The estimated external effective doses from concentrations of artificial radionuclides in soil samples ranged from 0.03 to 23.42 mSv/y. The individual doses were moderately correlated with external effective doses in the backyards (r = 0.38, p<0.01) and in the fields (r = 0.36, p<0.01); however, the individual doses were not significantly correlated with the external effective doses in front of the entrances (r = 0.01, p = 0.92). Our study confirmed that individual doses are low levels even in the evacuation order area in Kawauchi village, and external effective dose levels are certainly decreasing due to the decay of artificial radionuclides and the decontamination of contaminated soil. Long-term follow-up of individual doses as well as internal-exposure doses, environmental monitoring and reconstruction of infrastructure are needed so that residents may return to their hometowns after a nuclear disaster. PMID:25806523

Measurement of individual doses of radiation by personal dosimeter is important for the return of residents from evacuation order areas after nuclear disaster.

PubMed

Orita, Makiko; Hayashida, Naomi; Taira, Yasuyuki; Fukushima, Yoshiko; Ide, Juichi; Endo, Yuuko; Kudo, Takashi; Yamashita, Shunichi; Takamura, Noboru

2015-01-01

To confirm the availability of individual dose evaluation for the return of residents after the accident at the Fukushima Dai-ichi Nuclear Power Plant (FNPP), we evaluated individual doses of radiation as measured by personal dosimeters in residents who temporarily stayed in Evacuation Order Areas in Kawauchi village, which is partially located within a 20 km radius of the FNPP. We also compared individual doses with the external radiation doses estimated from the ambient dose rates and with doses estimated from the concentrations of radionuclides in the soil around each individual's house. Individual doses were significantly correlated with the ambient doses in front of the entrances to the houses (r = 0.90, p<0.01), in the backyards (r = 0.41, p<0.01) and in the nearby fields (r = 0.80, p<0.01). The maximum cumulative ambient doses in the backyards and fields around the houses were 6.38 and 9.27 mSv/y, respectively. The maximum cumulative individual dose was 3.28 mSv/y, and the median and minimum doses were 1.35 and 0.71 mSv/y. The estimated external effective doses from concentrations of artificial radionuclides in soil samples ranged from 0.03 to 23.42 mSv/y. The individual doses were moderately correlated with external effective doses in the backyards (r = 0.38, p<0.01) and in the fields (r = 0.36, p<0.01); however, the individual doses were not significantly correlated with the external effective doses in front of the entrances (r = 0.01, p = 0.92). Our study confirmed that individual doses are low levels even in the evacuation order area in Kawauchi village, and external effective dose levels are certainly decreasing due to the decay of artificial radionuclides and the decontamination of contaminated soil. Long-term follow-up of individual doses as well as internal-exposure doses, environmental monitoring and reconstruction of infrastructure are needed so that residents may return to their hometowns after a nuclear disaster.

Clinical Toxicities and Dosimetric Parameters After Whole-Pelvis Versus Prostate-Only Intensity-Modulated Radiation Therapy for Prostate Cancer

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

Deville, Curtiland, E-mail: deville@uphs.upenn.ed; Both, Stefan; Hwang, Wei-Ting

2010-11-01

Purpose: To assess whether whole-pelvis (WP) intensity-modulated radiation therapy (IMRT) is associated with increased toxicity compared with prostate-only (PO) IMRT. Methods and Materials: We retrospectively analyzed all patients with prostate cancer undergoing definitive IMRT to 79.2 Gy with concurrent androgen deprivation at our institution from November 2005 to May 2007 with a minimum follow-up of 12 months. Thirty patients received initial WP IMRT to 45 Gy in 1.8-Gy fractions, and thirty patients received PO IMRT. Study patients underwent computed tomography simulation and treatment planning by use of predefined dose constraints. Bladder and rectal dose-volume histograms, maximum genitourinary (GU) and gastrointestinalmore » (GI) Radiation Therapy Oncology Group toxicity grade, and late Grade 2 or greater toxicity-free survival curves were compared between the two groups by use of the Student t test, Fisher exact test, and Kaplan-Meier curve, respectively. Results: Bladder minimum dose, mean dose, median dose, volume receiving 5 Gy, volume receiving 20 Gy, volume receiving 40 Gy, and volume receiving 45 Gy and rectal minimum dose, median dose, and volume receiving 20 Gy were significantly increased in the WP group (all p values < 0.01). Maximum acute GI toxicity was limited to Grade 2 and was significantly increased in the WP group at 50% vs. 13% the PO group (p = 0.006). With a median follow-up of 24 months (range, 12-35 months), there was no difference in late GI toxicity (p = 0.884) or in acute or late GU toxicity. Conclusions: Despite dosimetric differences in the volume of bowel, bladder, and rectum irradiated in the low-dose and median-dose regions, WP IMRT results only in a clinically significant increase in acute GI toxicity, in comparison to PO IMRT, with no difference in GU or late GI toxicity.« less

The phototoxicity of phenothiazinium derivatives against Escherichia coli and Staphylococcus aureus.

PubMed

Phoenix, D A; Sayed, Z; Hussain, S; Harris, F; Wainwright, M

2003-10-24

Phenothiazinium dyes, and derivatives, were tested for toxicity to Escherichia coli and Staphylococcus aureus. The dyes were generally lipophilic (log P>1) and showed inherent dark toxicity (minimum lethal concentrations: 3.1-1000 microM). Dye illumination (total light dose of 3.15 J cm(-1) over 30 min) led to up to eight-fold reductions in minimum lethal concentrations. Most of the illuminated dyes showed significant relative singlet oxygen yields (phi'delta: 0.18-1.35) suggesting a type II mechanism of generating a phototoxic response. Although generally up to six-fold more effective against S. aureus, the dyes tested efficiently killed E. coli and may be of particular use in combating Gram-negative pathogens.

A randomized, double-blind, controlled clinical trial to evaluate the efficacy and safety of CJ-50300, a newly developed cell culture-derived smallpox vaccine, in healthy volunteers.

PubMed

Jang, Hee-Chang; Kim, Choong Jong; Kim, Kye Hyoung; Lee, Kwang-Hee; Byun, Young-Ho; Seong, Baik-Lin; Saletti, Giulietta; Czerkinsky, Cecil; Park, Wan Beom; Park, Sang-Won; Kim, Hong-Bin; Kim, Nam Joong; Oh, Myoung-don

2010-08-16

A randomized, double-blind, controlled clinical trial was conducted to evaluate the efficacy and safety of CJ-50300, a newly developed cell culture-derived smallpox vaccine, and to determine its minimum effective dose. The overall rates of cutaneous "take" reaction and humoral and cellular immunogenicity in CJ-50300 vaccinees were 100% (123/123), 99.2% (122/123), and 90.8% (109/120), respectively, and these rates did not differ significantly between the conventional-dose and the low-dose CJ-50300 (1.0x10(8) and 1.0x10(7) plaque-forming units/mL, respectively) (P>0.05 for each). No serious adverse reaction was observed. However, one case of possible generalized vaccinia occurred in the conventionally dosed group [ClinicalTrials.gov Identifier: NCT00607243].

Evaluation of serum theophylline concentrations following administration of sustained-release beads in applesauce to asthmatic preschool children.

PubMed

Leeder, J S; Robertson, C; Correia, J; Isles, A F; Levison, H; Macleod, S M

1986-02-01

A sustained-release theophylline preparation (Theo-Dur Sprinkle) was evaluated in young asthmatic patients aged 1 to 6 years and receiving a daily dose of 23.4 +/- 2.0 mg/kg (mean +/- SD) to determine, on the basis of serial serum concentrations obtained over a 12-hour dosing interval at steady state, the suitability of such a product in patients likely to metabolize the drug very rapidly. Peak theophylline concentrations of 15.1 +/- 4.1 mg/L were achieved 5.5 +/- 1.5 hours after dosing. The mean maximum to minimum concentration difference was 6.9 +/- 2.2 mg/L for the dosing interval studied. Fluctuations in theophylline concentration less than 100% were achieved in nine of the 12 study patients. Use of the "sprinkle-technique" with Theo-Dur Sprinkle appears to be a simple and effective method of maintaining acceptable fluctuations in serum theophylline concentrations in preschool asthmatic children.

75 FR 56981 - Notice of Decision To Issue Permits for the Importation of Sweet Limes From Mexico Into the...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-17

.... EFFECTIVE DATE: September 17, 2010. FOR FURTHER INFORMATION CONTACT: Mr. David Lamb, Import Specialist... fruits and vegetables into the United States from certain parts of the world to prevent plant pests from... accordance with 7 CFR part 305 with a minimum absorbed dose of 150 Gy. Each shipment of sweet limes must be...

[Exposure to fluorides from drinking water in the city of Aguascalientes, Mexico].

PubMed

Trejo-Vázquez, R; Bonilla-Petriciolet, A

2001-08-01

Determine the fluoride content in all the wells that supply drinking water to the city of Aguascalientes, Mexico, in order to establish the population's degree of exposure. The fluoride content of the 126 wells that supply drinking water to the city of Aguascalientes was determined, using the SPADNS method, in accordance with two Mexican regulations, NMX-AA-77-1982 and NMX-014-SSAI-1993. Using that data, we created fluoride isopleth maps showing the distribution of fluoride concentrations in the water supplies for the city of Aguascalientes. We also estimated exposure doses for the city's inhabitants. The mean analysis uncertainty was 3.9%. Seventy-three wells had a fluoride concentration of" 1.5 mg/L, which was the maximum permissible value set by the Mexican standards then in effect. All the maximum exposure doses surpassed the minimum risk level set by Agency for Toxic Substances and Disease Registry (ATSDR) of the Department of Health and Human Services of the United States of America. In the children under 1 year of age, even the minimum does was slightly higher than the ATSDR risk level. From estimating the fluoride exposure doses caused by water consumption in the city of Aguascalientes and comparing those doses with ones from other states in Mexico, we concluded that the fluoride intake in Aguascalientes represents a potential risk for inhabitants' health. The fluoride content of the city's drinking water should be reduced to 0.69 mg/L.

Emergency OSL/TL dosimetry with integrated circuits from mobile phones

NASA Astrophysics Data System (ADS)

Sholom, S.; McKeever, S. W. S.

2014-09-01

Integrated circuits (ICs) from several mobile phones were studied as possible emergency dosimeters using optically stimulated luminescence (OSL) and thermoluminescence (TL) techniques. Measurement protocols were developed for ICs that take into consideration the effect of sensitization of the samples with increasing dose as well as fading of the signals after sample exposure. It was found that the OSL technique has a higher sensitivity with ICs when compared to TL, while the TL signals were characterized by better stability with time after exposure. Values of minimum measurable doses were found to be in the range between a few tens of mGy and several tens of mGy for the tested samples. It was concluded that ICs from mobile phones could be used for emergency dose reconstruction.

Radiation inactivation of Paenibacillus larvae and sterilization of American Foul Brood (AFB) infected hives using Co-60 gamma rays.

PubMed

De Guzman, Zenaida M; Cervancia, Cleofas R; Dimasuay, Kris Genelyn B; Tolentino, Mitos M; Abrera, Gina B; Cobar, Ma Lucia C; Fajardo, Alejandro C; Sabino, Noel G; Manila-Fajardo, Analinda C; Feliciano, Chitho P

2011-10-01

The effectiveness of gamma radiation in inactivating the Philippine isolate of Paenibacillus larvae was investigated. Spores of P. larvae were irradiated at incremental doses (0.1, 0.2, 0.4, 0.8 and 1.6 kGy) of gamma radiation emitted by a ⁶⁰Co source. Surviving spores were counted and used to estimate the decimal reduction (D₁₀) value. A dose of 0.2 kGy was sufficient to inactivate 90% of the total recoverable spores from an initial count of 10⁵- 9 × 10³ spores per glass plate. The sterilizing effect of high doses of gamma radiation on the spores of P. larvae in infected hives was determined. In this study, a minimum dose (D(min)) of 15 kGy was tested. Beehives with sub-clinical infections of AFB were irradiated and examined for sterility. All the materials were found to be free of P. larvae indicating its susceptibility to γ-rays. After irradiation, there were no visible changes in the physical appearance of the hives' body, wax and frames. Thus, a dose of 15 kGy is effective enough for sterilization of AFB-infected materials. Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

Anal wall sparing effect of an endorectal balloon in 3D conformal and intensity-modulated prostate radiotherapy.

PubMed

Smeenk, Robert Jan; van Lin, Emile N J Th; van Kollenburg, Peter; Kunze-Busch, Martina; Kaanders, Johannes H A M

2009-10-01

To investigate the anal wall (Awall) sparing effect of an endorectal balloon (ERB) in 3D conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) for prostate cancer. In 24 patients with localized prostate carcinoma, two planning CT-scans were performed: with and without ERB. A prostate planning target volume (PTV) was defined, and the Awall was delineated, using two different methods. Three-field and 4-field 3D-CRT plans, and IMRT plans were generated with a prescription dose of 78Gy. In 144 treatment plans, the minimum dose (D(min)), maximum dose (D(max)), and mean dose (D(mean)) to the Awall were calculated, as well as the Awall volumes exposed to doses ranging from >or=20Gy to >or=70Gy (V(20)-V(70), respectively). In the 3D-CRT plans, an ERB significantly reduced D(mean), D(max), and V(30)-V(70). For IMRT all investigated dose parameters were significantly reduced by the ERB. The absolute reduction of D(mean) was 12Gy in 3D-CRT and was 7.5Gy in IMRT for both methods of Awall delineation. Application of an ERB showed a significant Awall sparing effect in both 3D-CRT and IMRT. This may lead to reduced late anal toxicity in prostate radiotherapy.

Herbicide mixtures at high doses slow the evolution of resistance in experimentally evolving populations of Chlamydomonas reinhardtii.

PubMed

Lagator, Mato; Vogwill, Tom; Mead, Andrew; Colegrave, Nick; Neve, Paul

2013-05-01

The widespread evolution of resistance to herbicides is a pressing issue in global agriculture. Evolutionary principles and practices are key to the management of this threat to global food security. The application of mixtures of herbicides has been advocated as an anti-resistance strategy, without substantial empirical support for its validation. We evolved experimentally populations of the unicellular green chlorophyte, Chlamydomonas reinhardtii, to minimum inhibitory concentrations (MICs) of single-herbicide modes of action and to pair-wise and three-way mixtures between different herbicides at various total combined doses. Herbicide mixtures were most effective when each component was applied at or close to its MIC. When doses were high, increasing the number of mixture components was also effective in reducing the evolution of resistance. Employing mixtures at low combined doses did not retard resistance evolution, even accelerating the evolution of resistance to some components. At low doses, increasing the number of herbicides in the mixture tended to select for more generalist resistance (cross-resistance). Our results reinforce findings from the antibiotic resistance literature and confirm that herbicide mixtures can be very effective for resistance management, but that mixtures should only be employed where the economic and environmental context permits the applications of high combined doses. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Tolerance of young infants to a single, large dose of vitamin A: a randomized community trial in Nepal.

PubMed

West, K P; Khatry, S K; LeClerq, S C; Adhikari, R; See, L; Katz, J; Shrestha, S R; Pradhan, E K; Pokhrel, R P; Sommer, A

1992-01-01

A randomized, double-masked trial was carried out in rural Nepal to investigate the incidence and severity of acute side-effects among neonates ( < 1 month of age) and infants aged 1-6 months who received a large, oral dose of vitamin A (15,000 retinol equivalents (RE) (50,000 IU) and 30,000 RE (100,000 IU), respectively) or placebo (75 RE (250 IU) and 150 RE (500 IU), respectively) in oil. Infants (vitamin A group, n = 1461; controls, n = 1379) were assessed for vomiting, loose stools, fever, and irritability during the 24 hours before and after dosing. Fontanelles were palpated 24 hours after dosing. Neonates exhibited no excess risk of adverse side-effects after receiving 15,000 RE. Compared with controls the older infants who ingested 30,000 RE had a 1.6% excess rate of vomiting (95% confidence interval (CI): 0.2-3.0%) and a 0.5% excess rate (95% CI: -0.1 to 1.1%) in the occurrence of bulging fontanelles. There were no other significant differences in the older infants. The controlled, periodic distribution of a single 15,000 RE dose of vitamin A therefore confers no apparent acute risk to young infants; a 30,000 RE dose is associated with a minimum risk of transient, acute side-effects.

Effects of nighttime single-dose administration of vasodilating vs sympatholytic antihypertensive agents on sleep blood pressure in hypertensive patients with sleep apnea syndrome.

PubMed

Kario, Kazuomi; Kuwabara, Mitsuo; Hoshide, Satoshi; Nagai, Michiaki; Shimpo, Masahisa

2014-06-01

Obstructive sleep apneas syndrome (OSAS) is associated with nocturnal hypertension with higher sleep blood pressure (BP) and its variability, both of which increase cardiovascular risk. In this crossover design study, the effect of nighttime single-dose administration of vasodilating (nifedipine 40 mg) vs sympatholytic (carvedilol 20 mg) antihypertensive agents on sleep BP in 11 hypertensive OSAS patients was evaluated. The authors recently developed a trigger sleep BP monitor with an oxygen-triggered function that initiates BP measurement when oxygen desaturation falls. The BP-lowering effects of nifedipine on the mean (P<.05) and minimum sleep systolic BPs (SBPs) (P<.01) were stronger than those of carvedilol. Sleep SBP surge (difference between the hypoxia-peak SBP measured by oxygen-triggered function and SBPs within 30 minutes before and after the peak SBP) was only significantly reduced by carvedilol (P<.05). The nighttime dosing of both vasodilating and sympatholytic antihypertensive drugs is effective to reduce sleep BP but with different BP-lowering profiles. ©2014 Wiley Periodicals, Inc.

MAOIs and transdermal delivery.

PubMed

Vandenberg, Chad M

2012-09-01

Although not currently considered a first-line treatment for depression due to safety and tolerability concerns, MAOIs are effective antidepressants, particularly for atypical or treatment-resistant depression. FDA-approved oral MAOIs inhibit both MAO-A and MAO-B; inhibition of MAO-A in the brain is required for an antidepressant effect, but inhibition in the intestinal tract can allow excessive absorption of tyramine, which can lead to hypertensive crisis. A transdermal formulation of selegiline delivers the medication directly into the circulatory system, bypassing the first-pass metabolism of the GI system and substantially reducing the risk for tyramine-related adverse events. The skin patch allows for a lower dose of the drug to achieve an antidepressant effect, maintains a steady dose of the medication over 24 hours, and avoids the need for dietary restrictions at the minimum effective dose of 6 mg/24 hours. MAOIs are useful treatment options for patients who have not responded to first-line treatments, and understanding their mechanism of action can help clinicians to accurately and safely prescribe these medications. © Copyright 2012 Physicians Postgraduate Press, Inc.

Guaranteed epsilon-optimal treatment plans with the minimum number of beams for stereotactic body radiation therapy

NASA Astrophysics Data System (ADS)

Yarmand, Hamed; Winey, Brian; Craft, David

2013-09-01

Stereotactic body radiation therapy (SBRT) is characterized by delivering a high amount of dose in a short period of time. In SBRT the dose is delivered using open fields (e.g., beam’s-eye-view) known as ‘apertures’. Mathematical methods can be used for optimizing treatment planning for delivery of sufficient dose to the cancerous cells while keeping the dose to surrounding organs at risk (OARs) minimal. Two important elements of a treatment plan are quality and delivery time. Quality of a plan is measured based on the target coverage and dose to OARs. Delivery time heavily depends on the number of beams used in the plan as the setup times for different beam directions constitute a large portion of the delivery time. Therefore the ideal plan, in which all potential beams can be used, will be associated with a long impractical delivery time. We use the dose to OARs in the ideal plan to find the plan with the minimum number of beams which is guaranteed to be epsilon-optimal (i.e., a predetermined maximum deviation from the ideal plan is guaranteed). Since the treatment plan optimization is inherently a multi-criteria-optimization problem, the planner can navigate the ideal dose distribution Pareto surface and select a plan of desired target coverage versus OARs sparing, and then use the proposed technique to reduce the number of beams while guaranteeing epsilon-optimality. We use mixed integer programming (MIP) for optimization. To reduce the computation time for the resultant MIP, we use two heuristics: a beam elimination scheme and a family of heuristic cuts, known as ‘neighbor cuts’, based on the concept of ‘adjacent beams’. We show the effectiveness of the proposed technique on two clinical cases, a liver and a lung case. Based on our technique we propose an algorithm for fast generation of epsilon-optimal plans.

Effects of high doses of oxytetracycline on metacarpophalangeal joint kinematics in neonatal foals.

PubMed

Kasper, C A; Clayton, H M; Wright, A K; Skuba, E V; Petrie, L

1995-07-01

Thirteen clinically normal Belgian-type foals were used to study the effects of high doses of oxytetracycline on metacarpophalangeal joint kinematics. Seven foals (treatment group) received 2 doses of oxytetracycline (3 g, IV). The first dose was given when foals were 4 days old; the second dose was given 24 hours later. Six foals (control group) received 2 doses of saline (0.9% NaCl) solution (15 ml, IV) at equivalent time periods. All foals were videotaped at a walk twice: immediately prior to the first treatment and 24 hours after the second treatment. The tapes were digitized, and metacarpophalangeal joint angle was measured along the palmar surface of the limb during 3 strides. The angular data were normalized for time, and data from the 3 strides were averaged to describe a representative stride. Repeated measures ANOVA was used to test for differences between groups and within groups over time. Values for stride duration, stance phase percentage, and minimum metacarpophalangeal joint angle obtained before treatment were not significantly different from values obtained after treatment. Maximum metacarpophalangeal joint angle, which occurred during the stance phase of the stride, and range of joint motion were significantly increased for foals in the treatment group, compared with foals in the control group.

Comparison of Transport Codes, HZETRN, HETC and FLUKA, Using 1977 GCR Solar Minimum Spectra

NASA Technical Reports Server (NTRS)

Heinbockel, John H.; Slaba, Tony C.; Tripathi, Ram K.; Blattnig, Steve R.; Norbury, John W.; Badavi, Francis F.; Townsend, Lawrence W.; Handler, Thomas; Gabriel, Tony A.; Pinsky, Lawrence S.;

Effect of crosslinking UHMWPE on its tensile and compressive creep performance.

PubMed

Lewis, G; Carroll, M

2001-01-01

The in vitro quasi-static tensile and compressive creep properties of three sets of GUR 1050 ultra-high-molecular-weight polyethylene (UHMWPE) specimens were obtained. These sets were: control (as-received stock); "low-gamma" (specimens were crosslinked using gamma radiation, with a minimum dose of 5 Mrad); and "high-gamma" (specimens were crosslinked using gamma radiation, with a minimum dose of 15 Mrad). The % crystallinity (%C) and crosslink density (rho(x)) of the specimens in the three sets were also obtained. It was found that, in both tension and compression, crosslinking resulted in a significant depreciation in the creep properties, relative to control. The trend in the creep results is explained in terms of the impact of crosslinking on the polymer's %C and rho(x). The present results are in contrast to literature reports that show that crosslinking enhances the wear resistance of the polymer. The implications of the present results, taken together with the aforementioned literature results, are fully discussed vis-a-vis the use of crosslinked UHMWPE for fabricating articular components for arthroplasties.

Dosimetry study for a new in vivo X-ray fluorescence (XRF) bone lead measurement system

NASA Astrophysics Data System (ADS)

Nie, Huiling; Chettle, David; Luo, Liqiang; O'Meara, Joanne

2007-10-01

A new 109Cd γ-ray induced bone lead measurement system has been developed to reduce the minimum detectable limit (MDL) of the system. The system consists of four 16 mm diameter detectors. It requires a stronger source compared to the "conventional" system. A dosimetry study has been performed to estimate the dose delivered by this system. The study was carried out by using human-equivalent phantoms. Three sets of phantoms were made to estimate the dose delivered to three age groups: 5-year old, 10-year old and adults. Three approaches have been applied to evaluate the dose: calculations, Monte Carlo (MC) simulations, and experiments. Experimental results and analytical calculations were used to validate MC simulation. The experiments were performed by placing Panasonic UD-803AS TLDs at different places in phantoms that representing different organs. Due to the difficulty of obtaining the organ dose and the whole body dose solely by experiments and traditional calculations, the equivalent dose and effective dose were calculated by MC simulations. The result showed that the doses delivered to the organs other than the targeted lower leg are negligibly small. The total effective doses to the three age groups are 8.45/9.37 μSv (female/male), 4.20 μSv, and 0.26 μSv for 5-year old, 10-year old and adult, respectively. An approval to conduct human measurements on this system has been received from the Research Ethics Board based on this research.

SU-E-T-296: Single Field Per Day Vs. Multiple Fields Per Day and the Impact On BED in Proton Therapy Treatment

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

Grantham, K; Wooten, H; Zhao, T

2014-06-01

Purpose: A common practice, in proton therapy, is to deliver a rotating subset of fields from the treatment plan for the daily fractions. This study compares the impact this practice has on the biological effective dose (BED) versus delivering all planned fields daily. Methods: For two scenarios (a phantom with a geometry approximating the anatomy of a prostate treatment with opposing lateral beams, and a clinical 3-field brain treatment), treatment plans were produced in Eclipse (Varian) to simulate delivery of one, two, and three fields per fraction. The RT-Dose file, structure set, and α/β ratios were processed using in-house MATLABmore » code to return a new RT-Dose file containing the BED (including a proton RBE of 1.1) which was imported back into Eclipse for analysis. Results: For targets and regions of field overlap in the treatment plan, BED is not affected by delivery regimen. In the phantom, BED in the femoral heads showed increased by 20% when a single field was used rather than two fields. In the brain treatment, the minimum BED to the left optic nerve and the pituitary gland increased by 13% and 10% respectively, for a one-field regime compared to three-fields per fraction. Comparing the two-field and threefield regimes, the optic nerve BED was not significantly affected and the minimum pituitary BED was 4% higher for two fields per day. Conclusion: Hypo-fractionation effects, in regions of non-overlap of fields, significantly increase the BED to the involved tissues by as much as 20%. Care should be taken to avoid inadvertently sacrificing plan effectiveness in the interest of reduced treatment time.« less

Technical Note: A proposal of air ventilation system design criteria for a clinical room in a heavy-ion medical facility.

PubMed

Kum, Oyeon

2018-06-01

An optimized air ventilation system design for a treatment room in Heavy-ion Medical Facility is an important issue in the aspects of nuclear safety because the activated air produced in a treatment room can directly affect the medical staff and the general public in the radiation-free area. Optimized design criteria of air ventilation system for a clinical room in 430 MeV/u carbon ion beam medical accelerator facility was performed by using a combination of MCNPX2.7.0 and CINDER'90 codes. Effective dose rate and its accumulated effective dose by inhalation and residual gamma were calculated for a normal treatment scenario (2 min irradiation for one fraction) as a function of decay time. Natural doses around the site were measured before construction and used as reference data. With no air ventilation system, the maximum effective dose rate was about 3 μSv/h (total dose of 90 mSv/y) and minimum 0.2 μSv/h (total dose of 6 mSv/y), which are over the legal limits for medical staff and for the general public. Although inhalation dose contribution was relatively small, it was considered seriously because of its long-lasting effects in the body. The integrated dose per year was 1.8 mSv/y in the radiation-free area with the 20-min rate of air ventilation system. An optimal air ventilation rate of 20 min is proposed for a clinical room, which also agrees with the best mechanical design value. © 2018 American Association of Physicists in Medicine.

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

PubMed

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

2013-11-01

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

SU-F-BRD-08: Guaranteed Epsilon-Optimal Treatment Plans with Minimum Number of Beams for SBRT Using RayStation

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

Yarmand, H; Winey, B; Craft, D

2014-06-15

Purpose: To efficiently find quality-guaranteed treatment plans with the minimum number of beams for stereotactic body radiation therapy using RayStation. Methods: For a pre-specified pool of candidate beams we use RayStation (a treatment planning software for clinical use) to identify the deliverable plan which uses all the beams with the minimum dose to organs at risk (OARs) and dose to the tumor and other structures in specified ranges. Then use the dose matrix information for the generated apertures from RayStation to solve a linear program to find the ideal plan with the same objective and constraints allowing use of allmore » beams. Finally we solve a mixed integer programming formulation of the beam angle optimization problem (BAO) with the objective of minimizing the number of beams while remaining in a predetermined epsilon-optimality of the ideal plan with respect to the dose to OARs. Since the treatment plan optimization is a multicriteria optimization problem, the planner can exploit the multicriteria optimization capability of RayStation to navigate the ideal dose distribution Pareto surface and select a plan of desired target coverage versus OARs sparing, and then use the proposed technique to reduce the number of beams while guaranteeing quality. For the numerical experiments two liver cases and one lung case with 33 non-coplanar beams are considered. Results: The ideal plan uses an impractically large number of beams. The proposed technique reduces the number of beams to the range of practical application (5 to 9 beams) while remaining in the epsilon-optimal range of 1% to 5% optimality gap. Conclusion: The proposed method can be integrated into a general algorithm for fast navigation of the ideal dose distribution Pareto surface and finding the treatment plan with the minimum number of beams, which corresponds to the delivery time, in epsilon-optimality range of the desired ideal plan. The project was supported by the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center and partially by RaySearch Laboratories.« less

Incidental irradiation of mediastinal and hilar lymph node stations during 3D-conformal radiotherapy for non-small cell lung cancer.

PubMed

Kepka, Lucyna; Bujko, Krzysztof; Zolciak-Siwinska, Agnieszka; Garmol, Dariusz

2008-01-01

To estimate the doses of incidental irradiation in particular lymph node stations (LNS) in different extents of elective nodal irradiation (ENI) in 3D-conformal radiotherapy (3D-CRT) for non-small cell lung cancer (NSCLC). METHODS; Doses of radiotherapy were estimated for particular LNS delineated according to the recommendations of the University of Michigan in 220 patients treated using 3D-CRT with different (extended, limited and omitted) extents of ENI. Minimum doses and volumes of LNS receiving 40 Gy or more (V40) were compared for omitted vs. limited+ extended ENI and limited vs. extended ENI. For omission of the ENI the minimum doses and V40 for particular LNS were significantly lower than for patients treated with ENI. For the limited ENI group, the minimum doses for LNS 5, 6 lower parts of 3A and 3P (not included in the elective area) did not differ significantly from doses given to respective LNS for extended ENI group. When the V40 values for extended and limited ENI were compared, no significant differences were seen for any LNS, except for group 1/2R, 1/2L. Incidental irradiation of untreated LNS seems play a part in case of limited ENI, but not in cases without ENI. For subclinical disease the delineation of uninvolved LNS 5, 6, and lower parts of 3A, 3P may be not necessary, because these stations receive the substantial part of irradiation incidentally, if LNS 4R, 4L, 7, and ipsilateral hilum are included in the elective area while this is not case for stations 1 and 2.

Adult clonidine overdose: prolonged bradycardia and central nervous system depression, but not severe toxicity.

PubMed

Isbister, Geoffrey K; Heppell, Simon P; Page, Colin B; Ryan, Nicole M

2017-03-01

There are limited reports of adult clonidine overdose. We aimed to describe the clinical effects and treatment of clonidine overdose in adults. This was a retrospective review of a prospective cohort of poisoned patients who took clonidine overdoses (>200 μg). Demographic information, clinical effects, treatment, complications (central nervous system and cardiovascular effects) and length of stay (LOS) were extracted from a clinical database or medical records. From 133 admissions for clonidine poisoning (1988-2015), no medical record was available in 14 and 11 took staggered ingestions. Of 108 acute clonidine overdoses (median age 27 years; 14-65 years; 68 females), 40 were clonidine alone ingestions and 68 were clonidine with co-ingestants. Median dose taken was 2100 μg (interquartile range [IQR]: 400-15,000 μg). Median LOS was 21h (IQR: 14-35 h) and there were no deaths. Glasgow coma score [GCS] <15 occurred in 73/108 (68%), and more patients taking co-ingestants (8/68; 12%) had coma (GCS <9) compared to clonidine alone (2/40; 5%). Miosis occurred in 31/108 (29%) cases. Median minimum HR was 48 bpm (IQR: 40-57 bpm), similar between clonidine alone and co-ingestant overdoses. There was a significant association between dose and minimum HR for clonidine alone overdoses (p = 0.02). 82/108 (76%) had bradycardia, median onset 2.5 h post-ingestion (IQR: 1.7-5.5 h) and median duration 20 h (2.5-83 h), similar for clonidine alone and co-ingestant overdoses. There were no arrhythmias. Three patients ingesting 8000-12,000 μg developed early hypertension. Median minimum systolic BP was 96 mmHg (IQR: 90-105 mmHg) and hypotension occurred in 26/108 (24%). 12/108 patients were intubated, but only 2 were clonidine alone cases. Treatments included activated charcoal (24), atropine (8) and naloxone (23). The median total naloxone dose was 2 mg (IQR: 1.2-2.4 mg), but only one patient given naloxone was documented to respond with partial improvement in GCS. Clonidine causes persistent but not life-threatening clinical effects. Most patients develop mild central nervous system depression and bradycardia. Naloxone was not associated with improved outcomes.

Influence of oxcarbazepine on the antinociceptive action of morphine and metamizole in mice.

PubMed

Pakulska, Wanda; Czarnecka, Elzbieta

2009-01-01

Numerous methods of management applied in order to obtain higher therapeutic efficacy of drugs with minimum adverse effects include taking advantage of interactions taking place between individual agents. Analgesics are combined with drugs belonging to other therapeutic groups, including, more and more frequently, antiepileptic agents. The influence of oxcarbazepine (10 mg/kg) on the antinociceptive effect of morphine (10 mg/kg) and metamizole (500 mg/kg) was investigated in mice using the hot-plate and tail-flick tests. All drugs were injected intraperitoneally (i.p.). Oxcarbazepine was administered 30 min prior to the injection of analgesic drugs. The reactions to noxious stimuli were measured 30, 60 and 90 min after the administration of an analgesic. The study was further conducted for 10 days with repeated drug doses. Single administration of oxcarbazepine enhanced the antinociceptive effect of a single dose of morphine, and 10-day administration led to a decrease of morphine tolerance in the hot-plate test. Oxcarbazepine administered in a single dose did not affect significantly the antinociceptive effect of metamizole in either of the tests. Multiple administration of oxcarbazepine enhanced the antinociceptive effect of metamizole in the hot-plate test. Oxcarbazepine alone, administered in a single and repeated doses, demonstrated an antinociceptive effect, but only for the hot-plate test, which indicates involvement of supraspinal structures in antinociception.

Effect of gamma-irradiation on degradation of alginate.

PubMed

Lee, Dong Wook; Choi, Won Seok; Byun, Myung Woo; Park, Hyun Jin; Yu, Yong-Man; Lee, Chong M

2003-07-30

The aqueous solution of alginate was irradiated by 60Co gamma-rays in the dose range of 10-500 kGy. To assess the effect of irradiation on the degradation of alginate, the irradiation-induced changes in the viscosity, molecular weight, color, monomer composition, and sequence were measured. The molecular weight of raw alginate was reduced from 300000 to 25000 when irradiated at 100 kGy. The degradation rate decreased and the chain breaks per molecule increased with increasing irradiation dose. The viscosity of irradiated alginate solution reached a near minimum as low as at 10 kGy. No appreciable color changes were observed in the samples irradiated at up to 100 kGy, but intense browning occurred beyond 200 kGy. The 13C NMR spectra showed that homopolymeric blocks, MM and GG, increased and the M/G ratio decreased with irradiation. Considering both the level of degradation and the color change of alginate, the optimum irradiation dose was found to be 100 kGy.

SU-F-18C-11: Diameter Dependency of the Radial Dose Distribution in a Long Polyethylene Cylinder

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

Bakalyar, D; McKenney, S; Feng, W

Purpose: The radial dose distribution in the central plane of a long cylinder following a long CT scan depends upon the diameter and composition of the cylinder. An understanding of this behavior is required for determining the spatial average of the dose in the central plane. Polyethylene, the material for construction of the TG200/ICRU phantom (30 cm in diameter) was used for this study. Size effects are germane to the principles incorporated in size specific dose estimates (SSDE); thus diameter dependency was explored as well. Method: ssuming a uniform cylinder and cylindrically symmetric conditions of irradiation, the dose distribution canmore » be described using a radial function. This function must be an even function of the radial distance due to the conditions of symmetry. Two effects are accounted for: The direct beam makes its weakest contribution at the center while the contribution due to scatter is strongest at the center and drops off abruptly at the outer radius. An analytic function incorporating these features was fit to Monte Carlo results determined for infinite polyethylene cylinders of various diameters. A further feature of this function is that it is integrable. Results: Symmetry and continuity dictate a local extremum at the center which is a minimum for the larger sizes. The competing effects described above can Resultin an absolute maximum occurring between the center and outer edge of the cylinders. For the smallest cylinders, the maximum dose may occur at the center. Conclusion: An integrable, analytic function can be used to characterize the radial dependency of dose for cylindrical CT phantoms of various sizes. One use for this is to help determine average dose distribution over the central cylinder plane when equilibrium dose has been reached.« less

Dependence of Mechanical and Thermal Properties of Thermoplastic Composites on Electron Beam Irradiation

NASA Astrophysics Data System (ADS)

Kim, Sok Won; Park, K.; Lee, S. H.; Kang, J. S.; Kang, K. H.

2007-06-01

Since the restrictions for environmental protection being strengthened, thermoplastics reinforced with natural fibers (NF’s), such as jute, kenaf, flax, etc. have appeared as alternatives to chemical plastics for automobile interior materials. In this study, the thermal conductivity, tensile strength, and deformation of several kinds of thermoplastic composites composed of 50% polypropylene (PP) and 50% natural fiber (NF) irradiated by an electron beam (energy: 0.5 MeV, dose: 0 20 kGy) were measured. The length and thickness of PP and NF are 80 ± 10 mm and 40 120 μm, respectively. The results show that the thermal conductivity and the tensile strength changed and became minimum, when the dose of the electron beam was 10 kGy. However, the effect of the dose on the deformation was not clear.

Trace element supplementation in the biogas production from wheat stillage--optimization of metal dosing.

PubMed

Schmidt, Thomas; Nelles, Michael; Scholwin, Frank; Pröter, Jürgen

2014-09-01

A trace element dosing strategy for the anaerobic digestion of wheat stillage was developed in this study. Mesophilic CSTR reactors were operated with the sulfuric substrate wheat stillage in some cases under trace element deficiency. After supplementing trace elements during the start-up, one of the elements of Fe, Ni, Co, Mo, and W were depleted in one digester while still augmenting the other elements to determine minimum requirements for each element. The depletion of Fe and Ni resulted in a rapid accumulation of volatile fatty acids while Co and W seem to have a long-term effect. Based on the results it was possible to reduce the dosing of trace elements, which is positive with reference to economic and environmental aspects. Copyright © 2014 Elsevier Ltd. All rights reserved.

Accuracy of the dose-shift approximation in estimating the delivered dose in SBRT of lung tumors considering setup errors and breathing motions.

PubMed

Karlsson, Kristin; Lax, Ingmar; Lindbäck, Elias; Poludniowski, Gavin

2017-09-01

Geometrical uncertainties can result in a delivered dose to the tumor different from that estimated in the static treatment plan. The purpose of this project was to investigate the accuracy of the dose calculated to the clinical target volume (CTV) with the dose-shift approximation, in stereotactic body radiation therapy (SBRT) of lung tumors considering setup errors and breathing motion. The dose-shift method was compared with a beam-shift method with dose recalculation. Included were 10 patients (10 tumors) selected to represent a variety of SBRT-treated lung tumors in terms of tumor location, CTV volume, and tumor density. An in-house developed toolkit within a treatment planning system allowed the shift of either the dose matrix or a shift of the beam isocenter with dose recalculation, to simulate setup errors and breathing motion. Setup shifts of different magnitudes (up to 10 mm) and directions as well as breathing with different peak-to-peak amplitudes (up to 10:5:5 mm) were modeled. The resulting dose-volume histograms (DVHs) were recorded and dose statistics were extracted. Generally, both the dose-shift and beam-shift methods resulted in calculated doses lower than the static planned dose, although the minimum (D 98% ) dose exceeded the prescribed dose in all cases, for setup shifts up to 5 mm. The dose-shift method also generally underestimated the dose compared with the beam-shift method. For clinically realistic systematic displacements of less than 5 mm, the results demonstrated that in the minimum dose region within the CTV, the dose-shift method was accurate to 2% (root-mean-square error). Breathing motion only marginally degraded the dose distributions. Averaged over the patients and shift directions, the dose-shift approximation was determined to be accurate to approximately 2% (RMS) within the CTV, for clinically relevant geometrical uncertainties for SBRT of lung tumors.

The use of rotation to fentanyl in cancer-related pain

PubMed Central

Dima, Delia; Tomuleasa, Ciprian; Frinc, Ioana; Pasca, Sergiu; Magdo, Lorand; Berindan-Neagoe, Ioana; Muresan, Mihai; Lisencu, Cosmin; Irimie, Alexandru; Zdrenghea, Mihnea

2017-01-01

Pain is commonly diagnosed with respect to cancer and heart diseases, being a major symptom in most neoplastic diseases. Uncontrolled pain leads to a decrease in the quality of life and an increase in the morbidity of the patient. Opioids represent the best analgetic supportive therapy and are frequently used in patients suffering from cancer and experiencing a high level of pain. Opioid treatment starts with a gradual titration of the dose until the minimum effective dose and the maximum tolerated dose are determined. Opioid rotation refers to the switch from one opioid to another in order to get a better response to analgetic therapy and reduce side effects. Fentanyl therapy is recommended to be continued during chemotherapy, radiotherapy, or in the case of surgical intervention. Rotation to fentanyl patches is an efficient and elegant solution for cancer patients, with reduced side effects. Opioid rotation, especially to fentanyl, was shown to increase the quality of life in patients with malignant disease. Finally, rotation to fentanyl is also advantageous from an economic point of view. PMID:28223843

Duration of protective immunity conferred by maternal tetanus toxoid immunization: further evidence from Matlab, Bangladesh.

PubMed Central

Koenig, M A; Roy, N C; McElrath, T; Shahidullah, M; Wojtyniak, B

1998-01-01

OBJECTIVES: Although maternal tetanus immunization has been shown to be highly effective in the prevention of neonatal tetanus, unresolved questions remain concerning the required minimum number of doses and the resulting duration of effective immunity. This study examined the duration of effective immunity against neonatal tetanus provided by maternal tetanus immunization. METHODS: A randomized, double-blind cholera vaccine trial of 41,571 children and nonpregnant adult women carried out in 1974 in the Matlab comparison area of rural Bangladesh provided a unique opportunity to address dose and immunity issues. RESULTS: Children of women who received either 1 or 2 injections of tetanus toxoid experienced 4- to 14-day mortality levels consistently lower than those of children of unimmunized mothers. Analysis of neonatal-tetanus-related mortality showed that 2 injections of tetanus toxoid provided significant protection for subsequent durations of up to 12 or 13 years. CONCLUSIONS: The data demonstrate that a limited-dose regimen of maternal tetanus toxoid provides significant and extended protection against the risk of neonatal tetanus death. PMID:9618617

SU-F-J-29: Dosimetric Effect of Image Registration ROI Size and Focus in Automated CBCT Registration for Spine SBRT

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

Magnelli, A; Smith, A; Chao, S

2016-06-15

Purpose: Spinal stereotactic body radiotherapy (SBRT) involves highly conformal dose distributions and steep dose gradients due to the proximity of the spinal cord to the treatment volume. To achieve the planning goals while limiting the spinal cord dose, patients are setup using kV cone-beam CT (kV-CBCT) with 6 degree corrections. The kV-CBCT registration with the reference CT is dependent on a user selected region of interest (ROI). The objective of this work is to determine the dosimetric impact of ROI selection. Methods: Twenty patients were selected for this study. For each patient, the kV-CBCT was registered to the reference CTmore » using three ROIs including: 1) the external body, 2) a large anatomic region, and 3) a small region focused in the target volume. Following each registration, the aligned CBCTs and contours were input to the treatment planning system for dose evaluation. The minimum dose, dose to 99% and 90% of the tumor volume (D99%, D90%), dose to 0.03cc and the dose to 10% of the spinal cord subvolume (V10Gy) were compared to the planned values. Results: The average deviations in the tumor minimum dose were 2.68%±1.7%, 4.6%±4.0%, 14.82%±9.9% for small, large and the external ROIs, respectively. The average deviations in tumor D99% were 1.15%±0.7%, 3.18%±1.7%, 10.0%±6.6%, respectively. The average deviations in tumor D90% were 1.00%±0.96%, 1.14%±1.05%, 3.19%±4.77% respectively. The average deviations in the maximum dose to the spinal cord were 2.80%±2.56%, 7.58%±8.28%, 13.35%±13.14%, respectively. The average deviation in V10Gy to the spinal cord were 1.69%±0.88%, 1.98%±2.79%, 2.71%±5.63%. Conclusion: When using automated registration algorithms for CBCT-Reference alignment, a small target-focused ROI results in the least dosimetric deviation from the plan. It is recommended to focus narrowly on the target volume to keep the spinal cord dose below tolerance.« less

Dosimetric verification of IMRT treatment planning using Monte Carlo simulations for prostate cancer

NASA Astrophysics Data System (ADS)

Yang, J.; Li, J.; Chen, L.; Price, R.; McNeeley, S.; Qin, L.; Wang, L.; Xiong, W.; Ma, C.-M.

2005-03-01

The purpose of this work is to investigate the accuracy of dose calculation of a commercial treatment planning system (Corvus, Normos Corp., Sewickley, PA). In this study, 30 prostate intensity-modulated radiotherapy (IMRT) treatment plans from the commercial treatment planning system were recalculated using the Monte Carlo method. Dose-volume histograms and isodose distributions were compared. Other quantities such as minimum dose to the target (Dmin), the dose received by 98% of the target volume (D98), dose at the isocentre (Diso), mean target dose (Dmean) and the maximum critical structure dose (Dmax) were also evaluated based on our clinical criteria. For coplanar plans, the dose differences between Monte Carlo and the commercial treatment planning system with and without heterogeneity correction were not significant. The differences in the isocentre dose between the commercial treatment planning system and Monte Carlo simulations were less than 3% for all coplanar cases. The differences on D98 were less than 2% on average. The differences in the mean dose to the target between the commercial system and Monte Carlo results were within 3%. The differences in the maximum bladder dose were within 3% for most cases. The maximum dose differences for the rectum were less than 4% for all the cases. For non-coplanar plans, the difference in the minimum target dose between the treatment planning system and Monte Carlo calculations was up to 9% if the heterogeneity correction was not applied in Corvus. This was caused by the excessive attenuation of the non-coplanar beams by the femurs. When the heterogeneity correction was applied in Corvus, the differences were reduced significantly. These results suggest that heterogeneity correction should be used in dose calculation for prostate cancer with non-coplanar beam arrangements.

The essential oil of Brazilian pepper, Schinus terebinthifolia Raddi in larval control of Stegomyia aegypti (Linnaeus, 1762).

PubMed

Silva, Ary G; Almeida, Drielle L; Ronchi, Silas N; Bento, Amarildo C; Scherer, Rodrigo; Ramos, Alessandro C; Cruz, Zilma Ma

2010-08-27

The ability of mosquitoes of the genus Aedes and its allies, such as Stegomyia, to transmit diseases such as dengue and yellow fever, makes them important in public health. This study aims to evaluate the use of the essential oil of Brazilian pepper in biological control of by assessing and quantifying the larvicidal effect against S. aegypti, the only available access to dengue control, and test its risk of genotoxicity with Salmonella typhimurium as an indicator of safety for its environmental use. The density of the oil was 0.8622 g mL-1. Gas chromatography coupled with mass spectrometry revealed six major constituents: δ-3-carene (55.43%), α-pinene (16.25%), sylvestrene (10.67%), germacrene D (2.17), β-myrcene (1.99%), and isoterpinolene (1.4%). The minimum inhibitory dose to larvae development was 862.20 μg mL-1. The median lethal dose (LD50) of the essential oil for larvae was between the concentrations of 172.44-344.88 μg mL-1. There was no mutagenic risk for the essential oil, since there were no biochemical or morphological changes in S. typhimurium after exposure to the essential oil. The minimum inhibitory essential oil concentration and the median lethal dose pointed to the value of the use of water dispersions of Brazilian pepper essential oil as an environmental safe natural larvicidal for S. aegypti.

Post-column infusion study of the 'dosing vehicle effect' in the liquid chromatography/tandem mass spectrometric analysis of discovery pharmacokinetic samples.

PubMed

Shou, Wilson Z; Naidong, Weng

2003-01-01

It has become increasingly popular in drug development to conduct discovery pharmacokinetic (PK) studies in order to evaluate important PK parameters of new chemical entities (NCEs) early in the discovery process. In these studies, dosing vehicles are typically employed in high concentrations to dissolve the test compounds in dose formulations. This can pose significant problems for the liquid chromatography/tandem mass spectrometric (LC/MS/MS) analysis of incurred samples due to potential signal suppression of the analytes caused by the vehicles. In this paper, model test compounds in rat plasma were analyzed using a generic fast gradient LC/MS/MS method. Commonly used dosing vehicles, including poly(ethylene glycol) 400 (PEG 400), polysorbate 80 (Tween 80), hydroxypropyl beta-cyclodextrin, and N,N-dimethylacetamide, were fortified into rat plasma at 5 mg/mL before extraction. Their effects on the sample analysis results were evaluated by the method of post-column infusion. Results thus obtained indicated that polymeric vehicles such as PEG 400 and Tween 80 caused significant suppression (> 50%, compared with results obtained from plasma samples free from vehicles) to certain analytes, when minimum sample cleanup was used and the analytes happened to co-elute with the vehicles. Effective means to minimize this 'dosing vehicle effect' included better chromatographic separations, better sample cleanup, and alternative ionization methods. Finally, a real-world example is given to illustrate the suppression problem posed by high levels of PEG 400 in sample analysis, and to discuss steps taken in overcoming the problem. A simple but effective means of identifying a 'dosing vehicle effect' is also proposed. Copyright 2003 John Wiley & Sons, Ltd.

Once-daily dosing vs. conventional dosing schedule of mesalamine and relapse of quiescent ulcerative colitis: systematic review and meta-analysis.

PubMed

Ford, Alexander C; Khan, Khurram J; Sandborn, William J; Kane, Sunanda V; Moayyedi, Paul

2011-12-01

Maintenance therapy with 5-aminosalicylates (5-ASAs) is recommended in patients with quiescent ulcerative colitis (UC), but compliance rates are low. Once-daily dosing may improve adherence, but impact on the relapse of disease activity is unclear as no previous meta-analysis has studied this issue. MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through April 2011). Eligible randomized controlled trials (RCTs) recruited adults with quiescent UC, and compared once-daily dosing of 5-ASAs with a more frequent dosing schedule of an identical total daily dose of the same 5-ASA drug. Minimum treatment duration was 6 months. Trials reported a dichotomous assessment of relapse of disease activity at last point of follow-up. Data concerning non-compliance and adverse events were extracted, where reported. Effect of once-daily vs. more frequent dosing schedule was reported as relative risk (RR) of relapse with a 95% confidence interval (CI). The search identified 3,061 citations, and seven RCTs containing 2,745 patients were eligible. All RCTs used mesalamine. Relapse rates were not significantly different between once-daily and conventional dosing schedules for mesalamine (RR of relapse=0.94; 95% CI: 0.82-1.08). Non-compliance (RR=0.87; 95% CI: 0.46-1.66) and adverse events were no more likely with once-daily dosing (RR=1.08; 95% CI: 0.97-1.20). Once-daily dosing with mesalamine is as effective as conventional dosing schedules for the prevention of relapse of quiescent UC, although there is no definitive evidence that compliance with once-daily dosing is better. Adverse events occur at a similar frequency.

A simple LC-MS/MS method using HILIC chromatography for the determination of fosfomycin in plasma and urine: application to a pilot pharmacokinetic study in humans.

PubMed

Parker, Suzanne L; Lipman, Jeffrey; Roberts, Jason A; Wallis, Steven C

2015-02-01

A high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, using hydrophilic interaction liquid chromatography (HILIC) chromatography for the analysis of fosfomycin in human plasma and urine, has been developed and validated. The plasma method uses a simple protein precipitation using a low volume sample (10 μL) and is suitable for the concentration range of 1 to 2000 μg/mL. The urine method involves a simple dilution of 10 μL of sample and is suitable for a concentration range of 0.1 to 10 mg/mL. The plasma and urine results, reported, respectively, are for recovery (68, 72%), inter-assay precision (≤9.1%, ≤8.1%) and accuracy (range -7.2 to 3.3%, -1.9 to 1.6%), LLOQ precision (4.7%, 3.1%) and accuracy (1.7% and 1.2%), and includes investigations into the linearity, stability and matrix effects. The method was used in a pilot pharmacokinetic study of a critically ill patient receiving i.v. fosfomycin, which measured a maximum and minimum plasma concentration of 222 μg/mL and 172 μg/mL, respectively, after the initial dose, and a maximum and minimum plasma concentration of 868 μg/mL and 591μg/mL, respectively, after the fifth dose. The urine concentration was 2.03 mg/mL after the initial dose and 0.29 mg/mL after the fifth dose. Copyright © 2014 Elsevier B.V. All rights reserved.

Low-dose mannitol (0.3 g kg(-1)) improves the pulsatility index and minimum diastolic blood flow velocity in traumatic brain injury.

PubMed

Nincevic, Zeljko; Mestrovic, Julije; Nincevic, Jasna; Sundov, Zeljko; Kuscevic, Dorjan

2015-01-01

The aim of the study was to investigate the effects of using low-dose mannitol (0.3 g kg(-1)) on the pulsatility index (PI) and minimum diastolic blood flow velocity (FV-min) of the middle cerebral artery in a traumatic brain injury (TBI). Low-dose mannitol (0.3 g kg(-1)) was administered to a group of 20 patients with a TBI. Transcranial Doppler (TCD) ultrasonography was used to monitor the PI and FV-min. The study included patients with a diffuse traumatic brain injury and Glasgow coma score < 8. The initial TCD ultrasonography values were pathological (PI > 1.4 and FV-min < 20 cm s(-1)). TCD ultrasonography examinations were carried out before mannitol administration, immediately after administration and 1, 2 and 3 hours after the administration of mannitol. A one-way analysis of variance revealed significant changes in the PI (F = 8.392; p < 0.001) and FV-min (F = 8.291; p = 0.001) after the use of mannitol. Low-dose mannitol administration appears to be efficacious for improving the indicators of disturbed circulation in a TBI (FV-min increase, PI decrease). The maximum decrease in the PI was recorded 1 hour after the administration of mannitol and was 10.9% of the initial value. The maximum increase in the FV-min was recorded 1 hour after administration and was 29.7% of the initial value. These changes were significant ∼ 2 hours later.

Efficacy and safety of lacosamide in infants and young children with refractory focal epilepsy.

PubMed

Grosso, Salvatore; Parisi, Pasquale; Spalice, Alberto; Verrotti, Alberto; Balestri, Paolo

2014-01-01

Lacosamide is effective and well-tolerated antiepileptic drug (AED) in both children and adults. This multicentric, prospective study investigates the efficacy and safety of lacosamide adjunctive therapy in children aged less than four years presenting with refractory focal seizures. Lacosamide was added to the baseline therapy at a starting dose of 1-2 mg/kg/day and titrated to the final dose, ranging from 7 to 15.5 mg/kg/day. Efficacy was evaluated after a three-month period of therapy. When possible, we compared the initial efficacy and the retention after a minimum of 12 months of lacosamide, with regard to loss of efficacy (defined as the return to the baseline seizure frequency). Twenty-four children were enrolled in the study. Mean age was 2.7 years. After a minimum three-month period of lacosamide add-on therapy, ten (42%) patients were responders (more than a 50% decrease in seizure frequency), of whom 4 (17%) became seizure free. Retention rate, after a minimum of 12 months of lacosamide, was evaluated in a group of 18 patients. In the latter group, eight patients (44%) were initial responders (three of whom seizure free). After 12 months of follow-up, four of them (22%) maintained the improvement, 2 (11%) of whom remained seizure free. A loss of efficacy was observed in 4 of the initial responders (50%). Adverse events were seen in 8 (33%) patients. We conclude that lacosamide is an effective and a well-tolerated antiepileptic drug in an etiologically wide range of focal seizures. Therefore, lacosamide might represent a possible therapeutic option in infants and young children affected by uncontrolled focal epilepsy. Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Irradiation and measurements of fluorinated ethylene-propylene-A on silicon solar cells in vacuum

NASA Technical Reports Server (NTRS)

Marsik, S. J.; Broder, J. D.

1975-01-01

Silicon monoxide (SiO) coated silicon solar cells covered with fluorinated ethylene-propylene-A (FEP-A) were irradiated by 1-MeV electrons in vacuum. The effect of irradiation on the light transmittance of FEP-A was checked by measuring the short-circuit current of the cells while in vacuum after each dose increment, immediately after the irradiation, and again after a minimum elapsed time of 16 hr. The results indicated no apparent loss in transmission due to irradiation of FEP-A and no delamination from the SiO surface while the cells were in vacuum, but embrittlement of FEP-A occurred at the accumulated dose.

SU-F-T-18: The Importance of Immobilization Devices in Brachytherapy Treatments of Vaginal Cuff

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

Shojaei, M; Dumitru, N; Pella, S

2016-06-15

Purpose: High dose rate brachytherapy is a highly localized radiation therapy that has a very high dose gradient. Thus one of the most important parts of the treatment is the immobilization. The smallest movement of the patient or applicator can result in dose variation to the surrounding tissues as well as to the tumor to be treated. We will revise the ML Cylinder treatments and their localization challenges. Methods: A retrospective study of 25 patients with 5 treatments each looking into the applicator’s placement in regard to the organs at risk. Motion possibilities for each applicator intra and inter fractionationmore » with their dosimetric implications were covered and measured in regard with their dose variance. The localization immobilization devices used were assessed for the capability to prevent motion before and during the treatment delivery. Results: We focused on the 100% isodose on central axis and a 15 degree displacement due to possible rotation analyzing the dose variations to the bladder and rectum walls. The average dose variation for bladder was 15% of the accepted tolerance, with a minimum variance of 11.1% and a maximum one of 23.14% on the central axis. For the off axis measurements we found an average variation of 16.84% of the accepted tolerance, with a minimum variance of 11.47% and a maximum one of 27.69%. For the rectum we focused on the rectum wall closest to the 120% isodose line. The average dose variation was 19.4%, minimum 11.3% and a maximum of 34.02% from the accepted tolerance values Conclusion: Improved immobilization devices are recommended. For inter-fractionation, localization devices are recommended in place with consistent planning in regards with the initial fraction. Many of the present immobilization devices produced for external radiotherapy can be used to improve the localization of HDR applicators during transportation of the patient and during treatment.« less

SU-E-T-206: Comparison of EBT and EBT3 RadioChromic Films in Radiation Field of Parotid Cancer Radiotherapy

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

Toosi, T Bahreyni; Mianaei, F Khorshidi; Ghorbani, M

Purpose: The aim of the current study is to compare EBT and EBT3 RadioChromic films in dosimetry of radiotherapy fields for treatment of parotid cancer. Methods: The calibrations of EBT and EBT3 films were performed with the same setups for doses ranging from 0.2 Gy to 5 Gy using 6 MV photon beam of a Siemens Primus linac. These films were scanned in color mode (RGB) by a Microtek (1000XL) scanner and the red color channel data was extracted. Treatment planning for parotid cancer radiation therapy was performed on a RANDO phantom. Skin dose was measured at different points inmore » the right anterior oblique (RAO) and right posterior oblique (RPO) fields by EBT and EBT3 films. Results: Dosimetry was performed with the same conditions for the two film types for calibration and in-phantom in parotid cancer radiotherapy. The measured net optical density (NOD) in EBT film was in some extent higher than that from EBT3 film. The minimum difference between these two films under calibration conditions was about 2.9% (for 0.2 Gy). However, the maximum difference was 35.5% (for 0.5 Gy). In the therapeutic fields of parotid cancer radiotherapy at different points, the measured dose from EBT film was higher than the EBT3 film. In these fields the minimum and maximum measured dose differences were 16.0% and 25.5%, respectively. Conclusion: With the same irradiation and reading conditions, EBT film demonstrates higher NOD than the EBT3 film. This effect may be related to the higher sensitivity of EBT film over EBT3 film. However, the obtained dose differences between these two films in low dose range can be due to the differences in fitting functions applied following the calibration process.« less

A single-gradient junction technique to replace multiple-junction shifts for craniospinal irradiation treatment

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

Hadley, Austin; Ding, George X., E-mail: george.ding@vanderbilt.edu

2014-01-01

Craniospinal irradiation (CSI) requires abutting fields at the cervical spine. Junction shifts are conventionally used to prevent setup error–induced overdosage/underdosage from occurring at the same location. This study compared the dosimetric differences at the cranial-spinal junction between a single-gradient junction technique and conventional multiple-junction shifts and evaluated the effect of setup errors on the dose distributions between both techniques for a treatment course and single fraction. Conventionally, 2 lateral brain fields and a posterior spine field(s) are used for CSI with weekly 1-cm junction shifts. We retrospectively replanned 4 CSI patients using a single-gradient junction between the lateral brain fieldsmore » and the posterior spine field. The fields were extended to allow a minimum 3-cm field overlap. The dose gradient at the junction was achieved using dose painting and intensity-modulated radiation therapy planning. The effect of positioning setup errors on the dose distributions for both techniques was simulated by applying shifts of ± 3 and 5 mm. The resulting cervical spine doses across the field junction for both techniques were calculated and compared. Dose profiles were obtained for both a single fraction and entire treatment course to include the effects of the conventional weekly junction shifts. Compared with the conventional technique, the gradient-dose technique resulted in higher dose uniformity and conformity to the target volumes, lower organ at risk (OAR) mean and maximum doses, and diminished hot spots from systematic positioning errors over the course of treatment. Single-fraction hot and cold spots were improved for the gradient-dose technique. The single-gradient junction technique provides improved conformity, dose uniformity, diminished hot spots, lower OAR mean and maximum dose, and one plan for the entire treatment course, which reduces the potential human error associated with conventional 4-shifted plans.« less

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

Suzuki, Minoru; Sakurai, Yoshinori; Masunaga, Shinichiro

Purpose: To investigate the feasibility of boron neutron capture therapy (BNCT) for malignant pleural mesothelioma (MPM) from a viewpoint of dose distribution analysis using Simulation Environment for Radiotherapy Applications (SERA), a currently available BNCT treatment planning system. Methods and Materials: The BNCT treatment plans were constructed for 3 patients with MPM using the SERA system, with 2 opposed anterior-posterior beams. The {sup 1}B concentrations in the tumor and normal lung in this study were assumed to be 84 and 24 ppm, respectively, and were derived from data observed in clinical trials. The maximum, mean, and minimum doses to the tumorsmore » and the normal lung were assessed for each plan. The doses delivered to 5% and 95% of the tumor volume, D{sub 05} and D{sub 95}, were adopted as the representative dose for the maximum and minimum dose, respectively. Results: When the D{sub 05} to the normal ipsilateral lung was 5 Gy-Eq, the D{sub 95} and mean doses delivered to the normal lung were 2.2-3.6 and 3.5-4.2 Gy-Eq, respectively. The mean doses delivered to the tumors were 22.4-27.2 Gy-Eq. The D{sub 05} and D{sub 95} doses to the tumors were 9.6-15.0 and 31.5-39.5 Gy-Eq, respectively. Conclusions: From a viewpoint of the dose-distribution analysis, BNCT has the possibility to be a promising treatment for MPM patients who are inoperable because of age and other medical illnesses.« less

Effects of Zika Virus Strain and Aedes Mosquito Species on Vector Competence.

PubMed

Ciota, Alexander T; Bialosuknia, Sean M; Zink, Steven D; Brecher, Matthew; Ehrbar, Dylan J; Morrissette, Madeline N; Kramer, Laura D

2017-07-01

In the Western Hemisphere, Zika virus is thought to be transmitted primarily by Aedes aegypti mosquitoes. To determine the extent to which Ae. albopictus mosquitoes from the United States are capable of transmitting Zika virus and the influence of virus dose, virus strain, and mosquito species on vector competence, we evaluated multiple doses of representative Zika virus strains in Ae. aegypti and Ae. albopictus mosquitoes. Virus preparation (fresh vs. frozen) significantly affected virus infectivity in mosquitoes. We calculated 50% infectious doses to be 6.1-7.5 log 10 PFU/mL; minimum infective dose was 4.2 log 10 PFU/mL. Ae. albopictus mosquitoes were more susceptible to infection than Ae. aegypti mosquitoes, but transmission efficiency was higher for Ae. aegypti mosquitoes, indicating a transmission barrier in Ae. albopictus mosquitoes. Results suggest that, although Zika virus transmission is relatively inefficient overall and dependent on virus strain and mosquito species, Ae. albopictus mosquitoes could become major vectors in the Americas.

Effects of Zika Virus Strain and Aedes Mosquito Species on Vector Competence

PubMed Central

Bialosuknia, Sean M.; Zink, Steven D.; Brecher, Matthew; Ehrbar, Dylan J.; Morrissette, Madeline N.; Kramer, Laura D.

2017-01-01

In the Western Hemisphere, Zika virus is thought to be transmitted primarily by Aedes aegypti mosquitoes. To determine the extent to which Ae. albopictus mosquitoes from the United States are capable of transmitting Zika virus and the influence of virus dose, virus strain, and mosquito species on vector competence, we evaluated multiple doses of representative Zika virus strains in Ae. aegypti and Ae. albopictus mosquitoes. Virus preparation (fresh vs. frozen) significantly affected virus infectivity in mosquitoes. We calculated 50% infectious doses to be 6.1–7.5 log10 PFU/mL; minimum infective dose was 4.2 log10 PFU/mL. Ae. albopictus mosquitoes were more susceptible to infection than Ae. aegypti mosquitoes, but transmission efficiency was higher for Ae. aegypti mosquitoes, indicating a transmission barrier in Ae. albopictus mosquitoes. Results suggest that, although Zika virus transmission is relatively inefficient overall and dependent on virus strain and mosquito species, Ae. albopictus mosquitoes could become major vectors in the Americas. PMID:28430564

Effects of white phosphorus on mallard reproduction

USGS Publications Warehouse

Vann, S.I.; Sparling, D.W.; Ottinger, M.A.

2000-01-01

Extensive waterfowl mortality involving thousands of ducks, geese, and swans has occurred annually at Eagle River Flats, Alaska since at least 1982. The primary agent for this mortality has been identified as white phosphorus. Although acute and subacute lethality have been described, sublethal effects are less well known. This study reports on the effects of white phosphorus on reproductive function in the mallard (Anas platyrhynchos) in captivity. Fertility, hatching success, teratogenicity, and egg laying frequency were examined in 70 adult female mallards who received up to 7 daily doses of 0, 0.5, 1.0, and 2.0 mg/kg of white phosphorus. Measurements of fertility and hatchability were reduced by the white phosphorus. Teratogenic effects were observed in embryos from hens dosed at all treatment levels. Egg laying frequency was reduced even at the lowest treatment level; treated hens required a greater number of days to lay a clutch of 12 eggs than control hens. After two doses at 2.0 mg/kg, all females stopped laying completely for a minimum of 10 days and laying frequency was depressed for at least 45 days. Fertility of 10 adult male mallards dosed with 1.0 mg/kg of white phosphorus did not differ from 10 controls, but plasma testosterone levels were significantly (p < 0.05) reduced in the treated males 1 day after dosing ended. These results provide evidence that productivity of free-ranging mallards may be impaired if they are exposed to white phosphorus at typical field levels.

Dosimetric Evaluation of Metal Artefact Reduction using Metal Artefact Reduction (MAR) Algorithm and Dual-energy Computed Tomography (CT) Method

NASA Astrophysics Data System (ADS)

Laguda, Edcer Jerecho

Purpose: Computed Tomography (CT) is one of the standard diagnostic imaging modalities for the evaluation of a patient's medical condition. In comparison to other imaging modalities such as Magnetic Resonance Imaging (MRI), CT is a fast acquisition imaging device with higher spatial resolution and higher contrast-to-noise ratio (CNR) for bony structures. CT images are presented through a gray scale of independent values in Hounsfield units (HU). High HU-valued materials represent higher density. High density materials, such as metal, tend to erroneously increase the HU values around it due to reconstruction software limitations. This problem of increased HU values due to metal presence is referred to as metal artefacts. Hip prostheses, dental fillings, aneurysm clips, and spinal clips are a few examples of metal objects that are of clinical relevance. These implants create artefacts such as beam hardening and photon starvation that distort CT images and degrade image quality. This is of great significance because the distortions may cause improper evaluation of images and inaccurate dose calculation in the treatment planning system. Different algorithms are being developed to reduce these artefacts for better image quality for both diagnostic and therapeutic purposes. However, very limited information is available about the effect of artefact correction on dose calculation accuracy. This research study evaluates the dosimetric effect of metal artefact reduction algorithms on severe artefacts on CT images. This study uses Gemstone Spectral Imaging (GSI)-based MAR algorithm, projection-based Metal Artefact Reduction (MAR) algorithm, and the Dual-Energy method. Materials and Methods: The Gemstone Spectral Imaging (GSI)-based and SMART Metal Artefact Reduction (MAR) algorithms are metal artefact reduction protocols embedded in two different CT scanner models by General Electric (GE), and the Dual-Energy Imaging Method was developed at Duke University. All three approaches were applied in this research for dosimetric evaluation on CT images with severe metal artefacts. The first part of the research used a water phantom with four iodine syringes. Two sets of plans, multi-arc plans and single-arc plans, using the Volumetric Modulated Arc therapy (VMAT) technique were designed to avoid or minimize influences from high-density objects. The second part of the research used projection-based MAR Algorithm and the Dual-Energy Method. Calculated Doses (Mean, Minimum, and Maximum Doses) to the planning treatment volume (PTV) were compared and homogeneity index (HI) calculated. Results: (1) Without the GSI-based MAR application, a percent error between mean dose and the absolute dose ranging from 3.4-5.7% per fraction was observed. In contrast, the error was decreased to a range of 0.09-2.3% per fraction with the GSI-based MAR algorithm. There was a percent difference ranging from 1.7-4.2% per fraction between with and without using the GSI-based MAR algorithm. (2) A range of 0.1-3.2% difference was observed for the maximum dose values, 1.5-10.4% for minimum dose difference, and 1.4-1.7% difference on the mean doses. Homogeneity indexes (HI) ranging from 0.068-0.065 for dual-energy method and 0.063-0.141 with projection-based MAR algorithm were also calculated. Conclusion: (1) Percent error without using the GSI-based MAR algorithm may deviate as high as 5.7%. This error invalidates the goal of Radiation Therapy to provide a more precise treatment. Thus, GSI-based MAR algorithm was desirable due to its better dose calculation accuracy. (2) Based on direct numerical observation, there was no apparent deviation between the mean doses of different techniques but deviation was evident on the maximum and minimum doses. The HI for the dual-energy method almost achieved the desirable null values. In conclusion, the Dual-Energy method gave better dose calculation accuracy to the planning treatment volume (PTV) for images with metal artefacts than with or without GE MAR Algorithm.

Pharmacological management of anticholinergic delirium - theory, evidence and practice.

PubMed

Dawson, Andrew H; Buckley, Nicholas A

2016-03-01

The spectrum of anticholinergic delirium is a common complication following drug overdose. Patients with severe toxicity can have significant distress and behavioural problems that often require pharmacological management. Cholinesterase inhibitors, such as physostigmine, are effective but widespread use has been limited by concerns about safety, optimal dosing and variable supply. Case series support efficacy in reversal of anticholinergic delirium. However doses vary widely and higher doses commonly lead to cholinergic toxicity. Seizures are reported in up to 2.5% of patients and occasional cardiotoxic effects are also recorded. This article reviews the serendipitous path whereby physostigmine evolved into the preferred anticholinesterase antidote largely without any research to indicate the optimal dosing strategy. Adverse events observed in case series should be considered in the context of pharmacokinetic/pharmacodynamic studies of physostigmine which suggest a much longer latency before the maximal increase in brain acetylcholine than had been previously assumed. This would favour protocols that use lower doses and longer re-dosing intervals. We propose based on the evidence reviewed that the use of cholinesterase inhibitors should be considered in anticholinergic delirium that has not responded to non-pharmacological delirium management. The optimal risk/benefit would be with a titrated dose of 0.5 to 1 mg physostigmine (0.01-0.02 mg kg(-1) in children) with a minimum delay of 10-15 min before re-dosing. Slower onset and longer acting agents such as rivastigmine would also be logical but more research is needed to guide the appropriate dose in this setting. © 2015 The British Pharmacological Society.

Optimisation techniques in vaginal cuff brachytherapy.

PubMed

Tuncel, N; Garipagaoglu, M; Kizildag, A U; Andic, F; Toy, A

2009-11-01

The aim of this study was to explore whether an in-house dosimetry protocol and optimisation method are able to produce a homogeneous dose distribution in the target volume, and how often optimisation is required in vaginal cuff brachytherapy. Treatment planning was carried out for 109 fractions in 33 patients who underwent high dose rate iridium-192 (Ir(192)) brachytherapy using Fletcher ovoids. Dose prescription and normalisation were performed to catheter-oriented lateral dose points (dps) within a range of 90-110% of the prescribed dose. The in-house vaginal apex point (Vk), alternative vaginal apex point (Vk'), International Commission on Radiation Units and Measurements (ICRU) rectal point (Rg) and bladder point (Bl) doses were calculated. Time-position optimisations were made considering dps, Vk and Rg doses. Keeping the Vk dose higher than 95% and the Rg dose less than 85% of the prescribed dose was intended. Target dose homogeneity, optimisation frequency and the relationship between prescribed dose, Vk, Vk', Rg and ovoid diameter were investigated. The mean target dose was 99+/-7.4% of the prescription dose. Optimisation was required in 92 out of 109 (83%) fractions. Ovoid diameter had a significant effect on Rg (p = 0.002), Vk (p = 0.018), Vk' (p = 0.034), minimum dps (p = 0.021) and maximum dps (p<0.001). Rg, Vk and Vk' doses with 2.5 cm diameter ovoids were significantly higher than with 2 cm and 1.5 cm ovoids. Catheter-oriented dose point normalisation provided a homogeneous dose distribution with a 99+/-7.4% mean dose within the target volume, requiring time-position optimisation.

Analgesic use of inhaled methoxyflurane: Evaluation of its potential nephrotoxicity.

PubMed

Dayan, A D

2016-01-01

Methoxyflurane is a volatile, halogenated analgesic, self-administered in a controlled low dose from the Penthrox(®) inhaler for short-term pain relief. It was formerly used in significantly higher doses to produce anaesthesia, when it caused a specific type of dose-related renal tubular damage. The pathogenesis of the renal damage and clinical use of methoxyflurane are discussed here with evidence that a low but effective analgesic dose is not associated with the risk of renal adverse effects. The maximum dose employed to produce analgesia is limited to methoxyflurane 6 mL/day and 15 mL/week, producing a minimum alveolar concentration (MAC) of 0.59 MAC-hours. Renal damage is due to the metabolism of methoxyflurane and release of fluoride ions. Exposure of humans to methoxyflurane ≤2.0 MAC-hours, resulting in serum fluoride ≤40 µmol/L, has not been associated with renal tubular toxicity. The safety margin of analgesic use of methoxyflurane in the Penthrox ((®)) inhaler is at least 2.7- to 8-fold, based on methoxyflurane MAC-hours or serum fluoride level, with clinical experience suggesting it is higher. It is concluded from clinical experience in emergency medicine, surgical procedures and various experimental and laboratory investigations that the analgesic use of methoxyflurane in subanaesthetic doses in the Penthrox inhaler does not carry a risk of nephrotoxicity. © The Author(s) 2015.

Multiple-Objective Optimal Designs for Studying the Dose Response Function and Interesting Dose Levels

PubMed Central

Hyun, Seung Won; Wong, Weng Kee

2016-01-01

We construct an optimal design to simultaneously estimate three common interesting features in a dose-finding trial with possibly different emphasis on each feature. These features are (1) the shape of the dose-response curve, (2) the median effective dose and (3) the minimum effective dose level. A main difficulty of this task is that an optimal design for a single objective may not perform well for other objectives. There are optimal designs for dual objectives in the literature but we were unable to find optimal designs for 3 or more objectives to date with a concrete application. A reason for this is that the approach for finding a dual-objective optimal design does not work well for a 3 or more multiple-objective design problem. We propose a method for finding multiple-objective optimal designs that estimate the three features with user-specified higher efficiencies for the more important objectives. We use the flexible 4-parameter logistic model to illustrate the methodology but our approach is applicable to find multiple-objective optimal designs for other types of objectives and models. We also investigate robustness properties of multiple-objective optimal designs to mis-specification in the nominal parameter values and to a variation in the optimality criterion. We also provide computer code for generating tailor made multiple-objective optimal designs. PMID:26565557

Multiple-Objective Optimal Designs for Studying the Dose Response Function and Interesting Dose Levels.

PubMed

Hyun, Seung Won; Wong, Weng Kee

2015-11-01

We construct an optimal design to simultaneously estimate three common interesting features in a dose-finding trial with possibly different emphasis on each feature. These features are (1) the shape of the dose-response curve, (2) the median effective dose and (3) the minimum effective dose level. A main difficulty of this task is that an optimal design for a single objective may not perform well for other objectives. There are optimal designs for dual objectives in the literature but we were unable to find optimal designs for 3 or more objectives to date with a concrete application. A reason for this is that the approach for finding a dual-objective optimal design does not work well for a 3 or more multiple-objective design problem. We propose a method for finding multiple-objective optimal designs that estimate the three features with user-specified higher efficiencies for the more important objectives. We use the flexible 4-parameter logistic model to illustrate the methodology but our approach is applicable to find multiple-objective optimal designs for other types of objectives and models. We also investigate robustness properties of multiple-objective optimal designs to mis-specification in the nominal parameter values and to a variation in the optimality criterion. We also provide computer code for generating tailor made multiple-objective optimal designs.

Computational method for the correction of proximity effect in electron-beam lithography (Poster Paper)

NASA Astrophysics Data System (ADS)

Chang, Chih-Yuan; Owen, Gerry; Pease, Roger Fabian W.; Kailath, Thomas

1992-07-01

Dose correction is commonly used to compensate for the proximity effect in electron lithography. The computation of the required dose modulation is usually carried out using 'self-consistent' algorithms that work by solving a large number of simultaneous linear equations. However, there are two major drawbacks: the resulting correction is not exact, and the computation time is excessively long. A computational scheme, as shown in Figure 1, has been devised to eliminate this problem by the deconvolution of the point spread function in the pattern domain. The method is iterative, based on a steepest descent algorithm. The scheme has been successfully tested on a simple pattern with a minimum feature size 0.5 micrometers , exposed on a MEBES tool at 10 KeV in 0.2 micrometers of PMMA resist on a silicon substrate.

An analysis of interplanetary space radiation exposure for various solar cycles

NASA Technical Reports Server (NTRS)

Badhwar, G. D.; Cucinotta, F. A.; O'Neill, P. M.; Wilson, J. W. (Principal Investigator)

1994-01-01

The radiation dose received by crew members in interplanetary space is influenced by the stage of the solar cycle. Using the recently developed models of the galactic cosmic radiation (GCR) environment and the energy-dependent radiation transport code, we have calculated the dose at 0 and 5 cm water depth; using a computerized anatomical man (CAM) model, we have calculated the skin, eye and blood-forming organ (BFO) doses as a function of aluminum shielding for various solar minima and maxima between 1954 and 1989. These results show that the equivalent dose is within about 15% of the mean for the various solar minima (maxima). The maximum variation between solar minimum and maximum equivalent dose is about a factor of three. We have extended these calculations for the 1976-1977 solar minimum to five practical shielding geometries: Apollo Command Module, the least and most heavily shielded locations in the U.S. space shuttle mid-deck, center of the proposed Space Station Freedom cluster and sleeping compartment of the Skylab. These calculations, using the quality factor of ICRP 60, show that the average CAM BFO equivalent dose is 0.46 Sv/year. Based on an approach that takes fragmentation into account, we estimate a calculation uncertainty of 15% if the uncertainty in the quality factor is neglected.

Effect of CT contrast on volumetric arc therapy planning (RapidArc and helical tomotherapy) for head and neck cancer

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

Liu, Alan J.; Vora, Nayana; Suh, Steve

2015-04-01

The objectives of the study were to evaluate the effect of intravenous contrast in the dosimetry of helical tomotherapy and RapidArc treatment for head and neck cancer and determine if it is acceptable during the computed tomography (CT) simulation to acquire only CT with contrast for treatment planning of head and neck cancer. Overall, 5 patients with head and neck cancer (4 men and 1 woman) treated on helical tomotherapy were analyzed retrospectively. For each patient, 2 consecutive CT scans were performed. The first CT set was scanned before the contrast injection and secondary study set was scanned 45 secondsmore » after contrast. The 2 CTs were autoregistered using the same Digital Imaging and Communications in Medicine coordinates. Tomotherapy and RapidArc plans were generated on 1 CT data set and subsequently copied to the second CT set. Dose calculation was performed, and dose difference was analyzed to evaluate the influence of intravenous contrast media. The dose matrix used for comparison included mean, minimum and maximum doses of planning target volume (PTV), PTV dose coverage, and V{sub 45} {sub Gy}, V{sub 30} {sub Gy}, and V{sub 20} {sub Gy} organ doses. Treatment planning on contrasted images generally showed a lower dose to both organs and target than plans on noncontrasted images. The doses for the points of interest placed in the organs and target rarely changed more than 2% in any patient. In conclusion, treatment planning using a contrasted image had insignificant effect on the dose to the organs and targets. In our opinion, only CT with contrast needs to be acquired during the CT simulation for head and neck cancer. Dose calculations performed on contrasted images can potentially underestimate the delivery dose slightly. However, the errors of planning on a contrasted image should not affect the result in clinically significant way.« less

Effect of TNF-α production inhibitors on the production of pro-inflammatory cytokines by peripheral blood mononuclear cells from HTLV-1-infected individuals.

PubMed

Luna, T; Santos, S B; Nascimento, M; Porto, M A F; Muniz, A L; Carvalho, E M; Jesus, A R

2011-11-01

Human T lymphotropic virus type 1 (HTLV-1) is the causal agent of myelopathy/tropical spastic paraparesis (HAM/TSP), a disease mediated by the immune response. HTLV-1 induces a spontaneous proliferation and production of pro-inflammatory cytokines by T cells, and increasing interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) levels are potentially involved in tissue damage in diseases related to HTLV-1. This exaggerated immune response is also due to an inability of the natural regulatory mechanisms to down-modulate the immune response in this group of patients. TNF-α inhibitors reduce inflammation and have been shown to improve chronic inflammatory diseases in clinical trials. The aim of this study was to evaluate the ability of pentoxifylline, forskolin, rolipram, and thalidomide to decrease in vitro production of TNF-α and IFN-γ in cells of HTLV-1-infected subjects. Participants of the study included 19 patients with HAM/TSP (mean age, 53 ± 11; male:female ratio, 1:1) and 18 HTLV-1 carriers (mean age, 47 ± 11; male:female ratio, 1:2.6). Cytokines were determined by ELISA in supernatants of mononuclear cell cultures. Pentoxifylline inhibited TNF-α and IFN-γ synthesis with the minimum dose used (50 µM). The results with forskolin were similar to those observed with pentoxifylline. The doses of rolipram used were 0.01-1 µM and the best inhibition of TNF-α production was achieved with 1 µM and for IFN-γ production it was 0.01 µM. The minimum dose of thalidomide used (1 µM) inhibited TNF-α production but thalidomide did not inhibit IFN-γ production even when the maximum dose (50 µM) was used. All drugs had an in vitro inhibitory effect on TNF-α production and, with the exception of thalidomide, all of them also decreased IFN-γ production.

Use of computer code for dose distribution studies in A 60CO industrial irradiator

NASA Astrophysics Data System (ADS)

Piña-Villalpando, G.; Sloan, D. P.

1995-09-01

This paper presents a benchmark comparison between calculated and experimental absorbed dose values tor a typical product, in a 60Co industrial irradiator, located at ININ, México. The irradiator is a two levels, two layers system with overlapping product configuration with activity around 300kCi. Experimental values were obtanied from routine dosimetry, using red acrylic pellets. Typical product was Petri dishes packages, apparent density 0.13 g/cm3; that product was chosen because uniform size, large quantity and low density. Minimum dose was fixed in 15 kGy. Calculated values were obtained from QAD-CGGP code. This code uses a point kernel technique, build-up factors fitting was done by geometrical progression and combinatorial geometry is used for system description. Main modifications for the code were related with source sumilation, using punctual sources instead of pencils and an energy and anisotropic emission spectrums were included. Results were, for maximum dose, calculated value (18.2 kGy) was 8% higher than experimental average value (16.8 kGy); for minimum dose, calculated value (13.8 kGy) was 3% higher than experimental average value (14.3 kGy).

Assessment of radiation exposure from cesium-137 contaminated roads for epidemiological studies in Seoul, Korea.

PubMed

Lee, Yun-Keun; Ju, Young-Su; Lee, Won Jin; Hwang, Seung Sik; Yim, Sang-Hyuk; Yoo, Sang-Chul; Lee, Jieon; Choi, Kyung-Hwa; Burm, Eunae; Ha, Mina

2015-01-01

We aimed to assess the radiation exposure for epidemiologic investigation in residents exposed to radiation from roads that were accidentally found to be contaminated with radioactive cesium-137 ((137)Cs) in Seoul. Using information regarding the frequency and duration of passing via the (137)Cs contaminated roads or residing/working near the roads from the questionnaires that were obtained from 8875 residents and the measured radiation doses reported by the Nuclear Safety and Security Commission, we calculated the total cumulative dose of radiation exposure for each person. Sixty-three percent of the residents who responded to the questionnaire were considered as ever-exposed and 1% of them had a total cumulative dose of more than 10 mSv. The mean (minimum, maximum) duration of radiation exposure was 4.75 years (0.08, 11.98) and the geometric mean (minimum, maximum) of the total cumulative dose was 0.049 mSv (<0.001, 35.35) in the exposed. An individual exposure assessment was performed for an epidemiological study to estimate the health risk among residents living in the vicinity of (137)Cs contaminated roads. The average exposure dose in the exposed people was less than 5% of the current guideline.

Optimal allocation of the limited oral cholera vaccine supply between endemic and epidemic settings.

PubMed

Moore, Sean M; Lessler, Justin

2015-10-06

The World Health Organization (WHO) recently established a global stockpile of oral cholera vaccine (OCV) to be preferentially used in epidemic response (reactive campaigns) with any vaccine remaining after 1 year allocated to endemic settings. Hence, the number of cholera cases or deaths prevented in an endemic setting represents the minimum utility of these doses, and the optimal risk-averse response to any reactive vaccination request (i.e. the minimax strategy) is one that allocates the remaining doses between the requested epidemic response and endemic use in order to ensure that at least this minimum utility is achieved. Using mathematical models, we find that the best minimax strategy is to allocate the majority of doses to reactive campaigns, unless the request came late in the targeted epidemic. As vaccine supplies dwindle, the case for reactive use of the remaining doses grows stronger. Our analysis provides a lower bound for the amount of OCV to keep in reserve when responding to any request. These results provide a strategic context for the fulfilment of requests to the stockpile, and define allocation strategies that minimize the number of OCV doses that are allocated to suboptimal situations. © 2015 The Authors.

Medical image enhancement using resolution synthesis

NASA Astrophysics Data System (ADS)

Wong, Tak-Shing; Bouman, Charles A.; Thibault, Jean-Baptiste; Sauer, Ken D.

2011-03-01

We introduce a post-processing approach to improve the quality of CT reconstructed images. The scheme is adapted from the resolution-synthesis (RS)1 interpolation algorithm. In this approach, we consider the input image, scanned at a particular dose level, as a degraded version of a high quality image scanned at a high dose level. Image enhancement is achieved by predicting the high quality image by classification based linear regression. To improve the robustness of our scheme, we also apply the minimum description length principle to determine the optimal number of predictors to use in the scheme, and the ridge regression to regularize the design of the predictors. Experimental results show that our scheme is effective in reducing the noise in images reconstructed from filtered back projection without significant loss of image details. Alternatively, our scheme can also be applied to reduce dose while maintaining image quality at an acceptable level.

The radiation enhancement of the sterility assurance levels of sterile fluids — A case study

NASA Astrophysics Data System (ADS)

Plessis, T. A. Du.; Rosekilly, I. C.

1995-02-01

A study was undertaken to determine the effect of low-dose gamma irradiation on aseptically admixed total parenteral nutrition (TPN) solutions to which large inocula of three test bacterial species, recognised as common contaminants of these products, were added. Attainable SALs of TPN solutions containing test bacteria were subsequently calculated. Results showed that a minimum absorbed radiation dose as low as 1.5 kGy improved the SAL of aseptically prepared TPN solutions from a SAL of 10 -3 to a value of less than 10 -8 for the microorganisms investigated. No measurable changes in amino acid, electrolyte, glucose and lipid components of the solutions were detected up to a dose of 8.3 kGy. Practical experience applying this radiation treatment of TPNs rendered excellent results leading to the routine application of the process in South Africa.

Efficacy of a novel formulation of metaflumizone plus amitraz for the treatment of sarcoptic mange in dogs.

PubMed

Fourie, L J; Kok, D J; du Plessis, A; Rugg, D

2007-12-15

A novel spot-on formulation containing metaflumizone plus amitraz (ProMeris/ProMeris Duo for Dogs, Fort Dodge Animal Health, Overland Park, KS) was evaluated for efficacy against sarcoptic mange mites in naturally infested dogs. Sixteen dogs were allocated to two equal groups and were housed individually. Eight of the dogs were treated topically with metaflumizone plus amitraz at the proposed minimum dose rate (20mg/kg of each of metaflumizone and amitraz, at a dose volume of 0.133ml/kg) on Days 0 and 28. The other eight were treated with metaflumizone plus amitraz at the proposed minimum dose rate on Days 0, 14, 28 and 42. To enumerate Sarcoptes scabiei mites, skin scrapings were taken on each of Days 2, 14, 28, 42 and 56. Clinical signs of mange and the extent of sarcoptic lesions were evaluated on each dog when scrapings were made. Evaluation of the efficacy of the treatment was based on the absence of mites supported by the absence of clinical signs associated with canine sarcoptic mange. Treatment with metaflumizone plus amitraz at the minimum proposed dose rate at monthly (two treatments) or two-weekly (four treatments) intervals resulted in a rapid reduction of mites and improved clinical signs. The overall cure rates at Day 56, based on zero mite counts and/or resolution of clinical signs were 75% and 83% of dogs for the monthly and two-weekly regimens, respectively.

Analysis of nodal coverage utilizing image guided radiation therapy for primary gynecologic tumor volumes

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

Ahmed, Faisal; Loma Linda University Medical Center, Department of Radiation Oncology, Loma Linda, CA; Sarkar, Vikren

Purpose: To evaluate radiation dose delivered to pelvic lymph nodes, if daily Image Guided Radiation Therapy (IGRT) was implemented with treatment shifts based on the primary site (primary clinical target volume [CTV]). Our secondary goal was to compare dosimetric coverage with patient outcomes. Materials and methods: A total of 10 female patients with gynecologic malignancies were evaluated retrospectively after completion of definitive intensity-modulated radiation therapy (IMRT) to their pelvic lymph nodes and primary tumor site. IGRT consisted of daily kilovoltage computed tomography (CT)-on-rails imaging fused with initial planning scans for position verification. The initial plan was created using Varian's Eclipsemore » treatment planning software. Patients were treated with a median radiation dose of 45 Gy (range: 37.5 to 50 Gy) to the primary volume and 45 Gy (range: 45 to 64.8 Gy) to nodal structures. One IGRT scan per week was randomly selected from each patient's treatment course and re-planned on the Eclipse treatment planning station. CTVs were recreated by fusion on the IGRT image series, and the patient's treatment plan was applied to the new image set to calculate delivered dose. We evaluated the minimum, maximum, and 95% dose coverage for primary and nodal structures. Reconstructed primary tumor volumes were recreated within 4.7% of initial planning volume (0.9% to 8.6%), and reconstructed nodal volumes were recreated to within 2.9% of initial planning volume (0.01% to 5.5%). Results: Dosimetric parameters averaged less than 10% (range: 1% to 9%) of the original planned dose (45 Gy) for primary and nodal volumes on all patients (n = 10). For all patients, ≥99.3% of the primary tumor volume received ≥ 95% the prescribed dose (V95%) and the average minimum dose was 96.1% of the prescribed dose. In evaluating nodal CTV coverage, ≥ 99.8% of the volume received ≥ 95% the prescribed dose and the average minimum dose was 93%. In evaluating individual IGRT sessions, we found that 6 patients had an estimated minimal nodal CTV dose less than 90% (range: 78 to 99%) of that planned. With a median follow-up of 42.5 months, 2 patients experienced systemic disease progression at an average of 19.6 months. One patient was found to have a local or regional failure with an average follow-up of 42 months. Conclusion: Using only 3 dimensional IGRT corrections in gynecological radiation allows excellent coverage of the primary target volume and good average nodal CTV coverage. If IGRT corrections are based on alignment to the primary tumor volume, and is only able to be corrected in 3 degrees, this can create situations in which nodal volumes may be under dosed. Utilizing multiple IGRT sessions appears to average out dose discrepancies over the course of treatment. The implication of underdosing in a single IGRT session needs further evaluation in future studies. Based on the concern of minimum dose to a nodal target volume, these findings may signal caution when using IGRT and IMRT in gynecological radiation patients. Possible techniques to overcome this situation may include averaging shifts between tumor and nodal volume, use of a treatment couch with 6° of freedom, deformable registration, or adaptive planning.« less

Effects of reference analgesics and psychoactive drugs on the noxious heat threshold of mice measured by an increasing-temperature water bath.

PubMed

Boros, Melinda; Benkó, Rita; Bölcskei, Kata; Szolcsányi, János; Barthó, Loránd; Pethő, Gábor

2013-12-01

The study aimed at validating an increasing-temperature water bath suitable for determining the noxious heat threshold for use in mice. The noxious heat threshold was determined by immersing the tail of the gently held awake mouse into a water container whose temperature was near-linearly increased at a rate of 24°C/min. until the animal withdrew its tail, that is, heating attained the noxious threshold. The effects of standard analgesic, neuroleptic and anxiolytic drugs were investigated in a parallel way on both the noxious heat threshold and the psychomotor activity assessed by the open field test. Morphine, diclofenac and metamizol (dipyrone) elevated the heat threshold of mice with minimum effective doses of 6, 30 and 1000 mg/kg i.p., respectively. These doses of morphine and diclofenac failed to induce any remarkable effect on psychomotor activity in the open field test while that of metamizol exerted a profound inhibition. The anxiolytic diazepam and the neuroleptic droperidol at doses evoking a mild and moderate, respectively, psychomotor inhibition failed to alter the heat threshold. Combination of a subliminal dose of morphine (regarding both antinociceptive and psychomotor inhibitory action) with diclofenac, metamizol, diazepam or droperidol at doses also subliminal regarding the thermal antinociceptive effect elevated the noxious heat threshold without major additional effects in the open field test. It is concluded that the increasing-temperature water bath is suitable for studying the thermal antinociceptive effects of morphine and diclofenac as well as the morphine-sparing action of diclofenac, metamizol, droperidol and diazepam. Behavioural testing is recommended when testing analgesics. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

Retrospective Cohort Study of Bronchial Doses and Radiation-Induced Atelectasis After Stereotactic Body Radiation Therapy of Lung Tumors Located Close to the Bronchial Tree

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

Karlsson, Kristin, E-mail: kristin.karlsson@karolinska.se; Department of Oncology-Pathology, Karolinska Institute, Stockholm; Nyman, Jan

2013-11-01

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

The Minimum Effective Dose of Lidocaine Needed to Block Evoked Potentials in the Sciatic Nerve of the Rat

DTIC Science & Technology

1998-10-01

which include the sciatic nerve, will be described. Gilman and Newman (1996) describe the PNS in their book, Manter and Gatz’s Essentials of Clinical ...Neural Blockade in Clinical Anesthesia and Management of Pain. He wrote that sensory and motor messages are transported along a nerve in the form of an...different groups of local anesthetics, the esters (procaine, chloroprocaine, tetracaine) and the amides (lidocaine, mepivacaine, bupivacaine , etidocaine

Effects of ketamine and lidocaine in combination on the sevoflurane minimum alveolar concentration in alpacas

PubMed Central

Queiroz-Williams, Patricia; Doherty, Thomas J.; da Cunha, Anderson F.; Leonardi, Claudia

2016-01-01

This study investigated the effects of ketamine and lidocaine in combination on the minimum alveolar concentration of sevoflurane (MACSEVO) in alpacas. Eight healthy, intact male, adult alpacas were studied on 2 separate occasions. Anesthesia was induced with SEVO, and baseline MAC (MACB) determination began 45 min after induction. After MACB determination, alpacas were randomly given either an intravenous (IV) loading dose (LD) and infusion of saline or a loading dose [ketamine = 0.5 mg/kg body weight (BW); lidocaine = 2 mg/kg BW] and an infusion of ketamine (25 μg/kg BW per minute) in combination with lidocaine (50 μg/kg BW per minute), and MACSEVO was re-determined (MACT). Quality of recovery, time-to-extubation, and time-to-standing, were also evaluated. Mean MACB was 1.88% ± 0.13% and 1.89% ± 0.14% for the saline and ketamine + lidocaine groups, respectively. Ketamine and lidocaine administration decreased (P < 0.05) MACB by 57% and mean MACT was 0.83% ± 0.10%. Saline administration did not change MACB. Time to determine MACB and MACT was not significantly different between the treatments. The quality of recovery, time-to-extubation, and time-to-standing, were not different between groups. The infusion of ketamine combined with lidocaine significantly decreased MACSEVO by 57% and did not adversely affect time-to-standing or quality of recovery. PMID:27127341

Effects of ketamine and lidocaine in combination on the sevoflurane minimum alveolar concentration in alpacas.

PubMed

Queiroz-Williams, Patricia; Doherty, Thomas J; da Cunha, Anderson F; Leonardi, Claudia

2016-04-01

This study investigated the effects of ketamine and lidocaine in combination on the minimum alveolar concentration of sevoflurane (MACSEVO) in alpacas. Eight healthy, intact male, adult alpacas were studied on 2 separate occasions. Anesthesia was induced with SEVO, and baseline MAC (MACB) determination began 45 min after induction. After MACB determination, alpacas were randomly given either an intravenous (IV) loading dose (LD) and infusion of saline or a loading dose [ketamine = 0.5 mg/kg body weight (BW); lidocaine = 2 mg/kg BW] and an infusion of ketamine (25 μg/kg BW per minute) in combination with lidocaine (50 μg/kg BW per minute), and MACSEVO was re-determined (MACT). Quality of recovery, time-to-extubation, and time-to-standing, were also evaluated. Mean MACB was 1.88% ± 0.13% and 1.89% ± 0.14% for the saline and ketamine + lidocaine groups, respectively. Ketamine and lidocaine administration decreased (P < 0.05) MACB by 57% and mean MACT was 0.83% ± 0.10%. Saline administration did not change MACB. Time to determine MACB and MACT was not significantly different between the treatments. The quality of recovery, time-to-extubation, and time-to-standing, were not different between groups. The infusion of ketamine combined with lidocaine significantly decreased MACSEVO by 57% and did not adversely affect time-to-standing or quality of recovery.

Mars surface radiation exposure for solar maximum conditions and 1989 solar proton events

NASA Technical Reports Server (NTRS)

Simonsen, Lisa C.; Nealy, John E.

1992-01-01

The Langley heavy-ion/nucleon transport code, HZETRN, and the high-energy nucleon transport code, BRYNTRN, are used to predict the propagation of galactic cosmic rays (GCR's) and solar flare protons through the carbon dioxide atmosphere of Mars. Particle fluences and the resulting doses are estimated on the surface of Mars for GCR's during solar maximum conditions and the Aug., Sep., and Oct. 1989 solar proton events. These results extend previously calculated surface estimates for GCR's at solar minimum conditions and the Feb. 1956, Nov. 1960, and Aug. 1972 solar proton events. Surface doses are estimated with both a low-density and a high-density carbon dioxide model of the atmosphere for altitudes of 0, 4, 8, and 12 km above the surface. A solar modulation function is incorporated to estimate the GCR dose variation between solar minimum and maximum conditions over the 11-year solar cycle. By using current Mars mission scenarios, doses to the skin, eye, and blood-forming organs are predicted for short- and long-duration stay times on the Martian surface throughout the solar cycle.

Suppression of ciprofloxacin-induced resistant Pseudomonas aeruginosa in a dynamic kill curve system.

PubMed

Wu, Benjamin M; Sabarinath, Sreedharan N; Rand, Kenneth; Johnson, Judith; Derendorf, Hartmut

2011-06-01

Current dosing approaches for treating microbial infections ignore resistant subpopulations. A clinical isolate of Pseudomonas aeruginosa was cultured in a dynamic in vitro kill curve system designed to simulate the half-lives of drugs in order to evaluate the drug-microbial response relationship. The first dose of ciprofloxacin (CIP) uses a concentration equivalent to the unbound fraction of a 200mg clinical dose. A second dose of 200mg or 600 mg CIP, or ceftriaxone (CFX) or gentamicin (GEN) was administered at 12h. Dynamics of the minimum inhibitory concentration (MIC) were assessed using Etest strips before and throughout the CIP treatment period. In addition, the microbroth dilution method was used to evaluate drug susceptibility across a wide range of antibiotics using samples from before and after CIP exposure. A significant loss of CIP effects was observed at the second dose. Cross-resistance to many antibiotics (cefoxitin, cefuroxime, cefotetan, ampicillin and ertapenem) was observed. GEN, but not CFX or high-dose CIP, was sufficient to suppress the developed resistant subpopulation following the initial CIP exposure. The CIP MIC increased substantially from 0.13 μg/mL pre dose to 4 μg/mL at 12h after a CIP dose. In addition, aztreonam induced a similar resistance pattern as CIP, indicating that induction of resistance was not limited to fluoroquinolones. In conclusion, the in vitro dynamic kill curve system revealed that aminoglycosides, more than other classes of antibiotics, were effective against the CIP-induced resistant subpopulations. Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

SU-F-T-01: Optimization of the Accelerated Partial Breast Brachytherapy Fractionation with Consideration of Physical Doses to Tumor and Organ at Risk

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

Fu, W; Huq, M

2016-06-15

Purpose: The accelerated partial breast irradiation (APBI) with brachytherapy prescribes 34Gy to be delivered in 10 fractions over 5 consecutive working days without considering the physical dose to the target and organs at risk (OARs) for an individual patient. The purpose of this study is to optimize the fractionation scheme by evaluating the radiation effect on tumor and OARs with a modified linear-quadratic (LQ) model based on dose-volume histograms (DVHs). Methods: Five breast patients treated with multilumen balloon brachytherapy were selected. The minimum skin and rib spacing were ranged from 2.5mm to 14.3mm and from 1.0mm to 25.0mm, respectively. Themore » LQ model parameters were set as: (1) breast: α=0.08, β=0.028, doubling time Tpot=14.4 days, and starting time Tk=21days; (2) skin: acute reaction α=0.101, β=0.009; late reaction α=0.064, β=0.029; (3) rib: α=0.3, β=0.12. Boundary dose Dt was 6 Gy for both target and OARs. The relation between radiation effects on the tumor (ET) and OARs (EOAR) were plotted for fraction number from 1 to 20. Results: The value of radiation effect from routine 3.4Gyx10 fractions was used as reference, ETref and EOARref. If set ET=ETref, the fractionation that results in minimum EOAR values correspond to the optimal fractionation. For these patients, the optimal numbers are 10 fractions for skin acute reaction, 18 fractions for skin and rib late reaction while the doses per fraction are 3.4Gy and 2.05–2.10Gy, respectively. If set EOAR=EOARref, the fractionation that results in a maximum ET value corresponds to the optimal fractionation. The optimal fractionation is 3.4Gyx10 fractions for skin acute reaction, and 2.10–2.25Gyx18 fractions for skin late reaction and rib. Conclusion: For APBI brachytherapy, the routine 3.4Gyx10 fractions is optimal fractionation for skin acute reaction, while 2.05–2.25Gyx18 fractions is optimal fractionation for late reaction of skin and rib.« less

Comparison of Dose Decrement from Intrafraction Motion for Prone and Supine Prostate Radiotherapy

PubMed Central

Olsen, Jeffrey; Parikh, Parag J; Watts, Michael; Noel, Camille E; Baker, Kenneth W; Santanam, Lakshmi; Michalski, Jeff M

2012-01-01

Background and Purpose Dose effects of intrafraction motion during prone prostate radiotherapy are unknown. We compared prone and supine treatment using real-time tracking data to model dose coverage. Material and Methods Electromagnetic tracking data was analyzed for 10 patients treated prone, and 15 treated supine, with IMRT for localized prostate cancer. Plans were generated using 0, 3, and 5 mm PTV expansions. Manual beam-hold interventions were applied to reposition the patient when translations exceeded a predetermined threshold. A custom software application (SWIFTER) used intrafraction tracking data acquired during beam-on to model delivered prostate dose, by applying rigid body transformations to the prostate structure contoured at simulation within the planned dose cloud. The delivered minimum prostate dose as a percentage of planned dose (Dmin%), and prostate volume covered by the prescription dose as a percentage of the planned volume (VRx%) were compared for prone and supine treatment. Results Dmin% was reduced for prone treatment for 0 (p=0.02) and 3 mm (p=0.03) PTV margins. VRx% was reduced for prone treatment only for 0 mm margins (p=0.002). No significant differences were found using 5 mm margins. Conclusions Intrafraction motion has a greater impact on target coverage for prone compared to supine prostate radiotherapy. PTV margins of 3 mm or less correlate with a significant decrease in delivered dose for prone treatment. PMID:22809590

Comparison of dose decrement from intrafraction motion for prone and supine prostate radiotherapy.

PubMed

Olsen, Jeffrey R; Parikh, Parag J; Watts, Michael; Noel, Camille E; Baker, Kenneth W; Santanam, Lakshmi; Michalski, Jeff M

2012-08-01

Dose effects of intrafraction motion during prone prostate radiotherapy are unknown. We compared prone and supine treatment using real-time tracking data to model dose coverage. Electromagnetic tracking data were analyzed for 10 patients treated prone, and 15 treated supine, with IMRT for localized prostate cancer. Plans were generated using 0 mm, 3 mm, and 5mm PTV expansions. Manual beam-hold interventions were applied to reposition the patient when translations exceeded a predetermined threshold. A custom software application (SWIFTER) used intrafraction tracking data acquired during beam-on model delivered prostate dose, by applying rigid body transformations to the prostate structure contoured at simulation within the planned dose cloud. The delivered minimum prostate dose as a percentage of planned dose (Dmin%), and prostate volume covered by the prescription dose as a percentage of the planned volume (VRx%) were compared for prone and supine treatment. Dmin% was reduced for prone treatment for 0 (p=0.02) and 3 mm (p=0.03) PTV margins. VRx% was reduced for prone treatment only for 0mm margins (p=0.002). No significant differences were found using 5 mm margins. Intrafraction motion has a greater impact on target coverage for prone compared to supine prostate radiotherapy. PTV margins of 3 mm or less correlate with a significant decrease in delivered dose for prone treatment. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

SU-E-J-58: Dosimetric Verification of Metal Artifact Effects: Comparison of Dose Distributions Affected by Patient Teeth and Implants

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

Lee, M; Kang, S; Lee, S

Purpose: Implant-supported dentures seem particularly appropriate for the predicament of becoming edentulous and cancer patients are no exceptions. As the number of people having dental implants increased in different ages, critical dosimetric verification of metal artifact effects are required for the more accurate head and neck radiation therapy. The purpose of this study is to verify the theoretical analysis of the metal(streak and dark) artifact, and to evaluate dosimetric effect which cause by dental implants in CT images of patients with the patient teeth and implants inserted humanoid phantom. Methods: The phantom comprises cylinder which is shaped to simulate themore » anatomical structures of a human head and neck. Through applying various clinical cases, made phantom which is closely allied to human. Developed phantom can verify two classes: (i)closed mouth (ii)opened mouth. RapidArc plans of 4 cases were created in the Eclipse planning system. Total dose of 2000 cGy in 10 fractions is prescribed to the whole planning target volume (PTV) using 6MV photon beams. Acuros XB (AXB) advanced dose calculation algorithm, Analytical Anisotropic Algorithm (AAA) and progressive resolution optimizer were used in dose optimization and calculation. Results: In closed and opened mouth phantom, because dark artifacts formed extensively around the metal implants, dose variation was relatively higher than that of streak artifacts. As the PTV was delineated on the dark regions or large streak artifact regions, maximum 7.8% dose error and average 3.2% difference was observed. The averaged minimum dose to the PTV predicted by AAA was about 5.6% higher and OARs doses are also 5.2% higher compared to AXB. Conclusion: The results of this study showed that AXB dose calculation involving high-density materials is more accurate than AAA calculation, and AXB was superior to AAA in dose predictions beyond dark artifact/air cavity portion when compared against the measurements.« less

Distribution of chloramphenicol to tissues, plasma and urine in pigs after oral intake of low doses.

PubMed

Aspenström-Fagerlund, Bitte; Nordkvist, Erik; Törnkvist, Anna; Wallgren, Per; Hoogenboom, Ron; Berendsen, Bjorn; Granelli, Kristina

2016-09-01

Toxic effects of chloramphenicol in humans caused the ban for its use in food-producing animals in the EU. A minimum required performance level (MRPL) was specified for chloramphenicol at 0.3 μg kg(-1) for various matrices, including urine. In 2012, residues of chloramphenicol were found in pig urine and muscle without signs of illegal use. Regarding its natural occurrence in straw, it was hypothesised that this might be the source, straw being compulsory for use as bedding material for pigs in Sweden. Therefore, we investigated if low daily doses of chloramphenicol (4, 40 and 400 μg/pig) given orally during 14 days could result in residues in pig tissues and urine. A dose-related increase of residues was found in muscle, plasma, kidney and urine (showing the highest levels), but no chloramphenicol was found in the liver. At the lowest dose, residues were below the MRPL in all tissues except in the urine. However, in the middle dose, residues were above the MRPL in all tissues except muscle, and at the highest dose in all matrices. This study proves that exposure of pigs to chloramphenicol in doses occurring naturally in straw could result in residues above the MRPL in plasma, kidney and especially urine.

Combining the Sterile Insect Technique with Wolbachia-Based Approaches: II- A Safer Approach to Aedes albopictus Population Suppression Programmes, Designed to Minimize the Consequences of Inadvertent Female Release

PubMed Central

Zhang, Dongjing; Lees, Rosemary Susan; Xi, Zhiyong; Gilles, Jeremie R. L.; Bourtzis, Kostas

2015-01-01

Due to the absence of a perfect method for mosquito sex separation, the combination of the sterile insect technique and the incompatible insect technique is now being considered as a potentially effective method to control Aedes albopictus. In this present study first we examine the minimum pupal irradiation dose required to induce complete sterility in Wolbachia triple-infected (HC), double-infected (GUA) and uninfected (GT) female Ae. albopictus. The HC line is a candidate for Ae. albopictus population suppression programmes, but due to the risk of population replacement which characterizes this triple infected line, the individuals to be released need to be additionally irradiated. After determining the minimum irradiation dose required for complete female sterility, we test whether sterilization is sufficient to prevent invasion of the triple infection from the HC females into double-infected (GUA) populations. Our results indicate that irradiated Ae. albopictus HC, GUA and GT strain females have decreased fecundity and egg hatch rate when irradiated, inversely proportional to the dose, and the complete sterilization of females can be acquired by pupal irradiation with doses above 28 Gy. PCR-based analysis of F1 and F2 progeny indicate that the irradiated HC females, cannot spread the new Wolbachia wPip strain into a small cage GUA population, released at a 1:5 ratio. Considering the above results, we conclude that irradiation can be used to reduce the risk of population replacement caused by an unintentional release of Wolbachia triple-infected Ae. albopictus HC strain females during male release for population suppression. PMID:26252474

Efficacy and safety of maropitant, a selective neurokinin 1 receptor antagonist, in two randomized clinical trials for prevention of vomiting due to motion sickness in dogs.

PubMed

Conder, G A; Sedlacek, H S; Boucher, J F; Clemence, R G

2008-12-01

Maropitant (Cerenia), a selective neurokinin(1) receptor antagonist, was evaluated for efficacy and safety in prevention of vomiting due to motion sickness in dogs in two randomized clinical trials. One-hundred eighty-nine dogs with a history of motion sickness were enrolled at 26 veterinary clinics (across 12 US states) across the two trials; of these, 163 were fully evaluable, 19 were evaluable only for safety, and seven were not evaluable. Each trial used a two-period crossover design. Each dog was treated orally with placebo or maropitant (minimum dose of 8 mg/kg body weight using unit dosing) tablets at approximately 2 h (Trial 1) or 10 h (Trial 2) before an automobile ride of approximately 60 min, during which dogs were observed for signs of motion sickness. Following a 10-14-day washout period, each dog was administered the opposite treatment and taken for another journey (same route, driver and vehicle). Maropitant reduced the occurrence of vomiting compared to placebo by 86.1% or 76.5% when given approximately 2 or 10 h prior to travel, respectively. No significant clinical signs were observed after maropitant treatment. Maropitant was safe and effective in preventing vomiting due to motion sickness in dogs when administered at a minimum dose of 8 mg/kg body weight as oral tablets 2 or 10 h prior to travel.

The essential oil of Brazilian pepper, Schinus terebinthifolia Raddi in larval control of Stegomyia aegypti (Linnaeus, 1762)

PubMed Central

2010-01-01

Background The ability of mosquitoes of the genus Aedes and its allies, such as Stegomyia, to transmit diseases such as dengue and yellow fever, makes them important in public health. This study aims to evaluate the use of the essential oil of Brazilian pepper in biological control of by assessing and quantifying the larvicidal effect against S. aegypti, the only available access to dengue control, and test its risk of genotoxicity with Salmonella typhimurium as an indicator of safety for its environmental use. Results The density of the oil was 0.8622 g mL-1. Gas chromatography coupled with mass spectrometry revealed six major constituents: δ-3-carene (55.43%), α-pinene (16.25%), sylvestrene (10.67%), germacrene D (2.17), β-myrcene (1.99%), and isoterpinolene (1.4%). The minimum inhibitory dose to larvae development was 862.20 μg mL-1. The median lethal dose (LD50) of the essential oil for larvae was between the concentrations of 172.44-344.88 μg mL-1. There was no mutagenic risk for the essential oil, since there were no biochemical or morphological changes in S. typhimurium after exposure to the essential oil. Conclusions The minimum inhibitory essential oil concentration and the median lethal dose pointed to the value of the use of water dispersions of Brazilian pepper essential oil as an environmental safe natural larvicidal for S. aegypti. PMID:20799936

SU-E-T-657: Quantitative Assessment of Plan Robustness for Helical Tomotherapy for Head and Neck Cancer Radiotherapy

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

Matney, J; Lian, J; Chera, B

2015-06-15

Introduction: Geometric uncertainties in daily patient setup can lead to variations in the planned dose, especially when using highly conformal techniques such as helical Tomotherapy. To account for the potential effect of geometric uncertainty, our clinical practice is to expand critical structures by 3mm expansion into planning risk volumes (PRV). The PRV concept assumes the spatial dose cloud is insensitive to patient positioning. However, no tools currently exist to determine if a Tomotherapy plan is robust to the effects of daily setup variation. We objectively quantified the impact of geometric uncertainties on the 3D doses to critical normal tissues duringmore » helical Tomotherapy. Methods: Using a Matlab-based program created and validated by Accuray (Madison, WI), the planned Tomotherapy delivery sinogram recalculated dose on shifted CT datasets. Ten head and neck patients were selected for analysis. To simulate setup uncertainty, the patient anatomy was shifted ±3mm in the longitudinal, lateral and vertical axes. For each potential shift, the recalculated doses to various critical normal tissues were compared to the doses delivered to the PRV in the original plan Results: 18 shifted scenarios created from Tomotherapy plans for three patients with head and neck cancers were analyzed. For all simulated setup errors, the maximum doses to the brainstem, spinal cord, parotids and cochlea were no greater than 0.6Gy of the respective original PRV maximum. Despite 3mm setup shifts, the minimum dose delivered to 95% of the CTVs and PTVs were always within 0.4Gy of the original plan. Conclusions: For head and neck sites treated with Tomotherapy, the use of a 3mm PRV expansion provide a reasonable estimate of the dosimetric effects of 3mm setup uncertainties. Similarly, target coverage appears minimally effected by a 3mm setup uncertainty. Data from a larger number of patients will be presented. Future work will include other anatomical sites.« less

No effect on QT intervals of mipomersen, a 2'-O-methoxyethyl modified antisense oligonucleotide targeting ApoB-100 mRNA, in a phase I dose escalation placebo-controlled study, and confirmed by a thorough QT (tQT) study, in healthy subjects.

PubMed

Yu, Rosie Z; Gunawan, Rudy; Li, Zhaoyang; Mittleman, Robert S; Mahmood, Asif; Grundy, John S; Singleton, Walter; Geary, Richard; Wang, Yanfeng

2016-03-01

The aim of this study to evaluate the effect of mipomersen on QT intervals in a phase I dose escalation, placebo-controlled study, and a thorough QT (tQT) study in healthy subjects. In the initial phase I study, 29 healthy subjects received either single or multiple (for 4 weeks) ascending doses of mipomersen (50-400 mg) administered subcutaneously (SC) or via a 2-h intravenous (IV) infusion, and 7 subjects received placebo. In the confirmative tQT study, 58 healthy subjects received placebo, 400 mg IV moxifloxacin, 200 mg SC, or 200 mg IV of mipomersen in a double-blind, 4-way crossover design with a minimum 5-day washout between treatments. ECG measurements were performed at baseline and selected time points (including Tmax). The correlation between QTcF intervals corrected for baseline and time-matched placebo when available with PK plasma exposure was evaluated by linear regression analysis. In the phase I study, no positive correlation between the PK exposure and ∆QTcF or ∆∆QTcF was observed within the wide dose or exposure range tested. Similar results were observed in the tQT study, where the predicted ΔΔQTcF and its upper bound of the 90% CI at Cmax of therapeutic and supratherapeutic dose were approximately -1.7 and 2.9 ms, respectively. Mipomersen showed no effect on QT intervals in both the phase I dose escalation study and the tQT study. These results support the proposal that QT assessment can be made in a phase I dose escalation study, and no tQT study may be necessary if the phase I dose escalation study showed a negative QT effect.

Drug interactions: volatile anesthetics and opioids.

PubMed

Glass, P S; Gan, T J; Howell, S; Ginsberg, B

1997-09-01

Multiple drugs are used to provide anesthesia. Volatile anesthetics are commonly combined with opioids. Several studies have demonstrated that small doses of opioid (i.e., within the analgesic range) result in a marked reduction in minimum alveolar concentration (MAC) of the volatile anesthetic that will prevent purposeful movement in 50% of patients at skin incision). Further increases in opioid dose provide only a further small reduction in MAC. Thus, a ceiling effect of the opioid is observed at a MAC value of the volatile anesthetic equal to its MAC awake. Recovery from anesthesia when an opioid is combined with a volatile anesthetic is dependent on the rate of decrease of both drugs to their respective concentrations that are associated with adequate spontaneous ventilation and awakening. Through an understanding of the pharmacodynamic interaction of volatile anesthetics with opioids and the pharmacokinetic processes responsible for the recovery from drug effect, optimal dosing schemes can thus be developed. A review of these pharmacodynamic and pharmacokinetic principles that will allow clinicians to administer drugs to provide a more optimal anesthetic is provided.

The range of minimum provoking doses in hazelnut-allergic patients as determined by double-blind, placebo-controlled food challenges.

PubMed

Wensing, M; Penninks, A H; Hefle, S L; Akkerdaas, J H; van Ree, R; Koppelman, S J; Bruijnzeel-Koomen, C A F M; Knulst, A C

2002-12-01

The risk for allergic reactions depends on the sensitivity of individuals and the quantities of offending food ingested. The sensitivity varies among allergic individuals, as does the threshold dose of a food allergen capable of inducing an allergic reaction. This study aimed at determining the distribution of minimum provoking doses of hazelnut in a hazelnut-allergic population. Thirty-one patients with a history of hazelnut-related allergic symptoms, a positive skin prick test to hazelnut and/or an elevated specific IgE level, were included. Double-blind, placebo-controlled food challenges (DBPCFC) were performed with seven increasing doses of dried hazelnut (1 mg to 1 g hazelnut protein) randomly interspersed with seven placebo doses. Twenty-nine patients had a positive challenge. Itching of the oral cavity and/or lips was the first symptom in all cases. Additional gastrointestinal symptoms were reported in five patients and difficulty in swallowing in one patient. Lip swelling was observed in two patients, followed by generalized urticaria in one of these. Threshold doses for eliciting subjective reactions varied from a dose of 1 mg up to 100 mg hazelnut protein (equivalent to 6.4-640 mg hazelnut meal). Extrapolation of the dose-response curve showed that 50% of our hazelnut-allergic population will suffer from an allergic reaction after ingestion of 6 mg (95% CI, 2-11 mg) of hazelnut protein. Objective symptoms were observed in two patients after 1 and 1,000 mg, respectively. DBPCFCs demonstrated threshold doses in half of the hazelnut-allergic patients similar to doses previously described to be hidden in consumer products. This stresses the need for careful labelling and strategies to prevent and detect contamination of food products with hazelnut residues.

Exercise Frequency and Fracture Risk in Older Adults-How Often Is Enough?

PubMed

Kemmler, Wolfgang; von Stengel, Simon; Kohl, Matthias

2017-12-01

Due to older people's low sports participation rates, exercise frequency may be the most critical component for designing exercise protocols that address fracture risk. The aims of the present article were to review and summarize the independent effect of exercise frequency (ExFreq) on the main determinants of fracture prevention, i.e., bone strength, fall frequency, and fall impact in older adults. Evidence collected last year suggests that there is a critical dose of ExFreq that just affects bone (i.e., BMD). Corresponding data for fall-related fracture risk are still sparse and inconsistent, however. The minimum effective dose (MED) of ExFreq that just favorably affects BMD at the lumbar spine and femoral neck has been found to vary between 2.1 and 2.5 sessions/week. Although this MED cannot necessarily be generalized to other cohorts, we speculate that this "critical exercise frequency" might not significantly vary among adult cohorts.

Passive dosimetry aboard the Mir Orbital Station: external measurements.

PubMed

Benton, E R; Benton, E V; Frank, A L

2002-10-01

This paper reports results from the first measurements made on the exterior of a LEO spacecraft of mean dose equivalent rate and average quality factor as functions of shielding depth for shielding less than 1 g/cm2 Al equivalent. Two sets of measurements were made on the outside of the Mir Orbital Station; one near solar maximum in June 1991 and one near solar minimum in 1997. Absorbed dose was measured using stacks of TLDs. LET spectrum from charged particles of LET infinity H2O > o r= 5keV/micrometers was measured using stacks of CR-39 PNTDs. Results from the TLD and PNTD measurements at a given shielding depth were combined to yield mean total dose rate, mean dose equivalent rate, and average quality factor. Measurements made near solar maximum tend to be greater than those made during solar minimum. Both mean dose rate and mean dose equivalent rate decrease by nearly four orders of magnitude within the first g/cm2 shielding illustrating the attenuation of both trapped electrons and low-energy trapped protons. In order to overcome problems with detector saturation after standard chemical processing, measurement of LET spectrum in the least shielded CR-39 PNTD layer (0.005 g/cm2 Al) was carried out using an atomic force microscope. c2002 Elsevier Science Ltd. All rights reserved.

Passive dosimetry aboard the Mir Orbital Station: external measurements

NASA Technical Reports Server (NTRS)

Benton, E. R.; Benton, E. V.; Frank, A. L.

2002-01-01

This paper reports results from the first measurements made on the exterior of a LEO spacecraft of mean dose equivalent rate and average quality factor as functions of shielding depth for shielding less than 1 g/cm2 Al equivalent. Two sets of measurements were made on the outside of the Mir Orbital Station; one near solar maximum in June 1991 and one near solar minimum in 1997. Absorbed dose was measured using stacks of TLDs. LET spectrum from charged particles of LET infinity H2O > o r= 5keV/micrometers was measured using stacks of CR-39 PNTDs. Results from the TLD and PNTD measurements at a given shielding depth were combined to yield mean total dose rate, mean dose equivalent rate, and average quality factor. Measurements made near solar maximum tend to be greater than those made during solar minimum. Both mean dose rate and mean dose equivalent rate decrease by nearly four orders of magnitude within the first g/cm2 shielding illustrating the attenuation of both trapped electrons and low-energy trapped protons. In order to overcome problems with detector saturation after standard chemical processing, measurement of LET spectrum in the least shielded CR-39 PNTD layer (0.005 g/cm2 Al) was carried out using an atomic force microscope. c2002 Elsevier Science Ltd. All rights reserved.

Investigation of the effects of head irradiation with gamma rays and protons on startle and pre-pulse inhibition behavior in mice.

PubMed

Haerich, Paul; Eggers, Cara; Pecaut, Michael J

2012-05-01

With the increased international emphasis on manned space exploration, there is a growing need to understand the impact of the spaceflight environment on health and behavior. One particularly important aspect of this environment is low-dose radiation. In the present studies, we first characterized the γ- and proton-irradiation dose effect on acoustic startle and pre-pulse inhibition behaviors in mice exposed to 0-5 Gy brain-localized irradiation, and assessed these effects 2 days later. Subsequently, we used 2 Gy to assess the time course of γ- and proton-radiation effects on startle reactivity 0-8 days after exposure. Exposures targeted the brain to minimize the impact of peripheral inflammation-induced sickness behavior. The effects of radiation on startle were subtle and acute. Radiation reduced the startle response at 2 and 5 Gy. Following a 2-Gy exposure, the response reached a minimum at the 2-day point. Proton and γ-ray exposures did not differ in their impact on startle. We found there were no effects of radiation on pre-pulse inhibition of the startle response.

Task-Specific Optimization of Mammographic Systems

DTIC Science & Technology

2007-03-01

in Appendix II. 5.3 The results from the previous step will guide the creation for recommendations on the minimum allowable dose for...Degrees Earned Robert Saunders graduated with a doctorate in physics from Duke University in May 2006. Research Opportunities Received based on ...of dose in digital mammography has a measurable but modest impact on diagnostic accuracy.

Task related doses in Spanish pressurized water reactors over the period 1988-1992

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

O`Donnell, P.; Labarta, T.; Amor, I.

1995-03-01

In order to evaluate in depth the collective dose trend and its correlation with the effectiveness of the practical application of the ALARA principle in Spanish nuclear facilities, and base the different policy lines to promote this criteria, the CSN has fullfilled an analysis of the task related doses data over the period 1988-1992. Previously, the CSN had required to the utilities the compilation of their refuelling outage collective dose from 1988 according with a predeterminate number of tasks, in order to have available a representative and retrospective set of data in an homogeneous way and coherent with the internationalmore » data banks on occupational exposure in NPP, as the CEC and the NEA ones. The scope of this analysis was the following: first, the collective dose summaries for outage tasks and departments for PWR and for BWR, including the minimum, maximum and average dose (and statistics data) for 18 different refuelling outage tasks and 12 personal departments for each generation of each type of rector, the task and department related collective dose trends in each plant and in each generation, and second, the dose reduction techniques having been used during that period in each plant and the relative level of adoption. In this presentation the main results and conclusions of the first part of the study are reviewed for PWR.« less

Radiation risk predictions for Space Station Freedom orbits

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Atwell, William; Weyland, Mark; Hardy, Alva C.; Wilson, John W.; Townsend, Lawrence W.; Shinn, Judy L.; Katz, Robert

1991-01-01

Risk assessment calculations are presented for the preliminary proposed solar minimum and solar maximum orbits for Space Station Freedom (SSF). Integral linear energy transfer (LET) fluence spectra are calculated for the trapped proton and GCR environments. Organ dose calculations are discussed using the computerized anatomical man model. The cellular track model of Katz is applied to calculate cell survival, transformation, and mutation rates for various aluminum shields. Comparisons between relative biological effectiveness (RBE) and quality factor (QF) values for SSF orbits are made.

Proton irradiation and endometriosis

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

Wood, D.H.; Yochmowitz, M.G.; Salmon, Y.L.

1983-08-01

Female rhesus monkeys given single total-body exposures of protons of varying energies developed endometriosis at a frequency significantly higher than that of nonirradiated animals of the same age. The minimum latency period was 7 years after exposure. The doses and energies of the radiation received were within the range that could be received by an aircrew member in near-earth orbit during a random solar flare event, leading to the conclusion that endometriosis should be a consideration in assessing the risk of delayed radiation effects in female crewmembers.

Penicillin dosing for pneumococcal pneumonia.

PubMed

Bryan, C S; Talwani, R; Stinson, M S

1997-12-01

Most textbook authors still endorse penicillin G as the specific antibiotic of choice for pneumococcal pneumonia. However, problems with early precise etiologic diagnosis of pneumonia and the emergence of drug-resistant pneumococci cause penicillin to be seldom used for this purpose today. A third explanation for the infrequent use of penicillin is lack of clear consensus dosing guidelines. Emergence of pneumococci resistant to the newer cephalosporins and concerns about overuse of vancomycin, however, have prompted renewed interest in the development of precise, rapid methods for diagnosis of pneumococcal pneumonia with the implication that penicillin might be used more frequently. We review several issues concerning penicillin dosing: intermittent vs continuous therapy, high dose vs low dose, relationship of dose to resistance, and cost-effective pharmacology. An optimum "high-dose" regimen for life-threatening pneumococcal pneumonia in a 70-kg adult consists of a 3 million unit (mu) loading dose followed by continuous infusion of 10 to 12 mu of freshly prepared drug every 12 h. The maintenance dose should be reduced in elderly patients and in patients with renal failure according to the following formula: dose (mu/24 h = 4+[creatinine clearance divided by 7]). This regimen provides a penicillin serum level of 16 to 20 microg/mL, which should suffice for all but the most highly resistant strains (minimum inhibitory concentration > or = 4 microg/mL). Newer cephalosporins and vancomycin can be reserved for patients with suspected meningitis or endocarditis or for localities in which highly resistant pneumococci are known to be prevalent.

Space radiation risks to the central nervous system

NASA Astrophysics Data System (ADS)

Cucinotta, Francis A.; Alp, Murat; Sulzman, Frank M.; Wang, Minli

2014-07-01

Central nervous system (CNS) risks which include during space missions and lifetime risks due to space radiation exposure are of concern for long-term exploration missions to Mars or other destinations. Possible CNS risks during a mission are altered cognitive function, including detriments in short-term memory, reduced motor function, and behavioral changes, which may affect performance and human health. The late CNS risks are possible neurological disorders such as premature aging, and Alzheimer's disease (AD) or other dementia. Radiation safety requirements are intended to prevent all clinically significant acute risks. However the definition of clinically significant CNS risks and their dependences on dose, dose-rate and radiation quality is poorly understood at this time. For late CNS effects such as increased risk of AD, the occurrence of the disease is fatal with mean time from diagnosis of early stage AD to death about 8 years. Therefore if AD risk or other late CNS risks from space radiation occur at mission relevant doses, they would naturally be included in the overall acceptable risk of exposure induced death (REID) probability for space missions. Important progress has been made in understanding CNS risks due to space radiation exposure, however in general the doses used in experimental studies have been much higher than the annual galactic cosmic ray (GCR) dose (∼0.1 Gy/y at solar maximum and ∼0.2 Gy/y at solar minimum with less than 50% from HZE particles). In this report we summarize recent space radiobiology studies of CNS effects from particle accelerators simulating space radiation using experimental models, and make a critical assessment of their relevance relative to doses and dose-rates to be incurred on a Mars mission. Prospects for understanding dose, dose-rate and radiation quality dependencies of CNS effects and extrapolation to human risk assessments are described.

Age, Sex, and Dose Effects of Nonbenzodiazepine Hypnotics on Hip Fracture in Nursing Home Residents.

PubMed

Dore, David D; Zullo, Andrew R; Mor, Vincent; Lee, Yoojin; Berry, Sarah D

2018-04-01

The Food and Drug Administration recommends a reduced dose of nonbenzodiazepine hypnotics in women, yet little is known about the age-, sex-, and dose-specific effects of these drugs on risk of hip fracture, especially among nursing home (NH) residents. We estimated the age-, sex-, and dose-specific effects of nonbenzodiazepine hypnotics on the rate of hip fracture among NH residents. Case-crossover study in US NHs. A total of 691 women and 179 men with hip fracture sampled from all US long-stay NH residents. Measures of patient characteristics were obtained from linked Medicare and the Minimum Data Set (2007-2008). The outcome was hospitalization for hip fracture with surgical repair. We estimated rate ratios (RRs) and 95% confidence intervals (CIs) from conditional logistic regression models for nonbenzodiazepine hypnotics (vs nonuse) comparing 0 to 29 days before hip fracture (hazard period) with 60 to 89 and 120 to 149 days before hip fracture (control periods). We stratified analyses by age, sex, and dose. The average RR of hip fracture was 1.7 (95% CI 1.5-1.9) for any use. The RR of hip fracture was higher for residents aged ≥90 years vs <70 years (2.2 vs 1.3); however, the CIs overlapped. No differences in the effect of the hypnotic on risk of hip fracture were evident by sex. Point estimates for hip fracture were greater with high-dose versus low-dose hypnotics (RR 1.9 vs 1.6 for any use), but these differences were highly compatible with chance. The rate of hip fracture in NH residents due to use of nonbenzodiazepine hypnotics was greater among older patients than among younger patients and, possibly, with higher doses than with lower doses. When clinicians are prescribing a nonbenzodiazepine hypnotic to any NH resident, doses of these drugs should be kept as low as possible, especially among those with advanced age. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Assessment of radiation exposure from cesium-137 contaminated roads for epidemiological studies in Seoul, Korea

PubMed Central

Lee, Yun-Keun; Ju, Young-Su; Lee, Won Jin; Hwang, Seung Sik; Yim, Sang-Hyuk; Yoo, Sang-Chul; Lee, Jieon; Choi, Kyung-Hwa; Burm, Eunae; Ha, Mina

2015-01-01

Objectives We aimed to assess the radiation exposure for epidemiologic investigation in residents exposed to radiation from roads that were accidentally found to be contaminated with radioactive cesium-137 (137Cs) in Seoul. Methods Using information regarding the frequency and duration of passing via the 137Cs contaminated roads or residing/working near the roads from the questionnaires that were obtained from 8875 residents and the measured radiation doses reported by the Nuclear Safety and Security Commission, we calculated the total cumulative dose of radiation exposure for each person. Results Sixty-three percent of the residents who responded to the questionnaire were considered as ever-exposed and 1% of them had a total cumulative dose of more than 10 mSv. The mean (minimum, maximum) duration of radiation exposure was 4.75 years (0.08, 11.98) and the geometric mean (minimum, maximum) of the total cumulative dose was 0.049 mSv (<0.001, 35.35) in the exposed. Conclusions An individual exposure assessment was performed for an epidemiological study to estimate the health risk among residents living in the vicinity of 137Cs contaminated roads. The average exposure dose in the exposed people was less than 5% of the current guideline. PMID:26184047

Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6–11 years-old than cumulative high doses of inhaled terbutaline

PubMed Central

Kaae, Rikke; Agertoft, Lone; Pedersen, Sören; Nordvall, S Lennart; Pedroletti, Christophe; Bengtsson, Thomas; Johannes-Hellberg, Ingegerd; Rosenborg, Johan

2004-01-01

Objectives To evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children. Methods Twenty boys and girls (6–11 years-old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxis®) 4.5 µg (F4.5) or terbutaline (Bricanyl®) 500 µg (T500) were inhaled cumulatively via a dry powder inhaler (Turbuhaler®) over 1 h (three patients) or 2.5 h (17 patients) and compared to a day of no treatment, in a randomised, double-blind (active treatments only), crossover trial. Blood pressure (BP), ECG, plasma potassium, glucose, lactate, and adverse events were monitored up to 10 h to assess tolerability and relative systemic dose potency. Results Formoterol and terbutaline had significant β2-adrenergic effects on most outcomes. Apart from the effect on systolic BP, QRS duration and PR interval, the systemic effects were significantly more pronounced with terbutaline than with formoterol. Thus, mean minimum plasma potassium, was suppressed from 3.56 (95% confidence interval, CI: 3.48–3.65) mmol l−1 on the day of no treatment to 2.98 (CI: 2.90–3.08) after 10 × F4.5 and 2.70 (CI: 2.61–2.78) mmol l−1 after 10 × T500, and maximum Q-Tc (heart rate corrected Q-T interval [Bazett's formula]) was prolonged from 429 (CI: 422–435) ms on the day of no treatment, to 455 (CI: 448–462) ms after 10 × F4.5 and 470 (CI: 463–476) ms after 10 × T500. Estimates of relative dose potency indicated that F4.5 µg had the same systemic activity as the clinically less effective dose of 250 µg terbutaline. The duration of systemic effects differed marginally between treatments. Spontaneously reported adverse events (most frequently tremor) were fewer with formoterol (78% of the children) than with terbutaline (95%). A serious adverse event occurred after inhalation of 45 µg formoterol over the 1 h dosing time, that prompted the extension of dosing time to 2.5 h. Conclusions Multiple inhalations over 2.5 h of formoterol (4.5 µg) via Turbuhaler® are at least as safe as and associated with less systemic effects than multiple inhalations of the clinically equipotent dose of terbutaline (500 µg) in children with asthma. PMID:15373934

Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6-11 years-old than cumulative high doses of inhaled terbutaline.

PubMed

Kaae, Rikke; Agertoft, Lone; Pedersen, Sören; Nordvall, S Lennart; Pedroletti, Christophe; Bengtsson, Thomas; Johannes-Hellberg, Ingegerd; Rosenborg, Johan

2004-10-01

To evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children. Twenty boys and girls (6-11 years-old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxis) 4.5 microg (F4.5) or terbutaline (Bricanyl) 500 microg (T500) were inhaled cumulatively via a dry powder inhaler (Turbuhaler) over 1 h (three patients) or 2.5 h (17 patients) and compared to a day of no treatment, in a randomised, double-blind (active treatments only), crossover trial. Blood pressure (BP), ECG, plasma potassium, glucose, lactate, and adverse events were monitored up to 10 h to assess tolerability and relative systemic dose potency. Formoterol and terbutaline had significant beta2-adrenergic effects on most outcomes. Apart from the effect on systolic BP, QRS duration and PR interval, the systemic effects were significantly more pronounced with terbutaline than with formoterol. Thus, mean minimum plasma potassium, was suppressed from 3.56 (95% confidence interval, CI: 3.48-3.65) mmol l(-1) on the day of no treatment to 2.98 (CI: 2.90-3.08) after 10 x F4.5 and 2.70 (CI: 2.61-2.78) mmol l(-1) after 10 x T500, and maximum Q-Tc (heart rate corrected Q-T interval [Bazett's formula]) was prolonged from 429 (CI: 422-435) ms on the day of no treatment, to 455 (CI: 448-462) ms after 10 x F4.5 and 470 (CI: 463-476) ms after 10 x T500. Estimates of relative dose potency indicated that F4.5 microg had the same systemic activity as the clinically less effective dose of 250 microg terbutaline. The duration of systemic effects differed marginally between treatments. Spontaneously reported adverse events (most frequently tremor) were fewer with formoterol (78% of the children) than with terbutaline (95%). A serious adverse event occurred after inhalation of 45 microg formoterol over the 1 h dosing time, that prompted the extension of dosing time to 2.5 h. Multiple inhalations over 2.5 h of formoterol (4.5 microg) via Turbuhaler) are at least as safe as and associated with less systemic effects than multiple inhalations of the clinically equipotent dose of terbutaline (500 microg) in children with asthma. Copyright 2004 Blackwell Publishing Ltd

Behavioural and cognitive effects of simvastatin dose used in stimulation of bone regeneration in rats.

PubMed

Sousa, Dircilei Nascimento de; Santana, Washington Macedo de; Ferreira, Vania Moraes; Duarte, Wagner Rodrigues

2014-03-01

To analyze the effects of simvastatin (SVT) in the locomotion, anxiety and memory of rats, as a reflection of the administration of a minimum dose capable of stimulating bone regeneration in defects in the calvariae. Surgical procedures were performed in 15 female Wistar rats, 2-month old, to insert the grafting material regenerator (Bone-ceramic®) and/or SVT, followed by behavioural and cognitive assessments in the 7th, 30th and 60th days post surgery. The SVT locally applied with the goal of bone regeneration in defects created in rat calvariae does not interfere with locomotion, anxiety levels and/or memories of rats, except for the first week following surgery, when an anxiolytic effect was observed, as a result of a possible central action. Failure to provoke any response within 30 and 60 days post surgical procedures suggests that SVT may constitute a good choice in stimulating bone regeneration without affecting the long term neural functions.

Leisure time physical activity and mortality: a detailed pooled analysis of the dose-response relationship.

PubMed

Arem, Hannah; Moore, Steven C; Patel, Alpa; Hartge, Patricia; Berrington de Gonzalez, Amy; Visvanathan, Kala; Campbell, Peter T; Freedman, Michal; Weiderpass, Elisabete; Adami, Hans Olov; Linet, Martha S; Lee, I-Min; Matthews, Charles E

2015-06-01

The 2008 Physical Activity Guidelines for Americans recommended a minimum of 75 vigorous-intensity or 150 moderate-intensity minutes per week (7.5 metabolic-equivalent hours per week) of aerobic activity for substantial health benefit and suggested additional benefits by doing more than double this amount. However, the upper limit of longevity benefit or possible harm with more physical activity is unclear. To quantify the dose-response association between leisure time physical activity and mortality and define the upper limit of benefit or harm associated with increased levels of physical activity. We pooled data from 6 studies in the National Cancer Institute Cohort Consortium (baseline 1992-2003). Population-based prospective cohorts in the United States and Europe with self-reported physical activity were analyzed in 2014. A total of 661,137 men and women (median age, 62 years; range, 21-98 years) and 116,686 deaths were included. We used Cox proportional hazards regression with cohort stratification to generate multivariable-adjusted hazard ratios (HRs) and 95% CIs. Median follow-up time was 14.2 years. Leisure time moderate- to vigorous-intensity physical activity. The upper limit of mortality benefit from high levels of leisure time physical activity. Compared with individuals reporting no leisure time physical activity, we observed a 20% lower mortality risk among those performing less than the recommended minimum of 7.5 metabolic-equivalent hours per week (HR, 0.80 [95% CI, 0.78-0.82]), a 31% lower risk at 1 to 2 times the recommended minimum (HR, 0.69 [95% CI, 0.67-0.70]), and a 37% lower risk at 2 to 3 times the minimum (HR, 0.63 [95% CI, 0.62-0.65]). An upper threshold for mortality benefit occurred at 3 to 5 times the physical activity recommendation (HR, 0.61 [95% CI, 0.59-0.62]); however, compared with the recommended minimum, the additional benefit was modest (31% vs 39%). There was no evidence of harm at 10 or more times the recommended minimum (HR, 0.69 [95% CI, 0.59-0.78]). A similar dose-response relationship was observed for mortality due to cardiovascular disease and to cancer. Meeting the 2008 Physical Activity Guidelines for Americans minimum by either moderate- or vigorous-intensity activities was associated with nearly the maximum longevity benefit. We observed a benefit threshold at approximately 3 to 5 times the recommended leisure time physical activity minimum and no excess risk at 10 or more times the minimum. In regard to mortality, health care professionals should encourage inactive adults to perform leisure time physical activity and do not need to discourage adults who already participate in high-activity levels.

GCR Environmental Models III: GCR Model Validation and Propagated Uncertainties in Effective Dose

NASA Technical Reports Server (NTRS)

Slaba, Tony C.; Xu, Xiaojing; Blattnig, Steve R.; Norman, Ryan B.

2014-01-01

This is the last of three papers focused on quantifying the uncertainty associated with galactic cosmic rays (GCR) models used for space radiation shielding applications. In the first paper, it was found that GCR ions with Z>2 and boundary energy below 500 MeV/nucleon induce less than 5% of the total effective dose behind shielding. This is an important finding since GCR model development and validation have been heavily biased toward Advanced Composition Explorer/Cosmic Ray Isotope Spectrometer measurements below 500 MeV/nucleon. Weights were also developed that quantify the relative contribution of defined GCR energy and charge groups to effective dose behind shielding. In the second paper, it was shown that these weights could be used to efficiently propagate GCR model uncertainties into effective dose behind shielding. In this work, uncertainties are quantified for a few commonly used GCR models. A validation metric is developed that accounts for measurements uncertainty, and the metric is coupled to the fast uncertainty propagation method. For this work, the Badhwar-O'Neill (BON) 2010 and 2011 and the Matthia GCR models are compared to an extensive measurement database. It is shown that BON2011 systematically overestimates heavy ion fluxes in the range 0.5-4 GeV/nucleon. The BON2010 and BON2011 also show moderate and large errors in reproducing past solar activity near the 2000 solar maximum and 2010 solar minimum. It is found that all three models induce relative errors in effective dose in the interval [-20%, 20%] at a 68% confidence level. The BON2010 and Matthia models are found to have similar overall uncertainty estimates and are preferred for space radiation shielding applications.

Effect of Hashimoto thyroiditis on low-dose radioactive-iodine remnant ablation.

PubMed

Kwon, Hyungju; Choi, June Young; Moon, Jae Hoon; Park, Hyo Jin; Lee, Won Woo; Lee, Kyu Eun

2016-04-01

Radioactive-iodine remnant ablation is an integral part of the papillary thyroid carcinoma (PTC) treatment. Although a minimum dose is usually recommended, there is controversy as to whether the low-dose (1100 MBq) radioactive-iodine remnant ablation is adequate for selected patients. A retrospective cohort study was conducted on 691 patients. Patients with no remnant thyroid on the follow-up whole body scan and low stimulated thyroglobulin (sTg) level (<2.0 ng/mL) were deemed as successful treatment cases. Initial low-dose radioactive-iodine remnant ablation was successful in 431 patients (62.3%). Multivariate analysis demonstrated a negative correlation between successful radioactive-iodine remnant ablation and coexisting Hashimoto thyroiditis based on histopathology diagnosis (odds ratio [OR] = 3.23; p < .001) as well as elevated preablation sTg (OR = 1.24; p < .001). Our data suggest that coexisting Hashimoto thyroiditis and elevated sTg are negative predictive factors for successful low-dose radioactive-iodine remnant ablation treatment. An appropriate risk-adjusted approach may improve the efficacy of radioactive-iodine remnant ablation treatment. © 2015 Wiley Periodicals, Inc. Head Neck 38: E730-E735, 2016. © 2015 Wiley Periodicals, Inc.

SU-E-T-374: Evaluation and Verification of Dose Calculation Accuracy with Different Dose Grid Sizes for Intracranial Stereotactic Radiosurgery

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

Han, C; Schultheiss, T

Purpose: In this study, we aim to evaluate the effect of dose grid size on the accuracy of calculated dose for small lesions in intracranial stereotactic radiosurgery (SRS), and to verify dose calculation accuracy with radiochromic film dosimetry. Methods: 15 intracranial lesions from previous SRS patients were retrospectively selected for this study. The planning target volume (PTV) ranged from 0.17 to 2.3 cm{sup 3}. A commercial treatment planning system was used to generate SRS plans using the volumetric modulated arc therapy (VMAT) technique using two arc fields. Two convolution-superposition-based dose calculation algorithms (Anisotropic Analytical Algorithm and Acuros XB algorithm) weremore » used to calculate volume dose distribution with dose grid size ranging from 1 mm to 3 mm with 0.5 mm step size. First, while the plan monitor units (MU) were kept constant, PTV dose variations were analyzed. Second, with 95% of the PTV covered by the prescription dose, variations of the plan MUs as a function of dose grid size were analyzed. Radiochomic films were used to compare the delivered dose and profile with the calculated dose distribution with different dose grid sizes. Results: The dose to the PTV, in terms of the mean dose, maximum, and minimum dose, showed steady decrease with increasing dose grid size using both algorithms. With 95% of the PTV covered by the prescription dose, the total MU increased with increasing dose grid size in most of the plans. Radiochromic film measurements showed better agreement with dose distributions calculated with 1-mm dose grid size. Conclusion: Dose grid size has significant impact on calculated dose distribution in intracranial SRS treatment planning with small target volumes. Using the default dose grid size could lead to under-estimation of delivered dose. A small dose grid size should be used to ensure calculation accuracy and agreement with QA measurements.« less

Osteoradionecrosis following treatment for head and neck cancer and the effect of radiotherapy dosimetry: the Guy's and St Thomas' Head and Neck Cancer Unit experience.

PubMed

De Felice, Francesca; Thomas, Christopher; Patel, Vinod; Connor, Steve; Michaelidou, Andriana; Sproat, Chris; Kwok, Jerry; Burke, Mary; Reilly, Damien; McGurk, Mark; Simo, Ricard; Lyons, Andrew; Oakley, Richard; Jeannon, Jean-Pierre; Lei, Mary; Urbano, Teresa Guerrero

2016-07-01

To analyze clinical features, dosimetric parameters, and outcomes of osteoradionecrosis (ORN). Thirty-six patients with ORN who had been previously treated with radiotherapy (RT) were retrospectively identified between January 2009 and April 2014. ORN volumes were contoured on planning computed tomography (CT) scans. Near maximum dose (D2%), minimum dose (Dmin), mean dose (Dmean), and percentage of bone volume receiving 50 Gy (V50) were examined. Clinical and dosimetric variables were considered to compare ORN resolution versus ORN persistence. Median interval time from end of RT to development of ORN was 6 months. Of the ORN cases, 61% were located in the mandible. Dmean to affected bone was 57.6 Gy, and 44% had a D2% 65 Gy or greater. Smoking was associated with ORN persistence on univariate analysis, but no factors were found to impact ORN resolution or progression on logistic regression. Prevention strategies for ORN development should be prioritized. Dose-volume parameters could have a role in preventing ORN. Copyright © 2016 Elsevier Inc. All rights reserved.

[Decision process of Notification Value by the Dose Index Registry system in X-ray computed tomography].

PubMed

Shinozaki, Masafumi; Muramatsu, Yoshihisa; Sasaki, Toru

2014-01-01

A new technical standard for X-ray computed tomography (CT) has been published by the National Electrical Manufacturers Association (NEMA) that allows the Alert Value and Notification Value for cumulative dose to be configurable by CT systems operators in conjunction with the XR-25 (Dose check) standard. In this study, a decision method of the Notification Values for reducing the radiation dose was examined using the dose index registry (DIR) system, during 122 continuous days from August 1, 2012 to November 30, 2012. CT images were obtained using the Discovery CT 750HD (GE Healthcare) and the dose index was calculated using the DoseWatch DIR system. The CT dose index-volume (CTDIvol) and dose-length product (DLP) were output from the DIR system in comma-separated value (CSV) file format for each examination protocol. All data were shown as a schematic boxplot using statistical processing software. The CTDIvol of a routine chest examination showed the following values (maximum: 23.84 mGy; minimum: 2.55 mGy; median: 7.60 mGy; 75% tile: 10.01 mGy; 25% tile: 6.54 mGy). DLP showed the following values (maximum: 944.56 mGy·cm; minimum: 97.25 mGy·cm; median: 307.35 mGy·cm; 75% tile: 406.87 mGy·cm; 25% tile: 255.75 mGy·cm). These results indicate that the 75% tile of CTDIvol and DLP as an initial value proved to be safe and efficient for CT examination and operation. We have thus established one way of determining the Notification Value from the output of the DIR system. Transfer back to the protocol of the CT and automated processing each numeric value in the DIR system is desired.

Motion induced interplay effects for VMAT radiotherapy.

PubMed

Edvardsson, Anneli; Nordström, Fredrik; Ceberg, Crister; Ceberg, Sofie

2018-04-19

The purpose of this study was to develop a method to simulate breathing motion induced interplay effects for volumetric modulated arc therapy (VMAT), to verify the proposed method with measurements, and to use the method to investigate how interplay effects vary with different patient- and machine specific parameters. VMAT treatment plans were created on a virtual phantom in a treatment planning system (TPS). Interplay effects were simulated by dividing each plan into smaller sub-arcs using an in-house developed software and shifting the isocenter for each sub-arc to simulate a sin 6 breathing motion in the superior-inferior direction. The simulations were performed for both flattening-filter (FF) and flattening-filter free (FFF) plans and for different breathing amplitudes, period times, initial breathing phases, dose levels, plan complexities, CTV sizes, and collimator angles. The resulting sub-arcs were calculated in the TPS, generating a dose distribution including the effects of motion. The interplay effects were separated from dose blurring and the relative dose differences to 2% and 98% of the CTV volume (ΔD 98% and ΔD 2% ) were calculated. To verify the simulation method, measurements were carried out, both static and during motion, using a quasi-3D phantom and a motion platform. The results of the verification measurements during motion were comparable to the results of the static measurements. Considerable interplay effects were observed for individual fractions, with the minimum ΔD 98% and maximum ΔD 2% being  -16.7% and 16.2%, respectively. The extent of interplay effects was larger for FFF compared to FF and generally increased for higher breathing amplitudes, larger period times, lower dose levels, and more complex treatment plans. Also, the interplay effects varied considerably with the initial breathing phase, and larger variations were observed for smaller CTV sizes. In conclusion, a method to simulate motion induced interplay effects was developed and verified with measurements, which allowed for a large number of treatment scenarios to be investigated. The simulations showed large interplay effects for individual fractions and that the extent of interplay effects varied with the breathing pattern, FFF/FF, dose level, CTV size, collimator angle, and the complexity of the treatment plan.

Motion induced interplay effects for VMAT radiotherapy

NASA Astrophysics Data System (ADS)

Edvardsson, Anneli; Nordström, Fredrik; Ceberg, Crister; Ceberg, Sofie

2018-04-01

The purpose of this study was to develop a method to simulate breathing motion induced interplay effects for volumetric modulated arc therapy (VMAT), to verify the proposed method with measurements, and to use the method to investigate how interplay effects vary with different patient- and machine specific parameters. VMAT treatment plans were created on a virtual phantom in a treatment planning system (TPS). Interplay effects were simulated by dividing each plan into smaller sub-arcs using an in-house developed software and shifting the isocenter for each sub-arc to simulate a sin6 breathing motion in the superior–inferior direction. The simulations were performed for both flattening-filter (FF) and flattening-filter free (FFF) plans and for different breathing amplitudes, period times, initial breathing phases, dose levels, plan complexities, CTV sizes, and collimator angles. The resulting sub-arcs were calculated in the TPS, generating a dose distribution including the effects of motion. The interplay effects were separated from dose blurring and the relative dose differences to 2% and 98% of the CTV volume (ΔD98% and ΔD2%) were calculated. To verify the simulation method, measurements were carried out, both static and during motion, using a quasi-3D phantom and a motion platform. The results of the verification measurements during motion were comparable to the results of the static measurements. Considerable interplay effects were observed for individual fractions, with the minimum ΔD98% and maximum ΔD2% being  ‑16.7% and 16.2%, respectively. The extent of interplay effects was larger for FFF compared to FF and generally increased for higher breathing amplitudes, larger period times, lower dose levels, and more complex treatment plans. Also, the interplay effects varied considerably with the initial breathing phase, and larger variations were observed for smaller CTV sizes. In conclusion, a method to simulate motion induced interplay effects was developed and verified with measurements, which allowed for a large number of treatment scenarios to be investigated. The simulations showed large interplay effects for individual fractions and that the extent of interplay effects varied with the breathing pattern, FFF/FF, dose level, CTV size, collimator angle, and the complexity of the treatment plan.

SU-E-T-279: Realization of Three-Dimensional Conformal Dose Planning in Prostate Brachytherapy

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

Li, Z; Jiang, S; Yang, Z

2014-06-01

Purpose: Successful clinical treatment in prostate brachytherapy is largely dependent on the effectiveness of pre-surgery dose planning. Conventional dose planning method could hardly arrive at a satisfy result. In this abstract, a three-dimensional conformal localized dose planning method is put forward to ensure the accuracy and effectiveness of pre-implantation dose planning. Methods: Using Monte Carlo method, the pre-calculated 3-D dose map for single source is obtained. As for multiple seeds dose distribution, the maps are combined linearly to acquire the 3-D distribution. The 3-D dose distribution is exhibited in the form of isodose surface together with reconstructed 3-D organs groupmore » real-timely. Then it is possible to observe the dose exposure to target volume and normal tissues intuitively, thus achieving maximum dose irradiation to treatment target and minimum healthy tissues damage. In addition, the exfoliation display of different isodose surfaces can be realized applying multi-values contour extraction algorithm based on voxels. The needles could be displayed in the system by tracking the position of the implanted seeds in real time to conduct block research in optimizing insertion trajectory. Results: This study extends dose planning from two-dimensional to three-dimensional, realizing the three-dimensional conformal irradiation, which could eliminate the limitations of 2-D images and two-dimensional dose planning. A software platform is developed using VC++ and Visualization Toolkit (VTK) to perform dose planning. The 3-D model reconstruction time is within three seconds (on a Intel Core i5 PC). Block research could be conducted to avoid inaccurate insertion into sensitive organs or internal obstructions. Experiments on eight prostate cancer cases prove that this study could make the dose planning results more reasonable. Conclusion: The three-dimensional conformal dose planning method could improve the rationality of dose planning by safely reducing the large target margin and avoiding dose dead zones for prostate cancer treatment. 1) National Natural Science Foundation of People's Republic of China (No. 51175373); 2) New Century Educational Talents Plan of Chinese Education Ministry (NCET-10-0625); 3) Scientific and Technological Major Project, Tianjin (No. 12ZCDZSY10600)« less

Concentration of 3H in ground water and estimation of committed effective dose due to ground water ingestion in some places in the Maharashtra state, India.

PubMed

Reddy, P J; Bhade, S P D; Kolekar, R V; Singh, Rajvir; Pradeepkumar, K S

2014-01-01

The measurement of tritium in environmental samples requires highest possible sensitivity. In the present study, the authors have optimised the counting window for the analysis of (3)H in environmental samples using the recently installed Ultra Low Level Quantulus 1220 Liquid Scintillation Counting at BARC to improve the detection limit of the system. The optimised counting window corresponding to the highest figure of merit of 883.8 was found to be 20-162 channels. Different brands of packaged drinking waters were analysed to select a blank that would define the system background. The minimum detectable activity (MDA) achieved was 1.5 Bq l(-1) for a total counting time of 500 min. The concentration of tritium in well and bore well water samples collected from the villages of Pune, villages located at 1.8 km from Tarapur Atomic Power Station, Kolhapur and Ratnagiri, was analysed. The activity concentration ranged from 0.55 to 3.66 Bq l(-1). The associated age-dependant dose from water ingestion in the study area was estimated. The effective committed dose recorded for different age classes is negligible compared with World Health Organization and US Environmental Protection Agency dose guidelines.

External beam radiotherapy for palliation of painful bone metastases: pooled data bioeffect dose response analysis of dose fractionation

NASA Astrophysics Data System (ADS)

Naveen, T.; Supe, Sanjay S.; Ganesh, K. M.; Samuel, Jacob

2009-01-01

Bone metastases develop in up to 70% of newly diagnosed cancer patients and result in immobility, anxiety, and depression, severely diminishing the patients quality of life. Radiotherapy is a frequently used modality for bone metastasis and has been shown to be effective in reducing metastatic bone pain and in some instances, causing tumor shrinkage or growth inhibition. There is controversy surrounding the optimal fractionation schedule and total dose of external beam radiotherapy, despite many randomized trials and overviews addressing the issue. This study was undertaken to apply BED to clinical fractionation data of radiotherapeutic management of bone metastases in order to arrive at optimum BED values for acceptable level of response rate. A computerised literature search was conducted to identify all prospective clinical studies that addressed the issue of fractionation for the treatment of bone metastasis. The results of these studies were pooled together to form the database for the analysis. A total of 4111 number of patients received radiation dose ranging from 4 to 40.5 Gy in 1 to 15 fractions with dose per fraction ranging from 2 to 10 Gy. Single fraction treatments were delivered in 2013 patients and the dose varied from 4 to 10 Gy. Multifraction treatments were delivered in 2098 patients and the dose varied from 15 to 40.5 Gy. The biological effective dose (BED) was evaluated for each fractionation schedule using the linear quadratic model and an α/β value of 10 Gy. Response rate increased significantly beyond a BED value of 14.4 Gy (p < 0.01). Based on our analysis and indications from the literature about higher retreatment and fracture rate of single fraction treatments, minimum BED value of 14.4 Gy is recommended.

Bladder accumulated dose in image-guided high-dose-rate brachytherapy for locally advanced cervical cancer and its relation to urinary toxicity

NASA Astrophysics Data System (ADS)

Zakariaee, Roja; Hamarneh, Ghassan; Brown, Colin J.; Gaudet, Marc; Aquino-Parsons, Christina; Spadinger, Ingrid

2016-12-01

The purpose of this study was to estimate locally accumulated dose to the bladder in multi-fraction high-dose-date (HDR) image-guided intracavitary brachytherapy (IG-ICBT) for cervical cancer, and study the locally-accumulated dose parameters as predictors of late urinary toxicity. A retrospective study of 60 cervical cancer patients who received five HDR IG-ICBT sessions was performed. The bladder outer and inner surfaces were segmented for all sessions and a bladder-wall contour point-set was created in MATLAB. The bladder-wall point-sets for each patient were registered using a deformable point-set registration toolbox called coherent point drift (CPD), and the fraction doses were accumulated. Various dosimetric and volumetric parameters were calculated using the registered doses, including r{{\\text{D}}n \\text{c{{\\text{m}}\\text{3}}}} (minimum dose to the most exposed n-cm3 volume of bladder wall), r V n Gy (wall volume receiving at least m Gy), and r\\text{EQD}{{2}n \\text{c{{\\text{m}}\\text{3}}}} (minimum equivalent biologically weighted dose to the most exposed n-cm3 of bladder wall), where n  =  1/2/5/10 and m  =  3/5/10. Minimum dose to contiguous 1 and 2 cm3 hot-spot volumes was also calculated. The unregistered dose volume histogram (DVH)-summed equivalent of r{{\\text{D}}n \\text{c{{\\text{m}}3}}} and r\\text{EQD}{{2}n \\text{c{{\\text{m}}3}}} parameters (i.e. s{{\\text{D}}n \\text{c{{\\text{m}}\\text{3}}}} and s\\text{EQD}{{2}n \\text{c{{\\text{m}}3}}} ) were determined for comparison. Late urinary toxicity was assessed using the LENT-SOMA scale, with toxicity Grade 0-1 categorized as Controls and Grade 2-4 as Cases. A two-sample t-test was used to identify the differences between the means of Control and Case groups for all parameters. A binomial logistic regression was also performed between the registered dose parameters and toxicity grouping. Seventeen patients were in the Case and 43 patients in the Control group. Contiguous values were on average 16 and 18% smaller than parameters for 1 and 2 cm3 volumes, respectively. Contiguous values were on average 26 and 27% smaller than parameters. The only statistically significant finding for Case versus Control based on both methods of analysis was observed for r V3 Gy (p  =  0.01). DVH-summed parameters based on unregistered structure volumes overestimated the bladder dose in our patients, particularly when contiguous high dose volumes were considered. The bladder-wall volume receiving at least 3 Gy of accumulated dose may be a parameter of interest in further investigations of Grade 2+  urinary toxicity.

SU-F-T-35: Optimization of Bladder and Rectal Doses Using a Multi-Lumen Intracavitary Applicator for Gynecological Brachytherapy

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

Laoui, S; Dietrich, S; Sehgal, V

2016-06-15

Purpose: Radiation dose delivery for endometrial cancer using HDR techniques is limited by dose to bladder and rectum. A dosimetric study was performed using Varian Capri vaginal brachytherapy applicator to determine the optimal channel configuration which minimizes dose to bladder and rectum, while providing good target coverage. Methods: A total of 17 patients, 63 plans clinically delivered, and 252 simulated plans using Varian BrachyVision planning system were generated to investigate optimal channel configuration which results in minimum dose to bladder and rectum while providing adequate target coverage. The Capri applicator consists of 13 lumens arranged in two concentric rings, onemore » central lumen and six lumens per ring. Manual dose shaping is invariably required to lower the dose to critical organs. Three-dimensional plans were simulated for 4 channel arrangements, all 13 channels, channel 12 o’clock (close to bladder) and 6 o’clock (close to rectum) deactivated, central channel deactivated, and central channel in addition to 12 o’clock and 6 o’clock deactivated. A relationship between V100, the volume that receives the prescribed dose, and the amount of curie-seconds required to deliver it, was established. Results: Using all 13 channels results in maximum dose to bladder and rectum. Deactivating central channel in addition to 12 o’clock and 6 o’clock resulted in minimizing bladder and rectum doses but compromised target coverage. The relationship between V100, the volume that receives the prescribed dose, and the curie seconds was found to be linear. Conclusion: Deactivating channels 12 o’clock and 6 o’clock was shown to be the optimal configuration leading to minimum dose to bladder and rectum without compromising target coverage. The linear relationship between V100 and the curie- seconds can be used as a verification parameter.« less

A new chapter in the bisphenol A story: bisphenol S and bisphenol F are not safe alternatives to this compound.

PubMed

Eladak, Soria; Grisin, Tiphany; Moison, Delphine; Guerquin, Marie-Justine; N'Tumba-Byn, Thierry; Pozzi-Gaudin, Stéphanie; Benachi, Alexandra; Livera, Gabriel; Rouiller-Fabre, Virginie; Habert, René

2015-01-01

Bisphenol A (BPA) is a widely studied typical endocrine-disrupting chemical, and one of the major new issues is the safe replacement of this commonly used compound. Bisphenol S (BPS) and bisphenol F (BPF) are already or are planned to be used as BPA alternatives. With the use of a culture system that we developed (fetal testis assay [FeTA]), we previously showed that 10 nmol/L BPA reduces basal testosterone secretion of human fetal testis explants and that the susceptibility to BPA is at least 100-fold lower in rat and mouse fetal testes. Here, we show that addition of LH in the FeTA system considerably enhances BPA minimum effective concentration in mouse and human but not in rat fetal testes. Then, using the FeTA system without LH (the experimental conditions in which mouse and human fetal testes are most sensitive to BPA), we found that, as for BPA, 10 nmol/L BPS or BPF is sufficient to decrease basal testosterone secretion by human fetal testes with often nonmonotonic dose-response curves. In fetal mouse testes, the dose-response curves were mostly monotonic and the minimum effective concentrations were 1,000 nmol/L for BPA and BPF and 100 nmol/L for BPS. Finally, 10,000 nmol/L BPA, BPS, or BPF reduced Insl3 expression in cultured mouse fetal testes. This is the first report describing BPS and BPF adverse effects on a physiologic function in humans and rodents. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

The Advantages of Collimator Optimization for Intensity Modulated Radiation Therapy

NASA Astrophysics Data System (ADS)

Doozan, Brian

The goal of this study was to improve dosimetry for pelvic, lung, head and neck, and other cancers sites with aspherical planning target volumes (PTV) using a new algorithm for collimator optimization for intensity modulated radiation therapy (IMRT) that minimizes the x-jaw gap (CAX) and the area of the jaws (CAA) for each treatment field. A retroactive study on the effects of collimator optimization of 20 patients was performed by comparing metric results for new collimator optimization techniques in Eclipse version 11.0. Keeping all other parameters equal, multiple plans are created using four collimator techniques: CA 0, all fields have collimators set to 0°, CAE, using the Eclipse collimator optimization, CAA, minimizing the area of the jaws around the PTV, and CAX, minimizing the x-jaw gap. The minimum area and the minimum x-jaw angles are found by evaluating each field beam's eye view of the PTV with ImageJ and finding the desired parameters with a custom script. The evaluation of the plans included the monitor units (MU), the maximum dose of the plan, the maximum dose to organs at risk (OAR), the conformity index (CI) and the number of fields that are calculated to split. Compared to the CA0 plans, the monitor units decreased on average by 6% for the CAX method with a p-value of 0.01 from an ANOVA test. The average maximum dose remained within 1.1% difference between all four methods with the lowest given by CAX. The maximum dose to the most at risk organ was best spared by the CAA method, which decreased by 0.62% compared to the CA0. Minimizing the x-jaws significantly reduced the number of split fields from 61 to 37. In every metric tested the CAX optimization produced comparable or superior results compared to the other three techniques. For aspherical PTVs, CAX on average reduced the number of split fields, lowered the maximum dose, minimized the dose to the surrounding OAR, and decreased the monitor units. This is achieved while maintaining the same control of the PTV.

[Upper airway morphology in Down Syndrome patients under dexmedetomidine sedation].

PubMed

Subramanyam, Rajeev; Fleck, Robert; McAuliffe, John; Radhakrishnan, Rupa; Jung, Dorothy; Patino, Mario; Mahmoud, Mohamed

2016-01-01

Children with Down Syndrome are vulnerable to significant upper airway obstruction due to relative macroglossia and dynamic airway collapse. The objective of this study was to compare the upper airway dimensions of children with Down Syndrome and obstructive sleep apnea with normal airway under dexmedetomidine sedation. IRB approval was obtained. In this retrospective study, clinically indicated dynamic sagittal midline magnetic resonance images of the upper airway were obtained under low (1mcg/kg/h) and high (3mcg/kg/h) dose dexmedetomidine. Airway anteroposterior diameters and sectional areas were measured as minimum and maximum dimensions by two independent observers at soft palate (nasopharyngeal airway) and at base of the tongue (retroglossal airway). Minimum anteroposterior diameter and minimum sectional area at nasopharynx and retroglossal airway were significantly reduced in Down Syndrome compared to normal airway at both low and high dose dexmedetomidine. However, there were no significant differences between low and high dose dexmedetomidine in both Down Syndrome and normal airway. The mean apnea hypopnea index in Down Syndrome was 16±11. Under dexmedetomidine sedation, children with Down Syndrome and obstructive sleep apnea when compared to normal airway children show significant reductions in airway dimensions most pronounced at the narrowest points in the nasopharyngeal and retroglossal airways. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Upper airway morphology in Down Syndrome patients under dexmedetomidine sedation.

PubMed

Subramanyam, Rajeev; Fleck, Robert; McAuliffe, John; Radhakrishnan, Rupa; Jung, Dorothy; Patino, Mario; Mahmoud, Mohamed

2016-01-01

Children with Down Syndrome are vulnerable to significant upper airway obstruction due to relative macroglossia and dynamic airway collapse. The objective of this study was to compare the upper airway dimensions of children with Down Syndrome and obstructive sleep apnea with normal airway under dexmedetomidine sedation. IRB approval was obtained. In this retrospective study, clinically indicated dynamic sagittal midline magnetic resonance images of the upper airway were obtained under low (1mcg/kg/h) and high (3mcg/kg/h) dose dexmedetomidine. Airway anteroposterior diameters and sectional areas were measured as minimum and maximum dimensions by two independent observers at soft palate (nasopharyngeal airway) and at base of the tongue (retroglossal airway). Minimum anteroposterior diameter and minimum sectional area at nasopharynx and retroglossal airway were significantly reduced in Down Syndrome compared to normal airway at both low and high dose dexmedetomidine. However, there were no significant differences between low and high dose dexmedetomidine in both Down Syndrome and normal airway. The mean apnea hypopnea index in Down Syndrome was 16±11. Under dexmedetomidine sedation, children with Down Syndrome and obstructive sleep apnea when compared to normal airway children show significant reductions in airway dimensions most pronounced at the narrowest points in the nasopharyngeal and retroglossal airways. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Pharmacodynamics of oxytetracycline administered alone and in combination with carprofen in calves.

PubMed

Brentnall, C; Cheng, Z; McKellar, Q A; Lees, P

2012-09-15

The pharmacodynamics (PD) of oxytetracycline was investigated against a strain of Mannheimia haemolytica. In vitro measurements, comprising minimum inhibitory concentration (MIC), minimum bactericidal concentration and time-kill curves, were conducted in five matrices; Mueller Hinton Broth (MHB), cation-adjusted MHB (CAMHB) and calf serum, exudate and transudate. MICs were much higher in the biological fluids than in MHB and CAMHB. Ratios of MIC were, serum: CAMHB 19 : 1; exudate:CAMHB 16.1; transudate:CAMHB 14 : 1. Ex vivo data, generated in the tissue cage model of inflammation, demonstrated that oxytetracycline, administered to calves intramuscularly at a dose rate of 20 mg/kg, did not inhibit the growth of M haemolytica in serum, exudate and transudate, even at peak concentration. However, using in vitro susceptibility in CAMHB and in vivo-determined pharmacokinetic (PK) variables, average and minimum oxytetracycline concentrations relative to MIC (C(av)/MIC and C(min)/MIC) predicted achievement of efficacy for approximately 48 hours after dosing. Similar C(av)/MIC and C(min)/MIC data were obtained when oxytetracycline was administered in the presence of carprofen. PK-PD integration of data for oxytetracycline, based on MICs determined in the three biological fluids, suggests that it possesses, at most, limited direct killing activity against M haemolytica. These data raise questions concerning the mechanism(s) of action of oxytetracycline, when administered at clinically recommended dose rates.

Optimal shield mass distribution for space radiation protection

NASA Technical Reports Server (NTRS)

Billings, M. P.

1972-01-01

Computational methods have been developed and successfully used for determining the optimum distribution of space radiation shielding on geometrically complex space vehicles. These methods have been incorporated in computer program SWORD for dose evaluation in complex geometry, and iteratively calculating the optimum distribution for (minimum) shield mass satisfying multiple acute and protected dose constraints associated with each of several body organs.

Tabulated dose uniformity ratio and minimum dose data: rectangular 60Co source plaques

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

Galanter, L.

1971-01-01

The data tabulated herein extend to rectangular cobalt-60 plaques the information presented for square plaques in BNL 50145 (Revised). The user is referred to BNL 50145 (Revised) and to the other reports listed for a complete discussion of the parameters involved in data generation and for instructions on the use of these data in gamma irradiator design.

Process control and dosimetry in a multipurpose irradiation facility

NASA Astrophysics Data System (ADS)

Cabalfin, E. G.; Lanuza, L. G.; Solomon, H. M.

1999-08-01

Availability of the multipurpose irradiation facility at the Philippine Nuclear Research Institute has encouraged several local industries to use gamma radiation for sterilization or decontamination of various products. Prior to routine processing, dose distribution studies are undertaken for each product and product geometry. During routine irradiation, dosimeters are placed at the minimum and maximum dose positions of a process load.

Design and Synthesis of 4-Heteroaryl 1,2,3,4-Tetrahydroisoquinolines as Triple Reuptake Inhibitors

PubMed Central

2014-01-01

A series of 4-bicyclic heteroaryl 1,2,3,4-tetrahydroisoquinoline inhibitors of the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT) was discovered. The synthesis and structure–activity relationship (SAR) of these triple reuptake inhibitors (TRIs) will be discussed. Compound 10i (AMR-2), a very potent inhibitor of SERT, NET, and DAT, showed efficacy in the rat forced-swim and mouse tail suspension models with minimum effective doses of 0.3 and 1 mg/kg (po), respectively. At efficacious doses in these assays, 10i exhibited substantial occupancy levels at the three transporters in both rat and mouse brain. The study of the metabolism of 10i revealed the formation of a significant active metabolite, compound 13. PMID:25050161

Design and synthesis of 4-heteroaryl 1,2,3,4-tetrahydroisoquinolines as triple reuptake inhibitors.

PubMed

Liu, Shuang; Zha, Congxiang; Nacro, Kassoum; Hu, Min; Cui, Wenge; Yang, Yuh-Lin; Bhatt, Ulhas; Sambandam, Aruna; Isherwood, Matthew; Yet, Larry; Herr, Michael T; Ebeltoft, Sarah; Hassler, Carla; Fleming, Linda; Pechulis, Anthony D; Payen-Fornicola, Anne; Holman, Nicholas; Milanowski, Dennis; Cotterill, Ian; Mozhaev, Vadim; Khmelnitsky, Yuri; Guzzo, Peter R; Sargent, Bruce J; Molino, Bruce F; Olson, Richard; King, Dalton; Lelas, Snjezana; Li, Yu-Wen; Johnson, Kim; Molski, Thaddeus; Orie, Anitra; Ng, Alicia; Haskell, Roy; Clarke, Wendy; Bertekap, Robert; O'Connell, Jonathan; Lodge, Nicholas; Sinz, Michael; Adams, Stephen; Zaczek, Robert; Macor, John E

2014-07-10

A series of 4-bicyclic heteroaryl 1,2,3,4-tetrahydroisoquinoline inhibitors of the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT) was discovered. The synthesis and structure-activity relationship (SAR) of these triple reuptake inhibitors (TRIs) will be discussed. Compound 10i (AMR-2), a very potent inhibitor of SERT, NET, and DAT, showed efficacy in the rat forced-swim and mouse tail suspension models with minimum effective doses of 0.3 and 1 mg/kg (po), respectively. At efficacious doses in these assays, 10i exhibited substantial occupancy levels at the three transporters in both rat and mouse brain. The study of the metabolism of 10i revealed the formation of a significant active metabolite, compound 13.

Reconstruction of organ dose for external radiotherapy patients in retrospective epidemiologic studies

NASA Astrophysics Data System (ADS)

Lee, Choonik; Jung, Jae Won; Pelletier, Christopher; Pyakuryal, Anil; Lamart, Stephanie; Kim, Jong Oh; Lee, Choonsik

2015-03-01

Organ dose estimation for retrospective epidemiological studies of late effects in radiotherapy patients involves two challenges: radiological images to represent patient anatomy are not usually available for patient cohorts who were treated years ago, and efficient dose reconstruction methods for large-scale patient cohorts are not well established. In the current study, we developed methods to reconstruct organ doses for radiotherapy patients by using a series of computational human phantoms coupled with a commercial treatment planning system (TPS) and a radiotherapy-dedicated Monte Carlo transport code, and performed illustrative dose calculations. First, we developed methods to convert the anatomy and organ contours of the pediatric and adult hybrid computational phantom series to Digital Imaging and Communications in Medicine (DICOM)-image and DICOM-structure files, respectively. The resulting DICOM files were imported to a commercial TPS for simulating radiotherapy and dose calculation for in-field organs. The conversion process was validated by comparing electron densities relative to water and organ volumes between the hybrid phantoms and the DICOM files imported in TPS, which showed agreements within 0.1 and 2%, respectively. Second, we developed a procedure to transfer DICOM-RT files generated from the TPS directly to a Monte Carlo transport code, x-ray Voxel Monte Carlo (XVMC) for more accurate dose calculations. Third, to illustrate the performance of the established methods, we simulated a whole brain treatment for the 10 year-old male phantom and a prostate treatment for the adult male phantom. Radiation doses to selected organs were calculated using the TPS and XVMC, and compared to each other. Organ average doses from the two methods matched within 7%, whereas maximum and minimum point doses differed up to 45%. The dosimetry methods and procedures established in this study will be useful for the reconstruction of organ dose to support retrospective epidemiological studies of late effects in radiotherapy patients.

A revised burial dose estimation procedure for optical dating of youngand modern-age sediments

USGS Publications Warehouse

Arnold, L.J.; Roberts, R.G.; Galbraith, R.F.; DeLong, S.B.

2009-01-01

The presence of genuinely zero-age or near-zero-age grains in modern-age and very young samples poses a problem for many existing burial dose estimation procedures used in optical (optically stimulated luminescence, OSL) dating. This difficulty currently necessitates consideration of relatively simplistic and statistically inferior age models. In this study, we investigate the potential for using modified versions of the statistical age models of Galbraith et??al. [Galbraith, R.F., Roberts, R.G., Laslett, G.M., Yoshida, H., Olley, J.M., 1999. Optical dating of single and multiple grains of quartz from Jinmium rock shelter, northern Australia: Part I, experimental design and statistical models. Archaeometry 41, 339-364.] to provide reliable equivalent dose (De) estimates for young and modern-age samples that display negative, zero or near-zero De estimates. For this purpose, we have revised the original versions of the central and minimum age models, which are based on log-transformed De values, so that they can be applied to un-logged De estimates and their associated absolute standard errors. The suitability of these 'un-logged' age models is tested using a series of known-age fluvial samples deposited within two arroyo systems from the American Southwest. The un-logged age models provide accurate burial doses and final OSL ages for roughly three-quarters of the total number of samples considered in this study. Sensitivity tests reveal that the un-logged versions of the central and minimum age models are capable of producing accurate burial dose estimates for modern-age and very young (<350??yr) fluvial samples that contain (i) more than 20% of well-bleached grains in their De distributions, or (ii) smaller sub-populations of well-bleached grains for which the De values are known with high precision. Our results indicate that the original (log-transformed) versions of the central and minimum age models are still preferable for most routine dating applications, since these age models are better suited to the statistical properties of typical single-grain and multi-grain single-aliquot De datasets. However, the unique error properties of modern-age samples, combined with the problems of calculating natural logarithms of negative or zero-Gy De values, mean that the un-logged versions of the central and minimum age models currently offer the most suitable means of deriving accurate burial dose estimates for very young and modern-age samples. ?? 2009 Elsevier Ltd. All rights reserved.

Shading correction for cone-beam CT in radiotherapy: validation of dose calculation accuracy using clinical images

NASA Astrophysics Data System (ADS)

Marchant, T. E.; Joshi, K. D.; Moore, C. J.

2017-03-01

Cone-beam CT (CBCT) images are routinely acquired to verify patient position in radiotherapy (RT), but are typically not calibrated in Hounsfield Units (HU) and feature non-uniformity due to X-ray scatter and detector persistence effects. This prevents direct use of CBCT for re-calculation of RT delivered dose. We previously developed a prior-image based correction method to restore HU values and improve uniformity of CBCT images. Here we validate the accuracy with which corrected CBCT can be used for dosimetric assessment of RT delivery, using CBCT images and RT plans for 45 patients including pelvis, lung and head sites. Dose distributions were calculated based on each patient's original RT plan and using CBCT image values for tissue heterogeneity correction. Clinically relevant dose metrics were calculated (e.g. median and minimum target dose, maximum organ at risk dose). Accuracy of CBCT based dose metrics was determined using an "override ratio" method where the ratio of the dose metric to that calculated on a bulk-density assigned version of the image is assumed to be constant for each patient, allowing comparison to "gold standard" CT. For pelvis and head images the proportion of dose errors >2% was reduced from 40% to 1.3% after applying shading correction. For lung images the proportion of dose errors >3% was reduced from 66% to 2.2%. Application of shading correction to CBCT images greatly improves their utility for dosimetric assessment of RT delivery, allowing high confidence that CBCT dose calculations are accurate within 2-3%.

Determination of the starting dose in the first-in-human clinical trials with monoclonal antibodies: a systematic review of papers published between 1990 and 2013.

PubMed

Suh, Hoon Young; Peck, Carl C; Yu, Kyung-Sang; Lee, Howard

2016-01-01

A systematic review was performed to evaluate how the maximum recommended starting dose (MRSD) was determined in first-in-human (FIH) studies with monoclonal antibodies (mAbs). Factors associated with the choice of each MRSD determination method were also identified. PubMed was searched for FIH studies with mAbs published in English between January 1, 1990 and December 31, 2013, and the following information was extracted: MRSD determination method, publication year, therapeutic area, antibody type, safety factor, safety assessment results after the first dose, and number of dose escalation steps. Seventy-nine FIH studies with mAbs were identified, 49 of which clearly reported the MRSD determination method. The no observed adverse effects level (NOAEL)-based approach was the most frequently used method, whereas the model-based approach was the least commonly used method (34.7% vs 16.3%). The minimal anticipated biological effect level (MABEL)- or minimum effective dose (MED)-based approach was used more frequently in 2011-2013 than in 1990-2007 (31.6% vs 6.3%, P =0.036), reflecting a slow, but steady acceptance of the European Medicines Agency's guidance on mitigating risks for FIH clinical trials (2007). The median safety factor was much lower for the MABEL- or MED-based approach than for the other MRSD determination methods (10 vs 32.2-53). The number of dose escalation steps was not significantly different among the different MRSD determination methods. The MABEL-based approach appears to be safer and as efficient as the other MRSD determination methods for achieving the objectives of FIH studies with mAbs faster.

Pharmacokinetic Study of Intravenous Acetaminophen Administered to Critically Ill Multiple-Trauma Patients at the Usual Dosage and a New Proposal for Administration.

PubMed

Fuster-Lluch, Oscar; Zapater-Hernández, Pedro; Gerónimo-Pardo, Manuel

2017-10-01

The pharmacokinetic profile of intravenous acetaminophen administered to critically ill multiple-trauma patients was studied after 4 consecutive doses of 1 g every 6 hours. Eleven blood samples were taken (predose and 15, 30, 45, 60, 90, 120, 180, 240, 300, and 360 minutes postdose), and urine was collected (during 6-hour intervals between doses) to determine serum and urine acetaminophen concentrations. These were used to calculate the following pharmacokinetic parameters: maximum and minimum concentrations, terminal half-life, area under serum concentration-time curve from 0 to 6 hours, mean residence time, volume of distribution, and serum and renal clearance of acetaminophen. Daily doses of acetaminophen required to obtain steady-state minimum (bolus dosing) and average plasma concentrations (continuous infusion) of 10 μg/mL were calculated (10 μg/mL is the presumed lower limit of the analgesic range). Data are expressed as median [interquartile range]. Twenty-two patients were studied, mostly young (age 44 [34-64] years) males (68%), not obese (weight 78 [70-84] kg). Acetaminophen concentrations and pharmacokinetic parameters were these: maximum concentration 33.6 [25.7-38.7] μg/mL and minimum concentration 0.5 [0.2-2.3] μg/mL, all values below 10 μg/mL and 8 below the detection limit; half-life 1.2 [1.0-1.9] hours; area under the curve for 6 hours 34.7 [29.7-52.7] μg·h/mL; mean residence time 1.8 [1.3-2.6] hours; steady-state volume of distribution 50.8 [42.5-66.5] L; and serum and renal clearance 28.8 [18.9-33.7] L/h and 15 [11-19] mL/min, respectively. Theoretically, daily doses for a steady-state minimum concentration of 10 μg/mL would be 12.2 [7.8-16.4] g/day (166 [112-202] mg/[kg·day]); for an average steady-state concentration of 10 μg/mL, they would be 6.9 [4.5-8.1] g/day (91 [59-111] mg/[kg·day]). In conclusion, administration of acetaminophen at the recommended dosage of 1 g per 6 hours to critically ill multiple-trauma patients yields serum concentrations below 10 μg/mL due to increased elimination. To reach the 10 μg/mL target, and from a strictly pharmacokinetic point of view, continuous infusion may be more feasible than bolus dosing. Such a change in dosing strategy requires appropriate, pharmacokinetic-pharmacodynamic and specific safety study. © 2017, The American College of Clinical Pharmacology.

Comparison of three and four-field radiotherapy technique and the effect of laryngeal shield on vocal and spinal cord radiation dose in radiotherapy of non-laryngeal head and neck tumors

NASA Astrophysics Data System (ADS)

Pour, Noushin Hassan; Farajollahi, Alireza; Jamali, Masoud; Zeinali, Ahad; Jangjou, Amir Ghasemi

2018-03-01

Introduction: Due to the effect of radiation on both the tumor and the surrounding normal tissues, the side effects of radiation in normal tissues are expected. One of the important complications in the head and neck radiotherapy is the doses reached to the larynx and spinal cord of patients with non-laryngeal head and neck tumors. Materials and Methods: In this study, CT scan images of 25 patients with non-laryngeal tumors including; lymph nodes, tongue, oropharynx and nasopharynx were used. A three-field and a four-field treatment planning with and without laryngeal shield in 3D CRT technique were planned for each patient. Subsequently, the values of Dmin, Dmean, Dmax and Dose Volume Histogram from the treatment planning system and NTCP values of spinal cord and larynx were calculated with BIOPLAN and MATLAB software for all patients. Results: Statistical results showed that mean values of doses of larynx in both three and four-field methods were significantly different between with and without shield groups. Comparison of absorbed dose didn't show any difference between the three and four field methods (P>0.05). Using Shield, just the mean and minimum doses of spinal cord decreased in both three and four fields. The NTCP of the spinal cord and larynx by three and four-field methods with shield in the LKB and EUD models significantly are less than that of the three and four fields without shields, and in the four-field method NTCP of larynx is less than three radiation field. Conclusion: The results of this study indicate that there is no significant difference in doses reached to larynx and spinal cord between the treatments techniques, but laryngeal shield reduce dose and NTCP values in larynx considerably.

Effectiveness of two-sided UV-C treatments in inhibiting natural microflora and extending the shelf-life of minimally processed 'Red Oak Leaf' lettuce.

PubMed

Allende, Ana; McEvoy, James L; Luo, Yaguang; Artes, Francisco; Wang, Chien Y

2006-05-01

The use of UV-C radiation treatments to inhibit the microbial growth and extend the shelf-life of minimally processed 'Red Oak Leaf' lettuce was investigated. Initially, UV-C resistance of 20 bacterial strains from different genera often associated with fresh produce (Enterobacter, Erwinia, Escherichia, Leuconostoc, Pantoea, Pseudomonas, Rahnela, Salmonella, Serratia and Yersinia) were tested in vitro. Most of the bacterial strains were inhibited with the minimum dose (30 J m(-2)). Erwinia carotovora, Leuconostoc carnosum, Salmonella typhimurium, and Yersinia aldovae were the most resistant strains requiring a UV-C dose of 85 J m(-2) to completely inhibit growth. An in vivo study consisted of treating minimally processed 'Red Oak Leaf' lettuce (Lactuca sativa) with UV-C at three radiation doses (1.18, 2.37 and 7.11 kJ m(-2)) on each side of the leaves and storing the product under passive MAP conditions at 5 degrees C for up to 10 days. The gas composition inside packages varied significantly among the treatments, with CO2 concentrations positively and O2 concentrations negatively correlating with the radiation dose. All the radiation doses were effective in reducing the natural microflora of the product, although the highest doses showed the greatest microbial inhibitions. Taking into account the microbial limit set by Spanish legislation [Boletín Oficial del Estado (BOE), 2001. Normas de higiene para la elaboración, distribución y comercio de comidas preparadas, Madrid, Spain, Real Decreto 3484/2000, pp. 1435-1441], all UV-C treatments extended the shelf-life of the product. However, the 7.11 kJ m(-2) dose induced tissue softening and browning after 7 days of storage at 5 degrees C. Therefore, the use of two sided UV-C radiation, at the proper dose, is effective in reducing the natural microflora and extending the shelf-life of minimally processed 'Red Oak Leaf' lettuce.

Solar Modulation of Inner Trapped Belt Radiation Flux as a Function of Atmospheric Density

NASA Technical Reports Server (NTRS)

Lodhi, M. A. K.

2005-01-01

No simple algorithm seems to exist for calculating proton fluxes and lifetimes in the Earth's inner, trapped radiation belt throughout the solar cycle. Most models of the inner trapped belt in use depend upon AP8 which only describes the radiation environment at solar maximum and solar minimum in Cycle 20. One exception is NOAAPRO which incorporates flight data from the TIROS/NOAA polar orbiting spacecraft. The present study discloses yet another, simple formulation for approximating proton fluxes at any time in a given solar cycle, in particular between solar maximum and solar minimum. It is derived from AP8 using a regression algorithm technique from nuclear physics. From flux and its time integral fluence, one can then approximate dose rate and its time integral dose.

The timing of administration of a clinically relevant dose of losartan influences the healing process after contusion induced muscle injury.

PubMed

Kobayashi, Tetsuo; Uehara, Kenji; Ota, Shusuke; Tobita, Kimimasa; Ambrosio, Fabrisia; Cummins, James H; Terada, Satoshi; Fu, Freddie H; Huard, Johnny

2013-01-15

Losartan (Los) is a Food and Drug Administration-approved antihypertensive medication that has a well-tolerated side effect profile. We have demonstrated that treatment with Los immediately after injury was effective at promoting muscle healing and inducing an antifibrotic effect in a murine model of skeletal muscle injury. We initially investigated the minimum effective dose of Los administration immediately after injury and subsequently determined whether the timing of administering a clinically relevant dose of Los would influence its effectiveness at improving muscle healing after muscle injury. In the first part of this study, mice were administered 3, 10, 30, or 300 mg·kg(-1)·day(-1) of Los immediately after injury, and the healing process was evaluated histologically and physiologically 4 wk after injury. In the second study, the clinically relevant dose of 10 mg·kg(-1)·day(-1) was administered immediately or started at 3 or 7 days postinjury. The administration of 300 mg·kg(-1)·day(-1) immediately following injury led to a significant increase in muscle regeneration, a significant decrease in fibrosis, and an improvement in muscle function. Moreover, we observed a significant decrease in fibrosis and a significant increase in muscle regeneration at 4 wk postinjury, when the clinically relevant dose of 10 mg·kg(-1)·day(-1) was administered at 3 or 7 days postinjury. Functional evaluation also demonstrated a significant improvement compared with the injured untreated control when Los treatment was initiated 3 days after injury. Our study revealed accelerated muscle healing when the 300 mg·kg(-1)·day(-1) of Los was administered immediately after injury and a clinically relevant dose of 10 mg·kg(-1)·day(-1) of Los was administered at 3 or 7 days postinjury.

Method of predicting the mean lung dose based on a patient's anatomy and dose-volume histograms

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

Zawadzka, Anna, E-mail: a.zawadzka@zfm.coi.pl; Nesteruk, Marta; Department of Radiation Oncology, University Hospital Zurich and University of Zurich, Zurich

The aim of this study was to propose a method to predict the minimum achievable mean lung dose (MLD) and corresponding dosimetric parameters for organs-at-risk (OAR) based on individual patient anatomy. For each patient, the dose for 36 equidistant individual multileaf collimator shaped fields in the treatment planning system (TPS) was calculated. Based on these dose matrices, the MLD for each patient was predicted by the homemade DosePredictor software in which the solution of linear equations was implemented. The software prediction results were validated based on 3D conformal radiotherapy (3D-CRT) and volumetric modulated arc therapy (VMAT) plans previously prepared formore » 16 patients with stage III non–small-cell lung cancer (NSCLC). For each patient, dosimetric parameters derived from plans and the results calculated by DosePredictor were compared. The MLD, the maximum dose to the spinal cord (D{sub max} {sub cord}) and the mean esophageal dose (MED) were analyzed. There was a strong correlation between the MLD calculated by the DosePredictor and those obtained in treatment plans regardless of the technique used. The correlation coefficient was 0.96 for both 3D-CRT and VMAT techniques. In a similar manner, MED correlations of 0.98 and 0.96 were obtained for 3D-CRT and VMAT plans, respectively. The maximum dose to the spinal cord was not predicted very well. The correlation coefficient was 0.30 and 0.61 for 3D-CRT and VMAT, respectively. The presented method allows us to predict the minimum MLD and corresponding dosimetric parameters to OARs without the necessity of plan preparation. The method can serve as a guide during the treatment planning process, for example, as initial constraints in VMAT optimization. It allows the probability of lung pneumonitis to be predicted.« less

Lifespan extension and cancer prevention in HER-2/neu transgenic mice treated with low intermittent doses of rapamycin

PubMed Central

Popovich, Irina G; Anisimov, Vladimir N; Zabezhinski, Mark A; Semenchenko, Anna V; Tyndyk, Margarita L; Yurova, Maria N; Blagosklonny, Mikhail V

2014-01-01

Target of Rapamycin (TOR) is involved in cellular and organismal aging. Rapamycin extends lifespan and delays cancer in mice. It is important to determine the minimum effective dose and frequency of its administration that still extends lifespan and prevents cancer. Previously we tested 1.5 mg/kg of rapamycin given subcutaneously 6 times per two weeks followed by a two-week break (1.5 × 6/bi-weekly schedule: total of 6 injections during a 4-week period). This intermittent treatment prolonged lifespan and delayed cancer in cancer-prone female FVB/N HER-2/neu mice. Here, the dose was decreased from 1.5 mg/kg to 0.45 mg/kg per injection. This treatment was started at the age of 2 months (group Rap-2), 4 months (Rap-4), and 5 months (Rap-5). Three control groups received the solvent from the same ages. Rapamycin significantly delayed cancer and decreased tumor burden in Rap-2 and Rap-5 groups, increased mean lifespan in Rap-4 and Rap-5 groups, and increased maximal lifespan in Rap-2 and Rap-5 groups. In Rap-4 group, mean lifespan extension was achieved without significant cancer prevention. The complex relationship between life-extension and cancer-prevention depends on both the direct effect of rapamycin on cancer cells and its anti-aging effect on the organism, which in turn prevents cancer indirectly. We conclude that total doses of rapamycin that are an order of magnitude lower than standard total doses can detectably extend life span in cancer-prone mice. PMID:24556924

Lifespan extension and cancer prevention in HER-2/neu transgenic mice treated with low intermittent doses of rapamycin.

PubMed

Popovich, Irina G; Anisimov, Vladimir N; Zabezhinski, Mark A; Semenchenko, Anna V; Tyndyk, Margarita L; Yurova, Maria N; Blagosklonny, Mikhail V

2014-05-01

Target of Rapamycin (TOR) is involved in cellular and organismal aging. Rapamycin extends lifespan and delays cancer in mice. It is important to determine the minimum effective dose and frequency of its administration that still extends lifespan and prevents cancer. Previously we tested 1.5 mg/kg of rapamycin given subcutaneously 6 times per two weeks followed by a two-week break (1.5 × 6/bi-weekly schedule: total of 6 injections during a 4-week period). This intermittent treatment prolonged lifespan and delayed cancer in cancer-prone female FVB/N HER-2/neu mice. Here, the dose was decreased from 1.5 mg/kg to 0.45 mg/kg per injection. This treatment was started at the age of 2 months (group Rap-2), 4 months (Rap-4), and 5 months (Rap-5). Three control groups received the solvent from the same ages. Rapamycin significantly delayed cancer and decreased tumor burden in Rap-2 and Rap-5 groups, increased mean lifespan in Rap-4 and Rap-5 groups, and increased maximal lifespan in Rap-2 and Rap-5 groups. In Rap-4 group, mean lifespan extension was achieved without significant cancer prevention. The complex relationship between life-extension and cancer-prevention depends on both the direct effect of rapamycin on cancer cells and its anti-aging effect on the organism, which in turn prevents cancer indirectly. We conclude that total doses of rapamycin that are an order of magnitude lower than standard total doses can detectably extend life span in cancer-prone mice.

Determination of radon and radium concentrations in drinking water samples around the city of Kutahya.

PubMed

Sahin, Latife; Cetinkaya, Hakan; Murat Saç, Müslim; Içhedef, Mutlu

2013-08-01

The concentration of radium and radon has been determined in drinking water samples collected from various locations of Kutahya city, Turkey. The water samples are taken from public water sources and tap water, with the collector chamber method used to measure the radon and radium concentration. The radon concentration ranges between 0.1 and 48.6±1.7 Bq l(-1), while the radium concentration varies from a minimum detectable activity of <0.02-0.7±0.2 Bq l(-1) in Kutahya city. In addition to the radon and radium levels, parameters such as pH, conductivity and temperature of the water, humidity, pressure, elevation and the coordinates of the sampling points have also been measured and recorded. The annual effective dose from radon and radium due to typical water usage has been calculated. The resulting contribution to the annual effective dose due to radon ingestion varies between 0.3 and 124.2 μSv y(-1); the contribution to the annual effective dose due to radium ingestion varies between 0 and 143.3 μSv y(-1); the dose contribution to the stomach due to radon ingestion varies between 0.03 and 14.9 μSv y(-1). The dose contribution due to radon inhalation ranges between 0.3 and 122.5 μSv y(-1), assuming a typical transfer of radon in water to the air. For the overwhelming majority of the Kutahya population, it is determined that the average radiation exposure from drinking water is less than 73.6 µSv y(-1).

UV dose measurements of photosensitive dermatosis patients by polycrystalline GaN-based portable self-data-acquisition UV monitors.

PubMed

Yagi, Shigeru; Iwanaga, Takeshi; Kojima, Hiroshi; Shoji, Yoshio; Suzuki, Seiji; Seno, Kunihiro; Mori, Hisayoshi; Tokura, Yoshiki; Takigawa, Masahiro; Moriwaki, Shin-Ichi

2002-12-01

We have developed a UV monitor with polycrystalline (poly-) gallium nitride (GaN) UV sensors and evaluated its performance from the viewpoint of its effectiveness for use with photosensitive dermatosis patients. The poly-GaN UV sensor is sensitive to UV light from 280 to 410 nm even without optical filters. The UV monitor is a portable self-data-acquisition instrument with a minimum detection level (defined as average UV intensity over 290 to 400 nm) of 2 microW/cm2 and can store UV dose data for 128 days. It allows easy measurement of four orders of magnitude of ambient UV intensity and dose from indoor light to direct solar radiation in summer. Trial use of the UV monitor by five xeroderma pigmentosum patients started in June 2000 and was carried out for 1 year. It was demonstrated that the UV monitor was useful in improving their quality of life.

Design and operation of internal dosimetry programs

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

LaBone, T.R.

1991-01-01

The proposed revision to USNRC 10 CFR 20 and the USDOE Order 5480.11 require intakes of radioactive material to be evaluated. Radiation dose limits are based on the sum of effective dose equivalent from intakes and the whole body dose from external sources. These significant changes in the regulations will require, at a minimum, a complete review of personnel monitoring programs to determine their adequacy. In this session we will review a systematic method of designing a routine personnel monitoring program that will comply with the requirements of the new regulations. Specific questions discussed are: (a) What are the goalsmore » and objectives of a routine personnel monitoring program (b) When is a routine personnel monitoring program required (c) What are the required capabilities of the routine personnel monitoring program (d) What should be done with the information generated in a personnel monitoring program Specific recommendations and interpretations are given in the session. 5 refs., 3 figs., 33 tabs.« less

Dose Equivalents for Antipsychotic Drugs: The DDD Method.

PubMed

Leucht, Stefan; Samara, Myrto; Heres, Stephan; Davis, John M

2016-07-01

Dose equivalents of antipsychotics are an important but difficult to define concept, because all methods have weaknesses and strongholds. We calculated dose equivalents based on defined daily doses (DDDs) presented by the World Health Organisation's Collaborative Center for Drug Statistics Methodology. Doses equivalent to 1mg olanzapine, 1mg risperidone, 1mg haloperidol, and 100mg chlorpromazine were presented and compared with the results of 3 other methods to define dose equivalence (the "minimum effective dose method," the "classical mean dose method," and an international consensus statement). We presented dose equivalents for 57 first-generation and second-generation antipsychotic drugs, available as oral, parenteral, or depot formulations. Overall, the identified equivalent doses were comparable with those of the other methods, but there were also outliers. The major strength of this method to define dose response is that DDDs are available for most drugs, including old antipsychotics, that they are based on a variety of sources, and that DDDs are an internationally accepted measure. The major limitations are that the information used to estimate DDDS is likely to differ between the drugs. Moreover, this information is not publicly available, so that it cannot be reviewed. The WHO stresses that DDDs are mainly a standardized measure of drug consumption, and their use as a measure of dose equivalence can therefore be misleading. We, therefore, recommend that if alternative, more "scientific" dose equivalence methods are available for a drug they should be preferred to DDDs. Moreover, our summary can be a useful resource for pharmacovigilance studies. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Global Associations between UVR Exposure and Current Eczema Prevalence in Children from ISAAC Phase Three.

PubMed

Fuertes, Elaine; Flohr, Carsten; Silverberg, Jonathan I; Standl, Marie; Strachan, David P

2017-06-01

We sought to examine the relationship globally between UVR dose exposure and current eczema prevalences. ISAAC Phase Three provided data on eczema prevalence for 13- to 14-year-olds in 214 centers in 87 countries and for 6- to 7-year-olds in 132 centers in 57 countries. Linear and nonlinear associations between (natural log transformed) eczema prevalence and the mean, maximum, minimum, standard deviation, and range of monthly UV dose exposures were assessed using linear mixed-effects regression models. For the 13- to 14-year-olds, the country-level eczema prevalence was positively and linearly associated with country-level monthly mean (prevalence ratio = 1.31 [95% confidence interval = 1.05-1.63] per kJ/m 2 ) and minimum (1.25 [1.06-1.47] per kJ/m 2 ) UVR dose exposure. Linear and nonlinear associations were also observed for other metrics of UV. Results were similar in trend, but nonsignificant, for the fewer centers with 6- to 7-year-olds (e.g., 1.24 [0.96-1.59] per kJ/m 2 for country-level monthly mean UVR). No consistent within-country associations were observed (e.g., 1.05 [0.89-1.23] and 0.92 [0.71-1.18] per kJ/m 2 for center-level monthly mean UVR for the 13- to 14- and 6- to 7-year-olds, respectively). These ecological results support a role for UVR exposure in explaining some of the variation in global childhood eczema prevalence. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2016-11-01

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

Accumulated Delivered Dose Response of Stereotactic Body Radiation Therapy for Liver Metastases

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

Swaminath, Anand; Massey, Christine; Brierley, James D.

2015-11-01

Purpose: To determine whether the accumulated dose using image guided radiation therapy is a stronger predictor of clinical outcomes than the planned dose in stereotactic body radiation therapy (SBRT) for liver metastases. Methods and Materials: From 2003 to 2009, 81 patients with 142 metastases were treated in institutional review board–approved SBRT studies (5-10 fractions). Patients were treated during free breathing (with or without abdominal compression) or with controlled exhale breath-holding. SBRT was planned on a static exhale computed tomography (CT) scan, and the minimum planning target volume dose to 0.5 cm{sup 3} (minPTV) was recorded. The accumulated minimum dose to themore » 0.5 cm{sup 3} gross tumor volume (accGTV) was calculated after performing dose accumulation from exported image guided radiation therapy data sets registered to the planning CT using rigid (2-dimensional MV/kV orthogonal) or deformable (3-dimensional/4-dimensional cone beam CT) image registration. Univariate and multivariate Cox regression models assessed the factors influencing the time to local progression (TTLP). Hazard ratios for accGTV and minPTV were compared using model goodness-of-fit and bootstrapping. Results: Overall, the accGTV dose exceeded the minPTV dose in 98% of the lesions. For 5 to 6 fractions, accGTV doses of >45 Gy were associated with 1-year local control of 86%. On univariate analysis, the cancer subtype (breast), smaller tumor volume, and increased dose were significant predictors for improved TTLP. The dose and volume were uncorrelated; the accGTV dose and minPTV dose were correlated and were tested separately on multivariate models. Breast cancer subtype, accGTV dose (P<.001), and minPTV dose (P=.02) retained significance in the multivariate models. The univariate hazard ratio for TTLP for 5-Gy increases in accGTV versus minPTV was 0.67 versus 0.74 (all patients; 95% confidence interval of difference 0.03-0.14). Goodness-of-fit testing confirmed the accGTV dose as a stronger dose–response predictor than the minPTV dose. Conclusions: The accGTV dose is a better predictor of TTLP than the minPTV dose for liver metastasis SBRT. The use of modern image guided radiation therapy in future analyses of dose–response outcomes should increase the concordance between the planned and delivered doses.« less

Effects of spot parameters in pencil beam scanning treatment planning.

PubMed

Kraan, Aafke Christine; Depauw, Nicolas; Clasie, Ben; Giunta, Marina; Madden, Tom; Kooy, Hanne M

2018-01-01

Spot size σ (in air at isocenter), interspot spacing d, and spot charge q influence dose delivery efficiency and plan quality in Intensity Modulated Proton Therapy (IMPT) treatment planning. The choice and range of parameters varies among different manufacturers. The goal of this work is to demonstrate the influence of the spot parameters on dose quality and delivery in IMPT treatment plans, to show their interdependence, and to make practitioners aware of the spot parameter values for a certain facility. Our study could help as a guideline to make the trade-off between treatment quality and time in existing PBS centers and in future systems. We created plans for seven patients and a phantom, with different tumor sites and volumes, and compared the effect of small-, medium-, and large-spot widths (σ = 2.5, 5, and 10 mm) and interspot distances (1σ, 1.5σ, and 1.75σ) on dose, spot charge, and treatment time. Moreover, we quantified how postplanning charge threshold cuts affect plan quality and the total number of spots to deliver, for different spot widths and interspot distances. We show the effect of a minimum charge (or MU) cutoff value for a given proton delivery system. Spot size had a strong influence on dose: larger spots resulted in more protons delivered outside the target region. We observed dose differences of 2-13 Gy (RBE) between 2.5 mm and 10 mm spots, where the amount of extra dose was due to dose penumbra around the target region. Interspot distance had little influence on dose quality for our patient group. Both parameters strongly influence spot charge in the plans and thus the possible impact of postplanning charge threshold cuts. If such charge thresholds are not included in the treatment planning system (TPS), it is important that the practitioner validates that a given combination of lower charge threshold, interspot spacing, and spot size does not result in a plan degradation. Low average spot charge occurs for small spots, small interspot distances, many beam directions, and low fractional dose values. The choice of spot parameters values is a trade-off between accelerator and beam line design, plan quality, and treatment efficiency. We recommend the use of small spot sizes for better organ-at-risk sparing and lateral interspot distances of 1.5σ to avoid long treatment times. We note that plan quality is influenced by the charge cutoff. Our results show that the charge cutoff can be sufficiently large (i.e., 10 6 protons) to accommodate limitations on beam delivery systems. It is, therefore, not necessary per se to include the charge cutoff in the treatment planning optimization such that Pareto navigation (e.g., as practiced at our institution) is not excluded and optimal plans can be obtained without, perhaps, a bias from the charge cutoff. We recommend that the impact of a minimum charge cut impact is carefully verified for the spot sizes and spot distances applied or that it is accommodated in the TPS. © 2017 American Association of Physicists in Medicine.

Analyzing a bioterror attack on the food supply: the case of botulinum toxin in milk.

PubMed

Wein, Lawrence M; Liu, Yifan

2005-07-12

We developed a mathematical model of a cows-to-consumers supply chain associated with a single milk-processing facility that is the victim of a deliberate release of botulinum toxin. Because centralized storage and processing lead to substantial dilution of the toxin, a minimum amount of toxin is required for the release to do damage. Irreducible uncertainties regarding the dose-response curve prevent us from quantifying the minimum effective release. However, if terrorists can obtain enough toxin, and this may well be possible, then rapid distribution and consumption result in several hundred thousand poisoned individuals if detection from early symptomatics is not timely. Timely and specific in-process testing has the potential to eliminate the threat of this scenario at a cost of <1 cent per gallon and should be pursued aggressively. Investigation of improving the toxin inactivation rate of heat pasteurization without sacrificing taste or nutrition is warranted.

Anti-diarrhoeal and anti-microbial activity of Flos populi (male inflorescence of Populus tomentosa Carrière) aqueous extracts.

PubMed

Xu, Qianqian; Shen, Zhiqiang; Wang, Yubo; Guo, Shijin; Li, Feng; Wang, Yanping; Zhou, Chunfeng

2013-07-09

Flos populi (male inflorescence of Populus tomentosa Carrière) has been traditionally used in East Asian countries for the treatment of various inflammatory diseases, strengthening the spleen and stomach, anti-rheumatic, anti-tumor and anti-diarrhoeal. To evaluate the in vivo or in vitro anti-diarrhoeal and anti-microbial activity of Flos populi aqueous extract. Acute toxicity of Flos populi aqueous extract (FPAE) was investigated. Castor oil-induced diarrhoea method was used to evaluate the anti-diarrhoeal activity, inhibition of defecation and diarrhoea were determined in mice, effects on castor oil-induced enteropooling, intestinal transit and intestinal fluid secretion in rats or mice. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of FPAE against strains of three clinical bacterial isolates and one reference strain were used to test the anti-microbial activity. The FPAE reduced the frequency of diarrhoea episodes and decreased the propulsion of charcoal meal through the gastrointestinal tract in a dose dependent manner. FPAE (100-500 mg/kg, p.o.) produced dose-dependent and significant (P<0.01) protection of mice against castor oil-induced diarrhoea. FPAE, dose-dependently and significantly (P< 0.01) delayed the onset of castor-oil induced diarrhoea, decreased the frequency of defecation, and reduced the severity of diarrhoea. Compared with control animals, FPAE, dose-dependently and significantly (P< 0.01) decreased the volume of castor oil-induced intestinal fluid secretion, and reduced the number, weight and wetness of faecal droppings. There was no deaths or abnormalities in behaviour seen in the acute toxicity test. The aqueous extract displayed anti-microbial effects to three species of bacteria in anti-microbial test. The findings of this study indicate that FPAE possesses anti-diarrhoeal property in rats and mice and confirm the ethnomedicinal use of Flos Populi as a valuable natural remedy for the treatment, management and/or control of diarrhoea. These results may support the fact that this plant is traditionally used to cure diarrhoea. Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

In HFREF patients, sacubitril/valsartan, given at relatively low doses, does not lead to increased mortality or hospitalization : A retrospective cohort study.

PubMed

De Vecchis, R; Ariano, C; Di Biase, G; Noutsias, M

2018-03-08

In heart failure with reduced left ventricular ejection fraction (HFREF) patients, the dosage of sacubitril/valsartan is modulated according to a gradual increase regimen. Nevertheless, if patients exhibit tolerability problems, a provisional reduction of the dose of sacubitril/valsartan or even its interruption are recommended. This study provides estimates of respective proportions of patients receiving minimum or intermediate doses of sacubitril/valsartan. In addition, a comparison was made to detect possible differences regarding all-cause mortality and heart failure hospitalization in patients treated with the recommended optimum dose compared to those receiving submaximum maintenance doses of sacubitril/valsartan. Patients treated with sacubitril/valsartan in addition to beta-blocker and mineralocorticoid receptor blocker were 68. Among them, 20 patients (29.4%), were identified as having clinical features that were contraindications to the administration of sacubitril/valsartan at full dose. The subsequent decision was to maintain an intermediate dose in 11 patients and to reduce the dose to the minimum level allowed, i.e., 24 mg/26 mg twice daily in nine patients. After a median follow-up of 5.25 months, no differences were found concerning the risk of all-cause death by comparing patients treated with reduced versus those subjected to target doses of sacubitril/valsartan (odds ratio [OR] = 1.666; 95% confidence interval [CI] = 0.256-10.823; p = 0.6266). Patients taking reduced doses had a similar risk of heart failure hospitalizations when compared to patients treated with the target dose (OR = 0.789; 95% CI: 0.077-8.0808; p = 1.00). During a median follow-up of 5.25 months, in the group of patients who had proven to be intolerant to the maximum dose of sacubitril/valsartan, use of reduced doses of the drug did not result in increased all-cause mortality or heart failure hospitalization compared to patients treated with sacubitril/valsartan at the target dose.

Single line source with and without vaginal loading and the impact on target coverage and organ at risk doses for cervix cancer Stages IB, II, and IIIB: treatment planning simulation in patients treated with MRI-guided adaptive brachytherapy in a multicentre study (EMBRACE).

PubMed

Nkiwane, Karen S; Pötter, Richard; Tanderup, Kari; Federico, Mario; Lindegaard, Jacob C; Kirisits, Christian

2013-01-01

Three-dimensional evaluation and comparison of target and organs at risk (OARs) doses from two traditional standard source loading patterns in the frame of MRI-guided cervical cancer brachytherapy for various clinical scenarios based on patient data collected in a multicenter trial setting. Two nonoptimized three-dimensional MRI-based treatment plans, Plan 1 (tandem and vaginal loading) and Plan 2 (tandem loading only), were generated for 134 patients from seven centers participating in the EMBRACE study. Both plans were normalized to point A (Pt. A). Target and OAR doses were evaluated in terms of minimum dose to 90% of the high-risk clinical target volume (HRCTV D90) grouped by tumor stage and minimum dose to the most exposed 2cm³ of the OARs volume. An HRCTV D90 ≥ Pt. A was achieved in 82% and 44% of the patients with Plans 1 and 2, respectively. Median HRCTV D90 with Plans 1 and 2 was 120% and 90% of Pt. A dose, respectively. Both plans had optimal dose coverage in 88% of Stage IB tumors; however, the tandem-only plan resulted in about 50% of dose reduction to the vagina and rectum. For Stages IIB and IIIB, Plan 1 had on average 35% better target coverage but with significant doses to OARs. Standard tandem loading alone results in good target coverage in most Stage IB tumors without violating OAR dose constraints. For Stage IIB tumors, standard vaginal loading improves the therapeutic window, however needs optimization to fulfill the dose prescription for target and OAR. In Stage IIIB, even optimized vaginal loading often does not fulfill the needs for dose prescription. The significant dose variation across various clinical scenarios for both target and OARs indicates the need for image-guided brachytherapy for optimal dose adaptation both for limited and advanced diseases. Copyright © 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Dose Calculation Evolution for Internal Organ Irradiation in Humans

NASA Astrophysics Data System (ADS)

Jimenez V., Reina A.

2007-10-01

The International Commission of Radiation Units (ICRU) has established through the years, a discrimination system regarding the security levels on the prescription and administration of doses in radiation treatments (Radiotherapy, Brach therapy, Nuclear Medicine). The first level is concerned with the prescription and posterior assurance of dose administration to a point of interest (POI), commonly located at the geometrical center of the region to be treated. In this, the effects of radiation around that POI, is not a priority. The second level refers to the dose specifications in a particular plane inside the patient, mostly the middle plane of the lesion. The dose is calculated to all the structures in that plane regardless if they are tumor or healthy tissue. In this case, the dose is not represented by a point value, but by level curves called "isodoses" as in a topographic map, so you can assure the level of doses to this particular plane, but it also leave with no information about how this values go thru adjacent planes. This is why the third level is referred to the volumetrical description of doses so these isodoses construct now a volume (named "cloud") that give us better assurance about tissue irradiation around the volume of the lesion and its margin (sub clinical spread or microscopic illness). This work shows how this evolution has resulted, not only in healthy tissue protection improvement but in a rise of tumor control, quality of life, better treatment tolerance and minimum permanent secuelae.

Dose estimates for the local inhabitants from 210Po ingestion via dietary sources at a proposed uranium mining site in India.

PubMed

Giri, Soma; Jha, V N; Singh, Gurdeep; Tripathi, R M

2012-07-01

To study the distribution of (210)Po activity in food in Bagjata in East Singhbhum, India. (210)Po were analyzed in the food samples of plant origin such as cereals, pulses, fruits, vegetables and food of animal origin such fish, chicken, egg, etc., in and around Bagjata uranium mining area as a part of baseline study after acid digestion. The intake and ingestion dose of the radionuclide was estimated. The general range of (210)Po activity in all the dietary components ranged widely from <0.2-36 Bqkg(-1)(fresh). In the food of plant origin, the minimum activity of (210)Po was estimated in vegetables while maximum in pulses. In food of animal origin, the observed minimum activity of (210)Po was in eggs and the maximum observed was in chicken samples. The intake of (210)Po considering all dietary components was found to be 464 Bq.Y(-1) while the ingestion dose was calculated to be 557 μSv.Y(-1), respectively. The estimated doses are reflecting the natural background dose via the route of ingestion, which is much below the 1 mSv limit set in the International Commission on Radiological Protection (ICRP) recommendations. The study confirms that current levels of (210)Po do not pose a significant radiological risk to the local inhabitants.

Geometric parameter analysis to predetermine optimal radiosurgery technique for the treatment of arteriovenous malformation

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

Mestrovic, Ante; Clark, Brenda G.; Department of Medical Physics, British Columbia Cancer Agency, Vancouver, British Columbia

2005-11-01

Purpose: To develop a method of predicting the values of dose distribution parameters of different radiosurgery techniques for treatment of arteriovenous malformation (AVM) based on internal geometric parameters. Methods and Materials: For each of 18 previously treated AVM patients, four treatment plans were created: circular collimator arcs, dynamic conformal arcs, fixed conformal fields, and intensity-modulated radiosurgery. An algorithm was developed to characterize the target and critical structure shape complexity and the position of the critical structures with respect to the target. Multiple regression was employed to establish the correlation between the internal geometric parameters and the dose distribution for differentmore » treatment techniques. The results from the model were applied to predict the dosimetric outcomes of different radiosurgery techniques and select the optimal radiosurgery technique for a number of AVM patients. Results: Several internal geometric parameters showing statistically significant correlation (p < 0.05) with the treatment planning results for each technique were identified. The target volume and the average minimum distance between the target and the critical structures were the most effective predictors for normal tissue dose distribution. The structure overlap volume with the target and the mean distance between the target and the critical structure were the most effective predictors for critical structure dose distribution. The predicted values of dose distribution parameters of different radiosurgery techniques were in close agreement with the original data. Conclusions: A statistical model has been described that successfully predicts the values of dose distribution parameters of different radiosurgery techniques and may be used to predetermine the optimal technique on a patient-to-patient basis.« less

An Update on Treatment of Pediatric Chronic Non-Infectious Uveitis.

PubMed

Sood, Arjun B; Angeles-Han, Sheila T

2017-03-01

There are no standardized treatment protocols for pediatric non-infectious uveitis. Topical corticosteroids are the typical first-line agent, although systemic corticosteroids are used in intermediate, posterior and panuveitic uveitis. Corticosteroids are not considered to be long-term therapy due to potential ocular and systemic side effects. In children with severe and/or refractory uveitis, timely management with higher dose disease-modifying antirheumatic drugs (DMARDs) and biologic agents is important. Increased doses earlier in the disease course may lead to improved disease control and better visual outcomes. In general, methotrexate is the usual first-line steroid-sparing agent and given as a subcutaneous weekly injection at >0.5 mg/kg/dose or 10-15 mg/m2 due to better bioavailability. Other DMARDs, for instance mycophenolate, azathioprine, and cyclosporine are less common treatments for pediatric uveitis. Anti-tumor necrosis factor-alpha agents, primarily infliximab and adalimumab are used as second line agents in children refractory to methotrexate, or as first-line treatment in those with severe complicated disease at presentation. Infliximab may be given at a minimum of 7.5 mg/kg/dose every 4 weeks after loading doses, up to 20 mg/kg/dose. Adalimumab may be given up to 20 or 40 mg weekly. In children who fail anti-tumor necrosis factor-alpha agents, develop anti-tumor necrosis factor-alpha antibodies, experience adverse effects, or have difficulty with tolerance, there is less data available regarding subsequent treatment. Promising results have been noted with tocilizumab infusions every 2-4 weeks, abatacept monthly infusions and rituximab.

An Update on Treatment of Pediatric Chronic Non-Infectious Uveitis

PubMed Central

Sood, Arjun B.; Angeles-Han, Sheila T.

2017-01-01

Opinion Statement There are no standardized treatment protocols for pediatric non-infectious uveitis. Topical corticosteroids are the typical first-line agent, although systemic corticosteroids are used in intermediate, posterior and panuveitic uveitis. Corticosteroids are not considered to be long-term therapy due to potential ocular and systemic side effects. In children with severe and/or refractory uveitis, timely management with higher dose disease-modifying antirheumatic drugs (DMARDs) and biologic agents is important. Increased doses earlier in the disease course may lead to improved disease control and better visual outcomes. In general, methotrexate is the usual first-line steroid-sparing agent and given as a subcutaneous weekly injection at >0.5 mg/kg/dose or 10–15 mg/m2 due to better bioavailability. Other DMARDs, for instance mycophenolate, azathioprine, and cyclosporine are less common treatments for pediatric uveitis. Anti-tumor necrosis factor-alpha agents, primarily infliximab and adalimumab are used as second line agents in children refractory to methotrexate, or as first-line treatment in those with severe complicated disease at presentation. Infliximab may be given at a minimum of 7.5 mg/kg/dose every 4 weeks after loading doses, up to 20 mg/kg/dose. Adalimumab may be given up to 20 or 40 mg weekly. In children who fail anti-tumor necrosis factor-alpha agents, develop anti-tumor necrosis factor-alpha antibodies, experience adverse effects, or have difficulty with tolerance, there is less data available regarding subsequent treatment. Promising results have been noted with tocilizumab infusions every 2–4 weeks, abatacept monthly infusions and rituximab. PMID:28944162

Effect of weekly high-dose vitamin D3 supplementation on serum cholecalciferol concentrations in pregnant women.

PubMed

Dimitris, Michelle C; Perumal, Nandita; Craig-Barnes, Hayley A; Leadley, Michael; Mahmud, Abdullah A; Baqui, Abdullah H; Roth, Daniel E

2016-04-01

Vitamin D status is conventionally defined by the serum concentration of 25-hydroxyvitamin D. However, it has been proposed that the serum cholecalciferol concentration (D3) also determines functional vitamin D sufficiency. The objective of this study was to describe the effect of weekly high-dose vitamin D3 supplementation on inter-dose serum D3 in pregnant women. We conducted a sub-study of a completed randomized double-blind placebo-controlled trial of vitamin D3 (35,000 IU/week) supplementation in late pregnancy (AViDD trial) in Dhaka, Bangladesh. This study included pregnant women enrolled at 26-29 weeks gestation who fully adhered to the prenatal supplement intervention for ≥8 consecutive weeks and for whom serum samples were available for D3 analysis (n=65). Serum D3 was uniformly low at enrolment. Mean D3 increased and was maximal at 1 day after vitamin D dose administration (152.09nmol/L, SD 25.11nmol/L) and remained significantly higher in VitD vs. Pl at 7 days (29.59nmol/L vs. 1.92nmol/L, p=0.007). Daily average of the group mean D3 during the week following dosing was 66.97nmol/L in VitD versus 2.13nmol/L in Pl. In conclusion, serum D3 remained significantly elevated throughout the week following ≥8 consecutive weekly doses of 35,000 IU D3 in pregnant women. However, the clinically significant minimum threshold of serum D3 remains to be established. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of the treatment efficacy between tigecycline plus high-dose cefoperazone-sulbactam and tigecycline monotherapy against ventilator-associated pneumonia caused by extensively drug-resistant Acinetobacter baumannii.

PubMed

Qin, Youfa; Zhang, Jie; Wu, Lei; Zhang, Dailong; Fu, Lunjiao; Xue, Xiaoyan

2018-03-01

The present study examined the effect of high-dose cefoperazone-sulbactam combined with tigecycline against ventilator-associated pneumonia (VAP) caused by extensively drug-resistant Acinetobacter baumannii(XDR-AB). 42 patients with VAP due to XDR-AB infection were randomized into two groups: the TIG group (received tigecycline injection) and the TIG+CFS group (received tigecycline and cefoperazone-sulbactam (1 : 1) injection). Pulsed field gel electrophoresis (PFGE) was used for genotyping the isolated XDR-AB. The microdilution method was used to test the minimum inhibitory concentration (MIC) of cefoperazone-sulbactam or tigecycline in vitro and the combined effect was determined with the checkerboard method. The total combined effectiveness rate (including all patients who demonstrated an improved condition) was significantly higher in the TIG+CFS group (85.7%) compared with the TIG group (47.6%) (p = 0.010). No significant differences were noted with regard to the adverse reactions between the two groups. The 42 isolated XDR-AB strains were classified into four types. The MIC of the two drugs in combination was significantly lower than that of each drug used alone (p < 0.05). High dose of cefoperazone-sulbactam can improve the antimicrobial activity of tigecycline against XDR-AB.
.

Combined carboplatin plus ifosfamide and cisplatin in patients with advanced ovarian carcinoma. A phase I-II study. GOCS (Gynecological Oncology Cooperative Study).

PubMed

Lorusso, V; Leone, B; Di Vagno, G; Manzione, L; Palmeri, S; Vallejo, C; Machiavelli, M; Nacci, G; Bilancia, D; Leonardi, V; Catino, A; Gargano, G; Loverro, G; Selvaggi, L; De Lena, M

1998-02-01

Because of the relative lack of overlapping toxicity, carboplatin (PPL) and cisplatin (CDDP) can be easily combined for treatment of ovarian cancer to increase total platinum dose intensity. Ifosfamide (IFO), one of the most effective single agents in ovarian cancer, has a low hematological toxicity when administered in continuous infusion. From January 1991 to December 1993, 34 patients with advanced ovarian cancer, previously untreated with chemo- or radiotherapy, were enrolled in a phase I-II study with the aim of determining the maximum tolerated dose (MTD) of CDDP (on day 8 of a 28-day cycle) in combination with PPL (300 mg/m2 on day 1) and IFO (4,000 mg/m2/24 h by continuous infusion on day 1). The initial dose level of CDDP was 40 mg/m2, which was continuously increased by 10 mg/m2 up to the MTD defined as one dose level below that inducing dose-limiting toxicity (DLT) in at least two-thirds of treated patients; no dose escalation was allowed in the same patient. Grade 3-4 leukopenia and thrombocytopenia were observed in 54 and 49% of patients, respectively. The DLT was reached at 70 mg/m2 and therefore the dose recommended for the phase II study was 60 mg/m2. Complete (CR) plus partial response was observed in 88% of patients with a 21% pathological CR. With a minimum follow-up of 32 months (median 40 months), median progression-free survival and overall survival were 21 and 39 months, respectively. In conclusion, the combination of CDDP, PPL, and IFO provides an effective regimen for ovarian cancer with an acceptable toxicity profile.

Influence of Zoledronic Acid on Atrial Electrophysiological Parameters and Electrocardiographic Measurements.

PubMed

Tisdale, James E; Allen, Matthew R; Overholser, Brian R; Jaynes, Heather A; Kovacs, Richard J

2015-06-01

Our objective was to determine effects of zoledronic acid (ZA) on atrial electrophysiological parameters and electrocardiographic measurements. Ex vivo perfusion study: Isolated guinea pig hearts were perfused with modified Krebs-Henseleit (K-H) buffer with or without ZA 0.07 mg/kg/L (each n = 6). In ZA-perfused hearts, atrial action potential at 90% repolarization (APD90 ) decreased more from baseline than in controls (-23.2% ± -5.1% vs. -2.1% ± -8.1%, P < 0 .0001), as did APD30 (-28.8% ± -3.8% vs. -2.1% ± -2.1%, P < 0.0001). In vivo dose-response study: Guinea pigs underwent intraperitoneal injections every 2 weeks in 1 of 4 groups (each n = 8): ZA 0.007 mg/kg (low-dose), ZA 0.07 mg/kg (medium-dose), ZA 0.7 mg/kg (high-dose), or placebo. Hearts were excised at 8 weeks and perfused with modified K-H. Atrial effective refractory period (ERP) was lower with medium- and high-dose ZA versus placebo (P = 0.004). Atrial APD30 was lower with high-dose ZA versus placebo, low and medium doses (P < 0.001). Canine ECG study: Mature female beagles received intravenous ZA 0.067 mg/kg or saline (placebo; each n = 6) every 2 weeks for 12 weeks. P wave dispersion was greater in the ZA group (7.7 ± 3.7 vs. 3.4 ± 2.6 ms, P = 0.04). There were no significant differences in P wave index, maximum or minimum P wave duration, or PR interval. ZA shortens left atrial APD and ERP and increases P wave dispersion. © 2015 Wiley Periodicals, Inc.

ESR/ERS white paper on lung cancer screening

PubMed Central

Bonomo, Lorenzo; Gaga, Mina; Nackaerts, Kristiaan; Peled, Nir; Prokop, Mathias; Remy-Jardin, Martine; von Stackelberg, Oyunbileg; Sculier, Jean-Paul

2015-01-01

Lung cancer is the most frequently fatal cancer, with poor survival once the disease is advanced. Annual low dose computed tomography has shown a survival benefit in screening individuals at high risk for lung cancer. Based on the available evidence, the European Society of Radiology and the European Respiratory Society recommend lung cancer screening in comprehensive, quality-assured, longitudinal programmes within a clinical trial or in routine clinical practice at certified multidisciplinary medical centres. Minimum requirements include: standardised operating procedures for low dose image acquisition, computer-assisted nodule evaluation, and positive screening results and their management; inclusion/exclusion criteria; expectation management; and smoking cessation programmes. Further refinements are recommended to increase quality, outcome and cost-effectiveness of lung cancer screening: inclusion of risk models, reduction of effective radiation dose, computer-assisted volumetric measurements and assessment of comorbidities (chronic obstructive pulmonary disease and vascular calcification). All these requirements should be adjusted to the regional infrastructure and healthcare system, in order to exactly define eligibility using a risk model, nodule management and quality assurance plan. The establishment of a central registry, including biobank and image bank, and preferably on a European level, is strongly encouraged. PMID:25929956

Detomidine reduces isoflurane anesthetic requirement (MAC) in horses.

PubMed

Steffey, Eugene P; Pascoe, Peter J

2002-10-01

To quantitate the dose- and time-related magnitude of the anesthetic sparing effect of, and selected physiological responses to detomidine during isoflurane anesthesia in horses. Randomized cross-over study. Three, healthy, young adult horses weighing 485 ± 14 kg. Horses were anesthetized on two occasions to determine the minimum alveolar concentration (MAC) of isoflurane in O 2 and then to measure the anesthetic sparing effect (time-related MAC reduction) following IV detomidine (0.03 and 0.06 mg kg -1 ). Selected common measures of cardiopulmonary function, blood glucose and urinary output were also recorded. Isoflurane MAC was 1.44 ± 0.07% (mean ± SEM). This was reduced by 42.8 ± 5.4% and 44.8 ± 3.0% at 83 ± 23 and 125 ± 36 minutes, respectively, following 0.03 and 0.06 mg kg -1 , detomidine. The MAC reduction was detomidine dose- and time-dependent. There was a tendency for mild cardiovascular and respiratory depression, especially following the higher detomidine dose. Detomidine increased both blood glucose and urine flow; the magnitude of these changes was time- and dose-dependent CONCLUSIONS: Detomidine reduces anesthetic requirement for isoflurane and increases blood glucose concentration and urine flow in horses. These changes were dose- and time-related. The results imply potent anesthetic sparing actions by detomidine. The detomidine-related increased urine flow should be considered in designing anesthetic protocols for individual horses. Copyright © 2002 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

Postantibiotic effect and postantibiotic sub-minimum inhibitory concentration effect of valnemulin against Staphylococcus aureus isolates from swine and chickens.

PubMed

Zhao, D H; Yu, Y; Zhou, Y F; Shi, W; Deng, H; Liu, Y H

2014-02-01

The postantibiotic effect (PAE) and postantibiotic sub-minimum inhibitory concentration (MIC) effect (PA-SME) of valnemulin against Staphylococcus aureus were investigated in vitro using a spectrophotometric technique and classic viable count method. A standard curve was constructed by regression analysis of the number of colonies and the corresponding optical density (OD) at 630 nm of the inoculum. After exposure to valnemulin at different concentrations for an hour, the antibiotic was removed by centrifuging and washing. The PA-SMEs were measured after initial exposure to valnemulin at 4 × the MIC, and then, valnemulin was added to reach corresponding desired concentrations in the resuspended culture. Samples were collected hourly until the culture became turbid. The results were calculated by converting the OD values into the counts of bacteria in accordance with the curve. The MIC of valnemulin against eight strains was identically 0.125 μg ml(-1) . The mean PAEs were 2.12 h (1 × MIC) and 5.06 h (4 × MIC), and the mean PA-SMEs were 6.85 h (0.1 × MIC), 9.12 h (0.2 × MIC) and 10.8 h (0.3 × MIC). The results showed that the strains with identical MICs exhibited different PAEs and PA-SMEs. Valnemulin produced prolonged PAE and PA-SME periods for Staph. aureus, supporting a longer dosing interval while formulating a daily administration dosage. In this study, valnemulin demonstrated prolonged postantibiotic effects and postantibiotic sub-MIC effects on strains of Staphylococcus aureus. The strains with identical MICs of valnemulin exhibited different PAEs and PA-SMEs. Staphylococcus aureus isolated from different species has little impact on the postantibiotic effect of valnemulin. The result suggests a longer dosing interval while formulating a daily administration dosage, and it may play a valuable role of valnemulin in treating Staph. aureus infections in animals. © 2013 The Society for Applied Microbiology.

SU-E-T-580: Comparison of Cervical Carcinoma IMRT Plans From Four Commercial Treatment Planning Systems (TPS)

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

Cao, Y; Li, R; Chi, Z

2014-06-01

Purpose: Different treatment planning systems (TPS) use different treatment optimization and leaf sequencing algorithms. This work compares cervical carcinoma IMRT plans optimized with four commercial TPSs to investigate the plan quality in terms of target conformity and delivery efficiency. Methods: Five cervical carcinoma cases were planned with the Corvus, Monaco, Pinnacle and Xio TPSs by experienced planners using appropriate optimization parameters and dose constraints to meet the clinical acceptance criteria. Plans were normalized for at least 95% of PTV to receive the prescription dose (Dp). Dose-volume histograms and isodose distributions were compared. Other quantities such as Dmin(the minimum dose receivedmore » by 99% of GTV/PTV), Dmax(the maximum dose received by 1% of GTV/PTV), D100, D95, D90, V110%, V105%, V100% (the volume of GTV/PTV receiving 110%, 105%, 100% of Dp), conformity index(CI), homogeneity index (HI), the volume of receiving 40Gy and 50 Gy to rectum (V40,V50) ; the volume of receiving 30Gy and 50 Gy to bladder (V30,V50) were evaluated. Total segments and MUs were also compared. Results: While all plans meet target dose specifications and normal tissue constraints, the maximum GTVCI of Pinnacle plans was up to 0.74 and the minimum of Corvus plans was only 0.21, these four TPSs PTVCI had significant difference. The GTVHI and PTVHI of Pinnacle plans are all very low and show a very good dose distribution. Corvus plans received the higer dose of normal tissue. The Monaco plans require significantly less segments and MUs to deliver than the other plans. Conclusion: To deliver on a Varian linear-accelerator, the Pinnacle plans show a very good dose distribution. Corvus plans received the higer dose of normal tissue. The Monaco plans have faster beam delivery.« less

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

NASA Astrophysics Data System (ADS)

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

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

Galactic cosmic ray transport methods and radiation quality issues

NASA Technical Reports Server (NTRS)

Townsend, L. W.; Wilson, J. W.; Cucinotta, F. A.; Shinn, J. L.

1992-01-01

An overview of galactic cosmic ray (GCR) interaction and transport methods, as implemented in the Langley Research Center GCR transport code, is presented. Representative results for solar minimum, exo-magnetospheric GCR dose equivalents in water are presented on a component by component basis for various thicknesses of aluminum shielding. The impact of proposed changes to the currently used quality factors on exposure estimates and shielding requirements are quantified. Using the cellular track model of Katz, estimates of relative biological effectiveness (RBE) for the mixed GCR radiation fields are also made.

Dose mapping using MCNP code and experiment for SVST-Co-60/B irradiator in Vietnam.

PubMed

Tran, Van Hung; Tran, Khac An

2010-06-01

By using MCNP code and ethanol-chlorobenzene (ECB) dosimeters the simulations and measurements of absorbed dose distribution in a tote-box of the Cobalt-60 irradiator, SVST-Co60/B at VINAGAMMA have been done. Based on the results Dose Uniformity Ratios (DUR), positions and values of minimum and maximum dose extremes in a tote-box, and efficiency of the irradiator for the different dummy densities have been gained. There is a good agreement between simulation and experimental results in comparison and they have valuable meanings for operation of the irradiator. Copyright 2010 Elsevier Ltd. All rights reserved.

Focal treatment of spasticity using botulinum toxin A in cerebral palsy cases of GMFCS level V: evaluation of adverse effects☆☆☆

PubMed Central

Tedesco, Ana Paula; Martins, Juliana Saccol; Nicolini-Panisson, Renata D’Agostini

2014-01-01

Objective To report on the experience of injections of botulinum toxin A (BTA) in a series of patients with cerebral palsy of Gross Motor Function Classification System (GMFCS) level V. Methods This was a retrospective case series study on 33 patients with cerebral palsy of GMFCS level V who received 89 sessions of BTA application (of which 84 were Botox® and five were other presentations), in which the basic aim was to look for adverse effects. Results The mean number of application sessions per patient was three, and the mean age at the time of each injection was 4 + 6 years (range: 1.6–13 years). The muscles that most frequently received injections were the gastrocnemius, hamstrings, hip adductors, biceps brachii and finger flexors. The mean total dose was 193 U and the mean dose per weight was 12.5 U/kg. Only one patient received anesthesia for the injections and no sedation was used in any case. No local or systemic adverse effects were observed within the minimum follow-up of one month. Conclusion The absence of adverse effects in our series was probably related to the use of low doses and absence of sedation or anesthesia. According to our data, BTA can be safely used for patients with cerebral palsy of GMFCS level V, using low doses and preferably without sedation or anesthesia. PMID:26229827

Nonparametric estimation of benchmark doses in environmental risk assessment

PubMed Central

Piegorsch, Walter W.; Xiong, Hui; Bhattacharya, Rabi N.; Lin, Lizhen

2013-01-01

Summary An important statistical objective in environmental risk analysis is estimation of minimum exposure levels, called benchmark doses (BMDs), that induce a pre-specified benchmark response in a dose-response experiment. In such settings, representations of the risk are traditionally based on a parametric dose-response model. It is a well-known concern, however, that if the chosen parametric form is misspecified, inaccurate and possibly unsafe low-dose inferences can result. We apply a nonparametric approach for calculating benchmark doses, based on an isotonic regression method for dose-response estimation with quantal-response data (Bhattacharya and Kong, 2007). We determine the large-sample properties of the estimator, develop bootstrap-based confidence limits on the BMDs, and explore the confidence limits’ small-sample properties via a short simulation study. An example from cancer risk assessment illustrates the calculations. PMID:23914133

SU-F-T-53: Treatment Planning with Inhomogeneity Correction for Intraoperative Radiotherapy Using KV X-Ray Beams

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

Chen, Y; Ghaly, M; Souri, S

Purpose: The current standard in dose calculation for intraoperative radiotherapy (IORT) using the ZEISS Intrabeam 50 kV x-ray system is based on depth dose measurements in water and no heterogeneous tissue effect has been taken into account. We propose an algorithm for pre-treatment planning including inhomogeneity correction based on data of depth dose measurements in various tissue phantoms for kV x-rays. Methods: Direct depth dose measurements were made in air, water, inner bone and cortical bone phantoms for the Intrabeam 50 kV x-rays with a needle applicator. The data were modelled by a function of power law combining exponential withmore » different parameters. Those phantom slabs used in the measurements were scanned to obtain CT numbers. The x-ray beam initiated from the source isocenter is ray-traced through tissues. The corresponding doses will be deposited/assigned at different depths. On the boundary of tissue/organ changes, the x-ray beam will be re-traced in new tissue/organ starting at an equivalent depth with the same dose. In principle, a volumetric dose distribution can be generated if enough directional beams are traced. In practice, a several typical rays traced may be adequate in providing estimates of maximum dose to the organ at risk and minimum dose in the target volume. Results: Depth dose measurements and modeling are shown in Figure 1. The dose versus CT number is shown in Figure 2. A computer program has been written for Kypho-IORT planning using those data. A direct measurement through 2 mm solid water, 2 mm inner bone, and 1 mm solid water yields a dose rate of 7.7 Gy/min. Our calculation shows 8.1±0.4 Gy/min, consistent with the measurement within 5%. Conclusion: The proposed method can be used to more accurately calculate the dose by taking into account the heterogeneous effect. The further validation includes comparison with Monte Carlo simulation.« less

Evaluation of On-Board kV Cone Beam Computed Tomography–Based Dose Calculation With Deformable Image Registration Using Hounsfield Unit Modifications

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

Onozato, Yusuke; Kadoya, Noriyuki, E-mail: kadoya.n@rad.med.tohoku.ac.jp; Fujita, Yukio

2014-06-01

Purpose: The purpose of this study was to estimate the accuracy of the dose calculation of On-Board Imager (Varian, Palo Alto, CA) cone beam computed tomography (CBCT) with deformable image registration (DIR), using the multilevel-threshold (MLT) algorithm and histogram matching (HM) algorithm in pelvic radiation therapy. Methods and Materials: One pelvis phantom and 10 patients with prostate cancer treated with intensity modulated radiation therapy were studied. To minimize the effect of organ deformation and different Hounsfield unit values between planning CT (PCT) and CBCT, we modified CBCT (mCBCT) with DIR by using the MLT (mCBCT{sub MLT}) and HM (mCBCT{sub HM})more » algorithms. To evaluate the accuracy of the dose calculation, we compared dose differences in dosimetric parameters (mean dose [D{sub mean}], minimum dose [D{sub min}], and maximum dose [D{sub max}]) for planning target volume, rectum, and bladder between PCT (reference) and CBCTs or mCBCTs. Furthermore, we investigated the effect of organ deformation compared with DIR and rigid registration (RR). We determined whether dose differences between PCT and mCBCTs were significantly lower than in CBCT by using Student t test. Results: For patients, the average dose differences in all dosimetric parameters of CBCT with DIR were smaller than those of CBCT with RR (eg, rectum; 0.54% for DIR vs 1.24% for RR). For the mCBCTs with DIR, the average dose differences in all dosimetric parameters were less than 1.0%. Conclusions: We evaluated the accuracy of the dose calculation in CBCT, mCBCT{sub MLT}, and mCBCT{sub HM} with DIR for 10 patients. The results showed that dose differences in D{sub mean}, D{sub min}, and D{sub max} in mCBCTs were within 1%, which were significantly better than those in CBCT, especially for the rectum (P<.05). Our results indicate that the mCBCT{sub MLT} and mCBCT{sub HM} can be useful for improving the dose calculation for adaptive radiation therapy.« less

[Measurements of vancomycin concentrations in the blood - a method of personalization the antibiotic therapy in patients with chronic kidney disease].

PubMed

Pondel, Joanna; Krajewski, Piotr; Królikowska, Natalia; Tobiasz, Aleksandra; Augustyniak-Bartosik, Hanna; Hurkacz, Magdalena

2017-04-21

Therapeutic Drug Monitoring is a recognized method of personalizing treatment, having particular application in patients with chronic kidney disease who have frequent infections, requiring administration of vancomycin. International guidelines indicate the need to adjust the dose of the drug to the state of renal function. The recommended therapeutic ranges of minimum and maximum levels should be achieved in order to increase the effectiveness and safety of treatment. The aim of this study was to evaluate the usefulness of measuring the concentration of vancomycin in patients with chronic kidney disease due to bacterial infection. The study included 96 adult patients with chronic kidney disease of varying severity treated with vancomycin Patients were divided into 3 groups: treated by haemodialysis (hd), after renal transplantations (ktx), do not require renal replacement therapy (nef). In subjects were examined the minimum and maximum concentrations of vancomycin in steady-state and were compared with recommended therapeutic ranges. Statistically significant decrease of inflammatory markers was observed only in patients treated with dialysis. In the other groups not significant changes in values of inflammatory parameters were confirmed. Trough concentrations of vancomycin marked in patients were consistent with the recommendation of EUCAST, but exceeded the value recommended by the manufacturers of the drug. Considering absolute values of the minimum concentrations, only about 50% of patients achieved the therapeutic range (58% for recommendation EUCAST and 36% for the manufacturer's instructions). Peak concentration values indicated in dialyzed patients were below the prescribed range of 20-50 mg/l and averaged 17.7 mg / l. In the other subgroups they were correct. The rating of the absolute values of the peak concentrations of vancomycin also showed that only 46% (64% in the ktx, 30% - hd and 53% - nef) was within the recommended range, while 50% were classified as concentrations of sub-therapeutic (36% in the ktx, 42% of the nef group and 65% in hd). Vancomycin concentrations measured in patients with chronic kidney disease, both minimum and maximum, were not fully comply with the recommended therapeutic ranges, despite the use of doses determined based on a calculation of glomerular filtration rate. This points to the need for particularly careful monitoring of therapy and analysis of antibiotic concentrations to improve the effectiveness and reduce the incidence of undesirable consequences of treatment.

Retrospective dosimetry using OSL of tooth enamel and dental repair materials irradiated under wet and dry conditions.

PubMed

Geber-Bergstrand, Therése; Bernhardsson, Christian; Mattsson, Sören; Rääf, Christopher L

2012-11-01

Following a radiological or nuclear emergency event, there is a need for quick and reliable dose estimations of potentially exposed people. In situations where dosimeters are not readily available, the dose estimations must be carried out using alternative methods. In the present study, the optically stimulated luminescence (OSL) properties of tooth enamel and different dental repair materials have been examined. Specimens of the materials were exposed to gamma and beta radiation in different types of liquid environments to mimic the actual irradiation situation in the mouth. Measurements were taken using a Risø TL/OSL reader, and irradiations were made using a (90)Sr/(90)Y source and a linear accelerator (6 MV photons). Results show that the OSL signal from tooth enamel decreases substantially when the enamel is kept in a wet environment. Thus, tooth enamel is not reliable for retrospective dose assessment without further studies of the phenomenon. Dental repair materials, on the other hand, do not exhibit the same effect when exposed to liquids. In addition, dose-response and fading measurements of the dental repair materials show promising results, making these materials highly interesting for retrospective dosimetry. The minimum detectable dose for the dental repair materials has been estimated to be 20-185 mGy.

Simulation of Earth-Moon-Mars Environments for the Assessment of Organ Doses

NASA Astrophysics Data System (ADS)

Kim, M. Y.; Schwadron, N. A.; Townsend, L.; Cucinotta, F. A.

2010-12-01

Space radiation environments for historically large solar particle events (SPE) and galactic cosmic rays (GCR) at solar minimum and solar maximum are simulated in order to characterize exposures to radio-sensitive organs for missions to low-Earth orbit (LEO), moon, and Mars. Primary and secondary particles for SPE and GCR are transported through the respective atmosphere of Earth or Mars, space vehicle, and astronaut’s body tissues using the HZETRN/QMSFRG computer code. In LEO, exposures are reduced compared to deep space because particles are deflected by the Earth’s magnetic field and absorbed by the solid body of the Earth. Geomagnetic transmission function as a function of altitude was applied for the particle flux of charged particles, and the shift of the organ exposures to higher velocity or lower stopping powers compared to those in deep space was analyzed. In the transport through Mars atmosphere, a vertical distribution of atmospheric thickness was calculated from the temperature and pressure data of Mars Global Surveyor, and the directional cosine distribution was implemented to describe the spherically distributed atmospheric distance along the slant path at each altitude. The resultant directional shielding by Mars atmosphere at solar minimum and solar maximum was used for the particle flux simulation at various altitudes on the Martian surface. Finally, atmospheric shielding was coupled with vehicle and body shielding for organ dose estimates. We made predictions of radiation dose equivalents and evaluated acute symptoms at LEO, moon, and Mars at solar minimum and solar maximum.

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

PubMed

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

2013-03-01

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

SU-F-T-185: Study of the Robustness of a Proton Arc Technique Based On PBS Beams

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

Wang, Z; Zheng, Y

Purpose: One potential technique to realize proton arc is through using PBS beams from many directions to form overlaid Bragg peak (OBP) spots and placing these OBP spots throughout the target volume to achieve desired dose distribution. In this study, we analyzed the robustness of this proton arc technique. Methods: We used a cylindrical water phantom of 20 cm in radius in our robustness analysis. To study the range uncertainty effect, we changed the density of the phantom by ±3%. To study the setup uncertainty effect, we shifted the phantom by 3 & 5 mm. We also combined the rangemore » and setup uncertainties (3mm/±3%). For each test plan, we performed dose calculation for the nominal and 6 disturbed scenarios. Two test plans were used, one with single OBP spot and the other consisting of 121 OBP spots covering a 10×10cm{sup 2} area. We compared the dose profiles between the nominal and disturbed scenarios to estimate the impact of the uncertainties. Dose calculation was performed with Gate/GEANT based Monte Carlo software in cloud computing environment. Results: For each of the 7 scenarios, we simulated 100k & 10M events for plans consisting of single OBP spot and 121 OBP spots respectively. For single OBP spot, the setup uncertainty had minimum impact on the spot’s dose profile while range uncertainty had significant impact on the dose profile. For plan consisting of 121 OBP spots, similar effect was observed but the extent of disturbance was much less compared to single OBP spot. Conclusion: For PBS arc technique, range uncertainty has significantly more impact than setup uncertainty. Although single OBP spot can be severely disturbed by the range uncertainty, the overall effect is much less when a large number of OBP spots are used. Robustness optimization for PBS arc technique should consider range uncertainty with priority.« less

Impact of treatment planning with deformable image registration on dose distribution for carbon-ion beam lung treatment using a fixed irradiation port and rotating couch.

PubMed

Kumagai, M; Mori, S; Yamamoto, N

2015-06-01

When using a fixed irradiation port, treatment couch rotation is necessary to increase beam angle selection. We evaluated dose variations associated with positional morphological changes to organs. We retrospectively chose the data sets of ten patients with lung cancer who underwent respiratory-gated CT at three different couch rotation angles (0°, 20° and -20°). The respective CT data sets are referred to as CT0, CT20 and CT-20. Three treatment plans were generated as follows: in Plan 1, all compensating bolus designs and dose distributions were calculated using CT0. To evaluate the rotation effect without considering morphology changes, in Plan 2, the compensating boli designed using CT0 were applied to the CT±20 images. Plan 3 involved compensating boli designed using the CT±20 images. The accumulated dose distributions were calculated using deformable image registration (DIR). A sufficient prescribed dose was calculated for the planning target volume (PTV) in Plan 1 [minimum dose received by a volume ≥95% (D95) > 95.8%]. By contrast, Plan 2 showed degraded dose conformation to the PTV (D95 > 90%) owing to mismatch of the bolus design to the morphological positional changes in the respective CT. The dose assessment results of Plan 3 were very close to those of Plan 1. Dose distribution is significantly affected by whether or not positional organ morphology changes are factored into dose planning. In treatment planning using multiple CT scans with different couch positions, it is mandatory to calculate the accumulated dose using DIR.

Evidence-based treatment of frequent heartburn: the benefits and limitations of over-the-counter medications.

PubMed

McRorie, Johnson W; Gibb, Roger D; Miner, Philip B

2014-06-01

This review summarizes the pharmacological effects of over-the-counter (OTC) heartburn drugs, and the implications for treating frequent heartburn. PubMed and SCOPUS were searched across all years to identify well-controlled, randomized clinical studies that assessed mechanism of action and efficacy. Antacids can transiently neutralize acid in the esophagus, but do not significantly affect gastric pH or prevent subsequent heartburn episodes. Histamine-2 receptor antagonists (H2 RAs) rapidly develop tolerance with repeat dosing, and exhibit an analgesic effect that may provide heartburn relief while leaving the esophagus exposed to acid. Proton pump inhibitors (PPIs) provide a sustained inhibition of gastric acid production, and are superior to antacids and H2 RAs for control of gastric acid and treatment of frequent heartburn. When recommending therapies for frequent heartburn, it is of particular importance to understand the strengths and weaknesses of available OTC medications. Antacids and H2 RAs are not recommended for treatment of frequent heartburn, while OTC PPIs are both indicated for, and effective for, treatment of frequent heartburn. A PPI dose of 20 mg is optimal for empiric treatment of frequent heartburn, and consistent with the 2013 treatment guidelines established by the American College of Gastroenterology (ACG) for treatment with a minimum effective dose. ©2014 The Author(s) ©2014 American Association of Nurse Practitioners.

Effect of thermal annealing on the thermoluminescent properties of nano-calcium fluoride and its dose-response characteristics.

PubMed

Mundupuzhakal, J K; Biswas, R H; Chauhan, S; Varma, V; Acharya, Y B; Chakrabarty, B S

2015-12-01

Nano-CaF2, prepared by the co-precipitation method, was annealed under different annealing conditions to improve its thermoluminescence (TL) characteristics. Different annealing parameters, such as temperature (400-700°C), duration (1-4 h) and environment (vacuum and air), were explored. The effect on TL sensitivity, peak position (Tm) and full-width at half-maximum (FWHM) with respect to the different annealing conditions are discussed as they are the measure of crystallinity of the material. Annealing temperature of 500°C with annealing duration of two and a half hours in vacuum provided the highest luminescence response (i.e. maximum sensitivity, minimum peak temperature and FWHM). Wide detectable dose range (5 mGy to 2 kGy), absence of thermal quenching and sufficient activation energy (1.04 eV) of this phosphor make it suitable for dosimetric applications. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Population pharmacokinetics of levofloxacin in Korean patients.

PubMed

Kiem, Sungmin; Ryu, Sung-Mun; Lee, Yun-Mi; Schentag, Jerome J; Kim, Yang-Wook; Kim, Hyeon-Kuk; Jang, Hang-Jae; Joo, Yong-Don; Jin, Kyubok; Shin, Jae-Gook; Ghim, Jong-Lyul

2016-08-01

Levofloxacin (LVFX) has different effects depending on the area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) ratio. While AUC can be expressed as dose/clearance (CL), we measured serial concentrations of LVFX in Koreans and tried to set a Korean-specific equation, estimating the CL of the antibiotic. In total, 38 patients, aged 18-87 years, received once daily intravenous LVFX doses of 500 mg or 250 mg, depending on their renal function. Four plasma samples were obtained according to a D optimal sampling design. The population pharmacokinetic (PK) parameters of LVFX were estimated using non-linear mixed-effect modeling (NONMEM, ver. 7.2). The CL of LVFX was dependent on creatinine clearance (CLCR) as a covariate. The mean population PK parameters of LVFX in Koreans were as follows: CL (l/hour) = 6.19 ×  (CLCR/75)(1.32). The CL of LVFX in Koreans is expected to be lower than that in Western people.

Alternative stitching method for massively parallel e-beam lithography

NASA Astrophysics Data System (ADS)

Brandt, Pieter; Tranquillin, Céline; Wieland, Marco; Bayle, Sébastien; Milléquant, Matthieu; Renault, Guillaume

2015-03-01

In this study a novel stitching method other than Soft Edge (SE) and Smart Boundary (SB) is introduced and benchmarked against SE. The method is based on locally enhanced Exposure Latitude without cost of throughput, making use of the fact that the two beams that pass through the stitching region can deposit up to 2x the nominal dose. The method requires a complex Proximity Effect Correction that takes a preset stitching dose profile into account. On a Metal clip at minimum half-pitch of 32 nm for MAPPER FLX 1200 tool specifications, the novel stitching method effectively mitigates Beam to Beam (B2B) position errors such that they do not induce increase in CD Uniformity (CDU). In other words, the same CDU can be realized inside the stitching region as outside the stitching region. For the SE method, the CDU inside is 0.3 nm higher than outside the stitching region. 5 nm direct overlay impact from B2B position errors cannot be reduced by a stitching strategy.

The anthelmintic effect of aqueous methanol extract of Combretum molle (R. Br. x. G. Don) (Combretaceae) in lambs experimentally infected with Haemonchus contortus.

PubMed

Simon, M K; Ajanusi, O J; Abubakar, M S; Idris, A L; Suleiman, M M

2012-06-08

The aqueous methanol extract from the stem-bark of Combretum molle was evaluated for anthelmintic activity in lambs infected with Haemonchus contortus using faecal egg count (FEC) reduction assay. The extract showed a dose-dependent reduction in FEC in infected animals. At doses of 500, 1000 and 2000 mg kg(-1), the extract caused FEC reduction of 63%, 69.25% and 96.23%, respectively. Similarly, the standard anthelmintic (albendazole) at a dose of 200 mg kg(-1) produced FEC reduction of 99.24%. FEC reduction produced by the extract at doses of 500 and 1000 mg kg(-1) is below the minimum standard of 90% FEC recommended by the World Association for the Advancement of Veterinary Parasitology (WAAVP). However, there was no significant (P>0.05) difference between the means of groups treated with 1000 mg kg(-1) and 2000 mg kg(-1) compared to that of albendazole. In this study, C. molle has shown a promising anthelmintic activity against experimental haemonchosis. Nonetheless, further studies to evaluate its detailed toxicity are required for the plant extract to be developed into a useful anthelmintic drug. There is also the need to evaluate other parts of the plant (root, leaves, fruits, etc.) for the same effect. Copyright © 2012 Elsevier B.V. All rights reserved.

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.

The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study

PubMed Central

Azman, Andrew S.; Luquero, Francisco J.; Ciglenecki, Iza; Grais, Rebecca F.; Sack, David A.; Lessler, Justin

2015-01-01

Background In 2013, a stockpile of oral cholera vaccine (OCV) was created for use in outbreak response, but vaccine availability remains severely limited. Innovative strategies are needed to maximize the health impact and minimize the logistical barriers to using available vaccine. Here we ask under what conditions the use of one dose rather than the internationally licensed two-dose protocol may do both. Methods and Findings Using mathematical models we determined the minimum relative single-dose efficacy (MRSE) at which single-dose reactive campaigns are expected to be as or more effective than two-dose campaigns with the same amount of vaccine. Average one- and two-dose OCV effectiveness was estimated from published literature and compared to the MRSE. Results were applied to recent outbreaks in Haiti, Zimbabwe, and Guinea using stochastic simulations to illustrate the potential impact of one- and two-dose campaigns. At the start of an epidemic, a single dose must be 35%–56% as efficacious as two doses to avert the same number of cases with a fixed amount of vaccine (i.e., MRSE between 35% and 56%). This threshold decreases as vaccination is delayed. Short-term OCV effectiveness is estimated to be 77% (95% CI 57%–88%) for two doses and 44% (95% CI −27% to 76%) for one dose. This results in a one-dose relative efficacy estimate of 57% (interquartile range 13%–88%), which is above conservative MRSE estimates. Using our best estimates of one- and two-dose efficacy, we projected that a single-dose reactive campaign could have prevented 70,584 (95% prediction interval [PI] 55,943–86,205) cases in Zimbabwe, 78,317 (95% PI 57,435–100,150) in Port-au-Prince, Haiti, and 2,826 (95% PI 2,490–3,170) cases in Conakry, Guinea: 1.1 to 1.2 times as many as a two-dose campaign. While extensive sensitivity analyses were performed, our projections of cases averted in past epidemics are based on severely limited single-dose efficacy data and may not fully capture uncertainty due to imperfect surveillance data and uncertainty about the transmission dynamics of cholera in each setting. Conclusions Reactive vaccination campaigns using a single dose of OCV may avert more cases and deaths than a standard two-dose campaign when vaccine supplies are limited, while at the same time reducing logistical complexity. These findings should motivate consideration of the trade-offs between one- and two-dose campaigns in resource-constrained settings, though further field efficacy data are needed and should be a priority in any one-dose campaign. PMID:26305226

Effect of resiniferatoxin on the noxious heat threshold temperature in the rat: a novel heat allodynia model sensitive to analgesics

PubMed Central

Almási, Róbert; Pethö, Gábor; Bölcskei, Kata; Szolcsányi, János

2003-01-01

An increasing-temperature hot plate (ITHP) was introduced to measure the noxious heat threshold (45.3±0.3°C) of unrestrained rats, which was reproducible upon repeated determinations at intervals of 5 or 30 min or 1 day. Morphine, diclofenac and paracetamol caused an elevation of the noxious heat threshold following i.p. pretreatment, the minimum effective doses being 3, 10 and 200 mg kg−1, respectively. Unilateral intraplantar injection of the VR1 receptor agonist resiniferatoxin (RTX, 0.048 nmol) induced a profound drop of heat threshold to the innocuous range with a maximal effect (8–10°C drop) 5 min after RTX administration. This heat allodynia was inhibited by pretreatment with morphine, diclofenac and paracetamol, the minimum effective doses being 1, 1 and 100 mg kg−1 i.p., respectively. The long-term sensory desensitizing effect of RTX was examined by bilateral intraplantar injection (0.048 nmol per paw) which produced, after an initial threshold drop, an elevation (up to 2.9±0.5°C) of heat threshold lasting for 5 days. The VR1 receptor antagonist iodo-resiniferatoxin (I-RTX, 0.05 nmol intraplantarly) inhibited by 51% the heat threshold-lowering effect of intraplantar RTX but not α,β-methylene-ATP (0.3 μmol per paw). I-RTX (0.1 or 1 nmol per paw) failed to alter the heat threshold either acutely (5–60 min) or on the long-term (5 days). The heat threshold of VR1 receptor knockout mice was not different from that of wild-type animals (45.6±0.5 vs 45.2±0.4°C). In conclusion, the RTX-induced drop of heat threshold measured by the ITHP is a novel heat allodynia model exhibiting a high sensitivity to analgesics. PMID:12746222

Shuttle radiation dose measurements in the International Space Station orbits

NASA Technical Reports Server (NTRS)

Badhwar, Gautam D.

2002-01-01

The International Space Station (ISS) is now a reality with the start of a permanent human presence on board. Radiation presents a serious risk to the health and safety of the astronauts, and there is a clear requirement for estimating their exposures prior to and after flights. Predictions of the dose rate at times other than solar minimum or solar maximum have not been possible, because there has been no method to calculate the trapped-particle spectrum at intermediate times. Over the last few years, a tissue-equivalent proportional counter (TEPC) has been flown at a fixed mid-deck location on board the Space Shuttle in 51.65 degrees inclination flights. These flights have provided data that cover the expected changes in the dose rates due to changes in altitude and changes in solar activity from the solar minimum to the solar maximum of the current 23rd solar cycle. Based on these data, a simple function of the solar deceleration potential has been derived that can be used to predict the galactic cosmic radiation (GCR) dose rates to within +/-10%. For altitudes to be covered by the ISS, the dose rate due to the trapped particles is found to be a power-law function, rho(-2/3), of the atmospheric density, rho. This relationship can be used to predict trapped dose rates inside these spacecraft to +/-10% throughout the solar cycle. Thus, given the shielding distribution for a location inside the Space Shuttle or inside an ISS module, this approach can be used to predict the combined GCR + trapped dose rate to better than +/-15% for quiet solar conditions.

DOSIMETRIC CONSEQUENCES OF USING CONTRAST-ENHANCED COMPUTED TOMOGRAPHIC IMAGES FOR INTENSITY-MODULATED STEREOTACTIC BODY RADIOTHERAPY PLANNING.

PubMed

Yoshikawa, Hiroto; Roback, Donald M; Larue, Susan M; Nolan, Michael W

2015-01-01

Potential benefits of planning radiation therapy on a contrast-enhanced computed tomography scan (ceCT) should be weighed against the possibility that this practice may be associated with an inadvertent risk of overdosing nearby normal tissues. This study investigated the influence of ceCT on intensity-modulated stereotactic body radiotherapy (IM-SBRT) planning. Dogs with head and neck, pelvic, or appendicular tumors were included in this retrospective cross-sectional study. All IM-SBRT plans were constructed on a pre- or ceCT. Contours for tumor and organs at risk (OAR) were manually constructed and copied onto both CT's; IM-SBRT plans were calculated on each CT in a manner that resulted in equal radiation fluence. The maximum and mean doses for OAR, and minimum, maximum, and mean doses for targets were compared. Data were collected from 40 dogs per anatomic site (head and neck, pelvis, and limbs). The average dose difference between minimum, maximum, and mean doses as calculated on pre- and ceCT plans for the gross tumor volume was less than 1% for all anatomic sites. Similarly, the differences between mean and maximum doses for OAR were less than 1%. The difference in dose distribution between plans made on CTs with and without contrast enhancement was tolerable at all treatment sites. Therefore, although caution would be recommended when planning IM-SBRT for tumors near "reservoirs" for contrast media (such as the heart and urinary bladder), findings supported the use of ceCT with this dose calculation algorithm for both target delineation and IM-SBRT treatment planning. © 2015 American College of Veterinary Radiology.

The total ozone and UV solar radiation over Stara Zagora, Bulgaria

NASA Astrophysics Data System (ADS)

Mendeva, B. D.; Gogosheva, Ts. N.; Petkov, B. H.; Krastev, D. G.

The results from direct ground-based solar UV irradiance measurements and the total ozone content (TOC) over Stara Zagora (42° 25'N, 25° 37'E), Bulgaria are presented. During the period 1999-2003 the TOC data show seasonal variations, typical for the middle latitudes - maximum in the spring and minimum in the autumn. The comparison between TOC ground-based data and Global Ozone Monitoring Experiment (GOME) satellite-borne ones shows a seasonal dependence of the differences between them. A strong negative relationship between the total ozone and the 305 nm wavelength irradiance was found. The dependence between the two variables is significant ( r = -0.62 ± 0.18) at 98% confidence level. The direct sun UV doses for some specific biological effects (erythema and eyes) are obtained. The estimation of the radiation amplification factor RAF shows that the ozone reduction by 1% increases the erythemal dose by 2.3%. The eye-damaging doses are more influenced by the TOC changes and in this case RAF = -2.7%. The amount of these biological doses depended on the solar altitude over the horizon. This dependence was not so strong when the total ozone content in the atmosphere was lower.

[Seven cases of parathyroidectomy for secondary hyperparathyroidism using methylene blue: suggestion for the method of methylene blue infusion].

PubMed

Kadoya, Tatsuo; Kinoshita, Yuki; Shiraishi, Munehiro; Uehara, Hirofumi; Yamamoto, Toshinori; Suetsugu, Keiko

2014-08-01

Intraoperative staining of the parathyroid glands with intravenously administered methylene blue is well described and has been demonstrated as an effective and safe method to facilitate parathyroidectomy. However, there have been several literatures of the development of postoperative neurological toxicity in patients who received methylene blue infusion during parathyroidectomy. We report the method of methylene blue infusion during parathyroidectomy at our institution. Seven adult patients who had undergone parathyroidectomy for secondary hyperparathyroidism associated with chronic renal failure were included in this study. Methylene blue was administered at a constant rate of 4 mg x kg(-1) x hr(-1) with a 1% solution just before the start of operation. The infusion was stopped after the first parathyroid gland was identified. The mean dose of methylene blue used was 2.2 +/- 0.8 mg x kg(-1). Consequently, the dose of methylene blue by this method could be decreased to less than half of the previously administered dose (6 mg x kg(-1)) at our institution. The dose of methylene blue used should be kept to the minimum required to identify the parathyroid glands in each case.

Comparison of Martian Meteorites and Martian Regolith as Shield Materials for Galactic Cosmic Rays

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee Y.; Thibeault, Sheila A.; Simonsen, Lisa C.; Wilson, John W.

1998-01-01

Theoretical calculations of radiation attenuation due to energetic galactic cosmic rays behind Martian rock and Martian regolith material have been made to compare their utilization as shields for advanced manned missions to Mars because the detailed chemical signature of Mars is distinctly different from Earth. The modified radiation fields behind the Martian rocks and the soil model were generated by solving the Boltzmann equation using a HZETRN system with the 1977 Solar Minimum environmental model. For the comparison of the attenuation characteristics, dose and dose equivalent are calculated for the five different subgroups of Martian rocks and the Martian regolith. The results indicate that changes in composition of subgroups of Martian rocks have negligible effects on the overall shielding properties because of the similarity of their constituents. The differences for dose and dose equivalent of these materials relative to those of Martian regolith are within 0.5 and 1 percent, respectively. Therefore, the analysis of Martian habitat construction options using in situ materials according to the Martian regolith model composition is reasonably accurate. Adding an epoxy to Martian regolith, which changes the major constituents of the material, enhances shielding properties because of the added hydrogenous constituents.

SU-E-J-113: The Influence of Optimizing Pediatric CT Simulator Protocols On the Treatment Dose Calculation in Radiotherapy

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

Zhang, Y; Zhang, J; Hu, Q

2014-06-01

Purpose: To investigate the possibility of applying optimized scanning protocols for pediatric CT simulation by quantifying the dosimetric inaccuracy introduced by using a fixed HU to density conversion. Methods: The images of a CIRS electron density reference phantom (Model 062) were acquired by a Siemens CT simulator (Sensation Open) using the following settings of tube voltage and beam current: 120 kV/190mA (the reference protocol used to calibrate CT for our treatment planning system (TPS)); Fixed 190mA combined with all available kV: 80, 100, and 140; fixed 120 kV and various current from 37 to 444 mA (scanner extremes) with intervalmore » of 30 mA. To avoid the HU uncertainty of point sampling in the various inserts of known electron densities, the mean CT numbers of the central cylindrical volume were calculated using DICOMan software. The doses per 100 MU to the reference point (SAD=100cm, Depth=10cm, Field=10X10cm, 6MV photon beam) in a virtual cubic phantom (30X30X30cm) were calculated using Eclipse TPS (calculation model: AcurosXB-11031) by assigning the CT numbers to HU of typical materials acquired by various protocols. Results: For the inserts of densities less than muscle, CT number fluctuations of all protocols were within the tolerance of 10 HU as accepted by AAPM-TG66. For more condensed materials, fixed kV yielded stable HU with any mA combination where largest disparities were found in 1750mg/cc insert: HU{sub reference}=1801(106.6cGy), HU{sub minimum}=1799 (106.6cGy, error{sub dose}=0.00%), HU{sub maximum}=1815 (106.8cGy, error{sub dose}=0.19%). Yet greater disagreements were observed with increasing density when kV was modified: HU{sub minimum}=1646 (104.5cGy, error{sub dose}=- 1.97%), HU{sub maximum}=2487 (116.4cGy, error{sub dose}=9.19%) in 1750mg/cc insert. Conclusion: Without affecting treatment dose calculation, personalized mA optimization of CT simulator can be conducted by fixing kV for a better cost-effectiveness of imaging dose and quality especially for children. Unless recalibrated, kV should be constant for all anatomical sites if diagnostic CT scanner is used as a simulator. This work was partially supported by Capital Medical Development Scientific Research Fund of China.« less

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

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

Cheung, J; Held, M; Morin, O

2015-06-15

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

The development and investigation of a prototype three-dimensional compensator for whole brain radiation therapy

NASA Astrophysics Data System (ADS)

Keall, Paul; Arief, Isti; Shamas, Sofia; Weiss, Elisabeth; Castle, Steven

2008-05-01

Whole brain radiation therapy (WBRT) is the standard treatment for patients with brain metastases, and is often used in conjunction with stereotactic radiotherapy for patients with a limited number of brain metastases, as well as prophylactic cranial irradiation. The use of open fields (conventionally used for WBRT) leads to higher doses to the brain periphery if dose is prescribed to the brain center at the largest lateral radius. These dose variations potentially compromise treatment efficacy and translate to increased side effects. The goal of this research was to design and construct a 3D 'brain wedge' to compensate dose heterogeneities in WBRT. Radiation transport theory was invoked to calculate the desired shape of a wedge to achieve a uniform dose distribution at the sagittal plane for an ellipsoid irradiated medium. The calculations yielded a smooth 3D wedge design to account for the missing tissue at the peripheral areas of the brain. A wedge was machined based on the calculation results. Three ellipsoid phantoms, spanning the mean and ± two standard deviations from the mean cranial dimensions were constructed, representing 95% of the adult population. Film was placed at the sagittal plane for each of the three phantoms and irradiated with 6 MV photons, with the wedge in place. Sagittal plane isodose plots for the three phantoms demonstrated the feasibility of this wedge to create a homogeneous distribution with similar results observed for the three phantom sizes, indicating that a single wedge may be sufficient to cover 95% of the adult population. The sagittal dose is a reasonable estimate of the off-axis dose for whole brain radiation therapy. Comparing the dose with and without the wedge the average minimum dose was higher (90% versus 86%), the maximum dose was lower (107% versus 113%) and the dose variation was lower (one standard deviation 2.7% versus 4.6%). In summary, a simple and effective 3D wedge for whole brain radiotherapy has been developed. The wedge gives a more uniform dose distribution than commonly used techniques. Further development and shape optimization may be necessary prior to clinical implementation.

Law of the Minimum paradoxes.

PubMed

Gorban, Alexander N; Pokidysheva, Lyudmila I; Smirnova, Elena V; Tyukina, Tatiana A

2011-09-01

The "Law of the Minimum" states that growth is controlled by the scarcest resource (limiting factor). This concept was originally applied to plant or crop growth (Justus von Liebig, 1840, Salisbury, Plant physiology, 4th edn., Wadsworth, Belmont, 1992) and quantitatively supported by many experiments. Some generalizations based on more complicated "dose-response" curves were proposed. Violations of this law in natural and experimental ecosystems were also reported. We study models of adaptation in ensembles of similar organisms under load of environmental factors and prove that violation of Liebig's law follows from adaptation effects. If the fitness of an organism in a fixed environment satisfies the Law of the Minimum then adaptation equalizes the pressure of essential factors and, therefore, acts against the Liebig's law. This is the the Law of the Minimum paradox: if for a randomly chosen pair "organism-environment" the Law of the Minimum typically holds, then in a well-adapted system, we have to expect violations of this law.For the opposite interaction of factors (a synergistic system of factors which amplify each other), adaptation leads from factor equivalence to limitations by a smaller number of factors.For analysis of adaptation, we develop a system of models based on Selye's idea of the universal adaptation resource (adaptation energy). These models predict that under the load of an environmental factor a population separates into two groups (phases): a less correlated, well adapted group and a highly correlated group with a larger variance of attributes, which experiences problems with adaptation. Some empirical data are presented and evidences of interdisciplinary applications to econometrics are discussed. © Society for Mathematical Biology 2010

Evaluation of the effect of ketoprofen and carprofen on platelet function in dogs studied by PFA-100 point-of-care analyser.

PubMed

Gaál, T; Halmay, Dóra; Kocsis, R; Abonyi-Tóth, Z

2007-09-01

The effect of two nonsteroidal anti-inflammatory drugs (carprofen and ketoprofen) on platelet adhesion and aggregation functions was evaluated by the PFA-100 analyser (Dade-Behring, CA, U.S.A.) using its collagen-adenosine diphosphate (ADP) and collagen-epinephrine (EPI) cartridges. The function of platelets was evaluated in 55 healthy dogs, in 7 dogs treated with ketoprofen and in 31 dogs treated with carprofen in a therapeutic dose for minimum 5 days. The therapeutic doses of carprofen had no effect on the closure time of PFA-100 (which is the marker of platelet function) but ketoprofen caused a significant increase when using collagen-EPI stimulation The closure times for both the healthy (control) and the treated dogs using EPI cartridges were often longer than the upper default cut-off point (300 sec) of the device. The PFA-100 analyser with collagen-ADP cartridges could be a useful tool for veterinary applications including the evaluation of platelet aggregation in dogs treated with NSAIDs. The upper cut-off point of PFA-100 might be extended.

Celecoxib, a specific COX-2 inhibitor, has no significant effect on methotrexate pharmacokinetics in patients with rheumatoid arthritis.

PubMed

Karim, A; Tolbert, D S; Hunt, T L; Hubbard, R C; Harper, K M; Geis, G S

1999-12-01

To determine the effects of celecoxib, a specific inhibitor of cyclooxygenase 2 (COX-2) on the renal clearance and plasma pharmacokinetic profile of stable methotrexate (MTX) doses in patients with rheumatoid arthritis (RA). Fourteen adult female patients with RA taking a stable weekly dose of MTX (5 to 15 mg/wk) for a minimum of 3 months were randomized to receive concomitantly either celecoxib (200 mg BID) or placebo for a period of 7 days in a single blind, 2 period crossover study of MTX pharmacokinetics and renal clearance. The plasma pharmacokinetic profile of MTX did not change significantly when celecoxib or a placebo was coadministered. The mean renal clearance of MTX alone, 7.98+/-2.18 l/h, was virtually unchanged by coadministration of celecoxib (7.94+/-1.61 l/h) or placebo (7.97+/-1.19 l/h). Celecoxib has no significant effect on the pharmacokinetics or renal clearance of MTX in patients with RA, although these results should be confirmed in prospective studies of elderly and renally impaired patients.

Optimization of the temporal pattern of radiation: An IMRT based study

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

Altman, Michael B.; Chmura, Steven J.; Deasy, Joseph O.

Purpose: To investigate how the temporal pattern of dose applied during a single-intensity modulated radiation therapy (IMRT) fraction can be arranged to maximize or minimize cell kill. Methods and Materials: Using the linear-quadratic repair-time model and a simplified IMRT delivery pattern model, the surviving fraction of cells for a single fraction was calculated for all permutations of the dose delivery pattern for an array of clinically based IMRT cases. Maximization of cell kill was achieved by concentrating the highest doses in the middle of a fraction, while minimization was achieved by spreading the highest doses between the beginning and end.more » The percent difference between maximum and minimum cell kill (%Diff{sub min/max}) and the difference between maximum and minimum total doses normalized to 2 Gy/fx ({delta}NTD{sub 2Gy}) was calculated for varying fraction durations (T), {alpha}/{beta} ratios, and doses/fx. Results: %Diff{sub min/max} and {delta}NTD{sub 2Gy} both increased with increasing T and with decreasing {alpha}/{beta}. The largest increases occurred with dose/fx. With {alpha}/{beta} = 3 Gy and 30 min/fx, %Diff{sub min/max} ranged from 2.7-5.3% for 2 Gy/fx to 48.6-74.1% for 10 Gy/fx, whereas {delta}NTD{sub 2Gy} ranged from 1.2 Gy-2.4 Gy for 30 fractions of 2 Gy/fx to 2.3-4.8 Gy for 2 fractions of 10.84 Gy/fx. Using {alpha}/{beta} = 1.5 Gy, an analysis of prostate hypofractionation schemes yielded differences in clinical outcome based on the pattern of applied dose ranging from 3.2%-6.1% of the treated population. Conclusions: Rearrangement of the temporal pattern of dose for a single IMRT fraction could be used to optimize cell kill and to directly, though modestly, affect treatment outcome.« less

Low-Dose Daily Intake of Vitamin K(2) (Menaquinone-7) Improves Osteocalcin γ-Carboxylation: A Double-Blind, Randomized Controlled Trials.

PubMed

Inaba, Naoko; Sato, Toshiro; Yamashita, Takatoshi

2015-01-01

Vitamin K is essential for bone health, but the effects of low-dose vitamin K intake in Japanese subjects remain unclear. We investigated the effective minimum daily menaquinone-7 dose for improving osteocalcin γ-carboxylation. Study 1 was a double-blind, randomized controlled dose-finding trial; 60 postmenopausal women aged 50-69 y were allocated to one of four dosage group and consumed 0, 50, 100, or 200 μg menaquinone-7 daily for 4 wk, respectively, with a controlled diet in accordance with recommended daily intakes for 2010 in Japan. Study 2 was a double-blind, randomized placebo-controlled trial based on the results of Study 1; 120 subjects aged 20-69 y were allocated to the placebo or MK-7 group and consumed 0 or 100 μg menaquinone-7 daily for 12 wk, respectively. In both studies, circulating carboxylated osteocalcin and undercarboxylated osteocalcin were measured. The carboxylated osteocalcin/undercarboxylated osteocalcin ratio decreased significantly from baseline in the 0 μg menaquinone-7 group, in which subjects consumed the recommended daily intake of vitamin K with vitamin K1 and menaquinone-4 (Study 1). Menaquinone-7 increased the carboxylated osteocalcin/undercarboxylated osteocalcin ratio dose dependently, and significant effects were observed in both the 100 and 200 μg groups compared with the 0 μg group. Undercarboxylated osteocalcin concentrations decreased significantly, and the carboxylated osteocalcin/undercarboxylated osteocalcin ratio increased significantly in the 100 μg menaquinone-7 group compared with the placebo group (Study 2). Daily menaquinone-7 intake ≥100 μg was suggested to improve osteocalcin γ-carboxylation.

Dose titration of BAF312 attenuates the initial heart rate reducing effect in healthy subjects

PubMed Central

Legangneux, Eric; Gardin, Anne; Johns, Donald

2013-01-01

Aim Previous studies have shown transient decreases in heart rate (HR) following administration of sphingosine 1‐phosphate (S1P) receptor modulators including BAF312. This study was conducted to determine whether dose titration of BAF312 reduces or eliminates these effects. Methods Fifty‐six healthy subjects were randomized 1:1:1:1 to receive BAF312 in one of two dose titration (DT) regimens (DT1 and DT2: 0.25–10 mg over 9–10 days), no titration (10 mg starting dose) or placebo. Pharmacodynamic and pharmacokinetic parameters were assessed. Results Neither DT1 nor DT2 resulted in clinically significant bradycardia or atrioventricular conduction effects. Both titration regimens showed a favourable difference on each of days 1–12 vs. the non‐titration regimen on day 1 for HR effects (P < 0.0001). On day 1, the geometric mean ratio of the fraction from the previous day in minimum daily HR between DT1 and non‐titration was 1.18 (95% confidence interval [CI] 1.13, 1.23) and 1.14 (95% CI 1.09, 1.18) for DT2 (both P < 0.05) with significant differences noted through to day 12. Non‐titration HRs showed considerable separation from placebo throughout the study. There was no statistically significant reduction in HR vs. placebo on day 1 in either titration regimen. On days 3–7 subjects in DT1 and DT2 experienced minor reductions in HR vs. placebo (approximately 5 beats min−1; P ≤ 0.0001). From days 9–12, HRs in both titration regimens were comparable with placebo. Conclusion Both titration regimens effectively attenuated the initial bradyarrhythmia observed on day 1 of treatment with BAF312 10 mg. PMID:22845008

Estimates of benefits and harms of prophylactic use of aspirin in the general population

PubMed Central

Cuzick, J.; Thorat, M. A.; Bosetti, C.; Brown, P. H.; Burn, J.; Cook, N. R.; Ford, L. G.; Jacobs, E. J.; Jankowski, J. A.; La Vecchia, C.; Law, M.; Meyskens, F.; Rothwell, P. M.; Senn, H. J.; Umar, A.

2015-01-01

Background Accumulating evidence supports an effect of aspirin in reducing overall cancer incidence and mortality in the general population. We reviewed current data and assessed the benefits and harms of prophylactic use of aspirin in the general population. Methods The effect of aspirin for site-specific cancer incidence and mortality, cardiovascular events was collated from the most recent systematic reviews. Studies identified through systematic Medline search provided data regarding harmful effects of aspirin and baseline rates of harms like gastrointestinal bleeding and peptic ulcer. Results The effects of aspirin on cancer are not apparent until at least 3 years after the start of use, and some benefits are sustained for several years after cessation in long-term users. No differences between low and standard doses of aspirin are observed, but there were no direct comparisons. Higher doses do not appear to confer additional benefit but increase toxicities. Excess bleeding is the most important harm associated with aspirin use, and its risk and fatality rate increases with age. For average-risk individuals aged 50–65 years taking aspirin for 10 years, there would be a relative reduction of between 7% (women) and 9% (men) in the number of cancer, myocardial infarction or stroke events over a 15-year period and an overall 4% relative reduction in all deaths over a 20-year period. Conclusions Prophylactic aspirin use for a minimum of 5 years at doses between 75 and 325 mg/day appears to have favourable benefit–harm profile; longer use is likely to have greater benefits. Further research is needed to determine the optimum dose and duration of use, to identify individuals at increased risk of bleeding, and to test effectiveness of Helicobacter pylori screening–eradication before starting aspirin prophylaxis. PMID:25096604

Pharmacokinetics of an oral extended-release formulation of doxycycline hyclate containing acrylic acid and polymethacrylate in dogs.

PubMed

Ruiz, Sara Melisa Arciniegas; Olvera, Lilia Gutiérrez; Chacón, Sara del Carmen Caballero; Estrada, Dinorah Vargas

2015-04-01

To determine the pharmacokinetics of doxycycline hyclate administered orally in the form of experimental formulations with different proportions of acrylic acid-polymethacrylate-based matrices. 30 healthy adult dogs. In a crossover study, dogs were randomly assigned (in groups of 10) to receive a single oral dose (20 mg/kg) of doxycycline hyclate without excipients (control) or extended-release formulations (ERFs) containing doxycycline, acrylic acid polymer, and polymethacrylate in the following proportions: 1:0.5:0.0075 (ERF1) or 1:1:0.015 (ERF2). Serum concentrations of doxycycline were determined for pharmacokinetic analysis before and at several intervals after each treatment. Following oral administration to the study dogs, each ERF resulted in therapeutic serum doxycycline concentrations for 48 hours, whereas the control treatment resulted in therapeutic serum doxycycline concentrations for only 24 hours. All pharmacokinetic parameters for ERF1 and ERF2 were significantly different; however, findings for ERF1 did not differ significantly from those for the control treatment. Results indicated that both ERFs containing doxycycline, acrylic acid polymer, and polymethacrylate had an adequate pharmacokinetic-pharmacodynamic relationship for a time-dependent drug and a longer release time than doxycycline alone following oral administration in dogs. Given the minimum effective serum doxycycline concentration of 0.26 μg/mL, a dose interval of 48 hours can be achieved for each tested ERF. This minimum inhibitory concentration has the potential to be effective against several susceptible bacteria involved in important infections in dogs. Treatment of dogs with either ERF may have several benefits over treatment with doxycycline alone.

Evaluation of hybrid inverse planning and optimization (HIPO) algorithm for optimization in real-time, high-dose-rate (HDR) brachytherapy for prostate.

PubMed

Pokharel, Shyam; Rana, Suresh; Blikenstaff, Joseph; Sadeghi, Amir; Prestidge, Bradley

2013-07-08

The purpose of this study is to investigate the effectiveness of the HIPO planning and optimization algorithm for real-time prostate HDR brachytherapy. This study consists of 20 patients who underwent ultrasound-based real-time HDR brachytherapy of the prostate using the treatment planning system called Oncentra Prostate (SWIFT version 3.0). The treatment plans for all patients were optimized using inverse dose-volume histogram-based optimization followed by graphical optimization (GRO) in real time. The GRO is manual manipulation of isodose lines slice by slice. The quality of the plan heavily depends on planner expertise and experience. The data for all patients were retrieved later, and treatment plans were created and optimized using HIPO algorithm with the same set of dose constraints, number of catheters, and set of contours as in the real-time optimization algorithm. The HIPO algorithm is a hybrid because it combines both stochastic and deterministic algorithms. The stochastic algorithm, called simulated annealing, searches the optimal catheter distributions for a given set of dose objectives. The deterministic algorithm, called dose-volume histogram-based optimization (DVHO), optimizes three-dimensional dose distribution quickly by moving straight downhill once it is in the advantageous region of the search space given by the stochastic algorithm. The PTV receiving 100% of the prescription dose (V100) was 97.56% and 95.38% with GRO and HIPO, respectively. The mean dose (D(mean)) and minimum dose to 10% volume (D10) for the urethra, rectum, and bladder were all statistically lower with HIPO compared to GRO using the student pair t-test at 5% significance level. HIPO can provide treatment plans with comparable target coverage to that of GRO with a reduction in dose to the critical structures.

Bone cancer occurrence among beagles given 239Pu as young adults.

PubMed

Lloyd, R D; Taylor, G N; Angus, W; Bruenger, F W; Miller, S C

1993-01-01

The occurrence of skeletal malignancies has been documented among 234 young adult beagles given single intravenous injections of monomeric 239Pu citrate. Occurrence has also been documented among 132 comparable control group animals surviving the minimum latent time period of 2.79 y for radiation-induced bone cancer, who were maintained for lifespan observation. Injected amounts ranged from about 0.02-106 kBq kg-1 body mass with factors of 2 or 3 between dose levels. There were 84 radiographically apparent bone tumors in 76 plutonium-injected dogs and one tumor in a control group dog. Most of these were osteosarcomas except for seven chondrosarcomas, one liposarcoma, and one plasma cell myeloma of bone. The relationship between percent of dogs at any dose level with bone malignancy and average skeletal dose at the presumed time of tumor initiation of 1 y before death appeared to be linear below about 1.3 Gy average skeletal dose. The observed data can be approximated by the expression A = 0.76 + 75 D, where A = percent of dogs with bone cancer at any dose level, D = average skeletal dose in Gy (for doses up to 1.3 Gy) at tumor initiation, and 0.76 represents the percent tumor response in the control animals not given plutonium. Similar analysis of our corresponding data for beagles given 226Ra, excluding the two highest dose levels (approximately 100% occurrence), yielded the expression A = 0.76 + 4.7 D, where D = the average skeletal dose in Gy (for doses up to 20 Gy) at 1 y before death. The ratio of coefficients indicates the effectiveness for bone cancer induction of 239Pu relative to 226Ra, or [(75 +/- 22.5)(4.7 +/- 0.47)-1] = 16 +/- 5 for a single, brief intake of either nuclide into blood.

Intake of dehydrated nopal (Opuntia ficus indica) improves bone mineral density and calciuria in adult Mexican women.

PubMed

Aguilera-Barreiro, María de Los Angeles; Rivera-Márquez, José Alberto; Trujillo-Arriaga, Héctor Miguel; Tamayo Y Orozco, Juan Alfredo; Barreira-Mercado, Eduardo; Rodríguez-García, Mario E

2013-01-01

The intake of dehydrated nopal (DN) at a high stage of maturity along with high calcium content could improve bone mineral density (BMD) and calciuria and thus prevent osteoporosis. To evaluate the effect of calcium intake from a vegetable source (DN) on BMD and calciuria covering a 2-year period in menopausal and non-menopausal women with low bone mass (LBM). The study was quasi-experimental, blinded, and randomized, and included 131 Mexican women aged 35-55. Urinary calcium/creatinine index (CCI) was determined; BMD was analyzed on lumbar spine and total hip regions. Four groups were studied: Control group (CG), women with normocalciuria and a minimum dose of DN; experimental group 1 (EG1), women with hypercalciuria and a minimum dose of DN; experimental group 2 (EG2), women with hypercalciuria, and a maximum dose of DN; and normal group (NG) for reference in BMD. After the first semester of treatment, calciuria levels in women from both experimental groups returned to normal, remaining constant for the rest of the treatment. The percentage difference in BMD increased in the total hip region in the CG (pre 4.5% and post 2.1%) and EG2 (pre 1.8% and post 2.5%) groups significantly in comparison to NG and EG1, which exhibited a significant decrease in their BMD. BMD increased only for the lumbar region in the EG2 group (premenopausal). The use of a vegetable calcium source such as nopal improves BMD in women with LBM in the total hip and lumbar spine regions principally in the premenopausal women, maintaining constant and normal calciuria levels.

Intake of dehydrated nopal (Opuntia ficus indica) improves bone mineral density and calciuria in adult Mexican women

PubMed Central

Aguilera-Barreiro, María de los Angeles; Rivera-Márquez, José Alberto; Trujillo-Arriaga, Héctor Miguel; Tamayo y Orozco, Juan Alfredo; Barreira-Mercado, Eduardo; Rodríguez-García, Mario E

2013-01-01

Background The intake of dehydrated nopal (DN) at a high stage of maturity along with high calcium content could improve bone mineral density (BMD) and calciuria and thus prevent osteoporosis. Objective To evaluate the effect of calcium intake from a vegetable source (DN) on BMD and calciuria covering a 2-year period in menopausal and non-menopausal women with low bone mass (LBM). Methods The study was quasi-experimental, blinded, and randomized, and included 131 Mexican women aged 35–55. Urinary calcium/creatinine index (CCI) was determined; BMD was analyzed on lumbar spine and total hip regions. Four groups were studied: Control group (CG), women with normocalciuria and a minimum dose of DN; experimental group 1 (EG1), women with hypercalciuria and a minimum dose of DN; experimental group 2 (EG2), women with hypercalciuria, and a maximum dose of DN; and normal group (NG) for reference in BMD. Results After the first semester of treatment, calciuria levels in women from both experimental groups returned to normal, remaining constant for the rest of the treatment. The percentage difference in BMD increased in the total hip region in the CG (pre 4.5% and post 2.1%) and EG2 (pre 1.8% and post 2.5%) groups significantly in comparison to NG and EG1, which exhibited a significant decrease in their BMD. BMD increased only for the lumbar region in the EG2 group (premenopausal). Conclusion The use of a vegetable calcium source such as nopal improves BMD in women with LBM in the total hip and lumbar spine regions principally in the premenopausal women, maintaining constant and normal calciuria levels. PMID:23704856

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

Markovic, M; Stathakis, S; Jurkovic, I

Purpose The aim for the study was to compare intrinsic characteristics of the nine detectors and evaluate their performance in non-equilibrium radiation dosimetry. Methods The intrinsic characteristics of the nine detectors that were evaluated are based on the composition and size of the active volume, operating voltage, initial recombination of the collected charge, temperature, the effective cross section of the detectors. The shortterm stability and collection efficiency has been investigated. The minimum radiation detection sensitivity and detectors leakage current has been measured. The sensitivity to changes in energy spectrum as well as change in incident beam angles were measured anmore » analyzed. Results The short-term stability of the measurements within every detector showed consistency in the measured values with the highest value of the standard deviation of the mean not exceeding 0.5%. Air ion chamber detectors showed minimum sensitivity to change in incident beam angles while diode detectors underestimated measurements up to 16%. Comparing the slope of the tangents for detector’s sensitivity curve, diode detectors illustrate more sensitivity to change in photon spectrum than ion chamber detectors. The change in radiation detection sensitivity with increase in dose delivered has been observed for semiconductor detectors with maximum deviation 0.01% for doses between 1 Gy and 10 Gy. Leakage current has been mainly influenced by bias voltage (ion chamber detectors) and room light intensity (diode detectors). With dose per pulse varying from 1.47E−4 to 5.1E−4 Gy/pulse the maximum change in collection efficiency was 1.4% for the air ion chambers up to 8% for liquid filled ion chamber. Conclusion Broad range of measurements performed showed all the detectors susceptible to some limitations and while they are suitable for use in broad scope of applications, careful selection has to be made for particular range of measurements.« less

Intensity-modulated radiation therapy for pancreatic and prostate cancer using pulsed low–dose rate delivery techniques

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

Li, Jie; Lang, Jinyi; Wang, Pei

2014-01-01

Reirradiation of patients who were previously treated with radiotherapy is vastly challenging. Pulsed low–dose rate (PLDR) external beam radiotherapy has the potential to reduce normal tissue toxicities while providing significant tumor control for recurrent cancers. This work investigates treatment planning techniques for intensity-modulated radiation therapy (IMRT)-based PLDR treatment of various sites, including cases with pancreatic and prostate cancer. A total of 20 patients with clinical recurrence were selected for this study, including 10 cases with pancreatic cancer and 10 with prostate cancer. Large variations in the target volume were included to test the ability of IMRT using the existing treatmentmore » planning system and optimization algorithm to deliver uniform doses in individual gantry angles/fields for PLDR treatments. Treatment plans were generated with 10 gantry angles using the step-and-shoot IMRT delivery technique, which can be delivered in 3-minute intervals to achieve an effective low dose rate of 6.7 cGy/min. Instead of dose constraints on critical structures, ring structures were mainly used in PLDR-IMRT optimization. In this study, the PLDR-IMRT plans were compared with the PLDR-3-dimensional conformal radiation therapy (3DCRT) plans and the PLDR-RapidArc plans. For the 10 cases with pancreatic cancer that were investigated, the mean planning target volume (PTV) dose for each gantry angle in the PLDR-IMRT plans ranged from 17.6 to 22.4 cGy. The maximum doses ranged between 22.9 and 34.8 cGy. The minimum doses ranged from 8.2 to 17.5 cGy. For the 10 cases with prostate cancer that were investigated, the mean PTV doses for individual gantry angles ranged from 18.8 to 22.6 cGy. The maximum doses per gantry angle were between 24.0 and 34.7 cGy. The minimum doses per gantry angle ranged from 4.4 to 17.4 cGy. A significant reduction in the organ at risk (OAR) dose was observed with the PLDR-IMRT plan when compared with that using the PLDR-3DCRT plan. The volume receiving an 18-Gy (V{sub 18}) dose for the left and right kidneys was reduced by 10.6% and 12.5%, respectively, for the pancreatic plans. The volume receiving a 45-Gy (V{sub 45}) dose for the small bowel decreased from 65.3% to 45.5%. For the cases with prostate cancer, the volume receiving a 40-Gy (V{sub 40}) dose for the bladder and the rectum was reduced significantly by 25.1% and 51.2%, respectively. When compared with the RapidArc technique, the volume receiving a 30-Gy (V{sub 30}) dose for the left and the right kidneys was lower in the IMRT plans. For most OARs, no significant differences were observed between the PLDR-IMRT and the PLDR-RapidArc plans. These results clearly demonstrated that the PLDR-IMRT plan was suitable for PLDR pancreatic and prostate cancer treatments in terms of the overall plan quality. A significant reduction in the OAR dose was achieved with the PLDR-IMRT plan when compared with that using the PLDR-3DCRT plan. For most OARs, no significant differences were observed between the PLDR-IMRT and the PLDR-RapidArc plans. When compared with the PLDR-3DCRT plan, the PLDR-IMRT plan could provide superior target coverage and normal tissue sparing for PLDR reirradiation of recurrent pancreatic and prostate cancers. The PLDR-IMRT plan is an effective treatment choice for recurrent cancers in most cancer centers.« less

SU-E-T-492: Influence of Clipping PTV in Build-Up Region On IMRT Plan Quality and Deliverability

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

Sharma, S; Manigandan, D; Sahai, P

2015-06-15

Purpose: To study the influence of clipping PTV from body contour on plan quality and deliverability in build-up region for superficial target. Methods: Five previously treated patients of post-operative carcinoma of parotid were re-planned for IMRT (6MV X-rays, sliding window technique, five fields and 60Gy/30 fractions) using eclipse treatment planning system (TPS) by keeping dose volume constraints and all other parameters constant, only PTV was clipped from body contour by 0mm, 1mm, 2mm and 3mm respectively. Planned fluence was transferred to previously scanned solid water phantom by placing I’matriXX array at 0.5cm depth (2mm slab+3mm inherent). Fluence was delivered bymore » Varian CL2300C/D linac at 99.5cm source to detector distance. Measured fluence was compared with TPS dose plane using 2D gamma evaluation using 3%/3mm DTA criteria. Total MU (monitor unit) required to deliver a plan was also noted. For plan quality, PTV, maximum-dose, minimum-dose, coverage index (CI=PTV volume covered by prescription dose/PTV) and heterogeneity index HI=D5/D95 were analyzed using dose volume histogram (DVH). Results: The Result of gamma function analysis for I’matriXX and TPS were 97.63±1.79%, 97.48±0.99, 98.08±0.89% and 98.01±0.78% at 0.5cm build-up depth for 0, 1, 2 and 3mm PTV clipping, respectively. I’matriXX measured dose was higher compared to TPS. Total MU required for delivering a plan were 552±61, 503±47, 436±24 and 407±22. Maximum-dose to PTV was 6635.80±62.01cGy, 6635.80±40.60cGy, 6608.43±51.07cGy and 6564.20±28.51cGy. Similarly, minimum-dose to PTV was 3306.23±458.56cGy, 3546.57±721.01cGy, 4591.43±298.81cGy and 4861.90±412.40cGy. CI was 0.9347±0.020, 0.9398±0.021, 0.9448±0.022 and 0.9481±0.021. Similarly, HI was 1.089±0.015, 1.084±0.014, 1.078±0.009 and 1.074±0.008 for 0, 1, 2 and 3mm PTV clipping, respectively. Conclusion: Gamma function analysis resulted in almost similar results. However, I’matriXX was overestimating the dose compared to TPS. MU required to deliver a plan decreases with increase in PTV clipping. CI, PTV minimum-dose and plan homogeneity increases with increase in PTV clipping from skin.« less

Detection of changes in DNA methylation induced by different doses of ground-base ion radiation in rice(oryza sativa L.)

NASA Astrophysics Data System (ADS)

Zhao, Qian; Sun, Yeqing; Wang, Wei; Wen, Bin

Spaceflight represents a very complex environmental condition with highly ionizing radiations (HZE). To further investigate the incentives of ion effects in space environment, we performed on-ground simulated HZE particle radiations to rice seeds with different cumulative doses (0Gy, 0.01Gy, 0.02Gy, 0.1Gy, 0.2Gy, 1Gy , 2Gy, 5Gy, 20Gy ). Using Methylation-Sensitive Amplification Polymorphism (MSAP) analysis technology, differential polymorphism sites of DNA methylation of seedlings were analysed and acquired. The results showed that changes of methylation and demethylation on CCGG sites had taken place after irradiated treatments in all doses. It was noted that there was a stimulating effect in low-dose radiation ≤1 Gy. The minimum proportion of DNA methylation polymorphism level was 3.15% in 0.1Gy, whereas the maximum proportion was 9.87% in 2Gy, interestingly the proportion reduced with radiation doses increased, suggesting the dosage effects of radiation. We further found that the CG site tended to have a higher proportion of cytosine methylation alterations than CNG site in six of the eight dose groups. The results also indicated that different dose treatment groups showed various frequencies of methylation variation patterns: The type of CG hypermethylation was higher than CG hypormethylation in four low-dose groups (<≤2 Gy) ,whereas the result presented the opposite trends in all high-dose groups(>≥1 Gy). In addition, the type of CNG hypormethylation was obviously higher than the CNG hypermethylation in seven dose groups. This result indicated that the methylation variation patterns caused by radiation had site preferences. To investigate the mechanisms of sequences underlying alterations in DNA methylation after ion irradiation, we isolated, cloned and sequenced a subset of bands which showed obvious mutational bias. BLAST analysis indicated that many sequences showed significant homology to known function genes, most of which were related to resistance to environmental stresses such as cytochrome P450-like protein , RelA/SpoT Homologue 2 , 12-oxo-phytodienoic acid reductase. The epigenetic changing of rice in low- or high-dose radiation in this research might provide new insights for further understanding of radiation mechanism of space environment.

A Complier Average Causal Effect Analysis of the Stimulant Reduction Intervention using Dosed Exercise Study.

PubMed

Carmody, Thomas; Greer, Tracy L; Walker, Robrina; Rethorst, Chad D; Trivedi, Madhukar H

2018-06-01

Exercise is a promising treatment for substance use disorders, yet an intention-to-treat analysis of a large, multi-site study found no reduction in stimulant use for exercise versus health education. Exercise adherence was sub-optimal; therefore, secondary post-hoc complier average causal effects (CACE) analysis was conducted to determine the potential effectiveness of adequately dosed exercise. The STimulant use Reduction Intervention using Dosed Exercise study was a randomized controlled trial comparing a 12 kcal/kg/week (KKW) exercise dose versus a health education control conducted at nine residential substance use treatment settings across the U.S. that are affiliated with the National Drug Abuse Treatment Clinical Trials Network. Participants were sedentary but medically approved for exercise, used stimulants within 30 days prior to study entry, and received a DSM-IV stimulant abuse or dependence diagnosis within the past year. A CACE analysis adjusted to include only participants with a minimum threshold of adherence (at least 8.3 KKW) and using a negative-binomial hurdle model focused on 218 participants who were 36.2% female, mean age 39.4 years ( SD =11.1), and averaged 13.0 ( SD =9.2) stimulant use days in the 30 days before residential treatment. The outcome was days of stimulant use as assessed by the self-reported TimeLine Follow Back and urine drug screen results. The CACE-adjusted analysis found a significantly lower probability of relapse to stimulant use in the exercise group versus the health education group (41.0% vs. 55.7%, p <.01) and significantly lower days of stimulant use among those who relapsed (5.0 days vs. 9.9 days, p <.01). The CACE adjustment revealed significant, positive effects for exercise. Further research is warranted to develop strategies for exercise adherence that can ensure achievement of an exercise dose sufficient to produce a significant treatment effect.

Organ shielding and doses in Low-Earth orbit calculated for spherical and anthropomorphic phantoms

NASA Astrophysics Data System (ADS)

Matthiä, Daniel; Berger, Thomas; Reitz, Günther

2013-08-01

Humans in space are exposed to elevated levels of radiation compared to ground. Different sources contribute to the total exposure with galactic cosmic rays being the most important component. The application of numerical and anthropomorphic phantoms in simulations allows the estimation of dose rates from galactic cosmic rays in individual organs and whole body quantities such as the effective dose. The male and female reference phantoms defined by the International Commission on Radiological Protection and the hermaphrodite numerical RANDO phantom are voxel implementations of anthropomorphic phantoms and contain all organs relevant for radiation risk assessment. These anthropomorphic phantoms together with a spherical water phantom were used in this work to translate the mean shielding of organs in the different anthropomorphic voxel phantoms into positions in the spherical phantom. This relation allows using a water sphere as surrogate for the anthropomorphic phantoms in both simulations and measurements. Moreover, using spherical phantoms in the calculation of radiation exposure offers great advantages over anthropomorphic phantoms in terms of computational time. In this work, the mean shielding of organs in the different voxel phantoms exposed to isotropic irradiation is presented as well as the corresponding depth in a water sphere. Dose rates for Low-Earth orbit from galactic cosmic rays during solar minimum conditions were calculated using the different phantoms and are compared to the results for a spherical water phantom in combination with the mean organ shielding. For the spherical water phantom the impact of different aluminium shielding between 1 g/cm2 and 100 g/cm2 was calculated. The dose equivalent rates were used to estimate the effective dose rate.

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

Foster, R; Ding, C; Jiang, S

Purpose Spine SRS/SAbR treatment plans typically require very steep dose gradients to meet spinal cord constraints and it is crucial that the dose distribution be accurate. However, these plans are typically calculated on helical free-breathing CT scans, which often contain motion artifacts. While the spine itself doesn’t exhibit very much intra-fraction motion, tissues around the spine, particularly the liver, do move with respiration. We investigated the dosimetric effect of liver motion on dose distributions calculated on helical free-breathing CT scans for spine SAbR delivered to the T and L spine. Methods We took 5 spine SAbR plans and used densitymore » overrides to simulate an average reconstruction CT image set, which would more closely represent the patient anatomy during treatment. The value used for the density override was 0.66 g/cc. All patients were planned using our standard beam arrangement, which consists of 13 coplanar step and shoot IMRT beams. The original plan was recalculated with the same MU on the “average” scan and target coverage and spinal cord dose were compared to the original plan. Results The average changes in minimum PTV dose, PTV coverage, max cord dose and volume of cord receiving 10 Gy were 0.6%, 0.8%, 0.3% and 4.4% (0.012 cc), respectively. Conclusion SAbR spine plans are surprisingly robust relative to surrounding organ motion due to respiration. Motion artifacts in helical planning CT scans do not cause clinically significant differences when these plans are re-calculated on pseudo-average CT reconstructions. This is likely due to the beam arrangement used because only three beams pass through the liver and only one beam passes completely through the density override. The effect of the respiratory motion on VMAT plans for spine SAbR is being evaluated.« less

Pharmacokinetics of a single intramuscular injection of ceftiofur crystalline-free acid in red-tailed hawks (Buteo jamaicensis).

PubMed

Sadar, Miranda J; Hawkins, Michelle G; Byrne, Barbara A; Cartoceti, Andrew N; Keel, Kevin; Drazenovich, Tracy L; Tell, Lisa A

2015-12-01

To determine the pharmacokinetics and adverse effects at the injection site of ceftiofur crystalline-free acid (CCFA) following IM administration of 1 dose to red-tailed hawks (Buteo jamaicensis). 7 adult nonreleasable healthy red-tailed hawks. In a randomized crossover study, CCFA (10 or 20 mg/kg) was administered IM to each hawk and blood samples were obtained. After a 2-month washout period, administration was repeated with the opposite dose. Muscle biopsy specimens were collected from the injection site 10 days after each sample collection period. Pharmacokinetic data were calculated. Minimum inhibitory concentrations of ceftiofur for various bacterial isolates were assessed. Mean peak plasma concentrations of ceftiofur-free acid equivalent were 6.8 and 15.1 μg/mL for the 10 and 20 mg/kg doses, respectively. Mean times to maximum plasma concentration were 6.4 and 6.7 hours, and mean terminal half-lives were 29 and 50 hours, respectively. Little to no muscle inflammation was identified. On the basis of a target MIC of 1 μg/mL and target plasma ceftiofur concentration of 4 μg/mL, dose administration frequencies for infections with gram-negative and gram-positive organisms were estimated as every 36 and 45 hours for the 10 mg/kg dose and every 96 and 120 hours for the 20 mg/kg dose, respectively. Study results suggested that CCFA could be administered IM to red-tailed hawks at 10 or 20 mg/kg to treat infections with ceftiofur-susceptible bacteria. Administration resulted in little to no inflammation at the injection site. Additional studies are needed to evaluate effects of repeated CCFA administration.

Density Dependence and Growth Rate: Evolutionary Effects on Resistance Development to Bt (Bacillus thuringiensis).

PubMed

Martinez, Jeannette C; Caprio, Michael A; Friedenberg, Nicholas A

2018-02-09

It has long been recognized that pest population dynamics can affect the durability of a pesticide, but dose remains the primary component of insect resistance management (IRM). For transgenic pesticidal traits such as Bt (Bacillus thuringiensis Berliner (Bacillales: Bacillaceae)), dose (measured as the mortality of susceptibles caused by a toxin) is a relatively fixed characteristic and often falls below the standard definition of high dose. Hence, it is important to understand how pest population dynamics modify durability and what targets they present for IRM. We used a deterministic model of a generic arthropod pest to examine how timing and strength of density dependence interacted with population growth rate and Bt mortality to affect time to resistance. As in previous studies, durability typically reached a minimum at intermediate doses. However, high population growth rates could eliminate benefits of high dose. The timing of density dependence had a more subtle effect. If density dependence operated simultaneously with Bt mortality, durability was insensitive to its strengths. However, if density dependence was driven by postselection densities, decreasing its strength could increase durability. The strength of density dependence could affect durability of both single traits and pyramids, but its influence depended on the timing of density dependence and size of the refuge. Our findings suggest the utility of a broader definition of high dose, one that incorporates population-dynamic context. That maximum growth rates and timing and strength of interactions causing density dependent mortality can all affect durability, also highlights the need for ecologically integrated approaches to IRM research. © The Author(s) 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The selective effect of plasma activated medium in an in vitro co-culture of liver cancer and normal cells

NASA Astrophysics Data System (ADS)

Duan, J.; Lu, X.; He, G.

2017-01-01

In this work, a co-culture system with liver cancer cell line HepG2 and normal cell line L02 is used to investigate the selective effect on cancer and normal cells by plasma activated medium (PAM), which is closer to the real environment where cancer cells develop. Besides, the co-culture system is a better model to study the selective effect than the widely used separate culture systems, where the cancer cell line and normal cell line are cultured independently. By using the co-culture system, it is found that there is an optimum dose of PAM to induce significant cancer cell apoptosis while keeping minimum damage to normal cells.

Collaborative study to assess the suitability of a candidate International Standard for yellow fever vaccine.

PubMed

Ferguson, Morag; Heath, Alan

2004-12-01

Yellow fever vaccines are routinely assayed by plaque assay. However, the results of these assays are then converted into mouse LD(50) using correlations/conversion factors which, in many cases, were established many years ago. The minimum required potency in WHO Recommendations is 10(3) LD(50)/dose. Thirteen participants from 8 countries participated in a collaborative study whose aim was to assess the suitability of two candidate preparations to serve as an International Standard for yellow fever vaccine. In addition, the study investigated the relationship between the mouse LD(50) test and plaque forming units with a view to updating the WHO recommendations. Plaque assays were more reproducible than mouse assays, as expected. Differences in sensitivities of plaque assays were observed between laboratories but these differences appear to be consistent within a laboratory for all samples and the expression of potency relative to the candidate standard vaccine improved the reproducibility of assays between laboratories. However, the use of potencies had little effect on the between laboratory variability in mouse LD(50) assays. There appears to be a consistent relationship between overall mean LD(50) and plaques titre for all study preparations other than sample E. The slope of the correlation curve is >1 and it would appear that 10(3) LD(50) is approximately equivalent to 10(4) plaque forming units (PFU), based on the overall means of all laboratory results. The First International Standard for yellow fever vaccine, NIBSC Code 99/616, has been established as the First International Standard for yellow fever vaccine by the Expert Committee of Biological Standards of the World Health Organisation. The International Standard has been arbitrarily assigned a potency of 10(4.5) International Units (IU) per ampoule. Manufacturers and National Control Laboratories are including the First International Standard for yellow fever vaccine in routine assays so that the minimum potency in IU of vaccines released for use and which meet the current minimum potency of 10(3) LD(50) in mouse assays, can be determined. These data will be analysed before a review of the WHO requirements, including the minimum potency per dose, is undertaken.

[Trial of eye drops recognizer for visually disabled persons].

PubMed

Okamoto, Norio; Suzuki, Katsuhiko; Mimura, Osamu

2009-01-01

The development of a device to enable the visually disabled to differentiate eye drops and their dose. The new instrument is composed of a voice generator and a two-dimensional bar-code reader (LS9208). We designed voice outputs for the visually disabled to state when (number of times) and where (right, left, or both) to administer eye drops. We then determined the minimum bar-code size that can be recognized. After attaching bar-codes of the appropriate size to the lateral or bottom surface of the eye drops container, the readability of the bar-codes was compared. The minimum discrimination bar-code size was 6 mm high x 8.5 mm long. Bar-codes on the bottom surface could be more easily recognized than bar-codes on the side. Our newly-developed device using bar-codes enables visually disabled persons to differentiate eye drops and their doses.

Biochemical changes in the skin of rats exposed to radiation against the background of thermal stress. [X rays; ATPase and creatine kinase activities

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

Matyushichev, V.B.; Taratukhin, V.R.; Shamratova, V.G.

1978-01-01

The effectiveness of exposing rats to different doses of x radiation after submitting them to a heat load, according to the tests of ATPase and creatine kinase activity of aqueous extracts of skin at the relatively late observation period was compared. The effects of the combined factors were monitored by means of a heat load (one group) and exposure to radiation alone in doses of 25, 50, 100, 250, and 400 R (5 groups). The obtained data are indicative of marked specificity of ATPase and creatine kinase reactions to the combined factors. Creatine kinase activity undergoes a 157% change, whereasmore » the mean relative deviation of ATPase activity constitutes only 71% of the normal level. The most effect loads are 36/sup 0/C + 25 R and 36/sup 0/C + 400 R. With all tested doses the extent of the effect of radiation on creatine kinase activity is only negligibly lower than the effectiveness of combined loads, whereas according to the ATPase test, radiation alone induces virtually the same changes in activity as combined factors. ATPase undergoes maximum change after irradiation in doses of 250 and 400 R; delivery of 25 to 100 R is associated with much less marked changes in activity. In contrast, creatine kinase demonstrates maximum sensitivity to radiation in a dosage of 25 R and minimum sensitivity, with a dosage of 100 R. Thermal stress (according to ATPase and creatine kinase activity) has a profound and quite substantial effect on processes of development of radiation lesion. It can be manifested by complete or partial summation of effects of each of the factors, mutual attenuation of effects, or absence of interaction between factors in the combination. All this is indicative of the complexity and differences in mechanisms of expression of effects of the factors used. (ERB)« less

Pterocarpus santalinus: a traditional herbal drug as a protectant against ibuprofen induced gastric ulcers.

PubMed

Narayan, Shoba; Devi, R S; Srinivasan, P; Shyamala Devi, C S

2005-11-01

The ethanol extract of Pterocarpus santalinus (PS) was evaluated for gastroprotection in rats using ibuprofen as the induction model. Rats treated with PS (100-400 mg/kg) showed a significant reduction in gastric lesions. PS at a dose of 200 mg/kg was found to be the minimum effective dose and hence further studies with that dose were carried out. PS treatment increased the LDH activity and decreased the lipid peroxidation levels. The extract had the ability to increase the antioxidant enzymes SOD, CAT and GPx when compared with the untreated but induced rats. The membrane bound ATPases - H(+)K(+)ATPase, Na(+)K(+)ATPase and Ca(2+)ATPases were increased upon the induction with ulcerogen. The treated group showed a decrease in the activities of these enzymes and also had the ability to restore the sodium and potassium ion concentrations to near normal levels, which were altered by ibuprofen mediated acid stimulation. The results suggest that the antiulcer properties of PS could traced to its acid inhibiting potential, antioxidant activity and the ability to maintain functional integrity of the cell membranes.

Ethical, legal, and social implications (ELSI) of microdose clinical trials.

PubMed

Kurihara, Chieko

2011-06-19

A "microdose clinical trial" (microdosing) is one kind of early phase exploratory clinical trial, administering the compound at doses estimated to have no pharmacological or toxicological effects, aimed at screening candidates for further clinical development. This article's objective is to clarify the ethical, legal, and social implications (ELSI) of such an exploratory minimum-risk human trial. The definition and non-clinical study requirements for microdosing have been harmonized among the European Union (EU), United States (US), and Japan. Being conducted according to these regulations, microdosing seems to be ethically well justified in terms of respect for persons, beneficence, justice, human dignity, and animal welfare. Three big projects have been demonstrating the predictability of therapeutic dose pharmacokinetics from microdosing. The article offers suggestions as how microdosing can become a more useful and socially accepted strategy. Copyright © 2011 Elsevier B.V. All rights reserved.

A New Direction in Ophthalmic Development: Nanoparticle Drug Delivery Systems.

PubMed

Andonova, Velichka Yordanova

2016-01-01

The purpose of each dosage form is to provide an optimal therapeutic effect with a minimum dose and with minimal side effects. This is particularly relevant for drugs that require systemic administration, higher dosing and/or show lower bioavailability. Тhe eye as an anatomical structure is an extremely protected organ. In this regard, providing an optimal bioavailability in the eye tissues, resulting in the desired therapeutic effect represents a major challenge. This is especially true for the treatment of diseases, affecting the posterior segment after topically administered drug formulations. The use of nano- and microcarriers of drug substances may be an appropriate technological approach, to provide a high bioavailability of the drug substance for a certain interval of time at the right place. The purpose of this review is to indicate how nano- and microcarriers of drug substances can solve the problems with the drug delivery in the ocular tissues, to indicate the possible hazards and side effects, depending on the polymer nature and route of administration, and to visualize the future potential of these carriers in the pharmaceutical practice. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Randomized trial of 3-dose regimens of tafenoquine (WR238605) versus low-dose primaquine for preventing Plasmodium vivax malaria relapse.

PubMed

Walsh, Douglas S; Wilairatana, Polrat; Tang, Douglas B; Heppner, D Gray; Brewer, Thomas G; Krudsood, Srivicha; Silachamroon, Udomsak; Phumratanaprapin, Weerapong; Siriyanonda, Duangsuda; Looareesuwan, Sornchai

2004-10-15

Tafenoquine is an 8-aminoquinoline developed as a more effective replacement for primaquine. In a previous dose-ranging study in Thailand, 3 tafenoquine regimens with total doses ranging from 500 mg to 3000 mg prevented relapse of Plasmodium vivax malaria in most patients when administered 2 days after receipt of a blood schizonticidal dose of chloroquine. To improve convenience and to begin comparison of tafenoquine with primaquine, 80 patients with P. vivax infection were randomized to receive 1 of the following 5 treatments 1 day after receiving a blood schizonticidal dose of chloroquine: (A) tafenoquine, 300 mg per day for 7 days (n=18); (B) tafenoquine, 600 mg per day for 3 days (n=19); (C) tafenoquine, 600 mg as a single dose (n=18); (D) no further treatment (n=13); or (E) primaquine base, 15 mg per day for 14 days (n=12). The minimum duration of protocol follow-up was 8 weeks, with additional follow-up to 24 weeks. Forty-six of 55 tafenoquine recipients, 10 of 13 recipients of chloroquine only, and 12 of 12 recipients of chloroquine plus primaquine completed at least 8 weeks of follow-up (or had relapse). There was 1 relapse among recipients of chloroquine plus tafenoquine, 8 among recipients of chloroquine only, and 3 among recipients of chloroquine plus primaquine. The rate of protective efficacy (determined on the basis of reduction in incidence density) for all recipients of chloroquine plus tafenoquine, compared with recipients of chloroquine plus primaquine, was 92.6% (95% confidence interval, 7.3%-99.9%; P=.042, by Fisher's exact test). Tafenoquine doses as low as a single 600-mg dose may be useful for prevention of relapse of P. vivax malaria in Thailand.

Radiation optic neuropathy after megavoltage external-beam irradiation: Analysis of time-dose factors

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

Parsons, J.T.; Bova, F.J.; Million, R.R.

1994-11-15

To investigate the risk of radiation-induced optic neuropathy according to total radiotherapy dose and fraction size, based on both retrospective and prospectively collected data. Between October 1964 and May 1989, 215 optic nerves in 131 patients received fractionated external-beam irradiation during the treatment of primary extracranial head and neck tumors. All patients had a minimum of 3 years of ophthalmologic follow-up (range, 3 to 21 years). The clinical end point was visual acuity of 20/100 or worse as a result of optic nerve injury. Anterior ischemic optic neuropathy developed in five nerves (at mean and median times of 32 andmore » 30 months, respectively, and a range of 2-4 years). Retrobulbar optic neuropathy developed in 12 nerves (at mean and median times of 47 and 28 months, respectively, and a range of 1-14 years). No injuries were observed in 106 optic nerves that received a total dose of <59 Gy. Among nerves that received doses of {ge} 60 Gy, the dose per fraction was more important than the total dose in producing optic neuropathy. The 15-year actuarial risk of optic compared with 47% when given in fraction sizes {ge}1.9 Gy. The data also suggest an increased risk of optic nerve injury with increasing age. As there is no effective treatment of radiation-induced optic neuropathy, efforts should be directed at its prevention by minimizing the total dose, paying attention to the dose per fraction to the nerve, and using reduced field techniques where appropriate to limit the volume of tissues that receive high-dose irradiation. 32 refs., 5 figs., 5 tabs.« less

Hypothyroidism as a Consequence of Intensity-Modulated Radiotherapy With Concurrent Taxane-Based Chemotherapy for Locally Advanced Head-and-Neck Cancer

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

Diaz, Roberto; Jaboin, Jerry J.; Morales-Paliza, Manuel

Purpose: To conduct a retrospective review of 168 consecutively treated locally advanced head-and-neck cancer (LAHNC) patients treated with intensity-modulated radiotherapy (IMRT)/chemotherapy, to determine the rate and risk factors for developing hypothyroidism. Methods and Materials: Intensity-modulated radiotherapy was delivered in 33 daily fractions to 69.3 Gy to gross disease and 56.1 Gy to clinically normal cervical nodes. Dose-volume histograms (DVHs) of IMRT plans were used to determine radiation dose to thyroid and were compared with DVHs using conventional three-dimensional radiotherapy (3D-RT) in 10 of these same patients randomly selected for replanning and with DVHs of 16 patients in whom the thyroidmore » was intentionally avoided during IMRT. Weekly paclitaxel (30 mg/m{sup 2}) and carboplatin area under the curve-1 were given concurrently with IMRT. Results: Sixty-one of 128 evaluable patients (47.7%) developed hypothyroidism after a median of 1.08 years after IMRT (range, 2.4 months to 3.9 years). Age and volume of irradiated thyroid were associated with hypothyroidism development after IMRT. Compared with 3D-RT, IMRT with no thyroid dose constraints resulted in significantly higher minimum, maximum, and median dose (p < 0.0001) and percentage thyroid volume receiving 10, 20, and 60 Gy (p < 0.05). Compared with 3D-RT, IMRT with thyroid dose constraints resulted in lower median dose and percentage thyroid volume receiving 30, 40, and 50 Gy (p < 0.005) but higher minimum and maximum dose (p < 0.005). Conclusions: If not protected, IMRT for LAHNC can result in higher radiation to the thyroid than with conventional 3D-RT. Techniques to reduce dose and volume of radiation to thyroid tissue with IMRT are achievable and recommended.« less

Dynamic Collimator Angle Adjustments During Volumetric Modulated Arc Therapy to Account for Prostate Rotations

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

Boer, Johan de; Wolf, Anne Lisa; Szeto, Yenny Z.

2015-04-01

Purpose: Rotations of the prostate gland induce considerable geometric uncertainties in prostate cancer radiation therapy. Collimator and gantry angle adjustments can correct these rotations in intensity modulated radiation therapy. Modern volumetric modulated arc therapy (VMAT) treatments, however, include a wide range of beam orientations that differ in modulation, and corrections require dynamic collimator rotations. The aim of this study was to implement a rotation correction strategy for VMAT dose delivery and validate it for left-right prostate rotations. Methods and Materials: Clinical VMAT treatment plans of 5 prostate cancer patients were used. Simulated left-right prostate rotations between +15° and −15° weremore » corrected by collimator rotations. We compared corrected and uncorrected plans by dose volume histograms, minimum dose (D{sub min}) to the prostate, bladder surface receiving ≥78 Gy (S78) and rectum equivalent uniform dose (EUD; n=0.13). Each corrected plan was delivered to a phantom, and its deliverability was evaluated by γ-evaluation between planned and delivered dose, which was reconstructed from portal images acquired during delivery. Results: On average, clinical target volume minimum dose (D{sub min}) decreased up to 10% without corrections. Negative left-right rotations were corrected almost perfectly, whereas D{sub min} remained within 4% for positive rotations. Bladder S78 and rectum EUD of the corrected plans matched those of the original plans. The average pass rate for the corrected plans delivered to the phantom was 98.9% at 3% per 3 mm gamma criteria. The measured dose in the planning target volume approximated the original dose, rotated around the simulated left-right angle, well. Conclusions: It is feasible to dynamically adjust the collimator angle during VMAT treatment delivery to correct for prostate rotations. This technique can safely correct for left-right prostate rotations up to 15°.« less

Acute, subacute toxicity and mutagenic effects of anacardic acids from cashew (Anacardium occidentale Linn.) in mice.

PubMed

Carvalho, Ana Laura Nicoletti; Annoni, Raquel; Silva, Paula Regina Pereira; Borelli, Primavera; Fock, Ricardo Ambrósio; Trevisan, Maria Teresa Salles; Mauad, Thais

2011-06-01

Anacardium occidentale Linn. (cashew) is a Brazilian plant that is usually consumed in natura and is used in folk medicine. Anacardic acids (AAs) in the cashew nut shell liquid are biologically active as gastroprotectors, inhibitors of the activity of various deleterious enzymes, antitumor agents and antioxidants. Yet, there are no reports of toxicity testing to guarantee their use in vivo models. We evaluated AAs biosafety by measuring the acute, subacute and mutagenic effects of AAs administration in BALB/c mice. In acute tests, BALB/c mice received a single oral dose of 2000 mg/kg, whereas animals in subacute tests received 300, 600 and 1000 mg/kg for 30 days. Hematological, biochemical and histological analyses were performed in all animals. Mutagenicity was measured with the acute micronucleus test 24h after oral administration of 250 mg/kg AAs. Our results showed that the AAs acute minimum lethal dose in BALB/c mice is higher than 2000 mg/kg since this concentration did not produce any symptoms. In subacute tests, females which received the highest doses (600 or 1000 mg/kg) were more susceptible, which was seen by slightly decreased hematocrit and hemoglobin levels coupled with a moderate increase in urea. Anacardic acids did not produce any mutagenic effects. The data indicate that doses less than 300 mg/kg did not produce biochemical and hematological alterations in BALB/c mice. Additional studies must be conducted to investigate the pharmacological potential of this natural substance in order to ensure their safe use in vivo. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Azithromycin in the treatment of uncomplicated genital chlamydial infections.

PubMed

Stamm, W E

1991-09-12

Chlamydia trachomatis is among the most prevalent of sexually transmitted diseases and causes serious sequelae, especially in women. A major difficulty facing the clinician has been the effective treatment of patients with chlamydial infections, since existing drugs require 7 or more days of multidose therapy, and hence considerable commitment from the patient. Many patients, especially those who are minimally symptomatic or asymptomatic, are likely to be noncompliant when given such multiple day regimens and thus may fail therapy. Azithromycin is an azalide antibiotic that has a minimum inhibitory concentration against C. trachomatis of between 0.03 and 0.25 mg/L, as well as good in vitro activity against other sexually transmitted pathogens that are often present concurrently. Azithromycin also achieves high intracellular concentrations, which may be beneficial in eradicating Chlamydia, an obligate intracellular pathogen. More importantly, azithromycin has high tissue bioavailability and a tissue half-life of between 2 and 4 days. These pharmacokinetic properties imply that the dosing period for azithromycin can be greatly reduced while still achieving high antimicrobial activity at sites of infection. Clinical experience to date shows that a single 1 g oral dose of azithromycin is as effective as a standard 7-day twice daily regimen of doxycycline and more effective than 7 days of ciprofloxacin in eradicating uncomplicated chlamydial genital infections. As such, azithromycin is the first single-dose therapy for the treatment of urethritis and cervicitis due to C. trachomatis. Single-dose therapy for chlamydial infection, which could be administered under supervision in the clinic, would be a significant advance in the management and public health control of chlamydial infections.

Sublingual buprenorphine is effective in the treatment of chronic pain syndrome.

PubMed

Malinoff, Herbert L; Barkin, Robert L; Wilson, Geoffrey

2005-01-01

Many patients with chronic pain have less than optimal therapeutic outcomes after prolonged treatment with opiate analgesics. Worsening of pain perception, functional capacity, and mood often result. Medical detoxification is often undertaken in this situation. Ninety-five consecutive patients (49 men and 46 women; age range, 26-84) with chronic noncancer pain (maldynia) were referred by local pain clinics for detoxification from long-term opiate analgesic (LTOA) therapy. All patients had failed treatment as manifest by increasing pain levels, worsening functional capacity, and, in 8%, the emergence of opiate addiction. Length of prior LTOA therapy ranged from 1.5 to 27 years (mean, 8.8 years). After a minimum of 12 hours of abstinence from all opiate analgesics, patients were given low doses of sublingual (SL) buprenorphine or buprenorphine/naloxone (Reckitt Benckiser). Maintenance dosing was individualized to treat chronic pain. Daily SL dose of buprenorphine ranged from 4 to 16 mg (mean, 8 mg) in divided doses. Mean duration of treatment is 8.8 months (range, 2.4-16.6 months). At clinic appointments, patients were assessed for pain reports, functional capacity, and mood inventory. Eighty-six percent of patients experienced moderate to substantial relief of pain accompanied by both improved mood and functioning. Patient and family satisfaction was robust. Only 6 patients discontinued therapy secondary to side effects and/or exacerbation of pain. In this open-label study, SL buprenorphine and buprenorphine/naloxone were well tolerated and safe and appeared to be effective in the treatment of chronic pain patients refractory to LTOA.

Field evaluations of the VD max approach for substantiation of a 25 kGy sterilization dose and its application to other preselected doses

NASA Astrophysics Data System (ADS)

Kowalski, John B.; Herring, Craig; Baryschpolec, Lisa; Reger, John; Patel, Jay; Feeney, Mary; Tallentire, Alan

2002-08-01

The International and European standards for radiation sterilization require evidence of the effectiveness of a minimum sterilization dose of 25 kGy but do not provide detailed guidance on how this evidence can be generated. An approach, designated VD max, has recently been described and computer evaluated to provide safe and unambiguous substantiation of a 25 kGy sterilization dose. The approach has been further developed into a practical method, which has been subjected to field evaluations at three manufacturing facilities which produce different types of medical devices. The three facilities each used a different overall evaluation strategy: Facility A used VD max for quarterly dose audits; Facility B compared VD max and Method 1 in side-by-side parallel experiments; and Facility C, a new facility at start-up, used VD max for initial substantiation of 25 kGy and subsequent quarterly dose audits. A common element at all three facilities was the use of 10 product units for irradiation in the verification dose experiment. The field evaluations of the VD max method were successful at all three facilities; they included many different types of medical devices/product families with a wide range of average bioburden and sample item portion values used in the verification dose experiments. Overall, around 500 verification dose experiments were performed and no failures were observed. In the side-by-side parallel experiments, the outcomes of the VD max experiments were consistent with the outcomes observed with Method 1. The VD max approach has been extended to sterilization doses >25 and <25 kGy; verification doses have been derived for sterilization doses of 15, 20, 30, and 35 kGy. Widespread application of the VD max method for doses other than 25 kGy must await controlled field evaluations and the development of appropriate specifications/standards.

Evaluation of CGP 39393 as the anticoagulant in cardiopulmonary bypass operation in a dog model.

PubMed

Walenga, J M; Koza, M J; Park, S J; Terrell, M R; Pifarré, R

1994-12-01

Recombinant desulphatohirudin HV1 (CGP 39393), a specific and potent peptidic inhibitor of thrombin, was evaluated as the sole anticoagulant in a dog model of cardiopulmonary bypass. CGP 39393 was administered as a bolus plus infusion for a 1-hour pump period at doses of 1.0 mg/kg + 0.75 mg.kg-1.h-1, 1.0 mg/kg + 1.50 mg.kg-1.h-1, 1.0 mg/kg + 2.25 mg.kg-1.h-1, or 1.0 mg/kg + 3.0 mg.kg-1.h-1 (n = 5 per group). The lowest dose was ineffective, as a high degree of clot formation (314 +/- 160 mg) occurred as determined by quantitation of protein deposits in the pump line filter. The three higher doses inhibited clot formation (35 to 44 mg) but did not reveal a dose-dependent effect (p = 0.308 between groups). All four doses produced the same amount of postoperative blood loss (6.5 to 10 g/kg over 2 hours; p = 0.215 between groups) and no oozing of blood from cut tissues (sternum, muscle, skin) during or after operation. No adverse hemodynamic or hematologic effects were observed. Animals were physiologically stable coming off pump, requiring minimal fluid replacement or other cardiovascular supportive measures. The chromogenic anti-IIa assay could be used to monitor CGP 39393. Some activated partial thromboplastin time and all activated clotting time values were off scale on pump, but they fell immediately after cardiopulmonary bypass, typically reaching near-normal levels within 30 to 60 minutes. No reversal of CGP 39393 was used, as blood levels declined rapidly after cessation of the infusion. This study in a dog model shows that CGP 39393 administered as a bolus plus infusion (minimum dose, 1.0 mg/kg + 1.50 mg.kg-1.h-1) can be used safely and effectively during cardiopulmonary bypass for cardiac operation.

Imidacloprid treatment of marsupials for fleas (Pygiopsylla hoplia).

PubMed

Baker, R T; Beveridge, I

2001-09-01

Two eastern barred bandicoots (Perameles gunnii), two eastern quells (Dasyunrus viverrinus), four fat-tailed dunnarts (Sminthopsis crassicaudata), a Leadbeater's possum (Gymnobelideus leadbeateri), a yellow-bellied glider (Petaurus australis), and a ring-tailed possum (Pseudocheirus peregrinus) were treated with imidacloprid (10.7 +/- 0.6 mg/kg topically, minimum dose 0.5 mg) after observation of fleas (Pygiopsylla hoplia) on animals and in their nest boxes. No live fleas or adverse reactions to imidacloprid were observed for 27 days following treatment. The ease of application, absence of toxicity, and long residual effect makes imidacloprid a useful drug for treating flea infestations in these marsupials.

Accuracy and optimal timing of activity measurements in estimating the absorbed dose of radioiodine in the treatment of Graves' disease

NASA Astrophysics Data System (ADS)

Merrill, S.; Horowitz, J.; Traino, A. C.; Chipkin, S. R.; Hollot, C. V.; Chait, Y.

2011-02-01

Calculation of the therapeutic activity of radioiodine 131I for individualized dosimetry in the treatment of Graves' disease requires an accurate estimate of the thyroid absorbed radiation dose based on a tracer activity administration of 131I. Common approaches (Marinelli-Quimby formula, MIRD algorithm) use, respectively, the effective half-life of radioiodine in the thyroid and the time-integrated activity. Many physicians perform one, two, or at most three tracer dose activity measurements at various times and calculate the required therapeutic activity by ad hoc methods. In this paper, we study the accuracy of estimates of four 'target variables': time-integrated activity coefficient, time of maximum activity, maximum activity, and effective half-life in the gland. Clinical data from 41 patients who underwent 131I therapy for Graves' disease at the University Hospital in Pisa, Italy, are used for analysis. The radioiodine kinetics are described using a nonlinear mixed-effects model. The distributions of the target variables in the patient population are characterized. Using minimum root mean squared error as the criterion, optimal 1-, 2-, and 3-point sampling schedules are determined for estimation of the target variables, and probabilistic bounds are given for the errors under the optimal times. An algorithm is developed for computing the optimal 1-, 2-, and 3-point sampling schedules for the target variables. This algorithm is implemented in a freely available software tool. Taking into consideration 131I effective half-life in the thyroid and measurement noise, the optimal 1-point time for time-integrated activity coefficient is a measurement 1 week following the tracer dose. Additional measurements give only a slight improvement in accuracy.

Image-Based 3D Treatment Planning for Vaginal Cylinder Brachytherapy: Dosimetric Effects of Bladder Filling on Organs at Risk

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

Hung, Jennifer; Shen Sui; De Los Santos, Jennifer F.

2012-07-01

Purpose: To investigate the dosimetric effects of bladder filling on organs at risk (OARs) using three-dimensional image-based treatment planning for vaginal cylinder brachytherapy. Methods and Materials: Twelve patients with endometrial or cervical cancer underwent postoperative high-dose rate vaginal cylinder brachytherapy. For three-dimensional planning, patients were simulated by computed tomography with an indwelling catheter in place (empty bladder) and with 180 mL of sterile water instilled into the bladder (full bladder). The bladder, rectum, sigmoid, and small bowel (OARs) were contoured, and a prescription dose was generated for 10 to 35 Gy in 2 to 5 fractions at the surface ormore » at 5 mm depth. For each OAR, the volume dose was defined by use of two different criteria: the minimum dose value in a 2.0-cc volume receiving the highest dose (D{sub 2cc}) and the dose received by 50% of the OAR volume (D{sub 50%}). International Commission on Radiation Units and Measurements (ICRU) bladder and rectum point doses were calculated for comparison. The cylinder-to-bowel distance was measured using the shortest distance from the cylinder apex to the contoured sigmoid or small bowel. Statistical analyses were performed with paired t tests. Results: Mean bladder and rectum D{sub 2cc} values were lower than their respective ICRU doses. However, differences between D{sub 2cc} and ICRU doses were small. Empty vs. full bladder did not significantly affect the mean cylinder-to-bowel distance (0.72 vs. 0.92 cm, p = 0.08). In contrast, bladder distention had appreciable effects on bladder and small bowel volume dosimetry. With a full bladder, the mean small bowel D{sub 2cc} significantly decreased from 677 to 408 cGy (p = 0.004); the mean bladder D{sub 2cc} did not increase significantly (1,179 cGy vs. 1,246 cGy, p = 0.11). Bladder distention decreased the mean D{sub 50%} for both the bladder (441 vs. 279 cGy, p = 0.001) and the small bowel (168 vs. 132 cGy, p = 0.001). Rectum and sigmoid volume doses were not affected by bladder filling. Conclusions: In high-dose rate vaginal cylinder brachytherapy, treatment with a distended bladder preferentially reduces high dose to the small bowel around the vaginal cuff without a significant change in dose to the bladder, rectum, or sigmoid.« less

Evaluation of Dose Uncertainty to the Target Associated With Real-Time Tracking Intensity-Modulated Radiation Therapy Using the CyberKnife Synchrony System.

PubMed

Iwata, Hiromitsu; Inoue, Mitsuhiro; Shiomi, Hiroya; Murai, Taro; Tatewaki, Koshi; Ohta, Seiji; Okawa, Kohei; Yokota, Naoki; Shibamoto, Yuta

2016-02-01

We investigated the dose uncertainty caused by errors in real-time tracking intensity-modulated radiation therapy (IMRT) using the CyberKnife Synchrony Respiratory Tracking System (SRTS). Twenty lung tumors that had been treated with non-IMRT real-time tracking using CyberKnife SRTS were used for this study. After validating the tracking error in each case, we did 40 IMRT planning using 8 different collimator sizes for the 20 patients. The collimator size was determined for each planning target volume (PTV); smaller ones were one-half, and larger ones three-quarters, of the PTV diameter. The planned dose was 45 Gy in 4 fractions prescribed at 95% volume border of the PTV. Thereafter, the tracking error in each case was substituted into calculation software developed in house and randomly added in the setting of each beam. The IMRT planning incorporating tracking errors was simulated 1000 times, and various dose data on the clinical target volume (CTV) were compared with the original data. The same simulation was carried out by changing the fraction number from 1 to 6 in each IMRT plan. Finally, a total of 240 000 plans were analyzed. With 4 fractions, the change in the CTV maximum and minimum doses was within 3.0% (median) for each collimator. The change in D99 and D95 was within 2.0%. With decreases in the fraction number, the CTV coverage rate and the minimum dose decreased and varied greatly. The accuracy of real-time tracking IMRT delivered in 4 fractions using CyberKnife SRTS was considered to be clinically acceptable. © The Author(s) 2014.

Radiation experiments on Cosmos 2044: K-7-41, parts A, B, C, D, E

NASA Technical Reports Server (NTRS)

Frank, A. L.; Benton, E. V.; Benton, E. R.; Dudkin, V. E.; Marenny, A. M.

1990-01-01

The Cosmos 2044 biosatellite mission offered the opportunity for radiation measurements under conditions which are seldom available (an inclination of 82.3 deg and attitude of 294 x 216 km). Measurements were made on the outside of the spacecraft under near-zero shielding conditions. Also, this mission was the first in which active temperature recorders (the ATR-4) were flown to record the temperature profiles of detector stacks. Measurements made on this mission provide a comparison and test for modeling of depth doses and LET spectra for orbital parameters previously unavailable. Tissue absorbed doses from 3480 rad (252 rad/d) down to 0.115 rad (8.33 mrad/d) were measured at different depths (0.0146 and 3.20 g/sq cm, respectively) with averaged TLD readings. The LET spectra yielded maximum and minimum values of integral flux of 27.3 x 10(exp -4) and 3.05 x 10(exp -4)/sq cm/s/sr, of dose rate of 7.01 and 1.20 mrad/d, and of dose equivalent rate of 53.8 and 11.6 mrem/d, for LET(sub infinity)-H2O is greater than or equal to 4 keV/micron. Neutron measurements yielded 0.018 mrem/d in the thermal region, 0.25 mrem/d in the resonance region and 3.3 mrem/d in the high energy region. The TLD depth dose and LET spectra were compared with calculations from the modeling codes. The agreement is good but some further refinements are in order. In comparing measurements on Cosmos 2044 with those from previous Cosmos missions (orbital inclinations of 62.8 deg) there is a greater spread (maximum to minimum) in depth doses and an increased contribution from GCRs, and higher LET particles, in the heavy particle fluxes.

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

Serin, E.; Codel, G.; Mabhouti, H.

Purpose: In small field geometries, the electronic equilibrium can be lost, making it challenging for the dose-calculation algorithm to accurately predict the dose, especially in the presence of tissue heterogeneities. In this study, dosimetric accuracy of Monte Carlo (MC) advanced dose calculation and sequential algorithms of Multiplan treatment planning system were investigated for small radiation fields incident on homogeneous and heterogeneous geometries. Methods: Small open fields of fixed cones of Cyberknife M6 unit 100 to 500 mm2 were used for this study. The fields were incident on in house phantom containing lung, air, and bone inhomogeneities and also homogeneous phantom.more » Using the same film batch, the net OD to dose calibration curve was obtained using CK with the 60 mm fixed cone by delivering 0- 800 cGy. Films were scanned 48 hours after irradiation using an Epson 1000XL flatbed scanner. The dosimetric accuracy of MC and sequential algorithms in the presence of the inhomogeneities was compared against EBT3 film dosimetry Results: Open field tests in a homogeneous phantom showed good agreement between two algorithms and film measurement For MC algorithm, the minimum gamma analysis passing rates between measured and calculated dose distributions were 99.7% and 98.3% for homogeneous and inhomogeneous fields in the case of lung and bone respectively. For sequential algorithm, the minimum gamma analysis passing rates were 98.9% and 92.5% for for homogeneous and inhomogeneous fields respectively for used all cone sizes. In the case of the air heterogeneity, the differences were larger for both calculation algorithms. Overall, when compared to measurement, the MC had better agreement than sequential algorithm. Conclusion: The Monte Carlo calculation algorithm in the Multiplan treatment planning system is an improvement over the existing sequential algorithm. Dose discrepancies were observed for in the presence of air inhomogeneities.« less

Experiment K-7-41: Radiation Experiments on Cosmos 2044

NASA Technical Reports Server (NTRS)

Benton, E. V.; Benton, E. R.; Frank, A. L.; Dudkin, V. E.; Marenny, A. M.; Kovalev, E. E.

1994-01-01

The Cosmos 2044 biosatellite mission offered the opportunity for radiation measurements under conditions which are seldom available (an inclination of 82.3 degrees and altitude of 294 x 216 km). Measurements were made on the outside of the spacecraft under near-zero shielding conditions. Also, this mission was the first in which active temperature recorders (the ATR-4) were flown to record the temperature profiles of detector stacks. Measurements made on this mission provide a comparison and test for modeling of depth doses and LET spectra for orbital parameters previously unavailable. Tissue absorbed doses from 3480 rad (252 rad/d) down to 0.115 rad (8.33 mrad/d) were measured at different depths (0.0146 and 3.20 g/sq. cm, respectively) with averaged TLD readings. The LET spectra yielded maximum and minimum values of integral flux of 27.3 x 10-4 and 3.05 x 10(exp -4) cm(exp -2).s(exp -1).sr(exp -4) of dose rate of 7.01 and 1.20 mrad/d, and of dose equivalent rate of 53.8 and 11.6 mrem/d, for LET(infinity).H2O is greater than or equal to 4 keV/micro-m. Neutron measurements yielded 0.018 mremld in the thermal region, 0.25 mrem/d in the resonance region and 3.3 mrem/d in the high energy region. The TLD depth dose and LET spectra have been compared with calculations from the modeling codes. The agreement is good but some further refinements are in order. In comparing measurements on Cosmos 2044 with those from previous Cosmos missions (orbital inclinations of 62.8 degrees) there is a greater spread (maximum to minimum) in depth doses and an increased contribution from GCR's, and higher LET particles, in the heavy particle fluxes.

Characterization of the a-Si EPID in the unity MR-linac for dosimetric applications.

PubMed

Torres-Xirau, I; Olaciregui-Ruiz, I; Baldvinsson, G; Mijnheer, B J; van der Heide, U A; Mans, A

2018-01-09

Electronic portal imaging devices (EPIDs) are frequently used in external beam radiation therapy for dose verification purposes. The aim of this study was to investigate the dose-response characteristics of the EPID in the Unity MR-linac (Elekta AB, Stockholm, Sweden) relevant for dosimetric applications under clinical conditions. EPID images and ionization chamber (IC) measurements were used to study the effects of the magnetic field, the scatter generated in the MR housing reaching the EPID, and inhomogeneous attenuation from the MR housing. Dose linearity and dose rate dependencies were also determined. The magnetic field strength at EPID level did not exceed 10 mT, and dose linearity and dose rate dependencies proved to be comparable to that on a conventional linac. Profiles of fields, delivered with and without the magnetic field, were indistinguishable. The EPID center had an offset of 5.6 cm in the longitudinal direction, compared to the beam central axis, meaning that large fields in this direction will partially fall outside the detector area and not be suitable for verification. Beam attenuation by the MRI scanner and the table is gantry angle dependent, presenting a minimum attenuation of 67% relative to the 90° measurement. Repeatability, observed over two months, was within 0.5% (1 SD). In order to use the EPID for dosimetric applications in the MR-linac, challenges related to the EPID position, scatter from the MR housing, and the inhomogeneous, gantry angle-dependent attenuation of the beam will need to be solved.

Characterization of the a-Si EPID in the unity MR-linac for dosimetric applications

NASA Astrophysics Data System (ADS)

Torres-Xirau, I.; Olaciregui-Ruiz, I.; Baldvinsson, G.; Mijnheer, B. J.; van der Heide, U. A.; Mans, A.

2018-01-01

Electronic portal imaging devices (EPIDs) are frequently used in external beam radiation therapy for dose verification purposes. The aim of this study was to investigate the dose-response characteristics of the EPID in the Unity MR-linac (Elekta AB, Stockholm, Sweden) relevant for dosimetric applications under clinical conditions. EPID images and ionization chamber (IC) measurements were used to study the effects of the magnetic field, the scatter generated in the MR housing reaching the EPID, and inhomogeneous attenuation from the MR housing. Dose linearity and dose rate dependencies were also determined. The magnetic field strength at EPID level did not exceed 10 mT, and dose linearity and dose rate dependencies proved to be comparable to that on a conventional linac. Profiles of fields, delivered with and without the magnetic field, were indistinguishable. The EPID center had an offset of 5.6 cm in the longitudinal direction, compared to the beam central axis, meaning that large fields in this direction will partially fall outside the detector area and not be suitable for verification. Beam attenuation by the MRI scanner and the table is gantry angle dependent, presenting a minimum attenuation of 67% relative to the 90° measurement. Repeatability, observed over two months, was within 0.5% (1 SD). In order to use the EPID for dosimetric applications in the MR-linac, challenges related to the EPID position, scatter from the MR housing, and the inhomogeneous, gantry angle-dependent attenuation of the beam will need to be solved.

On-line photolithography modeling using spectrophotometry and Prolith/2

NASA Astrophysics Data System (ADS)

Engstrom, Herbert L.; Beacham, Jeanne E.

1994-05-01

Spectrophotometry has been applied to optimizing photolithography processes in semiconductor manufacturing. For many years thin film measurement systems have been used in manufacturing for controlling film deposition processes. The combination of film thickness mapping with photolithography modeling has expanded the applications of this technology. Experimental measurements of dose-to-clear, the minimum light exposure dose required to fully develop a photoresist, are described. It is shown how dose-to-clear and photoresist contrast may be determined rapidly and conveniently from measurements of a dose exposure matrix on a monitor wafer. Such experimental measurements may underestimate the dose-to- clear because of thickness variations of the photoresist and underlying layers on the product wafer. Online modeling of the photolithographic process together with film thickness maps of the entire wafer can overcome this problem. Such modeling also provides maps of dose-to- clear and resist linewidth that can be used to estimate and optimize yield.

Cytoprotective doses of erythropoietin or carbamylated erythropoietin have markedly different procoagulant and vasoactive activities.

PubMed

Coleman, Thomas R; Westenfelder, Christof; Tögel, Florian E; Yang, Ying; Hu, Zhuma; Swenson, Leanne; Leuvenink, Henri G D; Ploeg, Rutger J; d'Uscio, Livius V; Katusic, Zvonimir S; Ghezzi, Pietro; Zanetti, Adriana; Kaushansky, Kenneth; Fox, Norma E; Cerami, Anthony; Brines, Michael

2006-04-11

Recombinant human erythropoietin (rhEPO) is receiving increasing attention as a potential therapy for prevention of injury and restoration of function in nonhematopoietic tissues. However, the minimum effective dose required to mimic and augment these normal paracrine functions of erythropoietin (EPO) in some organs (e.g., the brain) is higher than for treatment of anemia. Notably, a dose-dependent risk of adverse effects has been associated with rhEPO administration, especially in high-risk groups, including polycythemia-hyperviscosity syndrome, hypertension, and vascular thrombosis. Of note, several clinical trials employing relatively high dosages of rhEPO in oncology patients were recently halted after an increase in mortality and morbidity, primarily because of thrombotic events. We recently identified a heteromeric EPO receptor complex that mediates tissue protection and is distinct from the homodimeric receptor responsible for the support of erythropoiesis. Moreover, we developed receptor-selective ligands that provide tools to assess which receptor isoform mediates which biological consequence of rhEPO therapy. Here, we demonstrate that rhEPO administration in the rat increases systemic blood pressure, reduces regional renal blood flow, and increases platelet counts and procoagulant activities. In contrast, carbamylated rhEPO, a heteromeric receptor-specific ligand that is fully tissue protective, increases renal blood flow, promotes sodium excretion, reduces injury-induced elevation in procoagulant activity, and does not effect platelet production. These preclinical findings suggest that nonerythropoietic tissue-protective ligands, which appear to elicit fewer adverse effects, may be especially useful in clinical settings for tissue protection.

Cytoprotective doses of erythropoietin or carbamylated erythropoietin have markedly different procoagulant and vasoactive activities

PubMed Central

Coleman, Thomas R.; Westenfelder, Christof; Tögel, Florian E.; Yang, Ying; Hu, Zhuma; Swenson, LeAnne; Leuvenink, Henri G. D.; Ploeg, Rutger J.; d’Uscio, Livius V.; Katusic, Zvonimir S.; Ghezzi, Pietro; Zanetti, Adriana; Kaushansky, Kenneth; Fox, Norma E.; Cerami, Anthony; Brines, Michael

2006-01-01

Recombinant human erythropoietin (rhEPO) is receiving increasing attention as a potential therapy for prevention of injury and restoration of function in nonhematopoietic tissues. However, the minimum effective dose required to mimic and augment these normal paracrine functions of erythropoietin (EPO) in some organs (e.g., the brain) is higher than for treatment of anemia. Notably, a dose-dependent risk of adverse effects has been associated with rhEPO administration, especially in high-risk groups, including polycythemia–hyperviscosity syndrome, hypertension, and vascular thrombosis. Of note, several clinical trials employing relatively high dosages of rhEPO in oncology patients were recently halted after an increase in mortality and morbidity, primarily because of thrombotic events. We recently identified a heteromeric EPO receptor complex that mediates tissue protection and is distinct from the homodimeric receptor responsible for the support of erythropoiesis. Moreover, we developed receptor-selective ligands that provide tools to assess which receptor isoform mediates which biological consequence of rhEPO therapy. Here, we demonstrate that rhEPO administration in the rat increases systemic blood pressure, reduces regional renal blood flow, and increases platelet counts and procoagulant activities. In contrast, carbamylated rhEPO, a heteromeric receptor-specific ligand that is fully tissue protective, increases renal blood flow, promotes sodium excretion, reduces injury-induced elevation in procoagulant activity, and does not effect platelet production. These preclinical findings suggest that nonerythropoietic tissue-protective ligands, which appear to elicit fewer adverse effects, may be especially useful in clinical settings for tissue protection. PMID:16585502

Metformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis

PubMed Central

Loos, Julia A.; Dávila, Valeria A.; Rodrígues, Christian R.; Petrigh, Romina; Zoppi, Jorge A.; Crocenzi, Fernando A.; Cumino, Andrea C.

2017-01-01

Metformin (Met) is an anti-hyperglycemic and potential anti-cancer agent which may exert its anti-proliferative effects via the induction of energetic stress. In this study we investigated the in vitro and in vivo efficacy of Met against the larval stage of Echinococcus granulosus. Metformin showed significant dose- and time-dependent killing effects on in vitro cultured protoscoleces and metacestodes. Notably, the combination of Met together with the minimum effective concentration of ABZSO had a synergistic effect after days 3 and 12 on metacestodes and protoscoleces, respectively. Oral administration of Met (50 mg/kg/day) in E. granulosus-infected mice was highly effective in reducing the weight and number of parasite cysts, yet its combination with the lowest recommended dose of ABZ (5 mg/kg/day) was even more effective. Coincidentally, intracystic Met accumulation was higher in animals treated with both drugs compared to those administered Met alone. Furthermore, the safe plant-derived drug Met exhibited remarkable chemopreventive properties against secondary hydatidosis in mice. In conclusion, based on our experimental data, Met emerges as a promising anti-echinococcal drug as it has proven to efficiently inhibit the development and growth of the E. granulosus larval stage and its combination with ABZ may improve the current anti-parasitic therapy. PMID:28182659

Optimizing tamoxifen-inducible Cre/loxp system to reduce tamoxifen effect on bone turnover in long bones of young mice.

PubMed

Zhong, Zhendong A; Sun, Weihua; Chen, Haiyan; Zhang, Hongliang; Lay, Yu-An E; Lane, Nancy E; Yao, Wei

2015-12-01

For tamoxifen-dependent Cre recombinase, also known as CreER recombinase, tamoxifen (TAM) is used to activate the Cre to generate time- and tissue-specific mouse mutants. TAM is a potent CreER system inducer; however, TAM is also an active selective estrogen receptor modulator (SERM) that can influence bone homeostasis. The purpose of this study was to optimize the TAM dose for Cre recombinase activation while minimizing the effects of TAM on bone turnover in young growing mice. To evaluate the effects of TAM on bone turnover and bone mass, 1-month-old wild-type male and female mice were intraperitoneally injected with TAM at 0, 1, 10 or 100mg/kg/day for four consecutive days, or 100, 300 mg/kg/day for one day. The distal femurs were analyzed one month after the last TAM injection by microCT, mechanical test, and surface-based bone histomorphometry. Similar doses of TAM were used in Col1 (2.3 kb)-CreERT2; mT/mG reporter male mice to evaluate the dose-dependent efficacy of Cre-ER activation in bone tissue. A TAM dose of 100 mg/kg × 4 days significantly increased trabecular bone volume/total volume (BV/TV) of the distal femur, femur length, bone strength, and serum bone turnover markers compared to the 0mg control group. In contrast, TAM doses ≤ 10 mg/kg did not significantly change any of these parameters compared to the 0mg group, although a higher bone strength was observed in the 10mg group. Surface-based histomorphometry revealed that the 100mg/kg dose of TAM dose significantly increased trabecular bone formation and decreased periosteal bone formation at 1-week post-TAM treatment. Using the reporter mouse model Col1-CreERT2; mT/mG, we found that 10mg/kg TAM induced Col1-CreERT2 activity in bone at a comparable level to the 100mg/kg dose. TAM treatment at 100mg/kg/day × 4 days significantly affects bone homeostasis, resulting in an anabolic bone effect on trabecular bone in 1-month-old male mice. However, a lower dose of TAM at 10 mg/kg/day × 4 days can yield similar Col1-CreERT2 induction efficacy with minimum effects on bone turnover in young male mice. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of radioactive iodine therapy on carotid intima media thickness in patients with hyperthyroidism.

PubMed

Şanal, Bekir; Işık, İlknur; Korkmaz, Mehmet; Kucur, Cüneyt; Can, Fatma; Kilit, Türkan Paşalı; Kahraman, Cüneyt; Kaçar, Emre; Koçak, Ahmet

2016-01-01

The aim of this study was to evaluate the carotid intima media thickness (IMT) in patients with thyrotoxicosis who received radioactive iodine (RAI) treatment. This study was planned to be conducted with two different groups of people. There were 87 patients in the patient group and 98 controls. Participants were evaluated for atherosclerosis risk factors. Mean carotid IMT was measured from three consecutive traces at the common carotid artery bifurcation. The mean carotid IMT was 0.81 ± 0.20 in patient group and this was higher than the controls (0.68 ± 0.19) (p < 0.01). IM thickening was positively correlated with the applied RAI dose levels in the treatment group (p = 0.029). In patients with only HT, the data of the two groups showed a significant difference, with the average IMT being higher in the patient group than that of the control group (p: 0.011). RAI used in the treatment of thyrotoxicosis increases the IMT of carotid artery independent of age and sex. This treatment yields better results with higher doses, and this effect is more marked in patients with HT. Hence, we believe that it is necessary to calculate the dose properly for hyperthyroid cases in which treatment with RAI is planned. In particular, the patients with HT need to be treated with the minimum possible dose. Further, carotid arteries should be evaluated with US following RAI treatment.

Evaluation of the Reinforcing Effect of Quetiapine, Alone and in Combination with Cocaine, in Rhesus Monkeys.

PubMed

Brutcher, Robert E; Nader, Susan H; Nader, Michael A

2016-02-01

There are several case reports of nonmedicinal quetiapine abuse, yet there are very limited preclinical studies investigating quetiapine self-administration. The goal of this study was to investigate the reinforcing effects of quetiapine alone and in combination with intravenous cocaine in monkeys. In experiment 1, cocaine-experienced female monkeys (N = 4) responded under a fixed-ratio (FR) 30 schedule of food reinforcement (1.0-g banana-flavored pellets), and when responding was stable, quetiapine (0.003-0.1 mg/kg per injection) or saline was substituted for a minimum of five sessions; there was a return to food-maintained responding between doses. Next, monkeys were treated with quetiapine (25 mg, by mouth, twice a day) for approximately 30 days, and then the quetiapine self-administration dose-response curve was redetermined. In experiment 2, male monkeys (N = 6) self-administered cocaine under a concurrent FR schedule with food reinforcement (three food pellets) as the alternative to cocaine (0.003-0.3 mg/kg per injection) presentation. Once choice responding was stable, the effects of adding quetiapine (0.03 or 0.1 mg/kg per injection) to the cocaine solution were examined. In experiment 1, quetiapine did not function as a reinforcer, and chronic quetiapine treatment did not alter these effects. In experiment 2, cocaine choice increased in a dose-dependent fashion. The addition of quetiapine to cocaine resulted in increases in low-dose cocaine choice and number of cocaine injections in four monkeys, while not affecting high-dose cocaine preference. Thus, although quetiapine alone does not have abuse potential, there was evidence of enhancement of the reinforcing potency of cocaine. These results suggest that the use of quetiapine in cocaine-addicted patients should be monitored. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

SU-F-T-129: Impact of Radial Fluctuations in RBE for Therapeutic Proton Beams

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

Butkus, M; Palmer, T

Purpose: To evaluate the off axis relative biological effectiveness (RBE) for actively scanned proton beams and determine if a constant radial RBE can be assumed. Methods: The PHITS Monte Carlo code paired with a microscopic analytical function was used to determine probability distribution functions of the lineal energy in 0.3µm diameter spheres throughout a water phantom. Twenty million primary protons were simulated for a 0.6cm diameter pencil beam. Beam energies corresponding to Bragg Peak depths of 50, 100, 150, 200, 250, and 300mm were used and evaluated transversely every millimeter and radially for annuli of 1.0, 2.0, 3.0, 3.2, 3.4,more » 3.6, 4.0, 5.0, 10.0, 15.0, 20.0 and 25.0mm outer radius. The acquired probability distributions were reduced to dose-mean lineal energies and applied to the modified microdosimetric kinetic model, for human submandibular gland (HSG) cells, to calculate relative biological effectiveness (RBE) compared to 60Co beams at the 10% survival threshold. Results: RBE was generally seen to increase as distance from the central axis (CAX) increased. However, this increase was only seen in low dose regions and its overall effects on the transverse biological dose remains low. In the entrance region of the phantom (10mm depth), minimum and maximum calculated RBEs varied between 15.22 and 18.88% for different energies. At the Bragg peak, this difference ranged from 3.15 to 26.77%. Despite these rather large variations the dose-weighted RBE and the CAX RBE varied by less than 0.14% at 10mm depth and less than 0.16% at the Bragg peak. Similarly small variations were found at all depths proximal of the Bragg peak. Conclusion: Although proton RBE does vary radially, its overall effect on biological dose is minimal and the use of a radially constant RBE in treatment planning for scanned proton beams would not produce large errors.« less

The effect on esophagus after different radiotherapy techniques for early stage Hodgkin's lymphoma.

PubMed

Jørgensen, Anni Y S; Maraldo, Maja V; Brodin, Nils Patrik; Aznar, Marianne C; Vogelius, Ivan R; Rosenschöld, Per Munck Af; Petersen, Peter M; Specht, Lena

2013-10-01

The cure rate of early stage Hodgkin's lymphoma (HL) is excellent; investigating the late effects of treatment is thus important. Esophageal toxicity is a known side effect in patients receiving radiotherapy (RT) to the mediastinum, although little is known of this in HL survivors. This study investigates the dose to the esophagus in the treatment of early stage HL using different RT techniques. Estimated risks of early esophagitis, esophageal stricture and cancer are compared between treatments. We included 46 patients ≥ 15 years with supradiaphragmatic, clinical stage I-II HL, who received chemotherapy followed by involved node RT (INRT) to 30.6 Gy at our institution. INRT was planned with three-dimensional conformal RT (3DCRT). For each patient a volumetric modulated arc therapy (VMAT), proton therapy (PT) and mantle field (MF) treatment plan was simulated. Mean, maximum and minimum dose to the esophagus were extracted from the treatment plans. Risk estimates were based on dose-response models from clinical series with long-term follow-up. Statistical analyses were performed with repeated measures ANOVA using Bonferroni corrections. Mean dose to the esophagus was 16.4, 16.4, 14.7 and 34.2 Gy (p < 0.001) with 3DCRT, VMAT, PT and MF treatment, respectively. No differences were seen in the estimated risk of developing esophagitis, stricture or cancer with 3DCRT compared to VMAT (p = 1.000, p = 1.000, p = 0.356). PT performed significantly better with the lowest risk estimates on all parameters compared to the photon treatments, except compared to 3DCRT for stricture (p = 0.066). On all parameters the modern techniques were superior to MF treatment (p < 0.001). The estimated dose to the esophagus and the corresponding estimated risks of esophageal complications are decreased significantly with highly conformal RT compared to MF treatment. The number of patients presenting with late esophageal side effects will, thus, likely be minimal in the future.

Biochemical effects of glyphosate based herbicide, Excel Mera 71 on enzyme activities of acetylcholinesterase (AChE), lipid peroxidation (LPO), catalase (CAT), glutathione-S-transferase (GST) and protein content on teleostean fishes.

PubMed

Samanta, Palas; Pal, Sandipan; Mukherjee, Aloke Kumar; Ghosh, Apurba Ratan

2014-09-01

Effects of glyphosate based herbicide, Excel Mera 71 at a dose of 17.20mg/l on enzyme activities of acetylcholinesterase (AChE), lipid peroxidation (LPO), catalase (CAT), glutathione-S-transferase (GST) and protein content were measured in different tissues of two Indian air-breathing teleosts, Anabas testudineus (Bloch) and Heteropneustes fossilis (Bloch) during an exposure period of 30 days under laboratory condition. AChE activity was significantly increased in all the investigated tissues of both fish species and maximum elevation was observed in brain of H. fossilis, while spinal cord of A. testudineus showed minimum increment. Fishes showed significant increase LPO levels in all the tissues; highest was observed in gill of A. testudineus but lowest LPO level was observed in muscle of H. fossilis. CAT was also enhanced in both the fishes, while GST activity in liver diminished substantially and minimum was observed in liver of A. testudineus. Total protein content showed decreased value in all the tissues, maximum reduction was observed in liver and minimum in brain of A. testudineus and H. fossilis respectively. The results indicated that Excel Mera 71 caused serious alterations in the enzyme activities resulting into severe deterioration of fish health; so, AChE, LPO, CAT and GST can be used as suitable indicators of herbicidal toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

Update on the Worsening Particle Radiation Environment Observed by CRaTER and Implications for Future Human Deep-Space Exploration

NASA Astrophysics Data System (ADS)

Schwadron, N. A.; Rahmanifard, F.; Wilson, J.; Jordan, A. P.; Spence, H. E.; Joyce, C. J.; Blake, J. B.; Case, A. W.; de Wet, W.; Farrell, W. M.; Kasper, J. C.; Looper, M. D.; Lugaz, N.; Mays, L.; Mazur, J. E.; Niehof, J.; Petro, N.; Smith, C. W.; Townsend, L. W.; Winslow, R.; Zeitlin, C.

2018-03-01

Over the last decade, the solar wind has exhibited low densities and magnetic field strengths, representing anomalous states that have never been observed during the space age. As discussed by Schwadron, Blake, et al. (2014, https://doi.org/10.1002/2014SW001084), the cycle 23-24 solar activity led to the longest solar minimum in more than 80 years and continued into the "mini" solar maximum of cycle 24. During this weak activity, we observed galactic cosmic ray fluxes that exceeded theERobserved small solar energetic particle events. Here we provide an update to the Schwadron, Blake, et al. (2014, https://doi.org/10.1002/2014SW001084) observations from the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) on the Lunar Reconnaissance Orbiter. The Schwadron, Blake, et al. (2014, https://doi.org/10.1002/2014SW001084) study examined the evolution of the interplanetary magnetic field and utilized a previously published study by Goelzer et al. (2013, https://doi.org/10.1002/2013JA019404) projecting out the interplanetary magnetic field strength based on the evolution of sunspots as a proxy for the rate that the Sun releases coronal mass ejections. This led to a projection of dose rates from galactic cosmic rays on the lunar surface, which suggested a ˜20% increase of dose rates from one solar minimum to the next and indicated that the radiation environment in space may be a worsening factor important for consideration in future planning of human space exploration. We compare the predictions of Schwadron, Blake, et al. (2014, https://doi.org/10.1002/2014SW001084) with the actual dose rates observed by CRaTER in the last 4 years. The observed dose rates exceed the predictions by ˜10%, showing that the radiation environment is worsening more rapidly than previously estimated. Much of this increase is attributable to relatively low-energy ions, which can be effectively shielded. Despite the continued paucity of solar activity, one of the hardest solar events in almost a decade occurred in September 2017 after more than a year of all-clear periods. These particle radiation conditions present important issues that must be carefully studied and accounted for in the planning and design of future missions (to the Moon, Mars, asteroids, and beyond).

Effect of processing time delay on the dose response of Kodak EDR2 film.

PubMed

Childress, Nathan L; Rosen, Isaac I

2004-08-01

Kodak EDR2 film is a widely used two-dimensional dosimeter for intensity modulated radiotherapy (IMRT) measurements. Our clinical use of EDR2 film for IMRT verifications revealed variations and uncertainties in dose response that were larger than expected, given that we perform film calibrations for every experimental measurement. We found that the length of time between film exposure and processing can affect the absolute dose response of EDR2 film by as much as 4%-6%. EDR2 films were exposed to 300 cGy using 6 and 18 MV 10 x 10 cm2 fields and then processed after time delays ranging from 2 min to 24 h. An ion chamber measured the relative dose for these film exposures. The ratio of optical density (OD) to dose stabilized after 3 h. Compared to its stable value, the film response was 4%-6% lower at 2 min and 1% lower at 1 h. The results of the 4 min and 1 h processing time delays were verified with a total of four different EDR2 film batches. The OD/dose response for XV2 films was consistent for time periods of 4 min and 1 h between exposure and processing. To investigate possible interactions of the processing time delay effect with dose, single EDR2 films were irradiated to eight different dose levels between 45 and 330 cGy using smaller 3 x 3 cm2 areas. These films were processed after time delays of 1, 3, and 6 h, using 6 and 18 MV photon qualities. The results at all dose levels were consistent, indicating that there is no change in the processing time delay effect for different doses. The difference in the time delay effect between the 6 and 18 MV measurements was negligible for all experiments. To rule out bias in selecting film regions for OD measurement, we compared the use of a specialized algorithm that systematically determines regions of interest inside the 10 x 10 cm2 exposure areas to manually selected regions of interest. There was a maximum difference of only 0.07% between the manually and automatically selected regions, indicating that the use of a systematic algorithm to determine regions of interest in large and fairly uniform areas is not necessary. Based on these results, we recommend a minimum time of 1 h between exposure and processing for all EDR2 film measurements.

Computer program optimizes design of nuclear radiation shields

NASA Technical Reports Server (NTRS)

Lahti, G. P.

1971-01-01

Computer program, OPEX 2, determines minimum weight, volume, or cost for shields. Program incorporates improved coding, simplified data input, spherical geometry, and an expanded output. Method is capable of altering dose-thickness relationship when a shield layer has been removed.

Intensity-modulated radiation therapy with concurrent chemotherapy for locally advanced cervical and upper thoracic esophageal cancer.

PubMed

Wang, Shu-Lian; Liao, Zhongxing; Liu, Helen; Ajani, Jaffer; Swisher, Stephen; Cox, James D; Komaki, Ritsuko

2006-09-14

To evaluate the dosimetry, efficacy and toxicity of intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with locally advanced cervical and upper thoracic esophageal cancer. A retrospective study was performed on 7 patients who were definitively treated with IMRT and concurrent chemotherapy. Patients who did not receive IMRT radiation and concurrent chemotherapy were not included in this analysis. IMRT plans were evaluated to assess the tumor coverage and normal tissue avoidance. Treatment response was evaluated and toxicities were assessed. Five- to nine-beam IMRT were used to deliver a total dose of 59.4-66 Gy (median: 64.8 Gy) to the primary tumor with 6-MV photons. The minimum dose received by the planning tumor volume (PTV) of the gross tumor volume boost was 91.2%-98.2% of the prescription dose (standard deviation [SD]: 3.7%-5.7%). The minimum dose received by the PTV of the clinical tumor volume was 93.8%-104.8% (SD: 4.3%-11.1%) of the prescribed dose. With a median follow-up of 15 mo (range: 3-21 mo), all 6 evaluable patients achieved complete response. Of them, 2 developed local recurrences and 2 had distant metastases, 3 survived with no evidence of disease. After treatment, 2 patients developed esophageal stricture requiring frequent dilation and 1 patient developed tracheal-esophageal fistula. Concurrent IMRT and chemotherapy resulted in an excellent early response in patients with locally advanced cervical and upper thoracic esophageal cancer. However, local and distant recurrence and toxicity remain to be a problem. Innovative approaches are needed to improve the outcome.

Investigation of pulsed IMRT and VMAT for re-irradiation treatments: dosimetric and delivery feasibilities

NASA Astrophysics Data System (ADS)

Lin, Mu-Han; Price, Robert A., Jr.; Li, Jinsheng; Kang, Shengwei; Li, Jie; Ma, C.-M.

2013-11-01

Many tumor cells demonstrate hyperradiosensitivity at doses below ˜50 cGy. Together with the increased normal tissue repair under low dose rate, the pulsed low dose rate radiotherapy (PLDR), which separates a daily fractional dose of 200 cGy into 10 pulses with 3 min interval between pulses (˜20 cGy/pulse and effective dose rate 6.7 cGy min-1), potentially reduces late normal tissue toxicity while still providing significant tumor control for re-irradiation treatments. This work investigates the dosimetric and technical feasibilities of intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT)-based PLDR treatments using Varian Linacs. Twenty one cases (12 real re-irradiation cases) including treatment sites of pancreas, prostate, pelvis, lung, head-and-neck, and breast were recruited for this study. The lowest machine operation dose rate (100 MU min-1) was employed in the plan delivery. Ten-field step-and-shoot IMRT and dual-arc VMAT plans were generated using the Eclipse TPS with routine planning strategies. The dual-arc plans were delivered five times to achieve a 200 cGy daily dose (˜20 cGy arc-1). The resulting plan quality was evaluated according to the heterogeneity and conformity indexes (HI and CI) of the planning target volume (PTV). The dosimetric feasibility of retaining the hyperradiosensitivity for PLDR was assessed based on the minimum and maximum dose in the target volume from each pulse. The delivery accuracy of VMAT and IMRT at the 100 MU min-1 machine operation dose rate was verified using a 2D diode array and ion chamber measurements. The delivery reproducibility was further investigated by analyzing the Dynalog files of repeated deliveries. A comparable plan quality was achieved by the IMRT (CI 1.10-1.38 HI 1.04-1.10) and the VMAT (CI 1.08-1.26 HI 1.05-1.10) techniques. The minimum/maximum PTV dose per pulse is 7.9 ± 5.1 cGy/33.7 ± 6.9 cGy for the IMRT and 12.3 ± 4.1 cGy/29.2 ± 4.7 cGy for the VMAT. Six out of the 186 IMRT pulses (fields) were found to exceed 50 cGy maximum PTV dose per pulse while the maximum PTV dose per pulse was within 40 cGy for all the VMAT pulses (arcs). However, for VMAT plans, the dosimetric quality of the entire treatment plan was less superior for the breast cases and large irregular targets. The gamma passing rates for both techniques at the 100 MU min-1 dose rate were at least 94.1% (3%/3 mm) and the point dose measurements agreed with the planned values to within 2.2%. The average root mean square error of the leaf position was 0.93 ± 0.83 mm for IMRT and 0.53 ± 0.48 mm for VMAT based on the Dynalog file analysis. The RMS error of the leaf position was nearly identical for the repeated deliveries of the same plans. In general, both techniques are feasible for PLDR treatments. VMAT was more advantageous for PLDR with more uniform target dose per pulse, especially for centrally located tumors. However, for large, irregular and/or peripheral tumors, IMRT could produce more favorable PLDR plans. By taking the biological benefit of PLDR delivery and the dosimetric benefit of IMRT and VMAT, the proposed methods have a great potential for those previously-irradiated recurrent patients.

Prevention of posttraumatic hypoxaemia in isolated lower limb long bone fractures with a minimal prophylactic dose of corticosteroids.

PubMed

Babalis, George A; Yiannakopoulos, Christos K; Karliaftis, Konstantinos; Antonogiannakis, Emmanuel

2004-03-01

The efficacy of a minimum dose of methylprednisolone for the prevention of posttraumatic hypoxaemia and fat embolism syndrome (FES) was prospectively studied in 87 patients with isolated, closed or grade I open, femoral and tibial fractures. On admission, the patients were randomly allocated either to a control group given placebo (40 patients) or to a methylprednisolone-treated group (47 patients). A total dose of 6 mg/kg BW methylprednisolone (SoluMedrol, Upjohn) was administered intravenously, divided in six equal doses at 8 h intervals. Six patients (12.8%) in the control group and one patient (2.5%) in the trial group developed FES (P = 0.079) but the difference is not statistically significant. Twenty-four hours after admission, the steroid-treated patients displayed statistically significant higher p(O2) values compared to the control group (P = 0.035) and this difference persisted on the second and the third post-admission day as well (P = 0.008). No corticosteroid-related side-effects were noticed in any of the patients during hospitalisation. Our results support the prophylactic administration of methylprednisolone in small dosage to prevent posttraumatic hypoxaemia and probably FES in patients with isolated lower limb long bone fractures, especially when early fracture stabilisation is not possible.

Simulation of irradiation exposure of electronic devices due to heavy ion therapy with Monte Carlo Code MCNP6

NASA Astrophysics Data System (ADS)

Lapins, Janis; Guilliard, Nicole; Bernnat, Wolfgang; Buck, Arnulf

2017-09-01

During heavy ion irradiation therapy the patient has to be located exactly at the right position to make sure that the Bragg peak occurs in the tumour. The patient has to be moved in the range of millimetres to scan the ill tissue. For that reason a special table was developed which allows exact positioning. The electronic control can be located outside the surgery. But that has some disadvantage for the construction. To keep the system compact it would be much more comfortable to put the electronic control inside the surgery. As a lot of high energetic secondary particles are produced during the therapy causing a high dose in the room it is important to find positions with low dose rates. Therefore, investigations are needed where the electronic devices should be located to obtain a minimum of radiation, help to prevent the failure of sensitive devices. The dose rate was calculated for carbon ions with different initial energy and protons over the entire therapy room with Monte Carlo particle tracking using MCNP6. The types of secondary particles were identified and the dose rate for a thin silicon layer and an electronic mixture material was determined. In addition, the shielding effect of several selected material layers was calculated using MCNP6.

Acute effects of quercetin-3-O-glucoside on endothelial function and blood pressure: a randomized dose-response study.

PubMed

Bondonno, Nicola P; Bondonno, Catherine P; Rich, Lisa; Mas, Emilie; Shinde, Sujata; Ward, Natalie C; Hodgson, Jonathan M; Croft, Kevin D

2016-07-01

Epidemiologic studies have suggested that a flavonoid-rich diet can reduce the risk of developing cardiovascular disease. Certain flavonoids, in particular quercetin, have been shown to ameliorate endothelial dysfunction and reduce blood pressure (BP), possibly by increasing the bioavailability of the potent vasodilator nitric oxide (NO). Several studies have indicated that improvements in measures of cardiovascular health do not occur linearly, but rather, plateau or decrease with an increasing dose of flavonoids. We determined whether the acute administration of increasing doses of a common quercetin glycoside (quercetin-3-O-glucoside) improves endothelial function and reduces BP in a dose-dependent manner. We also explored whether any effects were correlated with changes in plasma NO production. A randomized, controlled, crossover study was performed in 15 healthy volunteers who each completed 5 visits with a minimum washout period of 1 wk between testing days. Participants received each of the following 5 interventions in a random order: 1) 0, 2) 50, 3) 100, 4) 200, or 5) 400 mg quercetin-3-O-glucoside. Endothelial function and BP were assessed before and 60 min after intervention. A blood sample was taken before and 90 min after intervention for the analysis of plasma nitrate and nitrite as markers of NO production as well as of plasma quercetin metabolites. Although we observed a significant correlation between the dose of quercetin-3-O-glucoside and plasma concentrations of total quercetin (R(2) = 0.52, P < 0.001) and isorhamnetin (R(2) = 0.12, P = 0.005), we showed no improvements in endothelial function or BP and no changes in NO production after any dose. From these results, we conclude that there are no acute changes in BP or the NO-mediated endothelium-dependent relaxation of the brachial artery with doses of quercetin ranging from 50 to 400 mg in healthy men and women. This trial was registered at www.anzctr.org.au as ACTRN12615001338550. © 2016 American Society for Nutrition.

CONCEPTUAL DESIGN STUDY OF A MOBILE GAMMA IRRADIATOR FOR FRUIT PRODUCE

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

None

1962-05-31

Engineering Drawings report available as CAPE-944. A conceptual design study was made of a mobile irradiator for radiopasteurization of strawberries, grapes, peaches, tomatoes, and lemons. Minimum radiation dose specification for the fruit ranged from 100,000 to 200,000 rads with maximum to minimum dose ratio in the range of 1.5 to 3. Minimum allowable production rates were in the range of 500 to 1000 lb of fruit/hr. The irradiator was required to be mobile, preferably on one truck capable of being put in operation one day after arrival at the site. Preliminary studies compared five types of irradiators, consisting of amore » single source slab, two package pass design; a double slab, single pass design; a single slab, four pass design; a line source rotary design; and a movable source, movable package design. It was concluded that a Co/sup 60/ irradiator can be built to meet the general requirements for radiopasteurization of fruit. The irradiator can be made mobile and can be mounted on a single trailer. The combined weight of the mobile unit would be 70 to 85 tons depending on the type of irradiator. This unit would require a special license from the State Highway Department. (C.H.)« less

Determinants of amikacin first peak concentration in critically ill patients.

PubMed

Boidin, Clément; Jenck, Sophie; Bourguignon, Laurent; Torkmani, Sejad; Roussey-Jean, Aurore; Ledochowski, Stanislas; Marry, Lucie; Ammenouche, Nacim; Dupont, Hervé; Marçon, Frédéric; Allaouchiche, Bernard; Bohé, Julien; Lepape, Alain; Goutelle, Sylvain; Friggeri, Arnaud

2018-04-16

Amikacin antimicrobial effect has been correlated with the ratio of the peak concentration (C max ) to the minimum inhibitory concentration. A target C max ≥ 60-80 mg/L has been suggested. It has been shown that such target is not achieved in a large proportion of critically ill patients in intensive care units. A retrospective analysis was performed to examine the determinants of C max ≥ 80 mg/L on the first peak in 339 critically ill patients treated by amikacin. The influence of available variables on C max target attainment was analyzed using a classification and regression tree (CART) and logistic regression. Mean C max in the 339 patients was 73.0 ± 23.9 mg/L, with a target attainment rate (TAR, C max ≥ 80 mg/L) of 37.5%. In CART analysis, the strongest predictor of amikacin target peak attainment was dose per kilogram of lean body weight (dose/LBW). TAR was 60.1% in patients with dose/LBW ≥ 37.8 vs. 19.9% in patients with lower dose/LBW (OR = 6.0 (95% CI: 3.6-10.2)). Renal function was a secondary predictor of C max . Logistic regression analysis identified dose per kilogram of ideal body weight (OR = 1.13 (95% CI: 1.09-1.17)) and creatinine clearance (OR = 0.993 (95% CI: 0.988-0.998)) as predictors of target peak achievement. Based on our results, an amikacin dose ≥ 37.8 mg/kg of LBW should be used to optimize the attainment of C max ≥ 80 mg/L after the first dose in critically ill patients. An even higher dose may be necessary in patients with normal renal function. © 2018 Société Française de Pharmacologie et de Thérapeutique.

Review and state of the art on radiation sterilization of medical devices

NASA Astrophysics Data System (ADS)

Dorpema, J. W.

Review and state of art of radiation sterilization Radiation as a sterilization method was designed in the years 1950-1960. The decade afterwards the application for sterilization of medical products and devices was developped. Extensive studies performed on both the physical, chemical and (micro) biological aspects revealed the requirements for safety and efficacy. These efforts were highly stimulated by the IAEA and resulted in a elegant sterilization method. In product manufacturing, where sterilization represents a final step in the production sequence, radiation has eversince reached its widest application in the field of medical devices. As a spin off it initiated new ideas and approaches towards sterilization in general. Consequently sterility was redefined in terms of a probabilistic concept (10-6) and the bioburden determination method was introduced as a tool for both quality control and potential instrument for dose setting. However these refinements also created controversies, whereby the dose requirements became divided for Europe and North America. Moreover studies recently performed in Europe suggest even a further extension of this opinion gap. Detailed studies, on the clinical effects of low dose treated products (12.5 - 17.5 kGy) are needed to counterbalance the dose suggestions extracted from statistically based dose determinations (> 28 kGy ) and the microbiological resistance determinations ( > 28 - 30 kGy). Dose setting based on risk classification could be considered for distinct product categories. In the mean time a general acceptance of the originally, in the early seventhies, established minimum dose of 25 kGy would seem a reasonable compromise. As the interest for radiation sterilization as the favourable, non polluting and simple method is increasing rapidly over the last five years, both gamma- and beta driven sterilization plants will be needed. Harmonization on sterilization dose therfore requires high priority.

Acute toxicity in five dogs after ingestion of a commercial snail and slug bait containing iron EDTA.

PubMed

Haldane, S L; Davis, R M

2009-07-01

This case series of five dogs describes the effects of ingesting large amounts of an iron EDTA snail-bait product. In all cases signs of toxicity occurred between 6 and 24 h after ingestion and included abdominal pain and haemorrhagic gastroenteritis. Two of the dogs had pretreatment serum iron levels measured and in both cases the levels were above normal limits. All of the dogs were treated with iron chelation therapy and supportive care including intravenous fluids, analgesics, gastric protectants and antibiotics. Chelation therapy with desferrioxamine mesylate did not cause adverse effects in any of the dogs and all survived to discharge. The effects of iron EDTA snail bait in dogs requires further study and minimum toxic doses need to be established.

Effects of Lidocaine, Dexmedetomidine or Their Combination on the Minimum Alveolar Concentration of Sevoflurane in Dogs

PubMed Central

MORAN-MUÑOZ, Rafael; IBANCOVICHI, J. A.; Gutierrez-BLANCO, Eduardo; ACEVEDO-ARCIQUE, Carlos M.; Victoria MORA, J. Mauro; TENDILLO, Francisco J.; SANTOS-GONZALEZ, Martin; YAMASHITA, Kazuto

2014-01-01

ABSTRACT The aim of this study was to determine the effects of lidocaine (LIDO) and dexmedetomidine (DEX) or their combination (LIDO–DEX), administered by constant-rate infusion (CRI), on the minimum alveolar concentration (MAC) of sevoflurane in dogs. Seven healthy mongrel dogs were used with a 2-week washout interval between treatments in this study. Anesthesia was induced with propofol and maintained with sevoflurane in oxygen, and MAC of sevoflurane was determined after 90 min equilibration period in the dogs (SEV-MACBASAL). Then, sevoflurane MAC was determined again in the dogs after 45 min equilibration period of one of the following treatments: an intravenous loading dose of lidocaine 2 mg/kg followed by 6 mg/kg/hr CRI (SEV-MACLIDO); an intravenous loading dose of dexmedetomidine 2 µg/kg followed by 2 µg/kg/hr CRI (SEV-MACDEX); or their combination (SEV-MACLIDO-DEX). These SEV-MACs were determined in duplicate. Data were analyzed using ANOVA and post hoc Tuckey test when appropriate. The SEV-MACBASAL was 1.82 ± 0.06%, SEV-MACLIDO was 1.38 ± 0.08%, SEV-MACDEX was 1.22 ± 0.10%, and SEV-MACLIDO-DEX was 0.78 ± 0.06%. The CRI administration of lidocaine, dexmedetomidine and their combination produced a significant reduction in the MAC of sevoflurane by 26.1 ± 9.0% (P<0.0001), 43.7 ± 11.8% (P<0.0002) and 54.4 ± 9.8% (P<0.0001), respectively. The MAC reduction was significantly greater after the CRI combination of lidocaine and dexmedetomidine when compared with lidocaine CRI (P<0.0001) or dexmedetomidine CRI treatments (P<0.025). PMID:24572631

High-purity Nisin Alone or in Combination with Sodium Hypochlorite Is Effective against Planktonic and Biofilm Populations of Enterococcus faecalis.

PubMed

Kajwadkar, Ruma; Shin, Jae M; Lin, Guo-Hao; Fenno, J Christopher; Rickard, Alexander H; Kapila, Yvonne L

2017-06-01

Nisin, a broad-spectrum bacteriocin, has recently been highlighted for its biomedical applications. To date, no studies have examined the antimicrobial and antibiofilm properties of high-purity (>95%) nisin (nisin ZP) on Enterococcus faecalis and biofilms formed by this species. We hypothesize that nisin can inhibit E. faecalis and reduce biofilm biomass, and combinations of nisin and sodium hypochlorite (NaOCl) will enhance the antibiofilm properties against E. faecalis biofilms. Using broth cultures, disc diffusion assays, and biofilm assays, we examined the effects of nisin on various E. faecalis growth parameters and biofilm properties (biovolume, thickness, and roughness). Confocal microscopy was used in conjunction with Imaris and Comstat2 software (Kongens Lyngby, Copenhagen, Denmark) to measure and analyze the biofilm properties. Nisin significantly decreased the growth of planktonic E. faecalis dose dependently. The minimum inhibitory concentrations against E. faecalis strains OG-1 and ATCC 29212 were 15 and 50 μg/mL, and the minimum bactericidal concentrations were 150 and 200 μg/mL, respectively. A reduction in biofilm biovolume and thickness was observed for biofilms treated with nisin at ≥10 μg/mL for 10 minutes. In addition, the combination of nisin with low doses of NaOCl enhanced the antibiofilm properties of both antimicrobial agents. Nisin alone or in combination with low concentrations of NaOCl reduces the planktonic growth of E. faecalis and disrupts E. faecalis biofilm structure. Our results suggest that nisin has potential as an adjunctive endodontic therapeutic agent and as an alternative to conventional NaOCl irrigation. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Experience of micromultileaf collimator linear accelerator based single fraction stereotactic radiosurgery: Tumor dose inhomogeneity, conformity, and dose fall off

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

Hong, Linda X.; Garg, Madhur; Lasala, Patrick

2011-03-15

Purpose: Sharp dose fall off outside a tumor is essential for high dose single fraction stereotactic radiosurgery (SRS) plans. This study explores the relationship among tumor dose inhomogeneity, conformity, and dose fall off in normal tissues for micromultileaf collimator (mMLC) linear accelerator (LINAC) based cranial SRS plans. Methods: Between January 2007 and July 2009, 65 patients with single cranial lesions were treated with LINAC-based SRS. Among them, tumors had maximum diameters {<=}20 mm: 31; between 20 and 30 mm: 21; and >30 mm: 13. All patients were treated with 6 MV photons on a Trilogy linear accelerator (Varian Medical Systems,more » Palo Alto, CA) with a tertiary m3 high-resolution mMLC (Brainlab, Feldkirchen, Germany), using either noncoplanar conformal fixed fields or dynamic conformal arcs. The authors also created retrospective study plans with identical beam arrangement as the treated plan but with different tumor dose inhomogeneity by varying the beam margins around the planning target volume (PTV). All retrospective study plans were normalized so that the minimum PTV dose was the prescription dose (PD). Isocenter dose, mean PTV dose, RTOG conformity index (CI), RTOG homogeneity index (HI), dose gradient index R{sub 50}-R{sub 100} (defined as the difference between equivalent sphere radius of 50% isodose volume and prescription isodose volume), and normal tissue volume (as a ratio to PTV volume) receiving 50% prescription dose (NTV{sub 50}) were calculated. Results: HI was inversely related to the beam margins around the PTV. CI had a ''V'' shaped relationship with HI, reaching a minimum when HI was approximately 1.3. Isocenter dose and mean PTV dose (as percentage of PD) increased linearly with HI. R{sub 50}-R{sub 100} and NTV{sub 50} initially declined with HI and then reached a plateau when HI was approximately 1.3. These trends also held when tumors were grouped according to their maximum diameters. The smallest tumor group (maximum diameters {<=}20 mm) had the most HI dependence for dose fall off. For treated plans, CI averaged 2.55{+-}0.79 with HI 1.23{+-}0.06; the average R{sub 50}-R{sub 100} was 0.41{+-}0.08, 0.55{+-}0.10, and 0.65{+-}0.09 cm, respectively, for tumors {<=}20 mm, between 20 and 30 mm, and >30 mm. Conclusions: Tumor dose inhomogeneity can be used as an important and convenient parameter to evaluate mMLC LINAC-based SRS plans. Sharp dose fall off in the normal tissue is achieved with sufficiently high tumor dose inhomogeneity. By adjusting beam margins, a homogeneity index of approximately 1.3 would provide best conformity for the authors' SRS system.« less

SU-F-T-188: A Robust Treatment Planning Technique for Proton Pencil Beam Scanning Cranial Spinal Irradiation

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

Zhu, M; Mehta, M; Badiyan, S

2016-06-15

Purpose: To propose a proton pencil beam scanning (PBS) cranial spinal irradiation (CSI) treatment planning technique robust against patient roll, isocenter offset and proton range uncertainty. Method: Proton PBS plans were created (Eclipse V11) for three previously treated CSI patients to 36 Gy (1.8 Gy/fractions). The target volume was separated into three regions: brain, upper spine and lower spine. One posterior-anterior (PA) beam was used for each spine region, and two posterior-oblique beams (15° apart from PA direction, denoted as 2PO-15) for the brain region. For comparison, another plan using one PA beam for the brain target (denoted as 1PA)more » was created. Using the same optimization objectives, 98% CTV was optimized to receive the prescription dose. To evaluate plan robustness against patient roll, the gantry angle was increased by 3° and dose was recalculated without changing the proton spot weights. On the re-calculated plan, doses were then calculated using 12 scenarios that are combinations of isocenter shift (±3mm in X, Y, and Z directions) and proton range variation (±3.5%). The worst-case-scenario (WCS) brain CTV dosimetric metrics were compared to the nominal plan. Results: For both beam arrangements, the brain field(s) and upper-spine field overlap in the T2–T5 region depending on patient anatomy. The maximum monitor unit per spot were 48.7%, 47.2%, and 40.0% higher for 1PA plans than 2PO-15 plans for the three patients. The 2PO-15 plans have better dose conformity. At the same level of CTV coverage, the 2PO-15 plans have lower maximum dose and higher minimum dose to the CTV. The 2PO-15 plans also showed lower WCS maximum dose to CTV, while the WCS minimum dose to CTV were comparable between the two techniques. Conclusion: Our method of using two posterior-oblique beams for brain target provides improved dose conformity and homogeneity, and plan robustness including patient roll.« less

Renal Shielding and Dosimetry for Patients With Severe Systemic Sclerosis Receiving Immunoablation With Total Body Irradiation in the Scleroderma: Cyclophosphamide or Transplantation Trial

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

Craciunescu, Oana I., E-mail: oana.craciunescu@duke.ed; Steffey, Beverly A.; Kelsey, Chris R.

2011-03-15

Purpose: To describe renal shielding techniques and dosimetry in delivering total body irradiation (TBI) to patients with severe systemic sclerosis (SSc) enrolled in a hematopoietic stem cell transplant protocol. Methods and Materials: The Scleroderma: Cyclophosphamide or Transplantation (SCOT) protocol uses a lymphoablative preparative regimen including 800 cGy TBI delivered in two 200-cGy fractions twice a day before CD34{sup +} selected autologous hematopoietic stem cell transplantation. Lung and kidney doses are limited to 200 cGy to protect organs damaged by SSc. Kidney block proximity to the spinal cord was investigated, and guidelines were developed for acceptable lumbar area TBI dosing. Informationmore » about kidney size and the organ shifts from supine to standing positions were recorded using diagnostic ultrasound (US). Minimum distance between the kidney blocks (dkB) and the lumbar spine region dose was recorded, and in vivo dosimetry was performed at several locations to determine the radiation doses delivered. Results: Eleven patients were treated at our center with an anteroposterior (AP)/posteroanterior (PA) TBI technique. A 10% to 20% dose inhomogeneity in the lumbar spine region was achieved with a minimum kidney block separation of 4 to 5 cm. The average lumbar spine dose was 179.6 {+-} 18.1 cGy, with an average dkB of 5.0 {+-} 1.0 cm. Kidney block shield design was accomplished using a combination of US and noncontrast computerized tomography (CT) or CT imaging alone. The renal US revealed a wide range of kidney displacement from upright to supine positions. Overall, the average in vivo dose for the kidney prescription point was 193.4 {+-} 5.1 cGy. Conclusions: The dose to the kidneys can be attenuated while maintaining a 10% to 20% dose inhomogeneity in the lumbar spine area. Kidneys were localized more accurately using both US and CT imaging. With this technique, renal function has been preserved, and the study continues to enroll patients.« less

TU-D-201-05: Validation of Treatment Planning Dose Calculations: Experience Working with MPPG 5.a

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

Xue, J; Park, J; Kim, L

2016-06-15

Purpose: Newly published medical physics practice guideline (MPPG 5.a.) has set the minimum requirements for commissioning and QA of treatment planning dose calculations. We present our experience in the validation of a commercial treatment planning system based on MPPG 5.a. Methods: In addition to tests traditionally performed to commission a model-based dose calculation algorithm, extensive tests were carried out at short and extended SSDs, various depths, oblique gantry angles and off-axis conditions to verify the robustness and limitations of a dose calculation algorithm. A comparison between measured and calculated dose was performed based on validation tests and evaluation criteria recommendedmore » by MPPG 5.a. An ion chamber was used for the measurement of dose at points of interest, and diodes were used for photon IMRT/VMAT validations. Dose profiles were measured with a three-dimensional scanning system and calculated in the TPS using a virtual water phantom. Results: Calculated and measured absolute dose profiles were compared at each specified SSD and depth for open fields. The disagreement is easily identifiable with the difference curve. Subtle discrepancy has revealed the limitation of the measurement, e.g., a spike at the high dose region and an asymmetrical penumbra observed on the tests with an oblique MLC beam. The excellent results we had (> 98% pass rate on 3%/3mm gamma index) on the end-to-end tests for both IMRT and VMAT are attributed to the quality beam data and the good understanding of the modeling. The limitation of the model and the uncertainty of measurement were considered when comparing the results. Conclusion: The extensive tests recommended by the MPPG encourage us to understand the accuracy and limitations of a dose algorithm as well as the uncertainty of measurement. Our experience has shown how the suggested tests can be performed effectively to validate dose calculation models.« less

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

Guo Baonian; Gossmann, Hans-Joachim; Toh, Terry

Angle control has been widely accepted as the key requirement for ion implantation in semiconductor device processing. From an ion implanter point of view, the incident ion direction should be measured and corrected by suitable techniques, such as XP-VPS for the VIISta implanter platform, to ensure precision ion placement in device structures. So called V-curves have been adopted to generate the wafer-based calibration using channeling effects as the Si lattice steer ions into a channeling direction. Thermal Wave (TW) or sheet resistance (Rs) can be used to determine the minimum of the angle response curve. Normally it is expected thatmore » the TW and Rs have their respective minima at identical angles. However, the TW and Rs response to the angle variations does depend on factors such as implant species, dose, and wafer temperature. Implant damage accumulation effects have to be considered for data interpretation especially for some 'abnormal' V-curve data. In this paper we will discuss some observed 'abnormal' angle responses, such as a) TW/Rs reverse trend for Arsenic beam, 2) 'W' shape of Rs Boron, and 3) apparent TW/Rs minimum difference for high tilt characterization, along with experimental data and TCAD simulations.« less

Effects of Nuclear Cross Sections at Different Energies on Space Radiation Exposure from Galactic Cosmic Rays

NASA Technical Reports Server (NTRS)

Li, Zi-Wei; Adams, James H., Jr.

2007-01-01

Space radiation from galactic cosmic rays (GCR) is a major hazard to space crews, especially in long duration human space explorations. For this reason, they will be protected by radiation shielding that fragments the GCR heavy ions. Here we investigate how sensitive the crew's radiation exposure is to nuclear fragmentation cross sections at different energies. We find that in deep space cross sections between about 0.2 and 1.2 GeV/u have the strongest effect on dose equivalent behind shielding in solar minimum GCR environments, and cross sections between about 0.6 and 1.7 GeV/u are the most important at solar maximum'. On the other hand, at the location of the International Space Station, cross sections at_higher -energies, between about 0.6 and 1.7 GeV /u at solar minimum and between about 1.7 and 3.4 GeV/u'at,solar maximum, are the most important This is. due-to the average geomagnetic cutoff for the ISS orbit. We also show the effect of uncertainties in the fragmentation cross sections on the elemental energy spectra behind shielding. These results help to focus the studies of fragmentation cross sections on the proper energy range in order to improve our predictions of crew exposures.

Sodium bicarbonate use and the risk of hypernatremia in thoracic aortic surgical patients with metabolic acidosis following deep hypothermic circulatory arrest

PubMed Central

Ghadimi, Kamrouz; Gutsche, Jacob T.; Ramakrishna, Harish; Setegne, Samuel L.; Jackson, Kirk R.; Augoustides, John G.; Ochroch, E. Andrew; Weiss, Stuart J.; Bavaria, Joseph E.; Cheung, Albert T.

2016-01-01

Objective: Metabolic acidosis after deep hypothermic circulatory arrest (DHCA) for thoracic aortic operations is commonly managed with sodium bicarbonate (NaHCO3). The purpose of this study was to determine the relationships between total NaHCO3 dose and the severity of metabolic acidosis, duration of mechanical ventilation, duration of vasoactive infusions, and Intensive Care Unit (ICU) or hospital length of stay (LOS). Methods: In a single center, retrospective study, 87 consecutive elective thoracic aortic operations utilizing DHCA, were studied. Linear regression analysis was used to test for the relationships between the total NaHCO3 dose administered through postoperative day 2, clinical variables, arterial blood gas values, and short-term clinical outcomes. Results: Seventy-five patients (86%) received NaHCO3. Total NaHCO3 dose averaged 136 ± 112 mEq (range: 0.0–535 mEq) per patient. Total NaHCO3 dose correlated with minimum pH (r = 0.41, P < 0.0001), minimum serum bicarbonate (r = −0.40, P < 0.001), maximum serum lactate (r = 0.46, P = 0.007), duration of metabolic acidosis (r = 0.33, P = 0.002), and maximum serum sodium concentrations (r = 0.29, P = 0.007). Postoperative hypernatremia was present in 67% of patients and peaked at 12 h following DHCA. Eight percent of patients had a serum sodium ≥ 150 mEq/L. Total NaHCO3 dose did not correlate with anion gap, serum chloride, not the duration of mechanical ventilator support, vasoactive infusions, ICU or hospital LOS. Conclusion: Routine administration of NaHCO3 was common for the management of metabolic acidosis after DHCA. Total dose of NaHCO3 was a function of the severity and duration of metabolic acidosis. NaHCO3 administration contributed to postoperative hypernatremia that was often severe. The total NaHCO3 dose administered was unrelated to short-term clinical outcomes. PMID:27397449

On the relationship of minimum detectable contrast to dose and lesion size in abdominal CT

NASA Astrophysics Data System (ADS)

Zhou, Yifang; Scott, Alexander, II; Allahverdian, Janet; Lee, Christina; Kightlinger, Blake; Azizyan, Avetis; Miller, Joseph

2015-10-01

CT dose optimization is typically guided by pixel noise or contrast-to-noise ratio that does not delineate low contrast details adequately. We utilized the statistically defined low contrast detectability to study its relationship to dose and lesion size in abdominal CT. A realistically shaped medium sized abdomen phantom was customized to contain a cylindrical void of 4 cm diameter. The void was filled with a low contrast (1% and 2%) insert containing six groups of cylindrical targets ranging from 1.2 mm to 7 mm in size. Helical CT scans were performed using a Siemens 64-slice mCT and a GE Discovery 750 HD at various doses. After the subtractions between adjacent slices, the uniform sections of the filtered backprojection reconstructed images were partitioned to matrices of square elements matching the sizes of the targets. It was verified that the mean values from all the elements in each matrix follow a Gaussian distribution. The minimum detectable contrast (MDC), quantified by the mean signal to background difference equal to the distribution’s standard deviation multiplied by 3.29, corresponding to 95% confidence level, was found to be related to the phantom specific dose and the element size by a power law (R^2  >  0.990). Independent readings on the 5 mm and 7 mm targets were compared to the measured contrast to the MDC ratios. The results showed that 93% of the cases were detectable when the measured contrast exceeds the MDC. The correlation of the MDC to the pixel noise and target size was also identified and the relationship was found to be the same for the scanners in the study. To quantify the impact of iterative reconstructions to the low contrast detectability, the noise structure was studied in a similar manner at different doses and with different ASIR blending fractions. The relationship of the dose to the blending fraction and low contrast detectability is presented.

SU-E-J-53: Dosimetric Evaluation at Volumetric Modulated Arc Therapy for Treatment of Prostate Cancer Using Single Or Double Arcs

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

Silva, D; Salmon, H; Pavan, G

2014-06-01

Purpose: Evaluate and compare retrospective prostate treatment plan using Volumetric Modulated Arc Therapy (RapidArc™ - Varian) technique with single or double arcs at COI Group. Methods: Ten patients with present prostate and seminal vesicle neoplasia were replanned as a target treatment volume and a prescribed dose of 78 Gy. A baseline planning, using single arc, was developed for each case reaching for the best result on PTV, in order to minimize the dose on organs at risk (OAR). Maintaining the same optimization objectives used on baseline plan, two copies for optimizing single and double arcs, have been developed. The plansmore » were performed with 10 MV photon beam energy on Eclipse software, version 11.0, making use of Trilogy linear accelerator with Millenium HD120 multileaf collimator. Comparisons on PTV have been performed, such as: maximum, minimum and mean dose, gradient dose, as well as the quantity of monitor units, treatment time and homogeneity and conformity index. OARs constrains dose have been evaluated, comparing both optimizations. Results: Regarding PTV coverage, the difference of the minimum, maximum and mean dose were 1.28%, 0.7% and 0.2% respectively higher for single arc. When analyzed the index of homogeneity found a difference of 0.99% higher when compared with double arcs. However homogeneity index was 0.97% lower on average by using single arc. The doses on the OARs, in both cases, were in compliance to the recommended limits RTOG 0415. With the use of single arc, the quantity of monitor units was 10,1% lower, as well as the Beam-On time, 41,78%, when comparing double arcs, respectively. Conclusion: Concerning the optimization of patients with present prostate and seminal vesicle neoplasia, the use of single arc reaches similar objectives, when compared to double arcs, in order to decrease the treatment time and the quantity of monitor units.« less

76 FR 38349 - Notice of Availability of Pest Risk Analysis for the Importation of Dragon Fruit From Thailand...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-30

... with 7 CFR part 305 with a minimum absorbed dose of 400 Gy. If the irradiation treatment is applied... attesting that the fruit received the required irradiation treatment. If the irradiation treatment is...

76 FR 46268 - Notice of Availability of Pest Risk Analyses for the Importation of Fresh Pitaya and Pomegranates...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-02

... 305 with a minimum absorbed dose of 150 Gy. If the irradiation treatment is applied outside the United... received the required irradiation treatment. If the irradiation treatment is applied upon arrival in the...

Effects of Nuclear Cross Sections at Different Energies on the Radiation Hazard from Galactic Cosmic Rays

NASA Technical Reports Server (NTRS)

Lin, Z. W.; Adams, J. H., Jr.

2006-01-01

The radiation hazard for astronauts from galactic cosmic rays is a major obstacle in long duration human space explorations. Space radiation transport codes have been developed to calculate radiation environment on missions to the Moon, Mars or beyond. We have studied how uncertainties in fragmentation cross sections at different energies affect the accuracy of predictions from such radiation transport. We find that, in deep space, cross sections between 0.3 and 0.85 GeV/u usually have the largest effect on dose-equivalent behind shielding in solar minimum GCR environments, and cross sections between 0.85 and 1.2 GeV/u have the largest effect in solar maximum GCR environments. At the International Space Station, cross sections at higher energies have the largest effect due to the geomagnetic cutoff.

Optimizing drug-dose alerts using commercial software throughout an integrated health care system.

PubMed

Saiyed, Salim M; Greco, Peter J; Fernandes, Glenn; Kaelber, David C

2017-11-01

All default electronic health record and drug reference database vendor drug-dose alerting recommendations (single dose, daily dose, dose frequency, and dose duration) were silently turned on in inpatient, outpatient, and emergency department areas for pediatric-only and nonpediatric-only populations. Drug-dose alerts were evaluated during a 3-month period. Drug-dose alerts fired on 12% of orders (104 098/834 911). System-level and drug-specific strategies to decrease drug-dose alerts were analyzed. System-level strategies included: (1) turning off all minimum drug-dosing alerts, (2) turning off all incomplete information drug-dosing alerts, (3) increasing the maximum single-dose drug-dose alert threshold to 125%, (4) increasing the daily dose maximum drug-dose alert threshold to 125%, and (5) increasing the dose frequency drug-dose alert threshold to more than 2 doses per day above initial threshold. Drug-specific strategies included changing drug-specific maximum single and maximum daily drug-dose alerting parameters for the top 22 drug categories by alert frequency. System-level approaches decreased alerting to 5% (46 988/834 911) and drug-specific approaches decreased alerts to 3% (25 455/834 911). Drug-dose alerts varied between care settings and patient populations. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

TH-CD-209-01: A Greedy Reassignment Algorithm for the PBS Minimum Monitor Unit Constraint

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

Lin, Y; Kooy, H; Craft, D

2016-06-15

Purpose: To investigate a Greedy Reassignment algorithm in order to mitigate the effects of low weight spots in proton pencil beam scanning (PBS) treatment plans. Methods: To convert a plan from the treatment planning system’s (TPS) to a deliverable plan, post processing methods can be used to adjust the spot maps to meets the minimum MU constraint. Existing methods include: deleting low weight spots (Cut method), or rounding spots with weight above/below half the limit up/down to the limit/zero (Round method). An alternative method called Greedy Reassignment was developed in this work in which the lowest weight spot in themore » field was removed and its weight reassigned equally among its nearest neighbors. The process was repeated with the next lowest weight spot until all spots in the field were above the MU constraint. The algorithm performance was evaluated using plans collected from 190 patients (496 fields) treated at our facility. The evaluation criteria were the γ-index pass rate comparing the pre-processed and post-processed dose distributions. A planning metric was further developed to predict the impact of post-processing on treatment plans for various treatment planning, machine, and dose tolerance parameters. Results: For fields with a gamma pass rate of 90±1%, the metric has a standard deviation equal to 18% of the centroid value. This showed that the metric and γ-index pass rate are correlated for the Greedy Reassignment algorithm. Using a 3rd order polynomial fit to the data, the Greedy Reassignment method had 1.8 times better metric at 90% pass rate compared to other post-processing methods. Conclusion: We showed that the Greedy Reassignment method yields deliverable plans that are closest to the optimized-without-MU-constraint plan from the TPS. The metric developed in this work could help design the minimum MU threshold with the goal of keeping the γ-index pass rate above an acceptable value.« less

Antimicrobial properties and mechanism of volatile isoamyl acetate, a main flavour component of Japanese sake (Ginjo-shu).

PubMed

Ando, H; Kurata, A; Kishimoto, N

2015-04-01

To evaluate the antimicrobial properties of the main Ginjo-flavour components of sake, volatile isoamyl acetate and isoamyl alcohol. Volatile isoamyl acetate and isoamyl alcohol both inhibited growth of the five yeast and 10 bacterial test strains. The minimum inhibitory dose and minimum bactericidal (fungicidal) dose of isoamyl acetate were higher than those of isoamyl alcohol. Escherichia coli and Acetobacter aceti were markedly sensitive to isoamyl acetate and isoamyl alcohol. In E. coli exposed to isoamyl acetate for 5 h, changes in expression were noted in proteins involved in sugar metabolism (MalE, MglB, TalB and PtsI), tricarboxylic acid cycle (AceA, Pfl and AcnB) and protein synthesis (EF-Tu, EF-G, and GlyS). Expression of acid and alcohol stress-response proteins was altered in E. coli exposed to isoamyl acetate. Esterase activity was detected in E. coli, suggesting that isoamyl acetate was hydrolyzed to acetic acid and isoamyl alcohol. Acetic acid and isoamyl alcohol damaged E. coli cell membranes and inactivated membrane proteins, impairing respiration. Volatile isoamyl acetate and isoamyl alcohol were effective in inactivating various micro-organisms, and antimicrobial mechanism of volatile isoamyl acetate against E. coli was clarified based on proteome analysis. To the best of our knowledge, this is the first report to examine the antimicrobial mechanism of volatile organic compound using proteome analysis combining two-dimensional difference gel electrophoresis with peptide mass fingerprinting. © 2015 The Society for Applied Microbiology.

Absorption of Bupivacaine after Administration of a Lozenge as Topical Treatment for Pain from Oral Mucositis.

PubMed

Mogensen, Stine; Sverrisdóttir, Eva; Sveinsdóttir, Kolbrún; Treldal, Charlotte; Jensen, Kenneth; Jensen, Anders Bonde; Kristensen, Claus Andrup; Jacobsen, Jette; Kreilgaard, Mads; Petersen, Janne; Andersen, Ove

2017-01-01

The aim was to investigate systemic exposure after administration of a novel bupivacaine lozenge in healthy individuals with normal mucosa and in head and neck cancer (HNC) patients with oral mucositis. A lozenge containing 5, 10, 25 and 50 mg bupivacaine, respectively, was administered as single dose to 10 healthy individuals, and a lozenge containing 25 mg bupivacaine was administered as single dose to 10 HNC patients with oral mucositis and as multiple doses to five patients with HNC. Blood samples were collected for 6 hr from the healthy individuals and 3 hr from the patients with HNC, respectively, after administration. The plasma concentration-time profiles of bupivacaine were fitted to pharmacokinetic models using nonlinear mixed-effects modelling, evaluating demographics and health status as covariates. The population pharmacokinetics (PK) of bupivacaine lozenge was best described by a two-compartment distribution model with absorption transit compartments. All the observed plasma concentrations were well below the bupivacaine concentrations (2000-2250 ng/ml) which have caused toxic symptoms. The PK model suggested that relative bioavailability was two times higher in HNC patients with oral mucositis grade 1-2 and three times higher in HNC patients with oral mucositis grade 3-4 than in the healthy individuals. Simulations showed that the plasma concentrations would be below the toxic limit after repeated dosing every second hour with 25 mg bupivacaine for five days. The 25-mg bupivacaine lozenges were safe without systemic toxic levels of bupivacaine or risk of side effects. Based on PK simulations of repeated doses of 25 mg every two hours for 16 hr a day, the lozenges can be administered with minimum risk of exceeding the toxic limit. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Radiation Measured with Different Dosimeters for ISS-Expedition 18-19/ULF2 on Board International Space Station during Solar Minimum

NASA Technical Reports Server (NTRS)

Zhou, Dazhuang; Gaza, R.; Roed, Y.; Semones, E.; Lee, K.; Steenburgh, R.; Johnson, S.; Flanders, J.; Zapp, N.

2010-01-01

Radiation field of particles in low Earth orbit (LEO) is mainly composed of galactic cosmic rays (GCR), solar energetic particles and particles in SAA (South Atlantic Anomaly). GCR are modulated by solar activity, at the period of solar minimum activity, GCR intensity is at maximum and the main contributor for space radiation is GCR. At present for space radiation measurements conducted by JSC (Johnson Space Center) SRAG (Space Radiation Analysis Group), the preferred active dosimeter sensitive to all LET (Linear Energy Transfer) is the tissue equivalent proportional counter (TEPC); the preferred passive dosimeters are thermoluminescence dosimeters (TLDs) and optically stimulated luminescence dosimeters (OSLDs) sensitive to low LET as well as CR-39 plastic nuclear track detectors (PNTDs) sensitive to high LET. For the method using passive dosimeters, radiation quantities for all LET can be obtained by combining radiation results measured with TLDs/OSLDs and CR-39 PNTDs. TEPC, TLDs/OSLDs and CR-39 detectors were used to measure the radiation field for the ISS (International Space Station) - Expedition 18-19/ULF2 space mission which was conducted from 15 November 2008 to 31 July 2009 - near the period of the recent solar minimum activity. LET spectra (differential and integral fluence, absorbed dose and dose equivalent) and radiation quantities were measured for positions TEPC, TESS (Temporary Sleeping Station, inside the polyethylene lined sleep station), SM-P 327 and 442 (Service Module - Panel 327 and 442). This paper presents radiation LET spectra measured with TEPC and CR-39 PNTDs and radiation dose measured with TLDs/OSLDs as well as the radiation quantities combined from results measured with passive dosimeters.

Neuroprotective and anticonvulsant effects of EGIS-8332, a non-competitive AMPA receptor antagonist, in a range of animal models

PubMed Central

Gigler, G; Móricz, K; ágoston, M; Simó, A; Albert, M; Benedek, A; Kapus, G; Kertész, S; Vegh, M; Barkóczy, J; Markó, B; Szabó, G; Matucz, É; Gacsályi, I; Lévay, G; Hársing, L G; Szénási, G

2007-01-01

Background and purpose: Blockade of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors is a good treatment option for a variety of central nervous system disorders. The present study evaluated the neuroprotective and anticonvulsant effects of EGIS-8332, a non-competitive AMPA receptor antagonist, as a potential drug candidate. Experimental approach: AMPA antagonist effects of EGIS-8332 were measured using patch-clamp techniques. Neuroprotective and anticonvulsant effects of EGIS-8332 were evaluated in various experimental models, relative to those of GYKI 53405. Key results: EGIS-8332 inhibited AMPA currents in rat cerebellar Purkinje cells and inhibited the AMPA- and quisqualate-induced excitotoxicity in primary cultures of telencephalon neurons (IC50=5.1-9.0 μM), in vitro. Good anticonvulsant actions were obtained in maximal electroshock-, sound- and chemically-induced seizures (range of ED50=1.4-14.0 mg kg−1 i.p.) in mice. Four days after transient global cerebral ischaemia, EGIS-8332 decreased neuronal loss in the hippocampal CA1 area in gerbils and rats. EGIS-8332 dose-dependently reduced cerebral infarct size after permanent middle cerebral artery occlusion in mice and rats (minimum effective dose=3 mg kg−1 i.p.). Side effects of EGIS-8332 emerged much above its pharmacologically active doses. A tendency for better efficacy of GYKI 53405 than that of EGIS-8332 was observed in anticonvulsant tests that reached statistical significance in few cases, while the contrary was perceived in cerebral ischaemia tests. Conclusions and implications: EGIS-8332 seems suitable for further development for the treatment of epilepsy, ischaemia and stroke based on its efficacy in a variety of experimental disease models, and on its low side effect potential. PMID:17603549

Optimization of the K-edge imaging for vulnerable plaques using gold nanoparticles and energy-resolved photon counting detectors: a simulation study

PubMed Central

Alivov, Yahya; Baturin, Pavlo; Le, Huy Q.; Ducote, Justin; Molloi, Sabee

2014-01-01

We investigated the effect of different imaging parameters such as dose, beam energy, energy resolution, and number of energy bins on image quality of K-edge spectral computed tomography (CT) of gold nanoparticles (GNP) accumulated in an atherosclerotic plaque. Maximum likelihood technique was employed to estimate the concentration of GNP, which served as a targeted intravenous contrast material intended to detect the degree of plaque's inflammation. The simulations studies used a single slice parallel beam CT geometry with an X-ray beam energy ranging between 50 and 140 kVp. The synthetic phantoms included small (3 cm in diameter) cylinder and chest (33x24 cm2) phantom, where both phantoms contained tissue, calcium, and gold. In the simulation studies GNP quantification and background (calcium and tissue) suppression task were pursued. The X-ray detection sensor was represented by an energy resolved photon counting detector (e.g., CdZnTe) with adjustable energy bins. Both ideal and more realistic (12% FWHM energy resolution) implementations of photon counting detector were simulated. The simulations were performed for the CdZnTe detector with pixel pitch of 0.5-1 mm, which corresponds to the performance without significant charge sharing and cross-talk effects. The Rose model was employed to estimate the minimum detectable concentration of GNPs. A figure of merit (FOM) was used to optimize the X-ray beam energy (kVp) to achieve the highest signal-to-noise ratio (SNR) with respect to patient dose. As a result, the successful identification of gold and background suppression was demonstrated. The highest FOM was observed at 125 kVp X-ray beam energy. The minimum detectable GNP concentration was determined to be approximately 1.06 μmol/mL (0.21 mg/mL) for an ideal detector and about 2.5 μmol/mL (0.49 mg/mL) for more realistic (12% FWHM) detector. The studies show the optimal imaging parameters at lowest patient dose using an energy resolved photon counting detector to image GNP in an atherosclerotic plaque. PMID:24334301

Anaesthetic induction with alfaxalone in the ball python (Python regius): dose response and effect of injection site.

PubMed

James, Lauren E; Williams, Catherine Ja; Bertelsen, Mads F; Wang, Tobias

2018-05-01

To characterise the minimum dose of intramuscular alfaxalone required to facilitate intubation for mechanical ventilation, and to investigate the impact of cranial versus caudal injection on anaesthetic depth. Randomised crossover study. Six healthy juvenile ball pythons (Python regius). Three dosages (10, 20 and 30 mg kg -1 ) of alfaxalone were administered to each python in a caudal location with a minimum 2 weeks washout. Induction and recovery were monitored by assessing muscle tone, righting reflex, response to a noxious stimulus and the ability to intubate. A subsequent experiment assessed the influence of injection site by comparing administration of 20 mg kg -1 alfaxalone in a cranial location (1 cm cranial to the heart) with the caudal site. Respiration rate was monitored throughout, and when intubation was possible, snakes were mechanically ventilated. Regardless of dose and injection site, maximum effect was reached within 10.0 ± 2.7 minutes. When administered at the caudal injection site, intubation was only successful after a dosage of 30 mg kg- 1 , which is higher than in previous reports for other reptiles. However, intubation was possible in all cases after 7.2 ± 1.6 minutes upon cranial administration of 20 mg kg -1 , and anaesthetic duration was significantly lengthened (p < 0.001). Both 30 mg kg -1 at the caudal site and 20 mg kg -1 at the cranial site led to apnoea approximately 10 minutes post-injection, at which time the snakes were intubated and mechanically ventilated. Alfaxalone provided rapid, smooth induction when administered intramuscularly to pythons, and may serve as a useful induction agent prior to provision of volatile anaesthetics. The same dosage injected in the cranial site led to deeper anaesthesia than when injected caudally, suggesting that shunting to the liver and first-pass metabolism of alfaxalone occur when injected caudally, via the renal portal system. Copyright © 2018 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

Retention of ion-implanted-xenon in olivine: Dependence on implantation dose

NASA Technical Reports Server (NTRS)

Melcher, C. L.; Tombrello, T. A.; Burnett, D. S.

1982-01-01

The diffusion of Xe in olivine, a major mineral in both meteorites and lunar samples, was studied. Xe ions were implanted at 200 keV into single-crystal synthetic-forsterite targets and the depth profiles were measured by alpha particle backscattering before and after annealing for 1 hour at temperatures up to 1500 C. The fraction of implanted Xe retained following annealing was strongly dependent on the implantation dose. Maximum retention of 100% occurred for an implantion dose of 3 x 10 to the 15th power Xe ions/sq cm. Retention was less at lower doses, with (approximately more than or = 50% loss at one hundred trillion Xe ions/sq cm. Taking the diffusion coefficient at this dose as a lower limit, the minimum activation energy necessary for Xe retention in a 10 micrometer layer for ten million years was calculated as a function of metamorphic temperature.

Complex, non-monotonic dose-response curves with multiple maxima: Do we (ever) sample densely enough?

PubMed

Cvrčková, Fatima; Luštinec, Jiří; Žárský, Viktor

2015-01-01

We usually expect the dose-response curves of biological responses to quantifiable stimuli to be simple, either monotonic or exhibiting a single maximum or minimum. Deviations are often viewed as experimental noise. However, detailed measurements in plant primary tissue cultures (stem pith explants of kale and tobacco) exposed to varying doses of sucrose, cytokinins (BA or kinetin) or auxins (IAA or NAA) revealed that growth and several biochemical parameters exhibit multiple reproducible, statistically significant maxima over a wide range of exogenous substance concentrations. This results in complex, non-monotonic dose-response curves, reminiscent of previous reports of analogous observations in both metazoan and plant systems responding to diverse pharmacological treatments. These findings suggest the existence of a hitherto neglected class of biological phenomena resulting in dose-response curves exhibiting periodic patterns of maxima and minima, whose causes remain so far uncharacterized, partly due to insufficient sampling frequency used in many studies.

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

NASA Astrophysics Data System (ADS)

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

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

Macular retinal ganglion cell-inner plexiform layer thickness in patients on hydroxychloroquine therapy.

PubMed

Lee, Min Gyu; Kim, Sang Jin; Ham, Don-Il; Kang, Se Woong; Kee, Changwon; Lee, Jaejoon; Cha, Hoon-Suk; Koh, Eun-Mi

2014-11-25

We evaluated macular ganglion cell-inner plexiform layer (GC-IPL) thickness using spectral-domain optical coherence tomography (SD-OCT) in patients with chronic exposure to hydroxychloroquine (HCQ). This study included 130 subjects, who were divided into three groups: Group 1A, 55 patients with HCQ use ≥5 years; Group 1B, 46 patients with HCQ use <5 years; and Group 2, 29 normal controls. In all patients with exposure to HCQ, fundus examination, automated threshold perimetry, fundus autofluorescence photography, SD-OCT, and GC-IPL thickness measurement using the Cirrus HD-OCT ganglion cell analysis algorithm were performed. Average and minimum macular GC-IPL thickness were compared between subjects groups, and correlations between GC-IPL thickness and duration or total dose of HCQ use were analyzed. Among the 101 patients of Group 1, six patients who showed clinically evident HCQ retinopathy also showed markedly thin macular GC-IPL. In addition, weak but significant negative correlations were observed between the average and minimum GC-IPL thickness of Group 1 patients and cumulative dose of HCQ, even when analyzing without the six patients with HCQ retinopathy. However, when analyzing after exclusion of patients with high cumulative doses (>1000 g), significant correlations were not observed. This study revealed that macular GC-IPL thickness did not show definite correlations with HCQ use. However, some patients, especially with HCQ retinopathy or high cumulative doses, showed thin GC-IPL. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Effect of Dosimetric Factors on Occurrence and Volume of Temporal Lobe Necrosis Following Intensity Modulated Radiation Therapy for Nasopharyngeal Carcinoma: A Case-Control Study

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

Zhou, Xin; Ou, Xiaomin; Xu, Tingting

Purpose: To determine dosimetric risk factors for the occurrence of temporal lobe necrosis (TLN) among nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiation therapy (IMRT) and to investigate the impact of dose-volume histogram (DVH) parameters on the volume of TLN lesions (V-N). Methods and Materials: Forty-three NPC patients who had developed TLN following IMRT and 43 control subjects free of TLN were retrospectively assessed. DVH parameters included maximum dose (Dmax), minimum dose (Dmin), mean dose (Dmean), absolute volumes receiving specific dose (Vds) from 20 to 76 Gy (V20-V76), and doses covering certain volumes (Dvs) from 0.25 to 6.0 cm{sup 3} (D0.25-D6.0).more » V-Ns were quantified with axial magnetic resonance images. Results: DVH parameters were ubiquitously higher in temporal lobes with necrosis than in healthy temporal lobes. Increased Vds and Dvs were significantly associated with higher risk of TLN occurrence (P<.05). In particular, Vds at a dose of ≥70 Gy were found with the highest odds ratios. A common increasing trend was detected between V-N and DVH parameters through trend tests (P for trend of <.05). Linear regression analysis showed that V45 had the strongest predictive power for V-N (adjusted R{sup 2} = 0.305, P<.0001). V45 of <15.1 cm{sup 3} was relatively safe as the dose constraint for preventing large TLN lesions with V-N of >5 cm{sup 3}. Conclusions: Dosimetric parameters are significantly associated with TLN occurrence and the extent of temporal lobe injury. To better manage TLN, it would be important to avoid both focal high dose and moderate dose delivered to a large area in TLs.« less

Estimation of the optimal dosing regimen of escitalopram in dogs: A dose occupancy study with [11C]DASB

PubMed Central

Polis, Ingeborgh; Dockx, Robrecht; Vlerick, Lise; Dobbeleir, Andre; Goethals, Ingeborg; Saunders, Jimmy; Sadones, Nele; Baeken, Chris; De Vos, Filip; Peremans, Kathelijne

2017-01-01

Although the favourable characteristics of escitalopram as being the most selective serotonin reuptake inhibitor and having an increased therapeutic efficacy via binding on an additional allosteric binding site of the serotonin transporter, its dosing regimen has not yet been optimized for its use in dogs. This study aimed to estimate the optimal dosing frequency and the required dose for achieving 80% occupancy of the serotonin transporters in the basal ganglia. The dosing frequency was investigated by determining the elimination half-life after a four day oral pre-treatment period with 0.83 mg/kg escitalopram (3 administrations/day) and a subsequent i.v. injection 0.83 mg/kg. Blood samples were taken up to 12 hours after i.v. injection and the concentration of escitalopram in plasma was analysed via LC-MSMS. The dose-occupancy relationship was then determined by performing two PET scans in five adult beagles: a baseline PET scan and a second scan after steady state conditions were achieved following oral treatment with a specific dose of escitalopram ranging from 0.5 to 2.5 mg/kg/day. As the elimination half-life was determined to be 6.7 hours a dosing frequency of three administrations a day was proposed for the second part of the study. Further it was opted for a treatment period of four days, which well exceeded the minimum period to achieve steady state conditions. The optimal dosing regimen to achieve 80% occupancy in the basal ganglia and elicit a therapeutic effect, was calculated to be 1.85 mg/kg/day, divided over three administrations. Under several circumstances, such as insufficient response to other SSRIs, concurrent drug intake or in research studies focused on SERT, the use of escitalopram can be preferred over the use of the already for veterinary use registered fluoxetine, however, in case of long-term treatment with escitalopram, regularly cardiac screening is recommended. PMID:28644875

Estimation of the optimal dosing regimen of escitalopram in dogs: A dose occupancy study with [11C]DASB.

PubMed

Taylor, Olivia; Van Laeken, Nick; Polis, Ingeborgh; Dockx, Robrecht; Vlerick, Lise; Dobbeleir, Andre; Goethals, Ingeborg; Saunders, Jimmy; Sadones, Nele; Baeken, Chris; De Vos, Filip; Peremans, Kathelijne

2017-01-01

Although the favourable characteristics of escitalopram as being the most selective serotonin reuptake inhibitor and having an increased therapeutic efficacy via binding on an additional allosteric binding site of the serotonin transporter, its dosing regimen has not yet been optimized for its use in dogs. This study aimed to estimate the optimal dosing frequency and the required dose for achieving 80% occupancy of the serotonin transporters in the basal ganglia. The dosing frequency was investigated by determining the elimination half-life after a four day oral pre-treatment period with 0.83 mg/kg escitalopram (3 administrations/day) and a subsequent i.v. injection 0.83 mg/kg. Blood samples were taken up to 12 hours after i.v. injection and the concentration of escitalopram in plasma was analysed via LC-MSMS. The dose-occupancy relationship was then determined by performing two PET scans in five adult beagles: a baseline PET scan and a second scan after steady state conditions were achieved following oral treatment with a specific dose of escitalopram ranging from 0.5 to 2.5 mg/kg/day. As the elimination half-life was determined to be 6.7 hours a dosing frequency of three administrations a day was proposed for the second part of the study. Further it was opted for a treatment period of four days, which well exceeded the minimum period to achieve steady state conditions. The optimal dosing regimen to achieve 80% occupancy in the basal ganglia and elicit a therapeutic effect, was calculated to be 1.85 mg/kg/day, divided over three administrations. Under several circumstances, such as insufficient response to other SSRIs, concurrent drug intake or in research studies focused on SERT, the use of escitalopram can be preferred over the use of the already for veterinary use registered fluoxetine, however, in case of long-term treatment with escitalopram, regularly cardiac screening is recommended.

A phase I open-label dose-escalation study of the anti-HER3 monoclonal antibody LJM716 in patients with advanced squamous cell carcinoma of the esophagus or head and neck and HER2-overexpressing breast or gastric cancer.

PubMed

Reynolds, Kerry Lynn; Bedard, Philippe L; Lee, Se-Hoon; Lin, Chia-Chi; Tabernero, Josep; Alsina, Maria; Cohen, Ezra; Baselga, José; Blumenschein, George; Graham, Donna M; Garrido-Laguna, Ignacio; Juric, Dejan; Sharma, Sunil; Salgia, Ravi; Seroutou, Abdelkader; Tian, Xianbin; Fernandez, Rose; Morozov, Alex; Sheng, Qing; Ramkumar, Thiruvamoor; Zubel, Angela; Bang, Yung-Jue

2017-09-12

Human epidermal growth factor receptor 3 (HER3) is important in maintaining epidermal growth factor receptor-driven cancers and mediating resistance to targeted therapy. A phase I study of anti-HER3 monoclonal antibody LJM716 was conducted with the primary objective to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE), and dosing schedule. Secondary objectives were to characterize safety/tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity. This open-label, dose-finding study comprised dose escalation, followed by expansion in patients with squamous cell carcinoma of the head and neck or esophagus, and HER2-overexpressing metastatic breast cancer or gastric cancer. During dose escalation, patients received LJM716 intravenous once weekly (QW) or every two weeks (Q2W), in 28-day cycles. An adaptive Bayesian logistic regression model was used to guide dose escalation and establish the RDE. Exploratory pharmacodynamic tumor studies evaluated modulation of HER3 signaling. Patients received LJM716 3-40 mg/kg QW and 20 mg/kg Q2W (54 patients; 36 patients at 40 mg/kg QW). No dose-limiting toxicities (DLTs) were reported during dose-escalation. One patient experienced two DLTs (diarrhea, hypokalemia [both grade 3]) in the expansion phase. The RDE was 40 mg/kg QW, providing drug levels above the preclinical minimum effective concentration. One patient with gastric cancer had an unconfirmed partial response; 17/54 patients had stable disease, two lasting >30 weeks. Down-modulation of phospho-HER3 was observed in paired tumor samples. LJM716 was well tolerated; the MTD was not reached, and the RDE was 40 mg/kg QW. Further development of LJM716 is ongoing. Clinicaltrials.gov registry number NCT01598077 (registered on 4 May, 2012).

Tranexamic acid therapy in ulcerative colitis

PubMed Central

Hollanders, D.; Thomson, Jean M.; Schofield, Phillip F.

1982-01-01

The antifibrinolytic drug tranexamic acid was assessed in controlling bleeding in 12 patients with left-sided proctocolitis. The study was designed as a double-blind cross-over trial employing a dose of 4·5 g of tranexamic acid/day together with identical placebo. A statistically significant reduction in rectal bleeding was achieved in 50% of cases with a minimum of side effects. Sigmoidoscopic grading of rectal mucosal appearances was improved. Frequency of diarrhoea and stool consistency were not altered. Tranexamic acid may have a part to play in the management of selected patients with ulcerative colitis in whom bleeding is difficult to control with orthodox treatment. PMID:6980404

Development and evaluation of a technique for in vivo monitoring of 60Co in human liver

NASA Astrophysics Data System (ADS)

Gomes, GH; Silva, MC; Mello, JQ; Dantas, ALA; Dantas, BM

2018-03-01

60Co is an artificial radioactive metal produced by activation of iron with neutrons. It decays by beta particles and gamma radiation and represents a risk of internal exposure of workers involved in the maintenance of nuclear power reactors. Intakes can be quantified through in vivo monitoring. This work describes the development of a technique for the quantification of 60Co in human liver. The sensitivity of the method is evaluated based on the minimum detectable effective doses. The results allow to state that the technique is suitable either for monitoring of occupational exposures or evaluation of accidental intakes.

Proton irradiation and endometriosis

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

Wood, D.H.; Yochmowitz, M.G.; Salmon, Y.L.

1983-08-01

It was found that female rhesus monkeys given single total-body exposures of protons of varying energies developed endometriosis at a frequency significantly higher than that of nonirradiated animals of the same age. The minimum latency period was determined to be 7 years after the proton exposure. The doses and energies of the radiation received by the experimental animals were within the range that could be received by an aircrew member in near-earth orbit during a random solar flare event. It is concluded that endometriosis should be a consideration in assessing the risk of delayed radiation effects in female crew members.more » 15 references.« less

Quantification of dose uncertainties for the bladder in prostate cancer radiotherapy based on dominant eigenmodes

NASA Astrophysics Data System (ADS)

Rios, Richard; Acosta, Oscar; Lafond, Caroline; Espinosa, Jairo; de Crevoisier, Renaud

2017-11-01

In radiotherapy for prostate cancer the dose at the treatment planning for the bladder may be a bad surrogate of the actual delivered dose as the bladder presents the largest inter-fraction shape variations during treatment. This paper presents PCA models as a virtual tool to estimate dosimetric uncertainties for the bladder produced by motion and deformation between fractions. Our goal is to propose a methodology to determine the minimum number of modes required to quantify dose uncertainties of the bladder for motion/deformation models based on PCA. We trained individual PCA models using the bladder contours available from three patients with a planning computed tomography (CT) and on-treatment cone-beam CTs (CBCTs). Based on the above models and via deformable image registration (DIR), we estimated two accumulated doses: firstly, an accumulated dose obtained by integrating the planning dose over the Gaussian probability distribution of the PCA model; and secondly, an accumulated dose obtained by simulating treatment courses via a Monte Carlo approach. We also computed a reference accumulated dose for each patient using his available images via DIR. Finally, we compared the planning dose with the three accumulated doses, and we calculated local dose variability and dose-volume histogram uncertainties.

Problems of long-term spinal opioid treatment in advanced cancer patients.

PubMed

Mercadante, S

1999-01-01

Epidural and intrathecal techniques are well established techniques in cancer pain. However, several questions remain unresolved. The several problems of long-term spinal opioid treatment in advance cancer patients were reviewed. Indications for the use of spinal opioids include patients treated by systemic opioids with effective pain relief but with unacceptable side effects, or unsuccessful treatment with sequential strong opioid drug trials despite escalating doses. Therefore, the previous aggressive treatment with systemic opioids would leave as failures patients with difficult pain syndromes unresponsive to opioids. The choice of external or totally implanted delivery systems is based on different clinical considerations. The use of externalized tunneled intrathecal catheters has not been associated with higher rates of complications and is easier to place and use at home in debilitated patients late in the course of their disease. The intrathecal administration has a lower incidence of catheter occlusion, lower malfunctioning rate, lower dose requirement, and more effective pain control. Due to the lower daily doses and volumes, intrathecal treatment proved to be more suitable for treatment at home by a continuous infusion than the epidural treatment. Advantages of infusion techniques are more evident when using local anesthetics, since intermittent administration of bupivacaine often results in motor paralysis and hemodynamic instability. Morphine is the opioid of choice. An epidural dose of 10% of the systemic dose is often used. However, intrathecal administration of opioids and bupivacaine may substantially improve pain relief in patients unresponsive to high epidural doses of these drugs, Bupivacaine-induced adverse effects, including sensory deficits, motor complaints, signs of autonomic dysfunction or neurotoxicity have been reported to not occur with bupivacaine doses less than 30-60 mg/day. Adjuvant drugs may further improve analgesia. Different ranges of technical complication rates have been reported in the literature, most of them being associated with epidural catheters. Subcutaneous tunneling and fixation of the catheter, bacterial filters, minimum changes of tubings, careful exit site care weekly, site protection and monitoring of any sign of infection to prevent infection, and training for family under supervision, are recommended. Areas for additional research include the use of spinal adjuvants, the ideal spinal morphine-bupivacaine ratio. methods to improve spinal opioid responsiveness and long-term catheter management with appropriate home care programs.

A risk index for pediatric patients undergoing diagnostic imaging with 99mTc-dimercaptosuccinic acid that accounts for body habitus

NASA Astrophysics Data System (ADS)

O'Reilly, Shannon E.; Plyku, Donika; Sgouros, George; Fahey, Frederic H.; Treves, S. Ted; Frey, Eric C.; Bolch, Wesley E.

2016-03-01

Published guidelines for administered activity to pediatric patients undergoing diagnostic nuclear medicine imaging are currently obtained through expert consensus of the minimum values as a function of body weight as required to yield diagnostic quality images. We have previously shown that consideration of body habitus is also important in obtaining diagnostic quality images at the lowest administered activity. The objective of this study was to create a series of computational phantoms that realistically portray the anatomy of the pediatric patient population which can be used to develop and validate techniques to minimize radiation dose while maintaining adequate image quality. To achieve this objective, we have defined an imaging risk index that may be used in future studies to develop pediatric patient dosing guidelines. A population of 48 hybrid phantoms consisting of non-uniform B-spline surfaces and polygon meshes was generated. The representative ages included the newborn, 1 year, 5 year, 10 year and 15 year male and female. For each age, the phantoms were modeled at their 10th, 50th, and 90th height percentile each at a constant 50th weight percentile. To test the impact of kidney size, the newborn phantoms were modeled with the following three kidney volumes:  -15%, average, and  +15%. To illustrate the impact of different morphologies on dose optimization, we calculated the effective dose for each phantom using weight-based 99mTc-DMSA activity administration. For a given patient weight, body habitus had a considerable effect on effective dose. Substantial variations were observed in the risk index between the 10th and 90th percentile height phantoms from the 50th percentile phantoms for a given age, with the greatest difference being 18%. There was a dependence found between kidney size and risk of radiation induced kidney cancer, with the highest risk indices observed in newborns with the smallest kidneys. Overall, the phantoms and techniques in this study can be used to provide data to refine dosing guidelines for pediatric nuclear imaging studies while taking into account the effects on both radiation dose and image quality. This work was supported by:R01 EB013558 with the National Institute for Biomedical Imaging and Bioengineering (NIBIB).

Somatic cell mutations at the glycophorin A locus in erythrocytes of atomic bomb survivors: Implications for radiation carcinogenesis

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

Kyoizumi, Seishi; Akiyama, Mitoshi; Tanabe, Kazumi

To clarify the relationship between somatic cell mutations and radiation exposure, the frequency of hemizygous mutant erythrocytes at the glycophorin A (GPA) locus was measured by flow cytometry for 1,226 heterozygous atomic bomb (A-bomb) survivors in HIroshima and Nagasaki. For statistical analysis, both GPA mutant frequency and radiation dose were log-transformed to normalize skewed distributions of these variables. The GPA mutant frequency increased slightly but significantly with age at testing and with the number of cigarettes smoked. Also, mutant frequency was significantly higher in males than in females even with adjustment for smoking and was higher to Hiroshima than inmore » Nagasaki. These characteristics of background GPA mutant frequency are qualitatively similar to those of background solid cancer incidence or mortality obtained from previous epidemiological studies of survivors. An analysis of the mutant frequency dose response using a descriptive model showed that the doubling dose is about 1.20 Sv [95% confidence interval (CI): 0.95-1.56], whereas the minimum dose for detecting a significant increase in mutant frequency is about 0.24 Sv (95% CI: 0.041-0.51). No significant effects of sex, city or age at the time of exposure on the dose response were detected. Interestingly, the doubling dose of the GPA mutant frequency was similar to that of solid cancer incidence in A-bomb survivors. This observation is in line with the hypothesis that radiation-induced somatic cell mutations are the major cause of excess cancer risk after radiation. 49 refs., 6 figs., 2 tabs.« less

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

Marsh, I; Otto, M; Weichert, J

Purpose: The focus of this work is to perform Monte Carlo-based dosimetry for several pediatric cancer xenografts in mice treated with a novel radiopharmaceutical {sup 131}I-CLR1404. Methods: Four mice for each tumor cell line were injected with 8–13 µCi/g of the {sup 124}124I-CLR1404. PET/CT images of each individual mouse were acquired at 5–6 time points over the span of 96–170 hours post-injection. Following acquisition, the images were co-registered, resampled, rescaled, corrected for partial volume effects (PVE), and masked. For this work the pre-treatment PET images of {sup 124}I-CLR1404 were used to predict therapeutic doses from {sup 131}I-CLR1404 at each timemore » point by assuming the same injection activity and accounting for the difference in physical decay rates. Tumors and normal tissues were manually contoured using anatomical and functional images. The CT and the PET images were used in the Geant4 (v9.6) Monte Carlo simulation to define the geometry and source distribution, respectively. The total cumulated absorbed dose was calculated by numerically integrating the dose-rate at each time point over all time on a voxel-by-voxel basis. Results: Spatial distributions of the absorbed dose rates and dose volume histograms as well as mean, minimum, maximum, and total dose values for each ROI were generated for each time point. Conclusion: This work demonstrates how mouse-specific MC-based dosimetry could potentially provide more accurate characterization of efficacy of novel radiopharmaceuticals in radionuclide therapy. This work is partially funded by NIH grant CA198392.« less

Mechanisms of inhibitory action of TRK-130 (Naltalimide), a μ-opioid receptor partial agonist, on the micturition reflex.

PubMed

Fujimura, Morihiro; Izumimoto, Naoki; Kanie, Sayoko; Kobayashi, Ryosuke; Yoshikawa, Satoru; Momen, Shinobu; Hirakata, Mikito; Komagata, Toshikazu; Okanishi, Satoshi; Iwata, Masashi; Hashimoto, Tadatoshi; Doi, Takayuki; Yoshimura, Naoki; Kawai, Koji

2017-04-01

To clarify the mechanism of inhibitory action of TRK-130 (Naltalimide), a unique µ-opioid receptor partial agonist, on the micturition reflex. The effect of TRK-130 on isovolumetric rhythmic bladder contractions (RBCs) was examined in guinea pigs, the effect of which was clarified by co-treatment with naloxone or in spinal cord transection. The effect of TRK-130 on urodynamic parameters was also observed in guinea pigs. In addition, the effect of TRK-130 on bladder contraction induced by peripheral stimulation of the pelvic nerve was investigated in rats. TRK-130 (0.001-0.01 mg/kg, iv) dose-dependently inhibited RBCs, which was dose-dependently antagonized by naloxone; however, the antagonism susceptibility was different from morphine (1 mg/kg, iv). The minimum effective dose (0.003 mg/kg) of TRK-130 remained similar in spinal cord-transected animals. TRK-130 (0.0025 mg/kg, iv) increased bladder capacity without changing the voiding efficiency, maximum flow rate, and intravesical pressure at the maximum flow rate, whereas oxybutynin (1 mg/kg, iv) increased the bladder capacity but affected the other parameters. TRK-130 (0.005 mg/kg, iv) did not produce significant changes on the bladder contractions induced by peripheral stimulation of the pelvic nerve, while oxybutynin (1 mg/kg, iv) significantly suppressed the bladder contractions. These results suggest that TRK-130 enhances the bladder storage function by modulating the afferent limb of the micturition reflex through µ-opioid receptors in the spinal cord. TRK-130 could be a more effective and safer therapeutic agent with a different fashion from antimuscarinics and conventional opioids for overactive bladder.

Treatment dose-response in amblyopia therapy: the Monitored Occlusion Treatment of Amblyopia Study (MOTAS).

PubMed

Stewart, Catherine E; Moseley, Merrick J; Stephens, David A; Fielder, Alistair R

2004-09-01

Amblyopia is the commonest visual disorder of childhood. Yet the contributions of the two principal treatments (spectacle wear and occlusion) to outcome are unknown. This study was undertaken to investigate the dose-response relationship of amblyopia therapy. The study comprised three distinct phases: baseline, in which repeat measures of visual function were undertaken to confirm the initial visual deficit; refractive adaptation: an 18-week period of spectacle wear with six weekly measurements of logarithm of the minimum angle of resolution (logMAR) visual acuity; occlusion: in which participants were prescribed 6 hours of "patching" per day. In the latter phase, occlusion was objectively monitored and logMAR visual acuity recorded at 2-week intervals until any observed gains had ceased. Data were obtained from 94 participants (mean age, 5.1 +/- 1.4 years) with amblyopia associated with strabismus (n = 34), anisometropia (n = 23), and both anisometropia and strabismus (n = 37). Eighty-six underwent refractive adaptation. Average concordance with patching was 48%. The relationship between logMAR visual acuity gain and total occlusion dose was monotonic and linear. Increasing dose rate beyond 2 h/d hastened the response but did not improve outcome. More than 80% of the improvement during occlusion occurred within 6 weeks. Treatment outcome was significantly better for children younger than 4 years (n = 17) than in those older than 6 years (n = 24; P = 0.0014). Continuous objective monitoring of the amount of patching therapy received has provided insight into the dose-response relationship of occlusion therapy for amblyopia. Patching is most effective within the first few weeks of treatment, even for those in receipt of a relatively small dose. Further studies are needed to elucidate the neural basis for the dose-response functions. Copyright Association for Research in Vision and Ophthalmology

Antimicrobial nisin acts against saliva derived multi-species biofilms without cytotoxicity to human oral cells

PubMed Central

Shin, Jae M.; Ateia, Islam; Paulus, Jefrey R.; Liu, Hongrui; Fenno, J. Christopher; Rickard, Alexander H.; Kapila, Yvonne L.

2015-01-01

Objectives: Nisin is a lantibiotic widely used for the preservation of food and beverages. Recently, investigators have reported that nisin may have clinical applications for treating bacterial infections. The aim of this study was to investigate the effects of ultra pure food grade Nisin ZP (>95% purity) on taxonomically diverse bacteria common to the human oral cavity and saliva derived multi-species oral biofilms, and to discern the toxicity of nisin against human cells relevant to the oral cavity. Methods: The minimum inhibitory concentrations and minimum bactericidal concentrations of taxonomically distinct oral bacteria were determined using agar and broth dilution methods. To assess the effects of nisin on biofilms, two model systems were utilized: a static and a controlled flow microfluidic system. Biofilms were inoculated with pooled human saliva and fed filter-sterilized saliva for 20–22 h at 37°C. Nisin effects on cellular apoptosis and proliferation were evaluated using acridine orange/ethidium bromide fluorescent nuclear staining and lactate dehydrogenase activity assays. Results: Nisin inhibited planktonic growth of oral bacteria at low concentrations (2.5–50 μg/ml). Nisin also retarded development of multi-species biofilms at concentrations ≥1 μg/ml. Specifically, under biofilm model conditions, nisin interfered with biofilm development and reduced biofilm biomass and thickness in a dose-dependent manner. The treatment of pre-formed biofilms with nisin resulted in dose- and time-dependent disruption of the biofilm architecture along with decreased bacterial viability. Human cells relevant to the oral cavity were unaffected by the treatment of nisin at anti-biofilm concentrations and showed no signs of apoptotic changes unless treated with much higher concentrations (>200 μg/ml). Conclusion: This work highlights the potential therapeutic value of high purity food grade nisin to inhibit the growth of oral bacteria and the development of biofilms relevant to oral diseases. PMID:26150809

(32)P measurment of urine samples and internal dose assessment for radiation workers in life science laboratories.

PubMed

Yoon, S; Pak, M-J; Park, S; Yoo, J; Ha, W-H; Jang, H-K; Kim, J K

2014-12-01

(32)P measurements of urine samples and internal dose assessments were conducted for workers in life science laboratories. A procedure for sample pre-treatment was established and validation was performed to exclude interference and to detect (32)P levels accurately. The detection conditions for Cherenkov radiation were evaluated and the accuracy of Cherenkov radiation measurements validated. The analytical and measurement procedures were applied to urine samples collected from 11 workers from life sciences laboratories. The results of the measurements generally indicated very low background radiation levels, but daily urine samples from two workers were above the minimum detectable activity. The (32)P concentrations for two of the workers were 29.3  ±  10.4 Bq•d(-1) and 24.1  ±  11.8 Bq•d(-1), respectively, at intake levels of 4.12 kBq and 2.61 kBq. The effective doses for these two workers were 4.6 μSv and 2.9 μSv. Overall, the results indicate very low levels of radioactivity, except for cases related to specific working conditions.

Focused ion beam micromachining of TiNi film on Si( 1 1 1 )

NASA Astrophysics Data System (ADS)

Xie, D. Z.; Ngoi, B. K. A.; Ong, A. S.; Fu, Y. Q.; Lim, B. H.

2003-11-01

Having an excellent shape memory effect, titanium-nickel (TiNi) thin films are often used for fabrication of microactuators in microelectromechanical systems. In this work, the Ga + focused ion beam (FIB) etching characteristics of TiNi thin films has been investigated. The thin films were deposited on Si(1 1 1) wafers by co-sputtering NiTi and Ti targets using a magnetron-sputtering system. Some patterns have been etched on the surface of the films by FIB. Atomic force microscopy has been used to analyze the surface morphology of the etched areas. It is found that the etched depth depends linearly on the ion dose per area with a slope of 0.259 μm/(nC/μm 2). However, the etching depth decreases with increasing the ion beam current. The root-mean-square (RMS) surface roughness changes nonlinearly with ion dose and reaches a minimum of about 5.00 nm at a dose of about 0.45 nC/μm 2. The RMS decreases with increasing ion beam current and reaches about 4.00 nm as the ion beam current is increased to 2 nA.

Sensory techniques for measuring differences in California navel oranges treated with doses of gamma-radiation below 0. 6 Kgray

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

O'Mahony, M.; Goldstein, L.R.

Navel oranges from California were given low post harvest doses of gamma radiation: 0.32-0.37 and 0.52-0.60 KGy (32-37 and 52-60 Krad); they were compared with nonirradiated controls for visual appearance, flavor by mouth, odor, taste and taste after sweetness suppression by gymnema sylvestre. Practiced judges were used as an analytical tool, with minimum cross-sensory interference, while untrained subjects were used to determine whether changes might be distinguished by nonexperts. Differences were found in appearance, flavor, taste and odor although they were less extreme at the lower dose. Untrained judges could discriminate the juice at the higher irradiation level only.

Dose titration of BAF312 attenuates the initial heart rate reducing effect in healthy subjects.

PubMed

Legangneux, Eric; Gardin, Anne; Johns, Donald

2013-03-01

Previous studies have shown transient decreases in heart rate (HR) following administration of sphingosine 1-phosphate (S1P) receptor modulators including BAF312. This study was conducted to determine whether dose titration of BAF312 reduces or eliminates these effects. Fifty-six healthy subjects were randomized 1:1:1:1 to receive BAF312 in one of two dose titration (DT) regimens (DT1 and DT2: 0.25-10 mg over 9-10 days), no titration (10 mg starting dose) or placebo. Pharmacodynamic and pharmacokinetic parameters were assessed. Neither DT1 nor DT2 resulted in clinically significant bradycardia or atrioventricular conduction effects. Both titration regimens showed a favourable difference on each of days 1-12 vs. the non-titration regimen on day 1 for HR effects (P < 0.0001). On day 1, the geometric mean ratio of the fraction from the previous day in minimum daily HR between DT1 and non-titration was 1.18 (95% confidence interval [CI] 1.13, 1.23) and 1.14 (95% CI 1.09, 1.18) for DT2 (both P < 0.05) with significant differences noted through to day 12. Non-titration HRs showed considerable separation from placebo throughout the study. There was no statistically significant reduction in HR vs. placebo on day 1 in either titration regimen. On days 3-7 subjects in DT1 and DT2 experienced minor reductions in HR vs. placebo (approximately 5 beats min⁻¹; P ≤ 0.0001). From days 9-12, HRs in both titration regimens were comparable with placebo. Both titration regimens effectively attenuated the initial bradyarrhythmia observed on day 1 of treatment with BAF312 10 mg. © 2012 Novartis Institutes for BioMedical Research (NIBIR). British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Preliminary results of radiation measurements on EURECA

NASA Technical Reports Server (NTRS)

Benton, E. V.; Frank, A. L.

1995-01-01

The eleven-month duration of the EURECA mission allows long-term radiation effects to be studied similarly to those of the Long Duration Exposure Facility (LDEF). Basic data can be generated for projections to crew doses and electronic and computer reliability on spacecraft missions. A radiation experiment has been designed for EURECA which uses passive integrating detectors to measure average radiation levels. The components include a Trackoscope, which employs fourteen plastic nuclear track detector (PNTD) stacks to measure the angular dependence of high LET (greater than or equal to 6 keV/micro m) radiation. Also included are TLD's for total absorbed doses, thermal/resonance neutron detectors (TRND's) for low energy neutron fluences and a thick PNTD stack for depth dependence measurements. LET spectra are derived from the PNTD measurements. Preliminary TLD results from seven levels within the detector array show that integrated does inside the flight canister varied from 18.8 +/- 0.6 cGy to 38.9 +/- 1.2 cGy. The TLD's oriented toward the least shielded direction averaged 53% higher in dose than those oriented away from the least shielded direction (minimum shielding toward the least shielded direction varied from 1.13 to 7.9 g/cm(exp 2), Al equivalent). The maximum dose rate on EURECA (1.16 mGy/day) was 37% of the maximum measured on LDEF and dose rates at all depths were less than measured on LDEF. The shielding external to the flight canister covered a greater solid angle about the canister than the LDEF experiments.

Simplified Solar Modulation Model of Inner Trapped Belt Proton Flux As a Function of Atmospheric Density

NASA Technical Reports Server (NTRS)

Wilson, Thomas L.; Lodhi, M. A. K.; Diaz, Abel B.

2005-01-01

No simple algorithm seems to exist for calculating proton fluxes and lifetimes in the Earth's inner, trapped radiation belt throughout the solar cycle. Most models of the inner trapped belt in use depend upon AP8 which only describes the radiation environment at solar maximum and solar minimum in Cycle 20. One exception is NOAAPRO which incorporates flight data from the TIROS/NOAA polar orbiting spacecraft. The present study discloses yet another, simple formulation for approximating proton fluxes at any time in a given solar cycle, in particular between solar maximum and solar minimum. It is derived from AP8 using a regression algorithm technique from nuclear physics. From flux and its time integral fluence, one can then approximate dose rate and its time integral dose. It has already been published in this journal that the absorbed dose rate, D, in the trapped belts exhibits a power law relationship, D = A(rho)(sup -n), where A is a constant, rho is the atmospheric density, and the index n is weakly dependent upon shielding. However, that method does not work for flux and fluence. Instead, we extend this idea by showing that the power law approximation for flux J is actually bivariant in energy E as well as density rho. The resulting relation is J(E,rho)approx.(sum of)A(E(sup n))rho(sup -n), with A itself a power law in E. This provides another method for calculating approximate proton flux and lifetime at any time in the solar cycle. These in turn can be used to predict the associated dose and dose rate.

Internal and external generalizability of temporal dose-response relationships for xerostomia following IMRT for head and neck cancer

PubMed Central

Thor, Maria; Owosho, Adepitan A; Clark, Haley D; Oh, Jung Hun; Riaz, Nadeem; Hovan, Allan; Tsai, Jillian; Thomas, Steven D; Yom, Sae Hee K; Wu, Jonn S; Huryn, Joseph M; Moiseenko, Vitali; Lee, Nancy Y; Estilo, Cherry L; Deasy, Joseph O

2016-01-01

Background and Purpose To study internal and external generalizability of temporal dose-response relationships for xerostomia after intensity-modulated radiotherapy (IMRT) for head and neck cancer, and to investigate potential amendments of the QUANTEC guidelines. Material and Methods Objective xerostomia was assessed in 121 patients (nCohort1=55; nCohort2=66) treated to 70Gy@2Gy in 2006–2015. Univariate and multivariate analyses (UVA, MVA with 1000 bootstrap populations) were conducted in Cohort1, and generalizability of the best-performing MVA model was investigated in Cohort2 (performance: AUC, p-values, and Hosmer-Lemeshow p-values (pHL)). Ultimately and for clinical guidance, minimum mean dose thresholds to the contralateral and the ipsilateral parotid glands (Dmeancontra, Dmeanipsi) were estimated from the generated dose-response curves. Results The observed xerostomia rate was 38%/47% (3 months) and 19%/23% (11–12 months) in Cohort1/Cohort2. Risk of xerostomia at 3 months increased for higher Dmeancontra and Dmeanipsi (Cohort1: 0.17•Dmeancontra+0.11•Dmeanipsi−8.13; AUC=0.90±0.05; p=0.0002±0.002; pHL=0.22±0.23; Cohort2: AUC=0.81; p<0.0001; pHL=0.27). The identified minimum Dmeancontra thresholds were lower than in the QUANTEC guidelines (Cohort1/Cohort2: Dmeancontra=12/19 Gy; Dmeancontra, Dmeanipsi=16, 25/20, 26 Gy). Conclusions Increased Dmeancontra and Dmeanipsi explain short-term xerostomia following IMRT. Our results also suggest decreasing Dmeancontra to below 20 Gy, while keeping Dmeanipsi to around 25 Gy. Long-term xerostomia was less frequent, and no dose-response relationship was established for this follow-up time. PMID:27890427

Internal and external generalizability of temporal dose-response relationships for xerostomia following IMRT for head and neck cancer.

PubMed

Thor, Maria; Owosho, Adepitan A; Clark, Haley D; Oh, Jung Hun; Riaz, Nadeem; Hovan, Allan; Tsai, Jillian; Thomas, Steven D; Yom, Sae Hee K; Wu, Jonn S; Huryn, Joseph M; Moiseenko, Vitali; Lee, Nancy Y; Estilo, Cherry L; Deasy, Joseph O

2017-02-01

To study internal and external generalizability of temporal dose-response relationships for xerostomia after intensity-modulated radiotherapy (IMRT) for head and neck cancer, and to investigate potential amendments of the QUANTEC guidelines. Objective xerostomia was assessed in 121 patients (n Cohort1 =55; n Cohort2 =66) treated to 70Gy@2Gy in 2006-2015. Univariate and multivariate analyses (UVA, MVA with 1000 bootstrap populations) were conducted in Cohort1, and generalizability of the best-performing MVA model was investigated in Cohort2 (performance: AUC, p-values, and Hosmer-Lemeshow p-values (p HL )). Ultimately and for clinical guidance, minimum mean dose thresholds to the contralateral and the ipsilateral parotid glands (Dmean contra , Dmean ipsi ) were estimated from the generated dose-response curves. The observed xerostomia rate was 38%/47% (3months) and 19%/23% (11-12months) in Cohort1/Cohort2. Risk of xerostomia at 3months increased for higher Dmean contra and Dmean ipsi (Cohort1: 0.17·Dmean contra +0.11·Dmean ipsi -8.13; AUC=0.90±0.05; p=0.0002±0.002; p HL =0.22±0.23; Cohort2: AUC=0.81; p<0.0001; p HL =0.27). The identified minimum Dmean contra thresholds were lower than in the QUANTEC guidelines (Cohort1/Cohort2: Dmean contra =12/19Gy; Dmean contra , Dmean ipsi =16, 25/20, 26Gy). Increased Dmean contra and Dmean ipsi explain short-term xerostomia following IMRT. Our results also suggest decreasing Dmean contra to below 20Gy, while keeping Dmean ipsi to around 25Gy. Long-term xerostomia was less frequent, and no dose-response relationship was established for this follow-up time. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Metam sodium reduces viability and infectivity of Eimeria oocysts.

PubMed

Fetterer, R H; Jenkins, M C; Miska, K B; Cain, G D

2010-06-01

Metam sodium (MS, sodium N-methyldithiocarbamate) is a widely used soil pesticide. Fumigation or chemical sterilization of poultry litter containing infectious oocysts could be an effective strategy to block the transmission of avian coccidia. In the current study, the effect of MS on the viability and infectivity of ocysts was investigated. The development of isolated, unsporulated oocysts of both Eimeria tenella and Eimeria maxima was inhibited, in a dose-related manner (IC(50) 8 to 14 microg/ml), by exposure to aqueous MS. Most treated oocysts failed to develop beyond early stages of sporulation. To determine the effect of MS on infectivity, isolated oocysts of E. tenella , Eimeria acervulina , and E. maxima were exposed for 24 hr to aqueous concentrations of MS ranging from 0 to 1,000 microg/ml. Treated oocysts were inoculated into chickens, and parameters of coccidiosis infection were compared to chickens inoculated with equal numbers of untreated oocysts. In a dose-related manner, MS significantly reduced the infectivity of oocysts with maximum effect observed at a dose of 300 microg/ml. When a mixture of oocysts containing 3 coccidian species was exposed to 300 microg/ml MS, from 0 to 24 hr, infectivity of oocysts was significantly reduced after a minimum of 12 hr of exposure. Treatment of aqueous slurries of litter samples obtained from commercial poultry houses, with 300 microg/ml MS for 24 hr, prevented the sporulation of eimerian oocysts in the litter samples relative to untreated control samples. The results indicate that MS could be used to reduce coccidial contamination of poultry litter.

Cytotoxic effects of treosulfan on prostate cancer cell lines.

PubMed

Feyerabend, Susan; Feil, Gerhard; Krug, Jutta; Kassen, Annette; Stenzl, Arnulf

2007-01-01

Despite various therapeutical options in metastatic prostate cancer, the lack of a curative approach motivates further investigations. Treosulfan is an alkylating agent that has proven its indication in the treatment of e.g. ovarian carcinoma. This study focused on the objective of evaluating the effect of in vitro intoxication of human prostate carcinoma cell lines with treosulfan. Human prostate cancer cell lines LNCaP, DU145 and PC3 were treated with treosulfan concentrations from 0.5-500 microM for up to six days. Analysis of cell viability was performed using colorimetric WST-1 assay. Control data were obtained from identical cell lines cultivated without treosulfan. Incubation with treosulfan inhibited cell viability and led to cell death in all cell lines in a dose- and time-dependent manner. After one day, viability of LNCaP, DU145 and PC3 cells was constantly reduced with a dose rate of at least 10 microM (p < 0.001), 10 microM (p < 0.0001) and 100 microM (p < 0.0001) treosulfan, respectively. Minimum dose rates leading to death of nearly all LNCaP, DU145 and PC3 cells were 250 microM, 100 microM and 200 microM treosulfan, respectively. The results demonstrate a sensitivity of prostate carcinoma cells to the cytotoxic activity of treosulfan. Therefore, treosulfan might be a promising compound for novel treatment protocols for prostate cancer.

Radon Concentration And Dose Assessment In Well Water Samples From Karbala Governorate Of Iraq

NASA Astrophysics Data System (ADS)

Al-Alawy, I. T.; Hasan, A. A.

2018-05-01

There are numerous studies around the world about radon concentrations and their risks to the health of human beings. One of the most important social characteristics is the use of water wells for irrigation, which is a major source of water pollution with radon gas. In the present study, six well water samples have been collected from different locations in Karbala governorate to investigate radon concentration level using CR-39 technique. The maximum value 4.112±2.0Bq/L was in Al-Hurr (Al-Qarih Al-Easariah) region, and the lowest concentration of radon was in Hay Ramadan region which is 2.156±1.4Bq/L, with an average value 2.84±1.65Bq/L. The highest result of annual effective dose (AED) was in Al-Hurr (Al-Qarih Al-Easariah) region which is equal to 15.00±3.9μSv/y, while the minimum was recorded in Hay Ramadan 7.86±2.8μSv/y, with an average value 10.35±3.1μSv/y. The current results have shown that the radon concentrations in well water samples are lower than the recommended limit 11.1Bq/L and the annual effective dose in these samples are lower than the permissible international limit 1mSv/y.

Heavy ion contributions to organ dose equivalent for the 1977 galactic cosmic ray spectrum

NASA Astrophysics Data System (ADS)

Walker, Steven A.; Townsend, Lawrence W.; Norbury, John W.

2013-05-01

Estimates of organ dose equivalents for the skin, eye lens, blood forming organs, central nervous system, and heart of female astronauts from exposures to the 1977 solar minimum galactic cosmic radiation spectrum for various shielding geometries involving simple spheres and locations within the Space Transportation System (space shuttle) and the International Space Station (ISS) are made using the HZETRN 2010 space radiation transport code. The dose equivalent contributions are broken down by charge groups in order to better understand the sources of the exposures to these organs. For thin shields, contributions from ions heavier than alpha particles comprise at least half of the organ dose equivalent. For thick shields, such as the ISS locations, heavy ions contribute less than 30% and in some cases less than 10% of the organ dose equivalent. Secondary neutron production contributions in thick shields also tend to be as large, or larger, than the heavy ion contributions to the organ dose equivalents.

Cosmic Ray Modulation and Radiation Dose of Aircrews During Possible Grand Minimum

NASA Astrophysics Data System (ADS)

Miyake, S.; Kataoka, R.; Sato, T.; Imada, S.; Miyahara, H.; Shiota, D.; Matsumoto, T.; Ueno, H.

2017-12-01

The Sun is exhibiting low solar activity levels since the descending phase of the last solar cycle, and it is likely to be continued as well as in the case of the past grand solar minima. The cosmic-ray modulation, which is the variation of the galactic cosmic ray (GCR) spectrum caused by the heliospheric environmental change, is basically anti-correlated with the solar activity. In the recent weak solar cycle, we thus expect that the flux of GCRs is getting higher than that in the previous solar cycles, leading to the increase in the radiation exposure in the space and atmosphere. In order to quantitatively evaluate the possible solar modulation of GCRs and resultant radiation exposure at flight altitude, we have developed the time-dependent and three-dimensional model of the cosmic-ray modulation. Our model can give the flux of GCRs anywhere in the heliosphere by assuming the variation of the solar wind speed, the strength of the heliospheric magnetic field (HMF), and its tilt angle. We solve the gradient-curvature drift motion of GCRs in the HMF, and therefore reproduce the 22-year variation of the cosmic-ray modulation. We also calculate the neutron monitor counting rate and the radiation dose of aircrews at flight altitude, by the air-shower simulation performed by PHITS (Particle and Heavy Ion Transport code System). In our previous study [1], we calculated the radiation dose at a flight altitude during the coming solar cycle by assuming the variation of the solar wind speed and the strength of the HMF expressed by sinusoidal curve, and obtained that an annual radiation dose of aircrews in 5 years around the next solar minimum will be up to 19% higher than that at the last cycle. In this study, we predict the new model of the heliospheric environmental change on the basis of a prediction model for the sunspot number. The quantitative predictions of the cosmic-ray modulation and the radiation dose at a flight altitude during possible Grand Minimum considering the new model for the heliospheric environmental change will be presented at the meeting. [1] S. Miyake, R. Kataoka, and T. Sato, Space Weather, 15, 589-605, 2017.

Dosimetric evaluation of integrated IMRT treatment of the chest wall and supraclavicular region for breast cancer after modified radical mastectomy

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

Yang, Bo; Wei, Xian-ding; Zhao, Yu-tian

2014-07-01

To investigate the dosimetric characteristics of irradiation of the chest wall and supraclavicular region as an integrated volume with intensity-modulated radiation therapy (IMRT) after modified radical mastectomy. This study included 246 patients who received modified radical mastectomy. The patients were scanned with computed tomography, and the chest wall (with or without the internal mammary lymph nodes) and supraclavicular region were delineated. For 143 patients, the chest wall and supraclavicular region were combined as an integrated planning volume and treated with IMRT. For 103 patients, conventional treatments were employed with 2 tangential fields for the chest wall, abutting a mixed fieldmore » of 6-MV x-rays (16 Gy) and 9-MeV electrons (34 Gy) for the upper supraclavicular region. The common prescription dose was 50 Gy/25 Fx/5 W to 90% of the target volume. The dosimetric characteristics of the chest wall, the supraclavicular region, and normal organs were compared. For the chest wall target, compared with conventional treatments, the integrated IMRT plans lowered the maximum dose, increased the minimum dose, and resulted in better conformity and uniformity of the target volume. There was an increase in minimum, average, and 95% prescription dose for the integrated IMRT plans in the supraclavicular region, and conformity and uniformity were improved. The V{sub 30} of the ipsilateral lung and V{sub 10}, V{sub 30}, and mean dose of the heart on the integrated IMRT plans were lower than those of the conventional plans. The V{sub 5} and V{sub 10} of the ipsilateral lung and V{sub 5} of the heart were higher on the integrated IMRT plans (p < 0.05) than on conventional plans. Without an increase in the radiation dose to organs at risk, the integrated IMRT treatment plans improved the dose distribution of the supraclavicular region and showed better dose conformity and uniformity of the integrated target volume of the chest wall and supraclavicular region.« less

A simple DVH generation technique for various radiotherapy treatment planning systems for an independent information system

NASA Astrophysics Data System (ADS)

Min, Byung Jun; Nam, Heerim; Jeong, Il Sun; Lee, Hyebin

2015-07-01

In recent years, the use of a picture archiving and communication system (PACS) for radiation therapy has become the norm in hospital environments and has been suggested for collecting and managing data using Digital Imaging and Communication in Medicine (DICOM) objects from different treatment planning systems (TPSs). However, some TPSs do not provide the ability to export the dose-volume histogram (DVH) in text or other format. In addition, plan review systems for various TPSs often allow DVH recalculations with different algorithms. These algorithms result in inevitable discrepancies between the values obtained with the recalculation and those obtained with TPS itself. The purpose of this study was to develop a simple method for generating reproducible DVH values by using the TPSs. Treatment planning information, including structures and delivered dose, was exported in the DICOM format from the Eclipse v8.9 or the Pinnacle v9.6 planning systems. The supersampling and trilinear interpolation methods were employed to calculate the DVH data from 35 treatment plans. The discrepancies between the DVHs extracted from each TPS and those extracted by using the proposed calculation method were evaluated with respect to the supersampling ratio. The volume, minimum dose, maximum dose, and mean dose were compared. The variations in DVHs from multiple TPSs were compared by using the MIM software v6.1, which is a commercially available treatment planning comparison tool. The overall comparisons of the volume, minimum dose, maximum dose, and mean dose showed that the proposed method generated relatively smaller discrepancies compared with TPS than the MIM software did compare with the TPS. As the structure volume decreased, the overall percent difference increased. The largest difference was observed in small organs such as the eye ball, eye lens, and optic nerve which had volume below 10 cc. A simple and useful technique was developed to generate a DVH with an acceptable error from a proprietary TPS. This study provides a convenient and common framework that will allow the use of a single well-managed storage solution for an independent information system.

76 FR 3075 - Notice of Decision to Allow Interstate Movement of Guavas From Hawaii Into the Continental United...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-19

... CONTACT: Mr. David Lamb, Import Specialist, PPQ, APHIS, 4700 River Road Unit 133, Riverdale, MD 20737-1236... part 305 with a minimum absorbed dose of 400 Gy. The guavas must be inspected by an inspector in Hawaii...

Radiobiological Impact of Reduced Margins and Treatment Technique for Prostate Cancer in Terms of Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP)

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

Jensen, Ingelise, E-mail: inje@rn.d; Carl, Jesper; Lund, Bente

2011-07-01

Dose escalation in prostate radiotherapy is limited by normal tissue toxicities. The aim of this study was to assess the impact of margin size on tumor control and side effects for intensity-modulated radiation therapy (IMRT) and 3D conformal radiotherapy (3DCRT) treatment plans with increased dose. Eighteen patients with localized prostate cancer were enrolled. 3DCRT and IMRT plans were compared for a variety of margin sizes. A marker detectable on daily portal images was presupposed for narrow margins. Prescribed dose was 82 Gy within 41 fractions to the prostate clinical target volume (CTV). Tumor control probability (TCP) calculations based on themore » Poisson model including the linear quadratic approach were performed. Normal tissue complication probability (NTCP) was calculated for bladder, rectum and femoral heads according to the Lyman-Kutcher-Burman method. All plan types presented essentially identical TCP values and very low NTCP for bladder and femoral heads. Mean doses for these critical structures reached a minimum for IMRT with reduced margins. Two endpoints for rectal complications were analyzed. A marked decrease in NTCP for IMRT plans with narrow margins was seen for mild RTOG grade 2/3 as well as for proctitis/necrosis/stenosis/fistula, for which NTCP <7% was obtained. For equivalent TCP values, sparing of normal tissue was demonstrated with the narrow margin approach. The effect was more pronounced for IMRT than 3DCRT, with respect to NTCP for mild, as well as severe, rectal complications.« less

Personalized versus standardized dosing strategies for the treatment of childhood amblyopia: study protocol for a randomized controlled trial.

PubMed

Moseley, Merrick J; Wallace, Michael P; Stephens, David A; Fielder, Alistair R; Smith, Laura C; Stewart, Catherine E

2015-04-25

Amblyopia is the commonest visual disorder of childhood in Western societies, affecting, predominantly, spatial visual function. Treatment typically requires a period of refractive correction ('optical treatment') followed by occlusion: covering the nonamblyopic eye with a fabric patch for varying daily durations. Recent studies have provided insight into the optimal amount of patching ('dose'), leading to the adoption of standardized dosing strategies, which, though an advance on previous ad-hoc regimens, take little account of individual patient characteristics. This trial compares the effectiveness of a standardized dosing strategy (that is, a fixed daily occlusion dose based on disease severity) with a personalized dosing strategy (derived from known treatment dose-response functions), in which an initially prescribed occlusion dose is modulated, in a systematic manner, dependent on treatment compliance. A total of 120 children aged between 3 and 8 years of age diagnosed with amblyopia in association with either anisometropia or strabismus, or both, will be randomized to receive either a standardized or a personalized occlusion dose regimen. To avoid confounding by the known benefits of refractive correction, participants will not be randomized until they have completed an optical treatment phase. The primary study objective is to determine whether, at trial endpoint, participants receiving a personalized dosing strategy require fewer hours of occlusion than those in receipt of a standardized dosing strategy. Secondary objectives are to quantify the relationship between observed changes in visual acuity (logMAR, logarithm of the Minimum Angle of Resolution) with age, amblyopia type, and severity of amblyopic visual acuity deficit. This is the first randomized controlled trial of occlusion therapy for amblyopia to compare a treatment arm representative of current best practice with an arm representative of an entirely novel treatment regimen based on statistical modelling of previous trial outcome data. Should the personalized dosing strategy demonstrate superiority over the standardized dosing strategy, then its adoption into routine practice could bring practical benefits in reducing the duration of treatment needed to achieve an optimal outcome. ISRCTN ISRCTN12292232.

Skeletal malignancies among beagles injected with 241Am.

PubMed

Lloyd, R D; Taylor, G N; Angus, W; Miller, S C; Boecker, B B

1994-02-01

Seventy skeletal malignancies in 44 dogs were identified among 117 beagles injected as young adults with graded dosages of approximately 0.07 to 104 kBq 241Am kg-1 and maintained for lifetime observation. All of these tumors were osteosarcomas except four fibrosarcomas of bone and four chondrosarcomas of bone. Of these 117 animals, 114 survived beyond the minimum age (of 2.79 y) for radiation-induced bone cancer, and all are now dead. An expression was derived that described the dependence of percent occurrence of bone sarcoma on skeletal radiation dose of A = 0.76 + 30D, where A = percent of dogs with skeletal malignancy within any dosage group, D = average skeletal dose (< 3 Gy) at 1 y before death (average skeletal dose was calculated to the presumed start of tumor growth, which we have taken to be 1 y before death), and 0.76 represents the lifetime percent malignant bone tumor response among 132 suitable control dogs in our colony not given any radioactivity. All dosage groups with skeletal doses of > 3 Gy at 1 y before death exhibited close to 100% occurrence and appeared to be beyond the region of linearity. Therefore, they were excluded from the derivation of this expression. Similar analysis of corresponding data for beagles given 226Ra as young adults, excluding the two highest dosage groups in which the bone tumor response was approximately 100%, yielded the expression, A = 0.76 + 4.7D, (D < 20 Gy). A ratio of the coefficients in these two expressions indicates the effectiveness at low radiation doses for bone-cancer induction of 241Am relative to 226Ra, or (30 +/- 2.6)(4.7 +/- 0.47)-1 = 6 +/- 0.8. This compares to the relative effectiveness at low radiation doses that was obtained earlier for a 239Pu:226Ra toxicity ratio of about 16 +/- 5.

Toxicity Profile and Pharmacokinetic Study of A Phase I Low-Dose Schedule-Dependent Radiosensitizing Paclitaxel Chemoradiation Regimen for Inoperable Non-Small-Cell Lung Cancer

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

Chen, Yuhchyau; Pandya, Kishan J.; Feins, Richard

Purpose: We report the toxicity profile and pharmacokinetic data of a schedule-dependent chemoradiation regimen using pulsed low-dose paclitaxel for radiosensitization in a Phase I study for inoperable non-small-cell lung cancer. Methods and Materials: Paclitaxel at escalating doses of 15 mg/m{sup 2}, 20 mg/m{sup 2}, and 25 mg/m{sup 2} were infused on Monday, Wednesday, and Friday with daily chest radiation in cohorts of 6 patients. Daily radiation was delayed for maximal G2/M arrest and apoptotic effect, an observation from preclinical investigations. Plasma paclitaxel concentration was determined by high-performance liquid chromatography. Results: Dose-limiting toxicities included 3 of 18 patients with Grade 3more » pneumonitis and 3 of 18 patients with Grade 3 esophagitis. There was no Grade 4 or 5 pneumonitis or esophagitis. There was also no Grade 3 or 4 neutropenia, thrombocytopenia, anemia or neuropathy. For Dose Levels I (15 mg/m{sup 2}), II (20 mg/m{sup 2}), and III (25 mg/m{sup 2}), the mean peak plasma level was 0.23 {+-} 0.06 {mu}mol/l, 0.32 {+-} 0.05 {mu}mol/l, and 0.52 {+-} 0.14 {mu}mol/l, respectively; AUC was 0.44 {+-} 0.09 {mu}mol/l, 0.61 {+-} 0.1 {mu}mol/l, and 0.96 {+-} 0.23 {mu}mol/l, respectively; and duration of drug concentration >0.05 {mu}mol/l (t > 0.05 {mu}mol/l) was 1.6 {+-} 0.3 h, 1.9 {+-} 0.2 h, and 3.0 {+-} 0.9 h, respectively. Conclusion: Pulsed low-dose paclitaxel chemoradiation is associated with low toxicity. Pharmacokinetic data showed that plasma paclitaxel concentration >0.05 {mu}mol/l for a minimum of 1.6 h was sufficient for effective radiosensitization.« less

Antibacterial activity of Litsea cubeba (Lauraceae, May Chang) and its effects on the biological response of common carp Cyprinus carpio challenged with Aeromonas hydrophila.

PubMed

Nguyen, H V; Caruso, D; Lebrun, M; Nguyen, N T; Trinh, T T; Meile, J-C; Chu-Ky, S; Sarter, S

2016-08-01

The aims of this study were to characterize the antibacterial activity and the chemotype of Litsea cubeba leaf essential oil (EO) harvested in North Vietnam and to investigate the biological effects induced by the leaf powder on growth, nonspecific immunity and survival of common carp (Cyprinus carpio) challenged with Aeromonas hydrophila. The EO showed the prevalence of linalool (95%, n = 5). It was bactericidal against the majority of tested strains, with minimum inhibitory concentrations ranging from 0·72 to 2·89 mg ml(-1) (Aer. hydrophila, Edwarsiella tarda, Vibrio furnissii, Vibrio parahaemolyticus, Streptococcus garvieae, Escherichia coli, Salmonella Typhimurium). The fish was fed with 0 (control), 2, 4 and 8% leaf powder supplementation diets for 21 days. Nonspecific immunity parameters (lysozyme, haemolytic and bactericidal activities of plasma) were assessed 21 days after feeding period and before the experimental infection. Weight gain, specific growth rate and feed conversion ratio were improved by supplementation of L. cubeba in a dose-related manner, and a significant difference appeared at the highest dose (8%) when compared to the control. The increase in plasma lysozyme was significant for all the treated groups. Haemolysis activity was higher for the groups fed with 4 and 8% plant powder. Antibacterial activity increased significantly for the 8% dose only. Litsea cubeba leaf powder increased nonspecific immunity of carps in dose-related manner. After infection with Aer. hydrophila, survivals of fish fed with 4 and 8% L. cubeba doses were significantly higher than those fed with 2% dose and the control. A range of 4-8% L. cubeba leaf powder supplementation diet (from specific linalool-rich chemotype) can be used in aquaculture to reduce antibiotic burden and impacts of diseases caused by Aer. hydrophila. © 2016 The Society for Applied Microbiology.

Research Findings on Xylitol and the Development of Xylitol Vehicles to Address Public Health Needs

PubMed Central

Milgrom, P.; Ly, K.A.; Rothen, M.

2013-01-01

Xylitol has been demonstrated to be a safe and effective tooth decay preventive agent when used habitually. Nevertheless, its application has been limited by absence of formulations that demand minimal adherence and are acceptable and safe in settings where chewing gum may not be allowed. A substantial literature suggests that a minimum of five to six grams and three exposures per day from chewing gum or candies are needed for a clinical effect. At the same time there is conflicting evidence in the literature from toothpaste studies suggesting that lower-doses and less frequent exposures might be effective. The growing use of xylitol as a sweetener in low amounts in foods and other consumables is, simultaneously, increasing the overall exposure of the public to xylitol and may have additive benefits. PMID:19710081

Early Results from the Advanced Radiation Protection Thick GCR Shielding Project

NASA Technical Reports Server (NTRS)

Norman, Ryan B.; Clowdsley, Martha; Slaba, Tony; Heilbronn, Lawrence; Zeitlin, Cary; Kenny, Sean; Crespo, Luis; Giesy, Daniel; Warner, James; McGirl, Natalie;

The impact of different dose response parameters on biologically optimized IMRT in breast cancer

NASA Astrophysics Data System (ADS)

Costa Ferreira, Brigida; Mavroidis, Panayiotis; Adamus-Górka, Magdalena; Svensson, Roger; Lind, Bengt K.

2008-05-01

The full potential of biologically optimized radiation therapy can only be maximized with the prediction of individual patient radiosensitivity prior to treatment. Unfortunately, the available biological parameters, derived from clinical trials, reflect an average radiosensitivity of the examined populations. In the present study, a breast cancer patient of stage I II with positive lymph nodes was chosen in order to analyse the effect of the variation of individual radiosensitivity on the optimal dose distribution. Thus, deviations from the average biological parameters, describing tumour, heart and lung response, were introduced covering the range of patient radiosensitivity reported in the literature. Two treatment configurations of three and seven biologically optimized intensity-modulated beams were employed. The different dose distributions were analysed using biological and physical parameters such as the complication-free tumour control probability (P+), the biologically effective uniform dose (\\bar{\\bar{D}} ), dose volume histograms, mean doses, standard deviations, maximum and minimum doses. In the three-beam plan, the difference in P+ between the optimal dose distribution (when the individual patient radiosensitivity is known) and the reference dose distribution, which is optimal for the average patient biology, ranges up to 13.9% when varying the radiosensitivity of the target volume, up to 0.9% when varying the radiosensitivity of the heart and up to 1.3% when varying the radiosensitivity of the lung. Similarly, in the seven-beam plan, the differences in P+ are up to 13.1% for the target, up to 1.6% for the heart and up to 0.9% for the left lung. When the radiosensitivity of the most important tissues in breast cancer radiation therapy was simultaneously changed, the maximum gain in outcome was as high as 7.7%. The impact of the dose response uncertainties on the treatment outcome was clinically insignificant for the majority of the simulated patients. However, the jump from generalized to individualized radiation therapy may significantly increase the therapeutic window for patients with extreme radio sensitivity or radioresistance, provided that these are identified. Even for radiosensitive patients a simple treatment technique is sufficient to maximize the outcome, since no significant benefits were obtained with a more complex technique using seven intensity-modulated beams portals.

Investigations of interference between electromagnetic transponders and wireless MOSFET dosimeters: a phantom study.

PubMed

Su, Zhong; Zhang, Lisha; Ramakrishnan, V; Hagan, Michael; Anscher, Mitchell

2011-05-01

To evaluate both the Calypso Systems' (Calypso Medical Technologies, Inc., Seattle, WA) localization accuracy in the presence of wireless metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters of dose verification system (DVS, Sicel Technologies, Inc., Morrisville, NC) and the dosimeters' reading accuracy in the presence of wireless electromagnetic transponders inside a phantom. A custom-made, solid-water phantom was fabricated with space for transponders and dosimeters. Two inserts were machined with positioning grooves precisely matching the dimensions of the transponders and dosimeters and were arranged in orthogonal and parallel orientations, respectively. To test the transponder localization accuracy with/without presence of dosimeters (hypothesis 1), multivariate analyses were performed on transponder-derived localization data with and without dosimeters at each preset distance to detect statistically significant localization differences between the control and test sets. To test dosimeter dose-reading accuracy with/without presence of transponders (hypothesis 2), an approach of alternating the transponder presence in seven identical fraction dose (100 cGy) deliveries and measurements was implemented. Two-way analysis of variance was performed to examine statistically significant dose-reading differences between the two groups and the different fractions. A relative-dose analysis method was also used to evaluate transponder impact on dose-reading accuracy after dose-fading effect was removed by a second-order polynomial fit. Multivariate analysis indicated that hypothesis 1 was false; there was a statistically significant difference between the localization data from the control and test sets. However, the upper and lower bounds of the 95% confidence intervals of the localized positional differences between the control and test sets were less than 0.1 mm, which was significantly smaller than the minimum clinical localization resolution of 0.5 mm. For hypothesis 2, analysis of variance indicated that there was no statistically significant difference between the dosimeter readings with and without the presence of transponders. Both orthogonal and parallel configurations had difference of polynomial-fit dose to measured dose values within 1.75%. The phantom study indicated that the Calypso System's localization accuracy was not affected clinically due to the presence of DVS wireless MOSFET dosimeters and the dosimeter-measured doses were not affected by the presence of transponders. Thus, the same patients could be implanted with both transponders and dosimeters to benefit from improved accuracy of radiotherapy treatments offered by conjunctional use of the two systems.

Chemical and sensory quality of fresh pomegranate fruits exposed to gamma radiation as quarantine treatment.

PubMed

Shahbaz, Hafiz Muhammad; Ahn, Jae-Jun; Akram, Kashif; Kim, Hyo-Young; Park, Eun-Joo; Kwon, Joong-Ho

2014-02-15

The U.S. Department of Agriculture in February 2012 approved the import of fresh pomegranates subjected to irradiation as a quarantine procedure with a minimum absorbed dose of 0.4kGy against different pests. This study evaluated the application of different gamma-irradiation doses (0.4, 1, and 2kGy) in fresh pomegranate fruits and their effect on the chemical and sensory characteristics. The total soluble solids, titratable acidity, and pH values remained unaffected up to 1kGy treatment. Irradiation caused a significant decrease in the total anthocyanins and phenolic content. A strong positive correlation was observed among the antioxidant activities, total phenolics and anthocyanin contents. In general, a stronger preference was shown by sensory panelists for the juice from irradiated fruits. This study provides research-based information about the application of irradiation as a quarantine disinfestation treatment to enhance the marketing and consumer acceptance of pomegranates. Copyright © 2013 Elsevier Ltd. All rights reserved.

Boron neutron capture therapy (BNCT) for glioblastoma multiforme: a phase II study evaluating a prolonged high-dose of boronophenylalanine (BPA).

PubMed

Henriksson, Roger; Capala, Jacek; Michanek, Annika; Lindahl, Sten-Ake; Salford, Leif G; Franzén, Lars; Blomquist, Erik; Westlin, Jan-Erik; Bergenheim, A Tommy

2008-08-01

To evaluate the efficacy and safety of boron neutron capture therapy (BNCT) for glioblastoma multiforme (GBM) using a novel protocol for the boronophenylalanine-fructose (BPA-F) infusion. This phase II study included 30 patients, 26-69 years old, with a good performance status of which 27 have undergone debulking surgery. BPA-F (900 mg BPA/kg body weight) was given i.v. over 6h. Neutron irradiation started 2h after the completion of the infusion. Follow-up reports were monitored by an independent clinical research institute. The boron-blood concentration during irradiation was 15.2-33.7 microg/g. The average weighted absorbed dose to normal brain was 3.2-6.1 Gy (W). The minimum dose to the tumour volume ranged from 15.4 to 54.3 Gy (W). Seven patients suffered from seizures, 8 from skin/mucous problem, 5 patients were stricken by thromboembolism and 4 from abdominal disturbances in close relation to BNCT. Four patients displayed 9 episodes of grade 3-4 events (WHO). At the time for follow-up, minimum ten months, 23 out of the 29 evaluable patients were dead. The median time from BNCT treatment to tumour progression was 5.8 months and the median survival time after BNCT was 14.2 months. Following progression, 13 patients were given temozolomide, two patients were re-irradiated, and two were re-operated. Patients treated with temozolomide lived considerably longer (17.7 vs. 11.6 months). The quality of life analysis demonstrated a progressive deterioration after BNCT. Although, the efficacy of BNCT in the present protocol seems to be comparable with conventional radiotherapy and the treatment time is shorter, the observed side effects and the requirement of complex infrastructure and higher resources emphasize the need of further phase I and II studies, especially directed to improve the accumulation of (10)B in tumour cells.

Bacterial radiosensitization by using radiation processing in combination with essential oil: Mechanism of action

NASA Astrophysics Data System (ADS)

Lacroix, Monique; Caillet, Stéphane; Shareck, Francois

2009-07-01

Spice extracts under the form of essential oils were tested for their efficiency to increase the relative radiosensitivity of Listeria monocytogenes and Escherichia coli O157H7 in culture media. The two pathogens were treated by gamma-irradiation alone or in combination with oregano essential oil to evaluate their mechanism of action. The membrane murein composition, and the intracellular and extracellular concentration of ATP was determined. The bacterial strains were treated with two irradiation doses: 1.2 kGy to induce cell damage and 3.5 kGy to cause cell death for L. monocytogenes. A dose of 0.4 kGy to induce cell damages, 1.1 kGy to obtain viable but nonculturable (VBNC) state and 1.3 kGy to obtain a lethal dose was also applied on E. coli O157H7. Oregano essential oil was used at 0.020% and 0.025% (w/v), which is the minimum inhibitory concentration (MIC) for L. monocytogenes. For E. coli O157H7, a concentration of 0.006% and 0.025% (w/v) which is the minimum inhibitory concentration was applied. The use of essential oils in combination with irradiation has permitted an increase of the bacterial radiosensitization by more than 3.1 times. All treatments had also a significant effect ( p⩽0.05) on the murein composition, although some muropeptides did not seem to be affected by the treatment. Each treatment influenced differently the relative percentage and number of muropeptides. There was a significant ( p⩽0.05) correlation between the reduction of intracellular ATP and increase in extracellular ATP following treatment of the cells with oregano oil. The reduction of intracellular ATP was even more important when essential oil was combined with irradiation, but irradiation of L. monocytogenes alone induced a significant decrease ( p⩽0.05) of the internal ATP without affecting the external ATP.

Does Cervical Interlaminar Epidural Steroid Injection with Low-Dose Lidocaine Cause Objective Upper Extremity Weakness? A Preliminary Study.

PubMed

McCormick, Zachary L; Nelson, Ariana; Kendall, Mark C; McCarthy, Robert J; Nagpal, Geeta; Walega, David R

2017-12-01

Low-dose local anesthetic is often used in cervical interlaminar epidural steroid injections (CIESI), yet its effect on upper extremity strength has not been studied. The presence of consequent weakness has potential implications for postprocedure safety. This study aimed to determine whether low-dose lidocaine in a C7-T1 CIESI causes objective weakness. Prospective case series. Academic pain center. Adults, cervical radicular pain. Participants underwent CIESI with 1 mL of 1% lidocaine (3 mL total injectate). Elbow flexion (EF), wrist extension (WE), elbow extension (EE), and handgrip strength were measured by dynamometry at baseline, 15 minutes, and 30 minutes postinjection. Changes in strength from baseline and the proportion of participants with a minimum perceptible change in EF, WE, EE, and handgrip strength (≥20%) and 95% confidence intervals (CIs) were calculated. Twenty-seven participants were included. At 15 and 30 minutes postinjection, there was no within-participant difference in EF, WE, EE, and handgrip strength from baseline overall. Nonetheless, five (19%, 95% CI = 4-33) of the participants demonstrated a 20% or greater strength decrease in at least one myotomal distribution. A 20% or greater decrease in strength was present in left EF 4% (95% CI = 0-11%), right EF 7% (95% CI = 0-17%), left WE 4% (95% CI = 0-11%), and right WE 7% (95% CI = 0-17%). The present data suggest that CIESI with an injectate volume of 3 mL that includes 1 mL of 1% lidocaine may result in objective upper extremity weakness that is above the minimum threshold of perception in a subset of patients. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Evaluation of the effects of a plasma activated medium on cancer cells

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

Mohades, S.; Laroussi, M., E-mail: mlarouss@odu.edu; Sears, J.

2015-12-15

The interaction of low temperature plasma with liquids is a relevant topic of study to the field of plasma medicine. This is because cells and tissues are normally surrounded or covered by biological fluids. Therefore, the chemistry induced by the plasma in the aqueous state becomes crucial and usually dictates the biological outcomes. This process became even more important after the discovery that plasma activated media can be useful in killing various cancer cell lines. Here, we report on the measurements of concentrations of hydrogen peroxide, a species known to have strong biological effects, produced by application of plasma tomore » a minimum essential culture medium. The activated medium is then used to treat SCaBER cancer cells. Results indicate that the plasma activated medium can kill the cancer cells in a dose dependent manner, retain its killing effect for several hours, and is as effective as apoptosis inducing drugs.« less

Initial experience with gamma knife surgery for endocrine ophthalmopathy.

PubMed

Antico, Julio C; Crovetto, Luis; Tenca, Eduardo; Artes, Carlos

2005-01-01

The aim of this study was to evaluate both the effectiveness and safety of the treatment of endocrine ophthalmopathy with gamma knife surgery (GKS). Five patients were included in a prospective study designed to assess the results of GKS of endocrine ophthalmopathy secondary to Graves disease. All the patients completed a 2-year follow-up period. During this period, the patients were evaluated both clinically and by means of additional methods, including computerized tomography and magnetic resonance imaging studies. The minimum dose delivered to the 50% isodose line was 6.5 Gy in all the patients. In all cases, a clinical improvement was observed. The best effect was seen in symptom regression related to soft-tissue involvement. No treatment-related side effects were detected. In light of the results obtained the authors consider that GKS may be a safe and effective way to treat endocrine ophthalmopathy.

Impact of cardiosynchronous brain pulsations on Monte Carlo calculated doses for synchrotron micro- and minibeam radiation therapy.

PubMed

Manchado de Sola, Francisco; Vilches, Manuel; Prezado, Yolanda; Lallena, Antonio M

2018-05-15

The purpose of this study was to assess the effects of brain movements induced by heartbeat on dose distributions in synchrotron micro- and minibeam radiation therapy and to develop a model to help guide decisions and planning for future clinical trials. The Monte Carlo code PENELOPE was used to simulate the irradiation of a human head phantom with a variety of micro- and minibeam arrays, with beams narrower than 100 μm and above 500 μm, respectively, and with radiation fields of 1 × 2 cm and 2 × 2 cm. The dose in the phantom due to these beams was calculated by superposing the dose profiles obtained for a single beam of 1 μm × 2 cm. A parameter δ, accounting for the total displacement of the brain during the irradiation and due to the cardiosynchronous pulsation, was used to quantify the impact on peak-to-valley dose ratios and the full width at half maximum. The difference between the maximum (at the phantom entrance) and the minimum (at the phantom exit) values of the peak-to-valley dose ratio reduces when the parameter δ increases. The full width at half maximum remains almost constant with depth for any δ value. Sudden changes in the two quantities are observed at the interfaces between the various tissues (brain, skull, and skin) present in the head phantom. The peak-to-valley dose ratio at the center of the head phantom reduces when δ increases, remaining above 70% of the static value only for minibeams and δ smaller than ∼200 μm. Optimal setups for brain treatments with synchrotron radiation micro- and minibeam combs depend on the brain displacement due to cardiosynchronous pulsation. Peak-to-valley dose ratios larger than 90% of the maximum values obtained in the static case occur only for minibeams and relatively large dose rates. © 2018 American Association of Physicists in Medicine.

Efficacy of high doses of oral penicillin versus amoxicillin in the treatment of adults with non-severe pneumonia attended in the community: study protocol for a randomised controlled trial

PubMed Central

2013-01-01

Background Streptococcus pneumoniae is the bacterial agent which most frequently causes pneumonia. In some Scandinavian countries, this infection is treated with penicillin V since the resistances of pneumococci to this antibiotic are low. Four reasons justify the undertaking of this study; firstly, the cut-off points which determine whether a pneumococcus is susceptible or resistant to penicillin have changed in 2008 and according to some studies published recently the pneumococcal resistances to penicillin in Spain have fallen drastically, with only 0.9% of the strains being resistant to oral penicillin (minimum inhibitory concentration>2 μg/ml); secondly, there is no correlation between pneumococcal infection by a strain resistant to penicillin and therapeutic failure in pneumonia; thirdly, the use of narrow-spectrum antibiotics is urgently needed because of the dearth of new antimicrobials and the link observed between consumption of broad-spectrum antibiotics and emergence and spread of antibacterial resistance; and fourthly, no clinical study comparing amoxicillin and penicillin V in pneumonia in adults has been published. Our aim is to determine whether high-dose penicillin V is as effective as high-dose amoxicillin for the treatment of uncomplicated community-acquired pneumonia. Methods We will perform a parallel group, randomised, double-blind, trial in primary healthcare centres in Spain. Patients aged 18 to 65 without significant associated comorbidity attending the physician with signs and symptoms of lower respiratory tract infection and radiological confirmation of the diagnosis of pneumonia will be randomly assigned to either penicillin V 1.6 million units thrice-daily during 10 days or amoxicillin 1,000 mg thrice-daily during 10 days. The main outcome will be clinical cure at 14 days, defined as absence of fever, resolution or improvement of cough, improvement of general wellbeing and resolution or reduction of crackles indicating that no other antimicrobial treatment will be necessary. Any clinical result other than the anterior will be considered as treatment failure. A total of 210 patients will be recruited to detect a non-inferiority margin of 15% between the two treatments with a minimum power of 80% considering an alpha error of 2.5% for a unilateral hypothesis and maximum possible losses of 15%. Discussion This pragmatic trial addresses the long-standing hypothesis that the administration of high doses of a narrow-spectrum antibiotic (penicillin V) in patients with non-severe pneumonia attended in the community is not less effective than high doses of amoxicillin (treatment currently recommended) in patients under the age of 65 years. Trial registration EudraCT number 2012-003511-63. PMID:23594463

The thermoluminescence response of doped SiO2 optical fibres subjected to photon and electron irradiations.

PubMed

Hashim, S; Al-Ahbabi, S; Bradley, D A; Webb, M; Jeynes, C; Ramli, A T; Wagiran, H

2009-03-01

Modern linear accelerators, the predominant teletherapy machine in major radiotherapy centres worldwide, provide multiple electron and photon beam energies. To obtain reasonable treatment times, intense electron beam currents are achievable. In association with this capability, there is considerable demand to validate patient dose using systems of dosimetry offering characteristics that include good spatial resolution, high precision and accuracy. Present interest is in the thermoluminescence response and dosimetric utility of commercially available doped optical fibres. The important parameter for obtaining the highest TL yield during this study is to know the dopant concentration of the SiO2 fibre because during the production of the optical fibres, the dopants tend to diffuse. To achieve this aim, proton-induced X-ray emission (PIXE), which has no depth resolution but can unambiguously identify elements and analyse for trace elements with detection limits approaching microg/g, was used. For Al-doped fibres, the dopant concentration in the range 0.98-2.93 mol% have been estimated, with equivalent range for Ge-doped fibres being 0.53-0.71 mol%. In making central-axis irradiation measurements a solid water phantom was used. For 6-MV photons and electron energies in the range 6, 9 and 12 MeV, a source to surface distance of 100 cm was used, with a dose rate of 400 cGy/min for photons and electrons. The TL measurements show a linear dose-response over the delivered range of absorbed dose from 1 to 4 Gy. Fading was found to be minimal, less than 10% over five days subsequent to irradiation. The minimum detectable dose for 6-MV photons was found to be 4, 30 and 900 microGy for TLD-100 chips, Ge- and Al-doped fibres, respectively. For 6-, 9- and 12-MeV electron energies, the minimum detectable dose were in the range 3-5, 30-50 and 800-1400 microGy for TLD-100 chip, Ge-doped and Al-doped fibres, respectively.

PTV margin determination in conformal SRT of intracranial lesions

PubMed Central

Parker, Brent C.; Shiu, Almon S.; Maor, Moshe H.; Lang, Frederick F.; Liu, H. Helen; White, R. Allen; Antolak, John A.

2002-01-01

The planning target volume (PTV) includes the clinical target volume (CTV) to be irradiated and a margin to account for uncertainties in the treatment process. Uncertainties in miniature multileaf collimator (mMLC) leaf positioning, CT scanner spatial localization, CT‐MRI image fusion spatial localization, and Gill‐Thomas‐Cosman (GTC) relocatable head frame repositioning were quantified for the purpose of determining a minimum PTV margin that still delivers a satisfactory CTV dose. The measured uncertainties were then incorporated into a simple Monte Carlo calculation for evaluation of various margin and fraction combinations. Satisfactory CTV dosimetric criteria were selected to be a minimum CTV dose of 95% of the PTV dose and at least 95% of the CTV receiving 100% of the PTV dose. The measured uncertainties were assumed to be Gaussian distributions. Systematic errors were added linearly and random errors were added in quadrature assuming no correlation to arrive at the total combined error. The Monte Carlo simulation written for this work examined the distribution of cumulative dose volume histograms for a large patient population using various margin and fraction combinations to determine the smallest margin required to meet the established criteria. The program examined 5 and 30 fraction treatments, since those are the only fractionation schemes currently used at our institution. The fractionation schemes were evaluated using no margin, a margin of just the systematic component of the total uncertainty, and a margin of the systematic component plus one standard deviation of the total uncertainty. It was concluded that (i) a margin of the systematic error plus one standard deviation of the total uncertainty is the smallest PTV margin necessary to achieve the established CTV dose criteria, and (ii) it is necessary to determine the uncertainties introduced by the specific equipment and procedures used at each institution since the uncertainties may vary among locations. PACS number(s): 87.53.Kn, 87.53.Ly PMID:12132939

76 FR 65988 - Importation of Mangoes From Australia

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-25

... irradiation to mitigate the risk of insect pests. The mangoes would also have to be accompanied by a... and adults of the order Lepidoptera, with irradiation in accordance with 7 CFR part 305, which..., which lists minimum absorbed irradiation doses for plant pests and classes of plant pests, includes a...

Characterisation of an anthropomorphic chest phantom for dose measurements in radiology beams

NASA Astrophysics Data System (ADS)

Henriques, L. M. S.; Cerqueira, R. A. D.; Santos, W. S.; Pereira, A. J. S.; Rodrigues, T. M. A.; Carvalho Júnior, A. B.; Maia, A. F.

2014-02-01

The objective of this study was to characterise an anthropomorphic chest phantom for dosimetric measurements of conventional radiology beams. This phantom was developed by a previous research project at the Federal University of Sergipe for image quality control tests. As the phantom consists of tissue-equivalent material, it is possible to characterise it for dosimetric studies. For comparison, a geometric chest phantom, consisting of PMMA (polymethylmethacrylate) with dimensions of 30×30×15 cm³ was used. Measurements of incident air kerma (Ki) and entrance surface dose (ESD) were performed using ionisation chambers. From the results, backscatter factors (BSFs) of the two phantoms were determined and compared with values estimated by CALDose_X software, based on a Monte Carlo simulation. For the technical parameters evaluated in this study, the ESD and BSF values obtained experimentally showed a good similarity between the two phantoms, with minimum and maximum difference of 0.2% and 7.0%, respectively, and showed good agreement with the results published in the literature. Organ doses and effective doses for the anthropomorphic phantom were also estimated by the determination of conversion coefficients (CCs) using the visual Monte Carlo (VMC) code. Therefore, the results of this study prove that the anthropomorphic thorax phantom proposed is a good tool to use in dosimetry and can be used for risk evaluation of X-ray diagnostic procedures.

Postharvest irradiation treatment for quarantine control of Drosophila suzukii (Diptera: Drosophilidae) in fresh commodities.

PubMed

Follett, Peter A; Swedman, Allison; Prices, Donald K

2014-06-01

Irradiation is a postharvest quarantine treatment option for exported commodities such as stone fruits and small fruits to prevent movement of the new invasive pest spotted wing drosophila, Drosophila suzukii (Walker) (Diptera: Drosophilidae). The effects of irradiation on larval and pupal development and adult reproduction in D. suzukii were examined. Larvae (first, second, and third instars) and pupae (1-2-d-old, 3-5-d-old, and 7-8-d-old) on diet were irradiated at target doses of 20, 30, 40, and 50 Gy in replicated factorial experiments and survival to the adult stage was recorded. Tolerance to radiation increased with increasing age and developmental stage. Males and females were equally susceptible. A radiation dose of 40 Gy applied to first- and second-instar larvae prevented adult emergence. The late-stage pupa was the most radiation-tolerant stage that occurs in fruit, and individuals irradiated at this stage readily emerged as adults; therefore, prevention of F1 adults was the desired treatment response for large-scale validation tests with naturally infested fruit. In large-scale tests, a radiation dose of 80 Gy applied to late-stage pupae in sweet cherries or grapes resulted in no production of F1 adults in > 33,000 treated individuals, which meets the zero tolerance requirement for market access. A minimum absorbed dose of 80 Gy is recommended for quarantine control of D. suzukii.

In-vitro and in-vivo anti-Trichophyton activity of essential oils by vapour contact.

PubMed

Inouye, S; Uchida, K; Yamaguchi, H

2001-05-01

The minimum inhibitory doses (MIDs) of essential oils by vapour contact to inhibit the growth of Trichophyton mentagrophytes and Trichophyton rubrum on agar medium were determined using airtight boxes. Among seven essential oils examined, cinnamon bark oil showed the least MID, followed by lemongrass, thyme and perilla oils. Lavender and tea tree oils showed moderate MID, and citron oil showed the highest MID, being 320 times higher than that of cinnamon bark oil. The MID values were less than the minimum inhibitory concentration (MIC) values determined by agar dilution assay. Furthermore, the minimum agar concentration (MAC) of essential oils absorbed from vapour was determined at the time of MID determination as the second antifungal measure. The MAC value by vapour contact was 1.4 to 4.7 times less than the MAC remaining in the agar at the time of MIC determination by agar dilution assay. Using selected essential oils, the anti-Trichophyton activity by vapour contact was examined in more detail. Lemongrass, thyme and perilla oils killed the conidia, inhibited germination and hyphal elongation at 1-4 micrograms ml-1 air, whereas lavender oil was effective at 40-160 micrograms ml-1 air. The in-vivo efficacy of thyme and perilla oils by vapour contact was shown against an experimental tinea pedis in guinea pigs infected with T. mentagrophytes. These results indicated potent anti-Trichophyton action of essential oils by vapour contact.

Effect of bolus fluid intake on energy expenditure values as determined by the doubly labeled water method

NASA Technical Reports Server (NTRS)

Drews, D.; Stein, T. P.

1992-01-01

The doubly labeled water (DLW, 2H(2)18O) method is a highly accurate method for measuring energy expenditure (EE). A possible source of error is bolus fluid intake before body water sampling. If there is bolus fluid intake immediately before body water sampling, the saliva may reflect the ingested water disproportionately, because the ingested water may not have had time to mix fully with the body water pool. To ascertain the magnitude of this problem, EE was measured over a 5-day period by the DLW method. Six subjects were dosed with 2H2(18)O. After the reference salivas for the two-point determination were obtained, subjects drank water (700-1,000 ml), and serial saliva samples were collected for the next 3 h. Expressing the postbolus saliva enrichments as a percentage of the prebolus value, we found 1) a minimum in the saliva isotopic enrichments were reached at approximately 30 min with the minimum for 2H (95.48 +/- 0.43%) being significantly lower than the minimum for 18O (97.55 +/- 0.44, P less than 0.05) and 2) EE values calculated using the postbolus isotopic enrichments are appreciably higher (19.9 +/- 7.5%) than the prebolus reference values. In conclusion, it is not advisable to collect saliva samples for DLW measurements within approximately 1 h of bolus fluid intake.

29 CFR 520.409 - When will authority to pay apprentices special minimum wages become effective and what is the...

Code of Federal Regulations, 2010 CFR

2010-07-01

... wages become effective and what is the special minimum wage rate? 520.409 Section 520.409 Labor... apprentices special minimum wages become effective and what is the special minimum wage rate? (a) An... Division. (b) The wage rate specified by the apprenticeship program becomes the special minimum wage rate...

A nicotinic acetylcholine receptor agonist affects honey bee sucrose responsiveness and decreases waggle dancing.

PubMed

Eiri, Daren M; Nieh, James C

2012-06-15

A nicotinic acetylcholine receptor agonist, imidacloprid, impairs memory formation in honey bees and has general effects on foraging. However, little is known about how this agonist affects two specific aspects of foraging: sucrose responsiveness (SR) and waggle dancing (which recruits nestmates). Using lab and field experiments, we tested the effect of sublethal doses of imidacloprid on (1) bee SR with the proboscis extension response assay, and (2) free-flying foragers visiting and dancing for a sucrose feeder. Bees that ingested imidacloprid (0.21 or 2.16 ng bee(-1)) had higher sucrose response thresholds 1 h after treatment. Foragers that ingested imidacloprid also produced significantly fewer waggle dance circuits (10.5- and 4.5-fold fewer for 50% and 30% sucrose solutions, respectively) 24 h after treatment as compared with controls. However, there was no significant effect of imidacloprid on the sucrose concentrations that foragers collected at a feeder 24 h after treatment. Thus, imidacloprid temporarily increased the minimum sucrose concentration that foragers would accept (short time scale, 1 h after treatment) and reduced waggle dancing (longer time scale, 24 h after treatment). The effect of time suggests different neurological effects of imidacloprid resulting from the parent compound and its metabolites. Waggle dancing can significantly increase colony food intake, and thus a sublethal dose (0.21 ng bee(-1), 24 p.p.b.) of this commonly used pesticide may impair colony fitness.

Duration of post-vaccination immunity to yellow fever in volunteers eight years after a dose-response study.

PubMed

de Menezes Martins, Reinaldo; Maia, Maria de Lourdes S; de Lima, Sheila Maria Barbosa; de Noronha, Tatiana Guimarães; Xavier, Janaina Reis; Camacho, Luiz Antonio Bastos; de Albuquerque, Elizabeth Maciel; Farias, Roberto Henrique Guedes; da Matta de Castro, Thalita; Homma, Akira

2018-06-27

In 2009, Bio-Manguinhos conducted a dose-response study with the yellow fever vaccine, administering the vaccine in the usual mean dose of 27,476 IU (full dose, reference) and in tapered doses (10,447 IU, 3013 IU, 587 IU, 158 IU, and 31 IU) by the usual subcutaneous route and usual volume (0.5 mL). Tapered doses were obtained by dilution in the manufacturer's laboratory, and the test batches presented industrial quality. Doses down to 587 IU showed similar immunogenicity to the full dose (27,476, reference), while the 158 IU and 31 IU doses displayed lower immunogenicity. Seropositivity was maintained at 10 months, except in the group that received the 31 IU dose. The current study aims to determine whether yellow fever seropositivity was maintained eight years after YF vaccination in non-revaccinated individuals. According to the current study's results, seropositivity was maintained in 85% of 318 participants and was similar across groups. The findings support the use of the yellow fever vaccine in fractional doses during outbreaks, but each fractional dose should have at least 587 IU. This study also supports the minimum dose required by WHO, 1000 IU. Clinicaltrials.gov NCT 03338231. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Predictive factors and management of rectal bleeding side effects following prostate cancer brachytherapy.

PubMed

Price, Jeremy G; Stone, Nelson N; Stock, Richard G

2013-08-01

To report on the incidence, nature, and management of rectal toxicities following individual or combination brachytherapy following treatment for prostate cancer over a 17-year period. We also report the patient and treatment factors predisposing to acute ≥ grade 2 proctitis. A total of 2752 patients were treated for prostate cancer between October 1990 and April 2007 with either low-dose-rate brachytherapy alone or in combination with androgen depletion therapy (ADT) or external beam radiation therapy (EBRT) and were followed for a median of 5.86 years (minimum 1.0 years; maximum 19.19 years). We investigated the 10-year incidence, nature, and treatment of acute and chronic rectal toxicities following BT. Using univariate, and multivariate analyses, we determined the treatment and comorbidity factors predisposing to rectal toxicities. We also outline the most common and effective management for these toxicities. Actuarial risk of ≥ grade 2 rectal bleeding was 6.4%, though notably only 0.9% of all patients required medical intervention to manage this toxicity. The majority of rectal bleeding episodes (72%) occurred within the first 3 years following placement of BT seeds. Of the 27 patients requiring management for their rectal bleeding, 18 underwent formalin treatment and nine underwent cauterization. Post-hoc univariate statistical analysis revealed that coronary artery disease (CAD), biologically effective dose, rectal volume receiving 100% of the prescription dose (RV100), and treatment modality predict the likelihood of grade ≥2 rectal bleeding. Only CAD, treatment type, and RV100 fit a Cox regression multivariate model. Low-dose-rate prostate brachytherapy is very well tolerated and rectal bleeding toxicities are either self-resolving or effectively managed by medical intervention. Treatment planning incorporating adjuvant ADT while minimizing RV100 has yielded the best toxicity-free survival following BT. Copyright © 2013 Elsevier Inc. All rights reserved.

Predictive Factors and Management of Rectal Bleeding Side Effects Following Prostate Cancer Brachytherapy

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

Price, Jeremy G.; Stone, Nelson N.; Stock, Richard G., E-mail: Richard.Stock@mountsinai.org

2013-08-01

Purpose: To report on the incidence, nature, and management of rectal toxicities following individual or combination brachytherapy following treatment for prostate cancer over a 17-year period. We also report the patient and treatment factors predisposing to acute ≥grade 2 proctitis. Methods and Materials: A total of 2752 patients were treated for prostate cancer between October 1990 and April 2007 with either low-dose-rate brachytherapy alone or in combination with androgen depletion therapy (ADT) or external beam radiation therapy (EBRT) and were followed for a median of 5.86 years (minimum 1.0 years; maximum 19.19 years). We investigated the 10-year incidence, nature, andmore » treatment of acute and chronic rectal toxicities following BT. Using univariate, and multivariate analyses, we determined the treatment and comorbidity factors predisposing to rectal toxicities. We also outline the most common and effective management for these toxicities. Results: Actuarial risk of ≥grade 2 rectal bleeding was 6.4%, though notably only 0.9% of all patients required medical intervention to manage this toxicity. The majority of rectal bleeding episodes (72%) occurred within the first 3 years following placement of BT seeds. Of the 27 patients requiring management for their rectal bleeding, 18 underwent formalin treatment and nine underwent cauterization. Post-hoc univariate statistical analysis revealed that coronary artery disease (CAD), biologically effective dose, rectal volume receiving 100% of the prescription dose (RV100), and treatment modality predict the likelihood of grade ≥2 rectal bleeding. Only CAD, treatment type, and RV100 fit a Cox regression multivariate model. Conclusions: Low-dose-rate prostate brachytherapy is very well tolerated and rectal bleeding toxicities are either self-resolving or effectively managed by medical intervention. Treatment planning incorporating adjuvant ADT while minimizing RV100 has yielded the best toxicity-free survival following BT.« less

Acute Exposure to High Dose γ-Radiation Results in Transient Activation of Bone Lining Cells

PubMed Central

Turner, Russell T.; Iwaniec, Urszula T.; Wong, Carmen P.; Lindenmaier, Laurence B.; Wagner, Lindsay A.; Branscum, Adam J.; Menn, Scott A.; Taylor, James; Zhang, Ye; Wu, Honglu; Sibonga, Jean D.

2014-01-01

The present studies investigated the cellular mechanisms for the detrimental effects of high dose whole body γ-irradiation on bone. In addition, radioadaptation and bone marrow transplantation were assessed as interventions to mitigate the skeletal complications of irradiation. Increased trabecular thickness and separation and reduced fractional cancellous bone volume, connectivity density, and trabecular number were detected in proximal tibia and lumbar vertebra 14 days following γ-irradiation with 6 Gy. To establish the cellular mechanism for the architectural changes, vertebrae were analyzed by histomorphometry 1, 3, and 14 days following irradiation. Marrow cell density decreased within 1 day (67% reduction, p<0.0001), reached a minimum value after 3 days (86% reduction, p<0.0001), and partially rebounded by 14 days (30% reduction, p=0.0025) following irradiation. In contrast, osteoblast-lined bone perimeter was increased by 290% (1 day, p=0.04), 1230% (3 days, p<0.0001), and 530% (14 days, p=0.003), respectively. There was a strong association between radiation-induced marrow cell death and activation of bone lining cells to express the osteoblast phenotype (Pearson correlation −0.85, p<0.0001). An increase (p=0.004) in osteoclast-lined bone perimeter was also detected with irradiation. A priming dose of γ-radiation (0.5 mGy), previously shown to reduce mortality, had minimal effect on the cellular responses to radiation and did not prevent detrimental changes in bone architecture. Bone marrow transplantation normalized marrow cell density, bone turnover, and most indices of bone architecture following irradiation. In summary, radiation-induced death of marrow cells is associated with 1) a transient increase in bone formation due, at least in part, to activation of bone lining cells, and 2) an increase in bone resorption due to increased osteoclast perimeter. Bone marrow transplantation is effective in mitigating the detrimental effects of acute exposure to high dose whole body γ-radiation on bone turnover. PMID:23954507

Pharmacodynamics of the Novel Antifungal Agent F901318 for Acute Sinopulmonary Aspergillosis Caused by Aspergillus flavus

PubMed Central

Negri, Clara E; Johnson, Adam; McEntee, Laura; Box, Helen; Whalley, Sarah; Schwartz, Julie A; Ramos-Martín, V; Livermore, Joanne; Kolamunnage-Dona, Ruwanthi; Colombo, Arnaldo L; Hope, William W

2018-01-01

Abstract Background Aspergillus flavus is one of the most common agents of invasive aspergillosis and is associated with high mortality. The orotomides are a new class of antifungal agents with a novel mechanism of action. An understanding of the pharmacodynamics (PD) of the lead compound F901318 is required to plan safe and effective regimens for clinical use. Methods The pharmacokinetics (PK) and PD of F901318 were evaluated by developing new in vitro and in vivo models of invasive fungal sinusitis. Galactomannan was used as a pharmacodynamic endpoint in all models. Mathematical PK-PD models were used to describe dose-exposure-response relationships. Results F901318 minimum inhibitory concentrations (MICs) ranged from 0.015 to 0.06 mg/L. F901318 induced a concentration-dependent decline in galactomannan. In the in vitro model, a minimum concentration:MIC of 10 resulted in suppression of galactomannan; however, values of approximately 10 and 9–19 when assessed by survival of mice or the decline in galactomannan, respectively, were equivalent or exceeded the effect induced by posaconazole. There was histological clearance of lung tissue that was consistent with the effects of F901318 on galactomannan. Conclusions F901318 is a potential new agent for the treatment of invasive infections caused by A flavus with PDs that are comparable with other first-line triazole agents. PMID:28968675

Effect of whole-body vibration therapy on health-related physical fitness in children and adolescents with disabilities: a systematic review.

PubMed

Matute-Llorente, Angel; González-Agüero, Alejandro; Gómez-Cabello, Alba; Vicente-Rodríguez, Germán; Casajús Mallén, José Antonio

2014-04-01

To summarize the current literature regarding the effects of whole-body vibration (WBV) therapy on the health-related physical fitness of children and adolescents with disabilities. A literature search using MEDLINE-PubMed, SPORT DISCUS, and EMBASE databases was conducted up to August 2013. A total of 22 articles were included in this review (eight randomized controlled trials, four non-randomized controlled trials, three case reports, and seven reviews). Most of the studies showed positive effects of WBV on health-related physical fitness in children and adolescents with disabilities. Overall, 10-20 minutes at least three times per week, for a minimum of 26 weeks, with high frequency (between 15 and 35 Hz) and low amplitude (no more than 4 mm of peak-to-peak displacement) might be an appropriate protocol to achieve improvement in body composition and muscular strength. Because no serious adverse events have been observed, WBV might be defined as a safe treatment to be applied in children and adolescents with disabling conditions. Further research is recommended to explore the minimum dose of exposure to WBV required to elicit an optimal response in children and adolescents for improving health-related physical fitness. These may be translated into a more specific WBV protocol. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

The DOPEX code: An application of the method of steepest descent to laminated-shield-weight optimization with several constraints

NASA Technical Reports Server (NTRS)

Lahti, G. P.

1972-01-01

A two- or three-constraint, two-dimensional radiation shield weight optimization procedure and a computer program, DOPEX, is described. The DOPEX code uses the steepest descent method to alter a set of initial (input) thicknesses for a shield configuration to achieve a minimum weight while simultaneously satisfying dose constaints. The code assumes an exponential dose-shield thickness relation with parameters specified by the user. The code also assumes that dose rates in each principal direction are dependent only on thicknesses in that direction. Code input instructions, FORTRAN 4 listing, and a sample problem are given. Typical computer time required to optimize a seven-layer shield is about 0.1 minute on an IBM 7094-2.

Acid-neutralizing capacity and sodium content of antacid products from Belgium.

PubMed

Gombatz, V W

1984-01-01

The acid-neutralizing capacity and sodium content of nine antacid products available in Belgium were evaluated and compared with typical values for Mylanta-II. Liquid and tablets of Mylanta-II have a higher acid-neutralizing capacity per unit dose than do all the other Belgian antacids tested. On a unit dose basis, the sodium contents of the Mylanta-II products are lower than those of all other Belgian antacids tested except Maalox products. Because the minimum recommended dose (MRD) of Mylanta-II liquid is 5 ml, while that of Maalox is 10 ml, the sodium content of the MRD of Mylanta-II liquid is lower than that of the MRD of any of the other Belgian liquid antacids tested.

Effect of applying cinnamaldehyde incorporated in wax on green mould decay in citrus fruits.

PubMed

Duan, Xiaofang; OuYang, Qiuli; Tao, Nengguo

2018-01-01

Green mould caused by Penicillium digitatum is the most damaging postharvest diseases of citrus fruit. Cinnamaldehyde (CA) is a food additive that has potential use in controlling postharvest disease of fruits and vegetables. In this study, the effectiveness of wax with CA (WCA) in controlling Ponkan (Citrus reticulata Blanco) green mould was investigated. The mycelial growth of P. digitatum was inhibited by CA in a dose-dependent manner. The minimum inhibitory concentration and minimum fungicidal concentration (MFC) were both 0.50 mL L -1 . In vivo tests demonstrated that WCA (1 × and 10 × MFC) applied to Ponkan fruits inoculated with P. digitatum could significantly decrease the incidence of green mould for up to 5 days. The WCA treatment increased the activities of catalase, superoxide dismutase, peroxidase, phenylalanine ammonia lyase, polyphenol oxidase, as well as the total phenols and flavonoids contents. Meanwhile, the treatment remarkably decreased the weight loss rate of fruits and maintained fruit quality. These results indicated that WCA treatment might induce defence responses against green mould in citrus fruit. Our findings suggest that WCA might be a promising approach in controlling green mould of citrus fruits. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Minimum Wages and Skill Acquisition: Another Look at Schooling Effects.

ERIC Educational Resources Information Center

Neumark, David; Wascher, William

2003-01-01

Examines the effects of minimum wage on schooling, seeking to reconcile some of the contradictory results in recent research using Current Population Survey data from the late 1970s through the 1980s. Findings point to negative effects of minimum wages on school enrollment, bolstering the findings of negative effects of minimum wages on enrollment…

Alternative stitching method for massively parallel e-beam lithography

NASA Astrophysics Data System (ADS)

Brandt, Pieter; Tranquillin, Céline; Wieland, Marco; Bayle, Sébastien; Milléquant, Matthieu; Renault, Guillaume

2015-07-01

In this study, a stitching method other than soft edge (SE) and smart boundary (SB) is introduced and benchmarked against SE. The method is based on locally enhanced exposure latitude without throughput cost, making use of the fact that the two beams that pass through the stitching region can deposit up to 2× the nominal dose. The method requires a complex proximity effect correction that takes a preset stitching dose profile into account. Although the principle of the presented stitching method can be multibeam (lithography) systems in general, in this study, the MAPPER FLX 1200 tool is specifically considered. For the latter tool at a metal clip at minimum half-pitch of 32 nm, the stitching method effectively mitigates beam-to-beam (B2B) position errors such that they do not induce an increase in critical dimension uniformity (CDU). In other words, the same CDU can be realized inside the stitching region as outside the stitching region. For the SE method, the CDU inside is 0.3 nm higher than outside the stitching region. A 5-nm direct overlay impact from the B2B position errors cannot be reduced by a stitching strategy.

Enhancement of bioavailability of cinnarizine from its beta-cyclodextrin complex on oral administration with DL-phenylalanine as a competing agent.

PubMed

Tokumura, T; Nanba, M; Tsushima, Y; Tatsuishi, K; Kayano, M; Machida, Y; Nagai, T

1986-04-01

The present investigation is concerned with an improvement of the bioavailability of cinnarizine by administering its beta-cyclodextrin complex together with another compound which competes with the beta-cyclodextrin molecule in complex formation in aqueous solution (competing agent). The bioavailability of cinnarizine on oral administration of the cinnarizine-beta-cyclodextrin inclusion complex was enhanced by the simultaneous administration of DL-phenylalanine as a competing agent, e.g., the AUC was 1.9 and 2.7 times as large as those of the cinnarizine-beta-cyclodextrin complex alone and cinnarizine alone, respectively. The enhancement of AUC and Cmax completely depended on the dose of DL-phenylalanine. It was found from these results that DL-phenylalanine acted as a competing agent in the GI tract and the minimum effective dose required of DL-phenylalanine might be 1 g for 50 mg of cinnarizine in the cinnarizine-beta-cyclodextrin complex. Evaluating the competing effect of DL-phenylalanine in vitro using an absorption simulator, it was found that the decreased penetration rate of cinnarizine through the artificial lipid barrier with addition of beta-cyclodextrin was restored with the addition of DL-phenylalanine.

Multivariate Analysis of Effects of Asthmatic Patient Respiratory Profiles on the In Vitro Performance of a Reservoir Multidose and a Capsule-Based Dry Powder Inhaler.

PubMed

Buttini, Francesca; Pasquali, Irene; Brambilla, Gaetano; Copelli, Diego; Alberi, Massimiliano Dagli; Balducci, Anna Giulia; Bettini, Ruggero; Sisti, Viviana

2016-03-01

The aim of this work was to evaluate the effect of two different dry powder inhalers, of the NGI induction port and Alberta throat and of the actual inspiratory profiles of asthmatic patients on in-vitro drug inhalation performances. The two devices considered were a reservoir multidose and a capsule-based inhaler. The formulation used to test the inhalers was a combination of formoterol fumarate and beclomethasone dipropionate. A breath simulator was used to mimic inhalatory patterns previously determined in vivo. A multivariate approach was adopted to estimate the significance of the effect of the investigated variables in the explored domain. Breath simulator was a useful tool to mimic in vitro the in vivo inspiratory profiles of asthmatic patients. The type of throat coupled with the impactor did not affect the aerodynamic distribution of the investigated formulation. However, the type of inhaler and inspiratory profiles affected the respirable dose of drugs. The multivariate statistical approach demonstrated that the multidose inhaler, released efficiently a high fine particle mass independently from the inspiratory profiles adopted. Differently, the single dose capsule inhaler, showed a significant decrease of fine particle mass of both drugs when the device was activated using the minimum inspiratory volume (592 mL).

Evidence-based exercise prescription for balance and falls prevention: a current review of the literature.

PubMed

Shubert, Tiffany E

2011-01-01

Falls are the leading cause of emergency department visits, hospital admissions, and unintentional death for older adults. Balance and strength impairments are common falls risk factors for community-dwelling older adults. Though physical therapists commonly treat balance and strength, standardized falls screening has not been fully incorporated into physical therapy practice and there is much variation in the frequency, intensity, and duration of therapy prescribed to achieve optimal results. For community-dwelling older adults, a progressive exercise program that focuses on moderate to high-intensity balance exercises appears to be one of the most effective interventions to prevent falls. For more frail older adults in institutional settings, exercise programs in addition to multifactorial interventions appear to show promise as effective falls prevention interventions. The minimum dose of exercise to protect an older adult against falls is 50 hours. This article describes the current best practices for physical therapists to effectively improve balance and manage falls risk in patients. The unique challenges and opportunities for physical therapists to incorporate evidence-based fall-prevention strategies are discussed. Innovative practice models incorporating evidence-based fall-prevention programs and partnerships with public health and aging service providers to create a continuum of care and achieve the optimal dose of balance training are presented.

Comparison of gamma and electron beam irradiation in reducing populations of E. coli artificially inoculated on mung bean, clover and fenugreek seeds, and affecting germination and growth of seeds

NASA Astrophysics Data System (ADS)

Fan, Xuetong; Sokorai, Kimberly; Weidauer, André; Gotzmann, Gaby; Rögner, Frank-Holm; Koch, Eckhard

2017-01-01

Sprouts have frequently been implicated in outbreaks of foodborne illnesses, mostly due to contaminated seeds. Intervention technologies to decontaminate seeds without affecting sprout yield are needed. In the present study, we compared gamma rays with electron beam in inactivating E. coli artificially inoculated on three seeds (fenugreek, clover and mung bean) that differed in size and surface morphology. Furthermore, the germination and growth of irradiated seeds were evaluated. Results showed that the D10 values (dose required to achieve 1 log reduction) for E. coli K12 on mung bean, clover, and fenugreek were 1.11, 1.21 and 1.40 kGy, respectively. To achieve a minimum 5-log reduction of E. coli, higher doses were needed on fenugreek than on mung bean or clover. Electron beam treatment at doses up to 12 kGy could not completely inactivate E. coli inoculated on all seeds even though most of the seeds were E. coli-free after 4-12 kGy irradiation. Gamma irradiation at doses up to 6 kGy did not significantly affect the germination rate of clover and fenugreek seeds but reduced the germination rate of mung bean seeds. Doses of 2 kGy gamma irradiation did not influence the growth of seeds while higher doses of gamma irradiation reduced the growth rate. Electron beam treatment at doses up to 12 kGy did not have any significant effect on germination or growth of the seeds. SEM imaging indicated there were differences in surface morphology among the three seeds, and E. coli resided in cracks and openings of seeds, making surface decontamination of seeds with low energy electron beam a challenge due to the low penetration ability. Overall, our results suggested that gamma rays and electron beam had different effects on E. coli inactivation and germination or growth of seeds. Future efforts should focus on optimization of electron bean parameters to increase penetration to inactivate E. coli without causing damage to the seeds.

Safety, Adherence and Acceptability of Intermittent Tenofovir/Emtricitabine as HIV Pre-Exposure Prophylaxis (PrEP) among HIV-Uninfected Ugandan Volunteers Living in HIV-Serodiscordant Relationships: A Randomized, Clinical Trial

PubMed Central

Kibengo, Freddie M.; Ruzagira, Eugene; Katende, David; Bwanika, Agnes N.; Bahemuka, Ubaldo; Haberer, Jessica E.; Bangsberg, David R.; Barin, Burc; Rooney, James F.; Mark, David; Chetty, Paramesh; Fast, Patricia; Kamali, Anatoli; Priddy, Frances H.

2013-01-01

Background Efficacy of oral pre-exposure prophylaxis (PrEP) in prevention of HIV acquisition has been evaluated using a daily regimen. However, adherence to long term daily medication is rarely perfect. Intermittent regimen may be a feasible alternative. Preclinical studies have demonstrated effectiveness of intermittent PrEP in SHIV prevention among animals. However, little is known about intermittent PrEP regimens. Design Seventy two HIV-uninfected volunteers in HIV serodiscordant couple relationships in Uganda were randomly assigned to receive daily oral Tenofovir/Emtricitabine (TDF/FTC-Truvada) or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral TDF/FTC or placebo in a 2:1:2:1 ratio. Volunteers and study staff were blinded to drug assignment, but not to regimen assignment. Methods Volunteers were followed for 4 months after randomization, with monthly clinical and laboratory safety assessments and comprehensive HIV risk reduction services. Adherence was monitored using medication event monitoring system (MEMS) and self-report. Sexual activity data were collected via daily short text message (SMS) and self-report. HIV-specific immune responses were assessed by IFN-γ ELISPOT. Results Both daily and intermittent oral TDF/FTC regimens were well tolerated. Median MEMS adherence rates were 98% (IQR: 93-100) for daily PrEP regimen, 91% (IQR: 73-97) for fixed intermittent dosing and 45% (IQR: 20-63) for post-coital dosing. SMS response rate was 74%, but increased to 80% after excluding server outages; results may have been affected by the novelty of this measure. The majority of volunteers expressed willingness with no particular preference for either regimen. Conclusions Both daily and intermittent oral PrEP dosing regimens were safe. Adherence was high for daily and fixed intermittent dosing; post-coital dosing was associated with poor adherence. Fixed intermittent PrEP regimens may be feasible especially if a minimum effective drug concentration correlating with HIV prevention can be achieved with this dosing. Registration Clinicaltrials.gov number NCT00931346 PMID:24086333

Central Nervous System Medication Burden and Serious Falls in Older Nursing Home Residents

PubMed Central

Hanlon, Joseph T.; Zhao, Xinhua; Naples, Jennifer G.; Aspinall, Sherrie L.; Perera, Subashan; Nace, David A.; Castle, Nicholas G.; Greenspan, Susan L.; Thorpe, Carolyn T.

2016-01-01

Objectives To examine the association between CNS medication burden and serious falls in those with a recent fall history. Design Nested-case control study; cases matched to four controls by age, gender, and date. Setting US nursing homes Participants 5,556 residents age ≥ 65 with a recent fall history admitted to a nursing home between 1/1–9/30/2010 and followed until discharge, death, or 12/31/2010. Measurements Outcome was serious falls as per Medicare Part A and B ICD/CPT codes. CNS burden, from Medicare Part D data, was calculated by dividing the daily dose of each CNS agent (i.e., specific antidepressants, antiepileptic, antipsychotic, benzodiazepine and opioid receptor agonists) received during the six days prior to the index (outcome) date by the minimum effective geriatric daily dose and summing the results across medications. Results There were 367 cases and 1468 matched controls. Those taking 3+ CNS standardized daily doses were more likely to have a serious fall than those not taking any CNS medications (Adjusted Odds Ratio 1.83; 95% confidence interval 1.35–2.48). There was no significant difference in fall risk for residents taking >0 to <3 CNS standardized daily doses compared to residents taking no CNS medications (Adjusted Odds Ratio 0.85; 95% CI 0.63–1.15). Conclusion CNS medication burden, approximately 3+ standardized daily doses, was associated with an increased risk of serious falls in nursing home residents with recent fall. Clinicians should be vigilant for opportunities to discontinue or decrease the doses of individual CNS medications and/or consider non-pharmacological alternatives. Such interventions that reduce use of CNS medications in nursing homes could reduce fall rates but further research is needed to confirm this. PMID:28152179

Improved plan quality with automated radiotherapy planning for whole brain with hippocampus sparing: a comparison to the RTOG 0933 trial.

PubMed

Krayenbuehl, J; Di Martino, M; Guckenberger, M; Andratschke, N

2017-10-02

Whole-brain radiation therapy (WBRT) with hippocampus sparing (HS) has been investigated by the radiation oncology working group (RTOG) 0933 trial for patients with multiple brain metastases. They showed a decrease of adverse neurocognitive effects with HS WBRT compared to WBRT alone. With the development of automated treatment planning system (aTPS) in the last years, a standardization of the plan quality at a high level was achieved. The goal of this study was to evaluate the feasibility of using an aTPS for the treatment of HS WBRT and see if the RTOG 0933 dose constraints could be achieved and improved. Ten consecutive patients treated with HS WBRT were enrolled in this study. 10 × 3 Gy was prescribed according to the RTOG 0933 protocol to 92% of the target volume (whole-brain excluding the hippocampus expanded by 5 mm in 3-dimensions). In contrast to RTOG 0933, the maximum allowed point dose to normal brain was significantly lowered and restricted to 36.5 Gy. All patients were planned with volumetric modulated arc therapy (VMAT) technique using four arcs. Plans were optimized using Auto-Planning (AP) (Philips Radiation Oncology Systems) with one single AP template and optimization. All the constraints from the RTOG 0933 trial were achieved. A significant improvement for the maximal dose to 2% of the brain with a reduction of 4 Gy was achieved (33.5 Gy vs. RTOG 37.5 Gy) and the minimum hippocampus dose was reduced by 10% (8.1 Gy vs. RTOG 9 Gy). A steep dose gradient around the hippocampus was achieved with a mean dose of 27.3 Gy at a distance between 0.5 cm and 1 cm from the hippocampus. The effective working time to optimize a plan was kept below 6'. Automated treatment planning for HS WBRT was able to fulfil all the recommendations from the RTOG 0933 study while significantly improving dose homogeneity and decreasing unnecessary hot spot in the normal brain. With this approach, a standardization of plan quality was achieved and the effective time required for plan optimization was minimized.

Low-Dose Ketamine Infusions for Highly Opioid-Tolerant Adults Following Spinal Surgery: A Retrospective Before-and-after Study.

PubMed

Vaid, Patrycja; Green, Theresa; Shinkaruk, Kelly; King-Shier, Kathryn

2016-04-01

Managing acute-on-chronic pain in opioid-tolerant individuals is complex and challenging; exploring new analgesia regimens for this population is essential. Ketamine is an N-methyl D-aspartate antagonist that blocks transmission of painful stimuli and could be a useful medication for this patient population. A new low-dose ketamine protocol as an adjunct to conventional pain therapy was implemented in a major urban Level 1 trauma center in Canada. A retrospective before-and-after chart review was conducted to explore the research question, "What is the effect of low-dose ketamine continuous intravenous infusions on pain of highly opioid-tolerant adults following spinal surgery?". All patients had spine surgery, used a minimum of 100 mg daily oral morphine equivalent preoperatively and were followed postoperatively by the hospital's Acute Pain Service. Data from individuals treated with conventional therapy during the year prior to protocol implementation were compared with data from patients who received conventional therapy plus ketamine post implementation. Outcome measures included pain scores and daily opioid consumption on postoperative days 0 through 5, time to ambulation, time to discharge, and adverse effects. There were no statistically significant differences between conventional therapy and conventional therapy plus ketamine. Ketamine may still be of benefit to patients with acute-on-chronic pain, although this was not evident in this study. Future research using more robust assessment tools to determine effectiveness of ketamine is required. Copyright © 2016 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Subchronic Toxicities of HZ1006, a Hydroxamate-Based Histone Deacetylase Inhibitor, in Beagle Dogs and Sprague-Dawley Rats.

PubMed

Zhang, Xiaofang; Zhang, Xiaodong; Yuan, Bojun; Ren, Lijun; Zhang, Tianbao; Lu, Guocai

2016-11-30

Histone deacetylase inhibitors (HDACIs), such as vorinostat and panobinostat, have been shown to have active effects on many hematologic malignancies, including multiple myeloma and cutaneous T-cell lymphoma. Hydroxamate-based (Hb) HDACIs have very good toxicity profiles and are currently being tested in phases I and II clinical trials with promising results in selected neoplasms, such as bladder carcinoma. One of the Hb-HDACIs, HZ1006, has been demonstrated to be a promising drug for clinical use. The aim of our study was to determine the possible target of toxicity and to identify a non-toxic dose of HZ1006 for clinical use. In our studies, the repeated dosage toxicity of HZ1006 in Beagle dogs and Sprague Dawley (SD) rats was identified. Dogs and rats received HZ1006 orally (0-80 and 0-120 mg/kg/day, respectively) on a continuous daily dosing agenda for 28 days following a 14-day dosage-free period. HZ1006's NOAEL (No Observed Adverse Effect Level) by daily oral administration for dogs and rats was 5 mg/kg and 60 mg/kg, respectively, and the minimum toxic dose was 20 and 120 mg/kg, respectively. All the side effects indicated that the digestive tract, the male reproductive tract, the respiratory tract and the hematological systems might be HZ1006 toxic targets in humans. HZ1006 could be a good candidate or a safe succedaneum to other existing HDACIs for the treatment of some solid tumor and hematologic malignancies.

The space radiation environment

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

Robbins, D E

There are three primary sources of space radiation: galactic cosmic rays (GCR), trapped belt radiation, and solar particle events (SPE). All are composed of ions, the nuclei of atoms. Their energies range from a few MeV u{sup -1} to over a GeV u{sup -1}. These ions can fragment when they interact with spacecraft materials and produce energetic neutrons and ions of lower atomic mass. Absorbed dose rates inside a typical spacecraft (like the Space Shuttle) in a low inclination (28.5 degrees) orbit range between 0.05 and 2 mGy d{sup -1} depending on the altitude and flight inclination (angle of orbitmore » with the equator). The quality factor of radiation in orbit depends on the relative contributions of trapped belt radiation and GCR, and the dose rate varies both with orbital altitude and inclination. The corresponding equivalent dose rate ranges between 0.1 and 4 mSv d{sup -1}. In high inclination orbits, like that of the Mir Space Station and as is planned for the International Space Station, blood-forming organ (BFO) equivalent dose rates as high as 1.5 mSv d{sup -1}. Thus, on a 1 y mission, a crew member could obtain a total dose of 0.55 Sv. Maximum equivalent dose rates measured in high altitude passes through the South Atlantic Anomaly (SAA) were 10 mSv h{sup -1}. For an interplanetary space mission (e.g., to Mars) annual doses from GCR alone range between 150 mSv y{sup -1} at solar maximum and 580 mSv y{sup -1} at solar minimum. Large SPE, like the October 1989 series, are more apt to occur in the years around solar maximum. In free space, such an event could contribute another 300 mSv, assuming that a warning system and safe haven can be effectively used with operational procedures to minimize crew exposures. Thus, the total dose for a 3 y mission to Mars could exceed 2 Sv.« less

Model-based dose calculations for COMS eye plaque brachytherapy using an anatomically realistic eye phantom

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

Lesperance, Marielle; Inglis-Whalen, M.; Thomson, R. M., E-mail: rthomson@physics.carleton.ca

Purpose : To investigate the effects of the composition and geometry of ocular media and tissues surrounding the eye on dose distributions for COMS eye plaque brachytherapy with{sup 125}I, {sup 103}Pd, or {sup 131}Cs seeds, and to investigate doses to ocular structures. Methods : An anatomically and compositionally realistic voxelized eye model with a medial tumor is developed based on a literature review. Mass energy absorption and attenuation coefficients for ocular media are calculated. Radiation transport and dose deposition are simulated using the EGSnrc Monte Carlo user-code BrachyDose for a fully loaded COMS eye plaque within a water phantom andmore » our full eye model for the three radionuclides. A TG-43 simulation with the same seed configuration in a water phantom neglecting the plaque and interseed effects is also performed. The impact on dose distributions of varying tumor position, as well as tumor and surrounding tissue media is investigated. Each simulation and radionuclide is compared using isodose contours, dose volume histograms for the lens and tumor, maximum, minimum, and average doses to structures of interest, and doses to voxels of interest within the eye. Results : Mass energy absorption and attenuation coefficients of the ocular media differ from those of water by as much as 12% within the 20–30 keV photon energy range. For all radionuclides studied, average doses to the tumor and lens regions in the full eye model differ from those for the plaque in water by 8%–10% and 13%–14%, respectively; the average doses to the tumor and lens regions differ between the full eye model and the TG-43 simulation by 2%–17% and 29%–34%, respectively. Replacing the surrounding tissues in the eye model with water increases the maximum and average doses to the lens by 2% and 3%, respectively. Substituting the tumor medium in the eye model for water, soft tissue, or an alternate melanoma composition affects tumor dose compared to the default eye model simulation by up to 16%. In the full eye model simulations, the average dose to the lens is larger by 7%–9% than the dose to the center of the lens, and the maximum dose to the optic nerve is 17%–22% higher than the dose to the optic disk for all radionuclides. In general, when normalized to the same prescription dose at the tumor apex, doses delivered to all structures of interest in the full eye model are lowest for{sup 103}Pd and highest for {sup 131}Cs, except for the tumor where the average dose is highest for {sup 103}Pd and lowest for {sup 131}Cs. Conclusions : The eye is not radiologically water-equivalent, as doses from simulations of the plaque in the full eye model differ considerably from doses for the plaque in a water phantom and from simulated TG-43 calculated doses. This demonstrates the importance of model-based dose calculations for eye plaque brachytherapy, for which accurate elemental compositions of ocular media are necessary.« less

Minimum Wage Laws and the Distribution of Employment.

ERIC Educational Resources Information Center

Lang, Kevin

The desirability of raising the minimum wage long revolved around just one question: the effect of higher minimum wages on the overall level of employment. An even more critical effect of the minimum wage rests on the composition of employment--who gets the minimum wage job. An examination of employment in eating and drinking establishments…

Detection of sub micro Gray dose levels using OSL phosphor LiMgPO4:Tb,B

NASA Astrophysics Data System (ADS)

Rawat, N. S.; Dhabekar, Bhushan; Muthe, K. P.; Koul, D. K.; Datta, D.

2017-04-01

Detection of sub micro Gray doses finds application in personnel and environmental monitoring, and nuclear forensics. Recently developed LiMgPO4:Tb,B (LMP) is highly sensitive Optically Stimulated Luminescence (OSL) phosphor with excellent dosimetric properties. The OSL emission spectrum of LMP consists of several peaks attributed to characteristic Tb3+ emission. The OSL emission peak at 380 nm is favorable for bi-alkali PMT used in RISO reader system. It is demonstrated that significant improvement in dose detection threshold can be realized for LMP by optimization of continuous wave (CW-) OSL parameters like stimulation intensity and readout time. The minimum measurable dose (MMD) as low as 0.49 μGy in readout time of less than 1 s at stimulation intensity of 32 mW/cm2 has been achieved using this phosphor. The recommendations for choice of parameters for personnel and environmental monitoring are also discussed.

INTEGRATED CIRCUITS FROM MOBILE PHONES AS POSSIBLE EMERGENCY OSL/TL DOSIMETERS.

PubMed

Sholom, S; McKeever, S W S

2016-09-01

In this article, optically stimulated luminescence (OSL) data are presented from integrated circuits (ICs) extracted from mobile phones. The purpose is to evaluate the potential of using OSL from components in personal electronic devices such as smart phones as a means of emergency dosimetry in the event of a large-scale radiological incident. ICs were extracted from five different makes and models of mobile phone. Sample preparation procedures are described, and OSL from the IC samples following irradiation using a (90)Sr/(90)Y source is presented. Repeatability, sensitivity, dose responses, minimum measureable doses, stability and fading data were examined and are described. A protocol for measuring absorbed dose is presented, and it was concluded that OSL from these components is a viable method for assessing dose in the days following a radiological incident. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.