Heavy particle irradiation, neurochemistry and behavior: thresholds, dose- response curves and recovery of function

NASA Astrophysics Data System (ADS)

Rabin, B.; Joseph, J.; Shukitt-Hale, B.

Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation- induced disruption of dopaminergic function disrupts a variety of behaviors that are dependent upon the integrity of the dopaminergic system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, spatial learning and memory (Morris water maze), and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current presentation will review the data relevant to the degree to which these characteristics are in fact common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity. Supported by N.A.S.A. Grant NAG9-1190.

Protein Binding and Astringent Taste of a Polymeric Procyanidin, 1,2,3,4,6-Penta-O-galloyl-β-D-glucopyranose, Castalagin and Grandinin

PubMed Central

Hofmann, Thomas; Glabasnia, Arne; Schwarz, Bernd; Wisman, Kimberly N.; Gangwer, Kelly A.; Hagerman, Ann E.

2008-01-01

The objective of the present investigation was to examine oral astringency and protein binding activity of four structurally well-defined tannins, namely procyanidin (epicatechin16(4→8)catechin), pentagalloyl glucose (1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose), castalagin, and grandinin, representing the three main structural categories of tannins, the proanthocyanidins, the gallotannins, and the ellagitannins. Astringency threshold and dose response were determined by the half-tongue test using a trained human panel. Protein binding stoichiometry and relative affinity were determined using radioiodinated bovine serum albumin in precipitation or competitive binding assays. Procyanidin and pentagalloyl glucose were perceived as highly astringent compounds and had relatively steep dose response curves but castalagin and grandinin had a lower mass threshold for detection. In vitro, procyanidin was the most effective protein precipitating agent, and grandinin the least. Increasing the temperature increased protein precipitation by the hydrolysable tannins, especially grandinin. All four polyphenols had higher relative affinity for proline-rich proteins than for bovine serum albumin. PMID:17147439

The role of nicotinic receptor alpha 7 subunits in nicotine discrimination.

PubMed

Stolerman, I P; Chamberlain, S; Bizarro, L; Fernandes, C; Schalkwyk, L

2004-03-01

The subtypes of nicotinic receptors at which the behavioural effects of nicotine originate are not fully understood. The experiments described here use mice lacking the alpha7 subunit of nicotinic receptors to investigate the role of alpha7-containing receptors in nicotine discrimination. Wild-type and alpha7-knockout mice were trained in a two-lever nicotine discrimination procedure using a tandem schedule of food reinforcement. Mutant mice exhibited baseline rates of lever-pressing as low as 52.2% of rates in wild-type controls (n=21-24). Mutant and wild-type mice acquired discrimination of nicotine (0.4 or 0.8 mg/kg) at a similar rate (n=10-12) and reached similar final levels of accuracy (71.9 +/- 4.4% and 90.8 +/- 3.1% after 60 training sessions for 0.4 and 0.8 mg/kg training doses, respectively, in mutant mice, as compared with 75.0 +/- 6.5% and 87.6 +/- 4.8% for wild types). The genotypes exhibited similar steep dose-response curves for nicotine discrimination. In both genotypes, dose-response curves for mice trained with 0.8 mg/kg of nicotine were displaced three- to four-fold to the right as compared with those for the mice trained with the smaller dose. The predominant effect of nicotine on the overall rate of responding was a reduction at the largest doses tested and there was no difference between the genotypes. The results suggest that nicotinic receptors containing the alpha7 subunit do not contribute to the discriminative stimulus or response-rate-depressant effects of nicotine, although they may regulate baseline rates of operant responding.

The use and QA of biologically related models for treatment planning: short report of the TG-166 of the therapy physics committee of the AAPM.

PubMed

Allen Li, X; Alber, Markus; Deasy, Joseph O; Jackson, Andrew; Ken Jee, Kyung-Wook; Marks, Lawrence B; Martel, Mary K; Mayo, Charles; Moiseenko, Vitali; Nahum, Alan E; Niemierko, Andrzej; Semenenko, Vladimir A; Yorke, Ellen D

2012-03-01

Treatment planning tools that use biologically related models for plan optimization and/or evaluation are being introduced for clinical use. A variety of dose-response models and quantities along with a series of organ-specific model parameters are included in these tools. However, due to various limitations, such as the limitations of models and available model parameters, the incomplete understanding of dose responses, and the inadequate clinical data, the use of biologically based treatment planning system (BBTPS) represents a paradigm shift and can be potentially dangerous. There will be a steep learning curve for most planners. The purpose of this task group is to address some of these relevant issues before the use of BBTPS becomes widely spread. In this report, the authors (1) discuss strategies, limitations, conditions, and cautions for using biologically based models and parameters in clinical treatment planning; (2) demonstrate the practical use of the three most commonly used commercially available BBTPS and potential dosimetric differences between biologically model based and dose-volume based treatment plan optimization and evaluation; (3) identify the desirable features and future directions in developing BBTPS; and (4) provide general guidelines and methodology for the acceptance testing, commissioning, and routine quality assurance (QA) of BBTPS.

Cooperativity to increase Turing pattern space for synthetic biology.

PubMed

Diambra, Luis; Senthivel, Vivek Raj; Menendez, Diego Barcena; Isalan, Mark

2015-02-20

It is hard to bridge the gap between mathematical formulations and biological implementations of Turing patterns, yet this is necessary for both understanding and engineering these networks with synthetic biology approaches. Here, we model a reaction-diffusion system with two morphogens in a monostable regime, inspired by components that we recently described in a synthetic biology study in mammalian cells.1 The model employs a single promoter to express both the activator and inhibitor genes and produces Turing patterns over large regions of parameter space, using biologically interpretable Hill function reactions. We applied a stability analysis and identified rules for choosing biologically tunable parameter relationships to increase the likelihood of successful patterning. We show how to control Turing pattern sizes and time evolution by manipulating the values for production and degradation relationships. More importantly, our analysis predicts that steep dose-response functions arising from cooperativity are mandatory for Turing patterns. Greater steepness increases parameter space and even reduces the requirement for differential diffusion between activator and inhibitor. These results demonstrate some of the limitations of linear scenarios for reaction-diffusion systems and will help to guide projects to engineer synthetic Turing patterns.

SU-E-T-573: Normal Tissue Dose Effect of Prescription Isodose Level Selection in Lung Stereotactic Body Radiation Therapy

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

Zhang, Q; Lei, Y; Zheng, D

Purpose: To evaluate dose fall-off in normal tissue for lung stereotactic body radiation therapy (SBRT) cases planned with different prescription isodose levels (IDLs), by calculating the dose dropping speed (DDS) in normal tissue on plans computed with both Pencil Beam (PB) and Monte-Carlo (MC) algorithms. Methods: The DDS was calculated on 32 plans for 8 lung SBRT patients. For each patient, 4 dynamic conformal arc plans were individually optimized for prescription isodose levels (IDL) ranging from 60% to 90% of the maximum dose with 10% increments to conformally cover the PTV. Eighty non-overlapping rind structures each of 1mm thickness weremore » created layer by layer from each PTV surface. The average dose in each rind was calculated and fitted with a double exponential function (DEF) of the distance from the PTV surface, which models the steep- and moderate-slope portions of the average dose curve in normal tissue. The parameter characterizing the steep portion of the average dose curve in the DEF quantifies the DDS in the immediate normal tissue receiving high dose. Provided that the prescription dose covers the whole PTV, a greater DDS indicates better normal tissue sparing. The DDS were compared among plans with different prescription IDLs, for plans computed with both PB and MC algorithms. Results: For all patients, the DDS was found to be the lowest for 90% prescription IDL and reached a highest plateau region for 60% or 70% prescription. The trend was the same for both PB and MC plans. Conclusion: Among the range of prescription IDLs accepted by lung SBRT RTOG protocols, prescriptions to 60% and 70% IDLs were found to provide best normal tissue sparing.« less

SU-F-T-449: Dosimetric Comparison of Acuros XB, Adaptive Convolve in Intensity Modulated Radiotherapy for Head and Neck Cancer

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

Uehara, R; Tachibana, H

Purpose: There have been several publications focusing on dose calculation in lung for a new dose calculation algorithm of Acuros XB (AXB). AXB could contribute to dose calculation for high-density media for bone and dental prosthesis rather than in lung. We compared the dosimetric performance of AXB, Adaptive Convolve (AC) in head and neck IMRT plans. Methods: In a phantom study, the difference in depth profile between AXB and AC was evaluated using Kodak EDR2 film sandwiched with tough water phantoms. 6 MV x-ray using the TrueBeam was irradiated. In a patient study, 20 head and neck IMRT plans hadmore » been clinically approved in Pinnacle3 and were transferred to Eclipse. Dose distribution was recalculated using AXB in Eclipse while maintaining AC-calculated monitor units and MLC sequence planned in Pinnacle. Subsequently, both the dose-volumetric data obtained using the two different calculation algorithms were compared. Results: The results in the phantom evaluation for the shallow area ahead of the build-up region shows over-dose for AXB and under-dose for AC, respectively. In the patient plans, AXB shows more hot spots especially around the high-density media than AC in terms of PTV (Max difference: 4.0%) and OAR (Max. difference: 1.9%). Compared to AC, there were larger dose deviations in steep dose gradient region and higher skin-dose. Conclusion: In head and neck IMRT plans, AXB and AC show different dosimetric performance for the regions inside the target volume around high-density media, steep dose gradient regions and skin-surface. There are limitations in skin-dose and complex anatomic condition using even inhomogeneous anthropomorphic phantom Thus, there is the potential for an increase of hot-spot in AXB, and an underestimation of dose in substance boundaries and skin regions in AC.« less

Positron emission tomography-guided conformal fast neutron therapy for glioblastoma multiforme

PubMed Central

Stelzer, Keith J.; Douglas, James G.; Mankoff, David A.; Silbergeld, Daniel L.; Krohn, Kenneth A.; Laramore, George E.; Spence, Alexander M.

2008-01-01

Glioblastoma multiforme (GBM) continues to be a difficult therapeutic challenge. Our study was conducted to determine whether improved survival and tumor control could be achieved with modern delivery of fast neutron radiation using three-dimensional treatment planning. Ten patients were enrolled. Eligibility criteria included pathologic diagnosis of GBM, age ≥ 18 years, and KPS ≥60. Patients underwent MRI and 18F-fluorodeoxyglucose PET (FDG PET) as part of initial three-dimensional treatment planning. Sequential targets were treated with noncoplanar fields to a total dose of 18 Gy in 16 fractions over 4 weeks. Median and 1-year overall survival were 55 weeks and 60%, respectively. One patient remains alive at last follow-up 255 weeks after diagnosis. Median progression-free survival was 16 weeks, and all patients had tumor progression by 39 weeks. Treatment was clinically well tolerated, but evidence of mild to moderate gliosis and microvascular sclerosis consistent with radiation injury was observed at autopsy in specimens taken from regions of contralateral brain that received approximately 6–10 Gy. Fast neutron radiation using modern imaging, treatment planning, and beam delivery was feasible to a total dose of 18 Gy, but tumor control probability was poor in comparison to that predicted from a dose-response model based on older studies. Steep dose-response curves for both tumor control and neurotoxicity continue to present a challenge to establishing a therapeutic window for fast neutron radiation in GBM, even with modern techniques. PMID:18055860

Organic Acids Regulation of Chemical-Microbial Phosphorus Transformations in Soils.

PubMed

Menezes-Blackburn, Daniel; Paredes, Cecilia; Zhang, Hao; Giles, Courtney D; Darch, Tegan; Stutter, Marc; George, Timothy S; Shand, Charles; Lumsdon, David; Cooper, Patricia; Wendler, Renate; Brown, Lawrie; Blackwell, Martin; Wearing, Catherine; Haygarth, Philip M

2016-11-01

We have used an integrated approach to study the mobility of inorganic phosphorus (P) from soil solid phase as well as the microbial biomass P and respiration at increasing doses of citric and oxalic acid in two different soils with contrasting agronomic P status. Citric or oxalic acids significantly increased soil solution P concentrations for doses over 2 mmol kg -1 . However, low organic acid doses (<2 mmol kg -1 ) were associated with a steep increase in microbial biomass P, which was not seen for higher doses. In both soils, treatment with the tribasic citric acid led to a greater increase in soil solution P than the dibasic oxalic acid, likely due to the rapid degrading of oxalic acids in soils. After equilibration of soils with citric or oxalic acids, the adsorbed-to-solution distribution coefficient (K d ) and desorption rate constants (k -1 ) decreased whereas an increase in the response time of solution P equilibration (T c ) was observed. The extent of this effect was shown to be both soil and organic acid specific. Our results illustrate the critical thresholds of organic acid concentration necessary to mobilize sorbed and precipitated P, bringing new insight on how the exudation of organic acids regulate chemical-microbial soil phosphorus transformations.

Toxicity of hydroxyurea in rats and dogs.

PubMed

Morton, Daniel; Reed, Lori; Huang, Wenhu; Marcek, John M; Austin-LaFrance, Robert; Northcott, Carrie A; Schelling, Scott H; Enerson, Bradley E; Tomlinson, Lindsay

2015-06-01

The toxicity of hydroxyurea, a treatment for specific neoplasms, sickle-cell disease, polycythemia, and thrombocytosis that kills cells in mitosis, was assessed in repeat-dose, oral gavage studies in rats and dogs and a cardiovascular study in telemetered dogs. Hydroxyurea produced hematopoietic, lymphoid, cardiovascular, and gastrointestinal toxicity with steep dose response curves. In rats dosed for 10 days, 50 mg/kg/day was tolerated; 500 mg/kg/day produced decreased body weight gain; decreased circulating leukocytes, erythrocytes, and platelets; decreased cellularity of thymus, lymph nodes, and bone marrow; and epithelial degeneration and/or dysplasia of the stomach and small intestine; 1,500 mg/kg/day resulted in deaths on day 5. In dogs, a single dose at ≥ 250 mg/kg caused prostration leading to unscheduled euthanasia. Dogs administered 50 mg/kg/day for 1 month had decreased circulating leukocytes, erythrocytes, and platelets; increased bone marrow cellularity with decreased maturing granulocytes; increased creatinine kinase activity; and increased iron pigment in bone marrow and hepatic sinusoidal cells. In telemetered dogs, doses ≥ 15 mg/kg decreased systolic blood pressure (BP); 50 mg/kg increased diastolic BP, heart rate, and change in blood pressure over time (+dP/dt), and decreased QT and PR intervals and maximum left ventricular systolic and end diastolic pressures with measures returning to control levels within 24 hr. © 2014 by The Author(s).

A comparison of simple and realistic eye models for calculation of fluence to dose conversion coefficients in a broad parallel beam incident of protons

NASA Astrophysics Data System (ADS)

Sakhaee, Mahmoud; Vejdani-Noghreiyan, Alireza; Ebrahimi-Khankook, Atiyeh

2015-01-01

Radiation induced cataract has been demonstrated among people who are exposed to ionizing radiation. To evaluate the deterministic effects of ionizing radiation on the eye lens, several papers dealing with the eye lens dose have been published. ICRP Publication 103 states that the lens of the eye may be more radiosensitive than previously considered. Detailed investigation of the response of the lens showed that there are strong differences in sensitivity to ionizing radiation exposure with respect to cataract induction among the tissues of the lens of the eye. This motivated several groups to look deeper into issue of the dose to a sensitive cell population within the lens, especially for radiations with low energy penetrability that have steep dose gradients inside the lens. Two sophisticated mathematical models of the eye including the inner structure have been designed for the accurate dose estimation in recent years. This study focuses on the calculations of the absorbed doses of different parts of the eye using the stylized models located in UF-ORNL phantom and comparison with the data calculated with the reference computational phantom in a broad parallel beam incident of protons with energies between 20 MeV and 10 GeV. The obtained results indicate that the total lens absorbed doses of reference phantom has good compliance with those of the more sensitive regions of stylized models. However, total eye absorbed dose of these models greatly differ with each other for lower energies.

Analysis of the response of PVA-GTA Fricke-gel dosimeters with clinical magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Collura, Giorgio; Gallo, Salvatore; Tranchina, Luigi; Abbate, Boris Federico; Bartolotta, Antonio; d'Errico, Francesco; Marrale, Maurizio

2018-01-01

Fricke gel dosimeters produced with a matrix of Poly-vinyl alcohol (PVA) cross-linked with glutaraldehyde (GTA) were analyzed with magnetic resonance imaging (MRI). Previous studies based on spectrophotometry showed valuable dosimetric features of these gels in terms of X-ray sensitivity and diffusion of the ferric ions produced after irradiation. In this study, MRI was performed on the gels at 1.5 T with a clinical scanner in order to optimize the acquisition parameters and obtain high contrast between irradiated and non-irradiated samples. The PVA gels were found to offer good linearity in the range of 0-10 Gy and a stable signal for several hours after irradiation. The sensitivity was about 40% higher compared to gels produced with agarose as gelling agent. The effect of xylenol orange (XO) on the MRI signal was also investigated: gel dosimeters made without XO show higher sensitivity to x-rays than those made with XO. The dosimetric accuracy of the 3D gels was investigated by comparing their MRI response to percentage depth dose and transversal dose profile measurements made with an ionization chamber in a water phantom. The comparison of PVA-GTA gels with and without XO showed that the chelating agent reduces the MRI sensitivity of the gels. Depth-dose and transversal dose profiles acquired by PVA-GTA gels without XO are more accurate and consistent with the ionization chamber data. However, diffusion effects hinder accurate measurements in the steep dose gradient regions and they should be further reduced by modifying the gel matrix and/or by minimizing the delay between irradiation and imaging.

Prolonged lateral steep position impairs respiratory mechanics during continuous lateral rotation therapy in respiratory failure.

PubMed

Schellongowski, Peter; Losert, Heidrun; Locker, Gottfried J; Laczika, Klaus; Frass, Michael; Holzinger, Ulrike; Bojic, Andja; Staudinger, Thomas

2007-04-01

To establish whether prolonged lateral steep position during continuous rotation therapy leads to improvement on pulmonary gas exchange, respiratory mechanics and hemodynamics. Prospective observational study. Intensive care unit of a university hospital. Twelve consecutive patients suffering from acute lung injury or adult respiratory distress syndrome undergoing continuous rotation therapy. Blood gas analysis, static lung compliance, blood pressure, cardiac index and pulmonary shunt fraction were measured in supine as well as in left and right lateral steep position at 62 degrees during continuous rotation therapy (phase I). Rotation was then stopped for 30 min with the patients in supine position, left and right lateral steep position, and the same measurements were performed every 10 min (phase II). Phase I and II revealed no significant changes in PaO(2)/FiO(2) ratio, mean arterial blood pressure, pulmonary shunt fraction, or cardiac index. Significantly lower static compliance was observed in lateral steep position than in supine position (p<0.001). Concomitantly, PaCO(2) was significantly lower in supine position than in left and right lateral steep position (p<0.01). Lateral steep positioning impairs the compliance of the respiratory system. Prolonged lateral steep position does not lead to benefits with respect to oxygenation or hemodynamics. Individual response to the different positions is unpredictable. The pauses in "extreme" positions should be as short as possible.

In vivo TLD dose measurements in catheter-based high-dose-rate brachytherapy.

PubMed

Adlienė, Diana; Jakštas, Karolis; Urbonavičius, Benas Gabrielis

2015-07-01

Routine in vivo dosimetry is well established in external beam radiotherapy; however, it is restricted mainly to detection of gross errors in high-dose-rate (HDR) brachytherapy due to complicated measurements in the field of steep dose gradients in the vicinity of radioactive source and high uncertainties. The results of in vivo dose measurements using TLD 100 mini rods and TLD 'pin worms' in catheter-based HDR brachytherapy are provided in this paper alongside with their comparison with corresponding dose values obtained using calculation algorithm of the treatment planning system. Possibility to perform independent verification of treatment delivery in HDR brachytherapy using TLDs is discussed. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Comparison of exposure assessment methods in a lung cancer case-control study: performance of a lifelong task-based questionnaire for asbestos and PAHs.

PubMed

Bourgkard, Eve; Wild, Pascal; Gonzalez, Maria; Févotte, Joëlle; Penven, Emmanuelle; Paris, Christophe

2013-12-01

To describe the performance of a lifelong task-based questionnaire (TBQ) in estimating exposures compared with other approaches in the context of a case-control study. A sample of 93 subjects was randomly selected from a lung cancer case-control study corresponding to 497 jobs. For each job, exposure assessments for asbestos and polycyclic aromatic hydrocarbons (PAHs) were obtained by expertise (TBQ expertise) and by algorithm using the TBQ (TBQ algorithm) as well as by expert appraisals based on all available occupational data (REFERENCE expertise) considered to be the gold standard. Additionally, a Job Exposure Matrix (JEM)-based evaluation for asbestos was also obtained. On the 497 jobs, the various evaluations were contrasted using Cohen's κ coefficient of agreement. Additionally, on the total case-control population, the asbestos dose-response relationship based on the TBQ algorithm was compared with the JEM-based assessment. Regarding asbestos, the TBQ-exposure estimates agreed well with the REFERENCE estimate (TBQ expertise: level-weighted κ (lwk)=0.68; TBQ algorithm: lwk=0.61) but less so with the JEM estimate (TBQ expertise: lwk=0.31; TBQ algorithm: lwk=0.26). Regarding PAHs, the agreements between REFERENCE expertise and TBQ were less good (TBQ expertise: lwk=0.43; TBQ algorithm: lwk=0.36). In the case-control study analysis, the dose-response relationship between lung cancer and cumulative asbestos based on the JEM is less steep than with the TBQ-algorithm exposure assessment and statistically non-significant. Asbestos-exposure estimates based on the TBQ were consistent with the REFERENCE expertise and yielded a steeper dose-response relationship than the JEM. For PAHs, results were less clear.

Ultraviolet-B radiation effects on inorganic nitrogen uptake by natural assemblages of oceanic plankton

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

Behrenfeld, M.J.; Lean, D.R.S.; Lee, H. II

1995-02-01

Ultraviolet-B radiation (UVBR: 290-320 nm) inhibited ammonium uptake ({rho}{sub NH4}) and nitrate uptake ({rho}{sub NO3}) in natural plankton assemblages collected during a transect from 37{degrees}N to 55{degrees}N in the Pacific Ocean. Comparison of responses in {rho}{sub NH4} to ambient solar- and lamp-enhanced UVBR spectra allowed calculation of an action spectrum for {rho}{sub NH4} inhibition. The slope of the action spectrum for {rho}{sub NH4} is half as steep as action spectra for UVBR inhibition of photosynthetic carbon uptake. Consequently, UVBR-induced photoinhibition of {rho}{sub NH4} extends to greater depths than inhibition of carbon fixation due to the greater relative effect of longermore » UVBR wavelengths. Inhibition of {rho}{sub NH4} was dependent upon UVBR dose when doses were weighted by the {rho}{sub NH4} action spectrum. Dependence of UVBR inhibition of {rho}{sub NH4} on dose rate was not apparent. We found that near-surface {rho}{sub NH4} and {rho}{sub NO3} can be overestimated in excess of 50% when measured using standard incubation vessels made of UVBR-absorbing materials such as polycarbonate. 68 refs., 9 figs., 1 tab.« less

A pharmacokinetic-pharmacodynamic model for intrathecal baclofen in patients with severe spasticity.

PubMed

Heetla, H W; Proost, J H; Molmans, B H; Staal, M J; van Laar, T

2016-01-01

Intrathecal baclofen (ITB) has proven to be an effective and safe treatment for severe spasticity. However, although ITB is used extensively, clinical decisions are based on very scarce pharmacokinetic-pharmacodynamic (PKPD) data. The aim of this study was to measure baclofen CSF concentrations and clinical effects after administration of various ITB boluses in patients with spasticity and to create a PKPD model for ITB. Twelve patients with severe spasticity received four different bolus doses of ITB (0, 25, 50, 75 μg and an optional dose of 100 μg), administered via a catheter with the tip at thoracic level (Th) 10. After each bolus, 10 CSF samples were taken at fixed time intervals, using a catheter with the tip located at Th12. Clinical effect was assessed by measuring spasticity with the Modified Ashworth Scale (MAS). These data were used to develop a PKPD model. All patients achieved an adequate spasmolytic effect with ITB doses varying from 50 to 100 μg. No serious side effects were observed. CSF baclofen concentrations, as well as the clinical effects, correlated significantly with ITB doses. The PK model predicted a steep spinal concentration gradient of ITB along the spinal axis. The clinical effect could be predicted using a delayed-effect model. ITB is an effective and safe therapy with, however, a steep concentration gradient along the spinal axis. This means that the administered baclofen is staying mainly around the catheter tip, which stresses the importance to position the ITB catheter tip closely to the targeted spinal level. © 2015 The British Pharmacological Society.

SU-E-T-643: Pure Alanine Dosimeter for Verification Dosimetry in IMRT

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

Al-Karmi, Anan M.; Zraiqat, Fadi

Purpose: The objective of this study was evaluation of accuracy of pure alanine dosimeters measuring intensity-modulated radiation therapy (IMRT) dose distributions in a thorax phantom. Methods: Alanine dosimeters were prepared in the form of 110 mg pure L-α-alanine powder filled into clear tissue-equivalent polymethylmethacrylate (PMMA) plastic tubes with the dimensions 25 mm length, 3 mm inner diameter, and 1 mm wall thickness. A dose-response calibration curve was established for the alanine by placing the dosimeters at 1.5 cm depth in a 30×30×30 cm{sup 3} solid water phantom and then irradiating on a linac with 6 MV photon beam at 10×10more » cm{sup 2} field size to doses ranging from 1 to 5 Gy. Electron paramagnetic resonance (EPR) spectroscopy was used to determine the absorbed dose in alanine. An IMRT treatment plan was designed for a commercial heterogeneous CIRS thorax phantom and the dose values were calculated at three different points located in tissue, lung, and bone equivalent materials. A set of dose measurements was carried out to compare measured and calculated dose values by placing the alanine dosimeters at those selected locations inside the thorax phantom and delivering the IMRT to the phantom. Results: The alanine dose measurements and the IMRT plan dose calculations were found to be in agreement within ±2%. Specifically, the deviations were −0.5%, 1.3%, and −1.7% for tissue, lung, and bone; respectively. The slightly large deviations observed for lung and bone may be attributed to tissue inhomogeneity, steep dose gradients in these regions, and uncontrollable changes in spectrometer conditions. Conclusion: The results described herein confirmed that pure alanine dosimeter was suitable for in-phantom dosimetry of IMRT beams because of its high sensitivity and acceptable accuracy. This makes the dosimeter a promising option for quality control of the therapeutic beams, complementing the commonly used ionization chambers, TLDs, and films.« less

Genital marginal failures after intensity-modulated radiation therapy (IMRT) in squamous cell anal cancer: no higher risk with IMRT when compared to 3DCRT.

PubMed

Dell'Acqua, V; Kobiela, J; Kraja, F; Leonardi, M C; Surgo, A; Zerella, M A; Arculeo, S; Fodor, C; Ricotti, R; Zampino, M G; Ravenda, S; Spinoglio, G; Biffi, R; Bazani, A; Luraschi, R; Vigorito, S; Spychalski, P; Orecchia, R; Glynne-Jones, R; Jereczek-Fossa, B A

2018-03-28

Intensity-modulated radiotherapy (IMRT) is considered the preferred option in squamous cell canal cancer (SCAC), delivering high doses to tumor volumes while minimizing dose to surrounding normal tissues. IMRT has steep dose gradients, but the technique is more demanding as deep understanding of target structures is required. To evaluate genital marginal failure in a cohort of patients with non-metastatic SCAC treated either with IMRT or 3DCRT and concurrent chemotherapy, 117 patients with SCAC were evaluated: 64 and 53 patients were treated with IMRT and 3DCRT techniques, respectively. All patients underwent clinical and radiological examination during their follow-up. Tumor response was evaluated with response evaluation criteria in solid tumors v1.1 guideline on regular basis. All patients' data were analyzed, and patients with marginal failure were identified. Concomitant chemotherapy was administered in 97 and 77.4% of patients in the IMRT and 3DCRT groups, respectively. In the IMRT group, the median follow-up was 25 months (range 6-78). Progressive disease was registered in 15.6% of patients; infield recurrence, distant recurrence and both infield recurrence and distant recurrence were identified in 5, 4 and 1 patient, respectively. Two out of 64 patients (3.1%) had marginal failures, localized at vagina/recto-vaginal septum and left perineal region. In the 3DCRT group, the median follow-up was 71.3 months (range 6-194 months). Two out of 53 patients (3.8%) had marginal failures, localized at recto-vaginal septum and perigenital structures. The rate of marginal failures was comparable in IMRT and 3DCRT groups (χ 2 test p = 0.85). In this series, the use of IMRT for the treatment of SCAC did not increase the rate of marginal failures offering improved dose conformity to the target. Dose constraints should be applied with caution-particularly in females with involvement of the vagina or the vaginal septum.

Dual-Gate p-GaN Gate High Electron Mobility Transistors for Steep Subthreshold Slope.

PubMed

Bae, Jong-Ho; Lee, Jong-Ho

2016-05-01

A steep subthreshold slope characteristic is achieved through p-GaN gate HEMT with dual-gate structure. Obtained subthreshold slope is less than 120 μV/dec. Based on the measured and simulated data obtained from single-gate device, breakdown of parasitic floating-base bipolar transistor and floating gate charged with holes are responsible to increase abruptly in drain current. In the dual-gate device, on-current degrades with high temperature but subthreshold slope is not changed. To observe the switching speed of dual-gate device and transient response of drain current are measured. According to the transient responses of drain current, switching speed of the dual-gate device is about 10(-5) sec.

Sphere of equivalence--a novel target volume concept for intraoperative radiotherapy using low-energy X rays.

PubMed

Herskind, Carsten; Griebel, Jürgen; Kraus-Tiefenbacher, Uta; Wenz, Frederik

2008-12-01

Accelerated partial breast radiotherapy with low-energy photons from a miniature X-ray machine is undergoing a randomized clinical trial (Targeted Intra-operative Radiation Therapy [TARGIT]) in a selected subgroup of patients treated with breast-conserving surgery. The steep radial dose gradient implies reduced tumor cell control with increasing depth in the tumor bed. The purpose was to compare the expected risk of local recurrence in this nonuniform radiation field with that after conventional external beam radiotherapy. The relative biologic effectiveness of low-energy photons was modeled using the linear-quadratic formalism including repair of sublethal lesions during protracted irradiation. Doses of 50-kV X-rays (Intrabeam) were converted to equivalent fractionated doses, EQD2, as function of depth in the tumor bed. The probability of local control was estimated using a logistic dose-response relationship fitted to clinical data from fractionated radiotherapy. The model calculations show that, for a cohort of patients, the increase in local control in the high-dose region near the applicator partly compensates the reduction of local control at greater distances. Thus a "sphere of equivalence" exists within which the risk of recurrence is equal to that after external fractionated radiotherapy. The spatial distribution of recurrences inside this sphere will be different from that after conventional radiotherapy. A novel target volume concept is presented here. The incidence of recurrences arising in the tumor bed around the excised tumor will test the validity of this concept and the efficacy of the treatment. Recurrences elsewhere will have implications for the rationale of TARGIT.

SU-F-T-06: Development of a Formalism for Practical Dose Measurements in Brachytherapy in the German Standard DIN 6803

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

Hensley, F; Chofor, N; Schoenfeld, A

2016-06-15

Purpose: In the steep dose gradients in the vicinity of a radiation source and due to the properties of the changing photon spectra, dose measurements in Brachytherapy usually have large uncertainties. Working group DIN 6803-3 is presently discussing recommendations for practical brachytherapy dosimetry incorporating recent theoretical developments in the description of brachytherapy radiation fields as well as new detectors and phantom materials. The goal is to prepare methods and instruments to verify dose calculation algorithms and for clinical dose verification with reduced uncertainties. Methods: After analysis of the distance dependent spectral changes of the radiation field surrounding brachytherapy sources, themore » energy dependent response of typical brachytherapy detectors was examined with Monte Carlo simulations. A dosimetric formalism was developed allowing the correction of their energy dependence as function of source distance for a Co-60 calibrated detector. Water equivalent phantom materials were examined with Monte Carlo calculations for their influence on brachytherapy photon spectra and for their water equivalence in terms of generating equivalent distributions of photon spectra and absorbed dose to water. Results: The energy dependence of a detector in the vicinity of a brachytherapy source can be described by defining an energy correction factor kQ for brachytherapy in the same manner as in existing dosimetry protocols which incorporates volume averaging and radiation field distortion by the detector. Solid phantom materials were identified which allow precise positioning of a detector together with small correctable deviations from absorbed dose to water. Recommendations for the selection of detectors and phantom materials are being developed for different measurements in brachytherapy. Conclusion: The introduction of kQ for brachytherapy sources may allow more systematic and comparable dose measurements. In principle, the corrections can be verified or even determined by measurement in a water phantom and comparison with dose distributions calculated using the TG43 dosimetry formalism. Project is supported by DIN Deutsches Institut fuer Normung.« less

An investigation of a PRESAGE® in-vivo dosimeter for brachytherapy

PubMed Central

Vidovic, A K; Juang, T; Meltsner, S; Adamovics, J; Chino, J; Steffey, B; Craciunescu, O; Oldham, M

2014-01-01

Determining accurate in-vivo dosimetry in brachytherapy treatment with high dose gradients is challenging. Here we introduce, investigate, and characterize a novel in-vivo dosimeter and readout technique with the potential to address this problem. A cylindrical (4 mm x 20 mm) tissue equivalent radiochromic dosimeter PRESAGE® In-Vivo (PRESAGE®-IV) is investigated. Two readout methods of the radiation induced change in optical density (OD) were investigated: (i) volume-averaged readout by spectrophotometer, and (ii) a line profile readout by 2D projection imaging utilizing a high-resolution (50 micron) telecentric optical system. Method (i) is considered the gold standard when applied to PRESAGE® in optical cuvettes. The feasibility of both methods was evaluated by comparison to standard measurements on PRESAGE® in optical cuvettes via spectrophotometer. An end-to-end feasibility study was performed by a side-by-side comparison with TLDs in an 192Ir HDR delivery. 7 and 8 Gy was delivered to PRESAGE®-IV and TLDs attached to the surface of a vaginal cylinder. Known geometry enabled direct comparison of measured dose with commissioned treatment planning system. A high-resolution readout study under a steep dose gradient region showed 98.9% (5%/1 mm) agreement between PRESAGE®-IV and Gafchromic® EBT2 Film. Spectrometer measurements exhibited a linear dose response between 0–15 Gy with sensitivity of 0.0133 ± 0.0007 ΔOD/(Gy·cm) at the 95% confidence interval. Method (ii) yielded a linear response with sensitivity of 0.0132 ± 0.0006 (ΔOD/Gy), within 2% of method (i). Method (i) has poor spatial resolution due to volume averaging. Method (ii) has higher resolution (~1mm) without loss of sensitivity or increased noise. Both readout methods are shown to be feasible. The end-to-end comparison revealed a 2.5% agreement between PRESAGE®-IV and treatment plan in regions of uniform high dose. PRESAGE®-IV shows promise for in-vivo dose verification, although improved sensitivity would be desirable. Advantages include high-resolution, convenience and fast, low-cost readout. PMID:24957850

An investigation of a PRESAGE® in vivo dosimeter for brachytherapy

NASA Astrophysics Data System (ADS)

Vidovic, A. K.; Juang, T.; Meltsner, S.; Adamovics, J.; Chino, J.; Steffey, B.; Craciunescu, O.; Oldham, M.

2014-07-01

Determining accurate in vivo dosimetry in brachytherapy treatment with high dose gradients is challenging. Here we introduce, investigate, and characterize a novel in vivo dosimeter and readout technique with the potential to address this problem. A cylindrical (4 mm × 20 mm) tissue equivalent radiochromic dosimeter PRESAGE® in vivo (PRESAGE®-IV) is investigated. Two readout methods of the radiation induced change in optical density (OD) were investigated: (i) volume-averaged readout by spectrophotometer, and (ii) a line profile readout by 2D projection imaging utilizing a high-resolution (50 micron) telecentric optical system. Method (i) is considered the gold standard when applied to PRESAGE® in optical cuvettes. The feasibility of both methods was evaluated by comparison to standard measurements on PRESAGE® in optical cuvettes via spectrophotometer. An end-to-end feasibility study was performed by a side-by-side comparison with TLDs in an 192Ir HDR delivery. 7 and 8 Gy was delivered to PRESAGE®-IV and TLDs attached to the surface of a vaginal cylinder. Known geometry enabled direct comparison of measured dose with a commissioned treatment planning system. A high-resolution readout study under a steep dose gradient region showed 98.9% (5%/1 mm) agreement between PRESAGE®-IV and Gafchromic® EBT2 Film. Spectrometer measurements exhibited a linear dose response between 0-15 Gy with sensitivity of 0.0133 ± 0.0007 ΔOD/(Gy ṡ cm) at the 95% confidence interval. Method (ii) yielded a linear response with sensitivity of 0.0132 ± 0.0006 (ΔOD/Gy), within 2% of method (i). Method (i) has poor spatial resolution due to volume averaging. Method (ii) has higher resolution (˜1 mm) without loss of sensitivity or increased noise. Both readout methods are shown to be feasible. The end-to-end comparison revealed a 2.5% agreement between PRESAGE®-IV and treatment plan in regions of uniform high dose. PRESAGE®-IV shows promise for in vivo dose verification, although improved sensitivity would be desirable. Advantages include high-resolution, convenience and fast, low-cost readout.

Effects of radiotherapy on parotid salivary sialochemistry in head and neck cancer patients.

PubMed

Gupta, S C; Singla, Alok; Singh, Mangal; Thaliath, B Paul; Geeta, Jaiswal

2009-12-01

To determine the effects of high dose irradiation on parotid salivary sodium and pH concentration at subsequent duration of 1.5, 3 and 6 months following radiotherapy. Eighty parotid glands of head and neck cancer patients were irradiated with mean dose of 66 Gy. The stimulated parotid flow (PF) was collected by a cannulation of Stenson's duct followed by analysis of sodium (PF sodium) by Easylyte Sodium/Potassium auto analyzer and pH by litmus narrow band pH paper. A steep elevation of PF sodium was found in post-RT period after 1.5 months of starting RT followed by gradual increase up to 6 months and pH changed towards acidity. A high dose of 66 Gy causes irreversible damage to parotid salivary duct system.

In vivo dose verification of IMRT treated head and neck cancer patients.

PubMed

Engström, Per E; Haraldsson, Pia; Landberg, Torsten; Sand Hansen, Hanne; Aage Engelholm, Svend; Nyström, Håkan

2005-01-01

An independent in vivo dose verification procedure for IMRT treatments of head and neck cancers was developed. Results of 177 intracavitary TLD measurements from 10 patients are presented. The study includes data from 10 patients with cancer of the rhinopharynx or the thyroid treated with dynamic IMRT. Dose verification was performed by insertion of a flexible naso-oesophageal tube containing TLD rods and markers for EPID and simulator image detection. Part of the study focussed on investigating the accuracy of the TPS calculations in the presence of inhomogeneities. Phantom measurements and Monte Carlo simulations were performed for a number of geometries involving lateral electronic disequilibrium and steep density shifts. The in vivo TLD measurements correlated well with the predictions of the treatment planning system with a measured/calculated dose ratio of 1.002+/-0.051 (1 SD, N=177). The measurements were easily performed and well tolerated by the patients. We conclude that in vivo intracavitary dosimetry with TLD is suitable and accurate for dose determination in intensity-modulated beams.

Potent analgesic effects of anticonvulsants on peripheral thermal nociception in rats

PubMed Central

Todorovic, Slobodan M; Rastogi, A J; Jevtovic-Todorovic, Vesna

2003-01-01

Anticonvulsant agents are commonly used to treat neuropathic pain conditions because of their effects on voltage- and ligand-gated channels in central pain pathways. However, their interaction with ion channels in peripheral pain pathways is poorly understood. Therefore, we studied the potential analgesic effects of commonly used anticonvulsant agents in peripheral nociception. We injected anticonvulsants intradermally into peripheral receptive fields of sensory neurons in the hindpaws of adult rats, and studied pain perception using the model of acute thermal nociception. Commonly used anticonvulsants such as voltage-gated Na+ channel blockers, phenytoin and carbamazepine, and voltage-gated Ca2+ channel blockers, gabapentin and ethosuximide, induced dose-dependent analgesia in the injected paw, with ED50 values of 0.30, 0.32 and 8, 410 μg per 100 μl, respectively. Thermal nociceptive responses were not affected in the contralateral, noninjected paws, indicating a lack of systemic effects with doses of anticonvulsants that elicited local analgesia. Hill slope coefficients for the tested anticonvulsants indicate that the dose–response curve was less steep for gabapentin than for phenytoin, carbamazepine and ethosuximide. Our data strongly suggest that cellular targets like voltage-gated Na+ and Ca2+ channels, similar to those that mediate the effects of anticonvulsant agents in the CNS, may exist in the peripheral nerve endings of rat sensory neurons. Thus, peripherally applied anticonvulsants that block voltage-gated Na+ and Ca2+ channels may be useful analgesics. PMID:12970103

Performance enhancement of Ge-on-Insulator tunneling FETs with source junctions formed by low-energy BF2 ion implantation

NASA Astrophysics Data System (ADS)

Katoh, Takumi; Matsumura, Ryo; Takaguchi, Ryotaro; Takenaka, Mitsuru; Takagi, Shinichi

2018-04-01

To clarify the process of formation of source regions of high-performance Ge n-channel tunneling field-effect transistors (TFETs), p+-n junctions formed by low-energy ion implantation (I/I) of BF2 atoms are characterized. Here, the formation of p+-n junctions with steep B profiles and low junction leakage is a key issue. The steepness of 5.7 nm/dec in profiles of B implanted into Ge is obtained for BF2 I/I at 3 keV with a dose of 4 × 1014 cm-2. Ge-on-insulator (GOI) n-TFETs with the source tunnel junctions formed by low-energy B and BF2 I/I are fabricated on GOI substrates and the device operation is confirmed. Although the performance at room temperature is significantly degraded by the source junction leakage current, an I on/I off ratio of 105 and the minimum sub-threshold swing (S.S.) of 130 mV/dec are obtained at 10 K. It is found that GOI n-TFETs with steeper B profiles formed by BF2 I/I have led to higher on current and a lower sub-threshold slope, demonstrating the effectiveness of steep B profiles in enhancing the GOI TFET performance.

A Bio-Realistic Analog CMOS Cochlea Filter With High Tunability and Ultra-Steep Roll-Off.

PubMed

Wang, Shiwei; Koickal, Thomas Jacob; Hamilton, Alister; Cheung, Rebecca; Smith, Leslie S

2015-06-01

This paper presents the design and experimental results of a cochlea filter in analog very large scale integration (VLSI) which highly resembles physiologically measured response of the mammalian cochlea. The filter consists of three specialized sub-filter stages which respectively provide passive response in low frequencies, actively tunable response in mid-band frequencies and ultra-steep roll-off at transition frequencies from pass-band to stop-band. The sub-filters are implemented in balanced ladder topology using floating active inductors. Measured results from the fabricated chip show that wide range of mid-band tuning including gain tuning of over 20 dB, Q factor tuning from 2 to 19 as well as the bio-realistic center frequency shift are achieved by adjusting only one circuit parameter. Besides, the filter has an ultra-steep roll-off reaching over 300 dB/dec. By changing biasing currents, the filter can be configured to operate with center frequencies from 31 Hz to 8 kHz. The filter is 9th order, consumes 59.5 ∼ 90.0 μW power and occupies 0.9 mm2 chip area. A parallel bank of the proposed filter can be used as the front-end in hearing prosthesis devices, speech processors as well as other bio-inspired auditory systems owing to its bio-realistic behavior, low power consumption and small size.

Transient response of a liquid injector to a steep-fronted transverse pressure wave

NASA Astrophysics Data System (ADS)

Lim, D.; Heister, S.; Stechmann, D.; Kan, B.

2017-12-01

Motivated by the dynamic injection environment posed by unsteady pressure gain combustion processes, an experimental apparatus was developed to visualize the dynamic response of a transparent liquid injector subjected to a single steep-fronted transverse pressure wave. Experiments were conducted at atmospheric pressure with a variety of acrylic injector passage designs using water as the working fluid. High-speed visual observations were made of the injector exit near field, and the extent of backflow and the time to refill the orifice passage were characterized over a range of injection pressures. A companion transient one-dimensional model was developed for interpretation of the results and to elucidate the trends with regard to the strength of the transverse pressure wave. Results from the model were compared with the experimental observations.

Transient response of a liquid injector to a steep-fronted transverse pressure wave

NASA Astrophysics Data System (ADS)

Lim, D.; Heister, S.; Stechmann, D.; Kan, B.

2018-07-01

Motivated by the dynamic injection environment posed by unsteady pressure gain combustion processes, an experimental apparatus was developed to visualize the dynamic response of a transparent liquid injector subjected to a single steep-fronted transverse pressure wave. Experiments were conducted at atmospheric pressure with a variety of acrylic injector passage designs using water as the working fluid. High-speed visual observations were made of the injector exit near field, and the extent of backflow and the time to refill the orifice passage were characterized over a range of injection pressures. A companion transient one-dimensional model was developed for interpretation of the results and to elucidate the trends with regard to the strength of the transverse pressure wave. Results from the model were compared with the experimental observations.

Transient river response, captured by channel steepness and its concavity

NASA Astrophysics Data System (ADS)

Vanacker, Veerle; von Blanckenburg, Friedhelm; Govers, Gerard; Molina, Armando; Campforts, Benjamin; Kubik, Peter W.

2015-01-01

Mountain rivers draining tropical regions are known to be great conveyor belts carrying efficiently more than half of the global sediment flux to the oceans. Many tropical mountain areas are located in tectonically active belts where the hillslope and stream channel morphology are rapidly evolving in response to changes in base level. Here, we report basin-wide denudation rates for an east-west transect through the tropical Andes. Hillslope and channel morphology vary systematically from east to west, reflecting the transition from high relief, strongly dissected topography in the escarpment zones into relatively low relief topography in the inter-Andean valley. The spatial pattern of differential denudation rates reflects the transient adjustment of the landscape to rapid river incision following tectonic uplift and river diversion. In the inter-Andean valley, upstream of the wave of incision, slopes and river channels display a relatively smooth, concave-up morphology and denudation rates (time scale of 104-105 a) are consistently low (3 to 200 mm/ka). In contrast, slopes and river channels of rejuvenated basins draining the eastern cordillera are steep to very steep; and the studied drainage basins show a wide range of denudation rate values (60 to 400 mm/ka) that increase systematically with increasing basin mean slope gradient, channel steepness, and channel convexity. Drainage basins that are characterised by strong convexities in their river longitudinal profiles systematically have higher denudation rates. As such, this is one of the first studies that provides field-based evidence of a correlation between channel concavity and basin mean denudation rates, consistent with process-based fluvial incision models.

Dosimetric evaluation of intrafractional tumor motion by means of a robot driven phantom

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

Richter, Anne; Wilbert, Juergen; Flentje, Michael

2011-10-15

Purpose: The aim of the work was to investigate the influence of intrafractional tumor motion to the accumulated (absorbed) dose. The accumulated dose was determined by means of calculations and measurements with a robot driven motion phantom. Methods: Different motion scenarios and compensation techniques were realized in a phantom study to investigate the influence of motion on image acquisition, dose calculation, and dose measurement. The influence of motion on the accumulated dose was calculated by employing two methods (a model based and a voxel based method). Results: Tumor motion resulted in a blurring of steep dose gradients and a reductionmore » of dose at the periphery of the target. A systematic variation of motion parameters allowed the determination of the main influence parameters on the accumulated dose. The key parameters with the greatest influence on dose were the mean amplitude and the pattern of motion. Investigations on necessary safety margins to compensate for dose reduction have shown that smaller safety margins are sufficient, if the developed concept with optimized margins (OPT concept) was used instead of the standard internal target volume (ITV) concept. Both calculation methods were a reasonable approximation of the measured dose with the voxel based method being in better agreement with the measurements. Conclusions: Further evaluation of available systems and algorithms for dose accumulation are needed to create guidelines for the verification of the accumulated dose.« less

Response prediction to antidepressants using scalp and source-localized loudness dependence of auditory evoked potential (LDAEP) slopes

PubMed Central

Jaworska, Natalia; Blondeau, Claude; Tessier, Pierre; Norris, Sandhaya; Fusee, Wendy; Blier, Pierre; Knott, Verner

2013-01-01

The loudness-dependence of the auditory evoked potential (LDAEP) slope may be inversely related to serotonin (5-HT) neurotransmission. Thus, steep LDAEPs tend to predict a positive response to selective serotonin reuptake inhibitor (SSRI) antidepressants, which augment 5-HT. However, LDAEPs also predict outcome to antidepressants indirectly altering 5-HT (e.g. bupropion). Hence, the LDAEP’s predicative specificity and sensitivity to antidepressant response/outcome remains elusive. Scalp N1, P2 and N1/P2 LDAEP slopes and standardized low resolution brain electromagnetic tomography (sLORETA)-localized N1 and P2 LDAEP slopes were assessed in depressed individuals (N=51) at baseline, 1 and 12 weeks post-treatment with one of three antidepressant regimens [escitalopram (ESC) + bupropion (BUP), ESC or BUP]. Clinical response was greatest with ESC+BUP at week 1. Treatment responders had steep N1 sLORETA-LDAEP baseline slopes while non-responders had shallow ones. P2 sLORETA-LDAEP slope increases at 1 week existed in responders; decreases were noted in non-responders. Exploratory analyses indicated that more BUP and ESC responders versus non-responders had steep baseline N1 sLORETA-LDAEP slopes. Additionally, slight decreases in scalp P2 LDAEP by week 1 existed for ESC treatment, while slope increases existed with ESC+BUP treatment. Only baseline N1 sLORETA-LDAEP discriminated treatment responders/non-responders. This work confirms that certain LDAEP measures are associated with treatment outcome and appear to be differentially modulated with varying antidepressant drug regimens, though this should be confirmed using larger samples. PMID:23360662

Influence of Media on Seasonal Influenza Epidemic Curves.

PubMed

Saito, Satoshi; Saito, Norihiro; Itoga, Masamichi; Ozaki, Hiromi; Kimura, Toshiyuki; Okamura, Yuji; Murakami, Hiroshi; Kayaba, Hiroyuki

2016-09-01

Theoretical investigations predicting the epidemic curves of seasonal influenza have been demonstrated so far; however, there is little empirical research using ever accumulated epidemic curves. The effects of vaccine coverage and information distribution on influenza epidemics were evaluated. Four indices for epidemics (i.e., onset-peak duration, onset-end duration, ratio of the onset-peak duration to onset-end duration and steepness of epidemic curves) were defined, and the correlations between these indices and anti-flu drug prescription dose, vaccine coverage, the volume of media and search trend on influenza through internet were analyzed. Epidemiological data on seasonal influenza epidemics from 2002/2003 to 2013/2014 excluding 2009/2010 season were collected from National Institute of Infectious Diseases of Japan. The onset-peak duration and its ratio to onset-end duration correlated inversely with the volume of anti-flu drug prescription. Onset-peak duration correlated positively with media information volume on influenza. The steepness of the epidemic curve, and anti-flu drug prescription dose inversely correlated with the volume of media information. Pre-epidemic search trend and media volume on influenza correlated with the vaccine coverage in the season. Vaccine coverage had no strong effect on epidemic curve. Education through media has an effect on the epidemic curve of seasonal influenza. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

A new respirometric endpoint-based biosensor to assess the relative toxicity of chemicals on immobilized human cells.

PubMed

Dragone, Roberto; Frazzoli, Chiara; Grappelli, Claudio; Campanella, Luigi

2009-01-01

Several functional and biochemical parameters have been proposed as biomarkers of effect of environmental pollutants. A rapid biosensor working with immobilized human U-937 cells was developed and applied to environmentally relevant chemicals with different structures and toxicological pathways, i.e. benzalkonium chloride, clofibric acid, diclofenac, mercury nitrate, ofloxacin, and sodium dodecyl sulphate. Respiration of cells was relied upon as a comprehensive biochemical effect for screening purposes. Analytical parameter (DeltappmO(2)) and toxicological index (respiratory inhibition, delta%) measured after 1h of exposure were utilized for dose-response relationship study. Results (toxicity rating scales based on delta(50)% and steepness) were compared with those obtained by the same approach previously optimized on Saccharomyces cerevisiae. The toxicity rating scale obtained by the biomarker based on human mitochondrial and cell metabolic activities compared well with previous scale obtained on yeast cells and with available in-vivo acute toxicity indexes; respiration was confirmed as toxicological endpoint reliably measurable by the biosensor.

A nonhuman primate model of the hematopoietic acute radiation syndrome plus medical management.

PubMed

Farese, Ann M; Cohen, Melanie V; Katz, Barry P; Smith, Cassandra P; Jackson, William; Cohen, Daniel M; MacVittie, Thomas J

2012-10-01

The development of medical countermeasures against the hematopoietic subsyndrome of the acute radiation syndrome requires well characterized and validated animal models. The model must define the radiation dose- and time-dependent relationships for mortality and major signs of morbidity to include other organ damage that may contribute to morbidity and mortality. Herein, the authors define these parameters for a nonhuman primate exposed to total body radiation and administered medical management. A blinded, randomized study (n = 48 rhesus macaques) determined the lethal dose-response relationship using bilateral 6 MV linear accelerator photon radiation to doses in the range of 7.20 to 8.90 Gy at 0.80 Gy min(-1). Following irradiation, animals were monitored for complete bloodcounts, body weight, temperature, diarrhea, and hydration status for 60 d. Animals were administered medical management consisting of intravenous fluids, prophylactic antibiotics, blood transfusions, anti-diarrheals, analgesics, and nutrition. The primary endpoint was survival at 60 d post-irradiation; secondary endpoints included hematopoietic-related parameters, number of transfusions, incidence of documented infection, febrile neutropenia, severity of diarrhea, mean survival time of decedents, and tissue histology. The study defined an LD30/60 of 7.06 Gy, LD50/60 of 7.52 Gy, and an LD70/60 of 7.99 Gy with a relatively steep slope of 1.13 probits per linear dose. This study establishes a rhesus macaque model of the hematopoietic acute radiation syndrome and shows the marked effect of medical management on increased survival and overall mean survival time for decedents. Furthermore, following a nuclear terrorist event, medical management may be the only treatment administered at its optimal schedule.

Improved safety margin for embryotoxicity in rats for the new endoperoxide artefenomel (OZ439) as compared to artesunate.

PubMed

Clark, Robert L; Edwards, Tammye L; Longo, Monica; Kinney, Joseph; Walker, Don K; Rhodes, Jon; Clode, Sally A; Rückle, Thomas; Wells, Timothy; Andenmatten, Nicole; Huber, Anna Christine

2018-04-17

Combination medicines including an artemisinin are the mainstay of antimalarial therapy. Artemisinins are potent embryotoxicants in animal species due to their trioxane moiety. As part of its development, the new synthetic trioxolane antimalarial artefenomel (OZ439) was tested in rat whole embryo culture and in rat embryo-fetal toxicity studies with dosing throughout organogenesis or with a single dose on Gestational Day (GD) 12. The single-dose studies included groups treated with artesunate to allow a direct comparison of the embryotoxicity of the two antimalarials and included toxicokinetics hematology and histological examination of embryos. In addition, the distribution of artefenomel-related material in plasma was determined after the administration of 14 C-artefenomel. Artefenomel and artesunate showed similar patterns of embryotoxicity including cardiovascular defects and resorption with a steep dose-response. They both also caused a depletion of circulating embryonic erythroblasts both in vitro and in vivo and decreases in maternal reticulocyte count. However, artefenomel was ∼250-fold less potent than the active metabolite of artesunate (dihydroartemisinin) as an embryotoxicant in vitro. The safety margin (based on AUC) for artefenomel administered on GD 12 was approximately 100-fold greater than that for artesunate. Also, unlike artesunate, artefenomel was not a selective developmental toxicant. The lesser embryotoxicity of artefenomel is likely linked to its original design which included two blocking side groups that had been introduced to lower the reactivity with ferrous iron. Our data support the hypothesis that artefenomel's improved safety margin is linked to a lower potential for inhibiting heme biosynthesis in embryonic erythroblasts. © 2017 The Authors. Birth Defects Research Published by Wiley Periodicals, Inc.

In Vivo Bioluminescent Monitoring of Therapeutic Efficacy and Pharmacodynamic Target Assessment of Antofloxacin against Escherichia coli in a Neutropenic Murine Thigh Infection Model.

PubMed

Zhou, Yu-Feng; Tao, Meng-Ting; He, Yu-Zhang; Sun, Jian; Liu, Ya-Hong; Liao, Xiao-Ping

2018-01-01

Antimicrobial resistance among uropathogens has increased the rates of infection-related morbidity and mortality. Antofloxacin is a novel fluoroquinolone with broad-spectrum antibacterial activity against urinary Gram-negative bacilli, such as Escherichia coli This study monitored the in vivo efficacy of antofloxacin using bioluminescent imaging and determined pharmacokinetic (PK)/pharmacodynamic (PD) targets against E. coli isolates in a neutropenic murine thigh infection model. The PK properties were determined after subcutaneous administration of antofloxacin at 2.5, 10, 40, and 160 mg/kg of body weight. Following thigh infection, the mice were treated with 2-fold-increasing doses of antofloxacin from 2.5 to 80 mg/kg administered every 12 h. Efficacy was assessed by quantitative determination of the bacterial burdens in thigh homogenates and was compared with the bioluminescent density. Antofloxacin demonstrated both static and killing endpoints in relation to the initial burden against all study strains. The PK/PD index area under the concentration-time curve (AUC)/MIC correlated well with efficacy ( R 2 = 0.92), and the dose-response relationship was relatively steep, as observed with escalating doses of antofloxacin. The mean free drug AUC/MIC targets necessary to produce net bacterial stasis and 1-log 10 and 2-log 10 kill for each isolate were 38.7, 66.1, and 147.0 h, respectively. In vivo bioluminescent imaging showed a rapid decrease in the bioluminescent density at free drug AUC/MIC exposures that exceeded the stasis targets. The integration of these PD targets combined with the results of PK studies with humans will be useful in setting optimal dosing regimens for the treatment of urinary tract infections due to E. coli . Copyright © 2017 American Society for Microbiology.

Independent dose verification system with Monte Carlo simulations using TOPAS for passive scattering proton therapy at the National Cancer Center in Korea

NASA Astrophysics Data System (ADS)

Shin, Wook-Geun; Testa, Mauro; Kim, Hak Soo; Jeong, Jong Hwi; Byeong Lee, Se; Kim, Yeon-Joo; Min, Chul Hee

2017-10-01

For the independent validation of treatment plans, we developed a fully automated Monte Carlo (MC)-based patient dose calculation system with the tool for particle simulation (TOPAS) and proton therapy machine installed at the National Cancer Center in Korea to enable routine and automatic dose recalculation for each patient. The proton beam nozzle was modeled with TOPAS to simulate the therapeutic beam, and MC commissioning was performed by comparing percent depth dose with the measurement. The beam set-up based on the prescribed beam range and modulation width was automated by modifying the vendor-specific method. The CT phantom was modeled based on the DICOM CT files with TOPAS-built-in function, and an in-house-developed C++ code directly imports the CT files for positioning the CT phantom, RT-plan file for simulating the treatment plan, and RT-structure file for applying the Hounsfield unit (HU) assignment, respectively. The developed system was validated by comparing the dose distributions with those calculated by the treatment planning system (TPS) for a lung phantom and two patient cases of abdomen and internal mammary node. The results of the beam commissioning were in good agreement of up to 0.8 mm2 g-1 for B8 option in both of the beam range and the modulation width of the spread-out Bragg peaks. The beam set-up technique can predict the range and modulation width with an accuracy of 0.06% and 0.51%, respectively, with respect to the prescribed range and modulation in arbitrary points of B5 option (128.3, 132.0, and 141.2 mm2 g-1 of range). The dose distributions showed higher than 99% passing rate for the 3D gamma index (3 mm distance to agreement and 3% dose difference) between the MC simulations and the clinical TPS in the target volume. However, in the normal tissues, less favorable agreements were obtained for the radiation treatment planning with the lung phantom and internal mammary node cases. The discrepancies might come from the limitations of the clinical TPS, which is the inaccurate dose calculation algorithm for the scattering effect, in the range compensator and inhomogeneous material. Moreover, the steep slope of the compensator, conversion of the HU values to the human phantom, and the dose calculation algorithm for the HU assignment also could be reasons of the discrepancies. The current study could be used for the independent dose validation of treatment plans including high inhomogeneities, the steep compensator, and riskiness such as lung, head & neck cases. According to the treatment policy, the dose discrepancies predicted with MC could be used for the acceptance decision of the original treatment plan.

Evaluation of various boluses in dose distribution for electron therapy of the chest wall with an inward defect

PubMed Central

Mahdavi, Hoda; Jabbari, Keyvan; Roayaei, Mahnaz

2016-01-01

Delivering radiotherapy to the postmastectomy chest wall can be achieved using matched electron fields. Surgical defects of the chest wall change the dose distribution of electrons. In this study, the improvement of dose homogeneity using simple, nonconformal techniques of thermoplastic bolus application on a defect is evaluated. The proposed phantom design improves the capability of film dosimetry for obtaining dose profiles of a patient's anatomical condition. A modeled electron field of a patient with a postmastectomy inward surgical defect was planned. High energy electrons were delivered to the phantom in various settings, including no bolus, a bolus that filled the inward defect (PB0), a uniform thickness bolus of 5 mm (PB1), and two 5 mm boluses (PB2). A reduction of mean doses at the base of the defect was observed by any bolus application. PB0 increased the dose at central parts of the defect, reduced hot areas at the base of steep edges, and reduced dose to the lung and heart. Thermoplastic boluses that compensate a defect (PB0) increased the homogeneity of dose in a fixed depth from the surface; adversely, PB2 increased the dose heterogeneity. This study shows that it is practical to investigate dose homogeneity profiles inside a target volume for various techniques of electron therapy. PMID:27051169

Spinal Cord Tolerance to Reirradiation With Single-Fraction Radiosurgery: A Swine Model

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

Medin, Paul M., E-mail: Paul.medin@utsouthwestern.edu; Foster, Ryan D.; Kogel, Albert J. van der

2012-07-01

Purpose: This study was performed to determine swine spinal cord tolerance to single-fraction, partial-volume irradiation 1 year after receiving uniform irradiation to 30 Gy in 10 fractions. Methods and Materials: A 10-cm length of spinal cord (C3-T1) was uniformly irradiated to 30 Gy in 10 consecutive fractions and reirradiated 1 year later with a single radiosurgery dose centered within the previously irradiated segment. Radiosurgery was delivered to a cylindrical volume approximately 5 cm in length and 2 cm in diameter, which was positioned laterally to the cervical spinal cord, resulting in a dose distribution with the 90%, 50%, and 10%more » isodose lines traversing the ipsilateral, central, and contralateral spinal cord, respectively. Twenty-three pigs were stratified into six dose groups with mean maximum spinal cord doses of 14.9 {+-} 0.1 Gy (n = 2), 17.1 {+-} 0.3 Gy (n = 3), 19.0 {+-} 0.1 Gy (n = 5), 21.2 {+-} 0.1 Gy (n = 5), 23.4 {+-} 0.2 Gy (n = 5), and 25.4 {+-} 0.4 Gy (n = 3). The mean percentage of spinal cord volumes receiving {>=}10 Gy for the same groups were 34% {+-} 1%, 40% {+-} 1%, 46% {+-} 3%, 52% {+-} 1%, 56 {+-} 3%, and 57% {+-} 1%. The study endpoint was motor neurologic deficit as determined by a change in gait during a 1- year follow-up period. Results: A steep dose-response curve was observed with a 50% incidence of paralysis (ED{sub 50}) for the maximum point dose of 19.7 Gy (95% confidence interval, 17.4-21.4). With two exceptions, histology was unremarkable in animals with normal neurologic status, while all animals with motor deficits showed some degree of demyelination and focal white matter necrosis on the irradiated side, with relative sparing of gray matter. Histologic comparison with a companion study of de novo irradiated animals revealed that retreatment responders had more extensive tissue damage, including infarction of gray matter, only at prescription doses >20 Gy. Conclusion: Pigs receiving spinal radiosurgery 1 year after receiving 30 Gy in 10 fractions were not at significantly higher risk of developing motor deficits than pigs that received radiosurgery alone.« less

Impact of geometric uncertainties on dose calculations for intensity modulated radiation therapy of prostate cancer

NASA Astrophysics Data System (ADS)

Jiang, Runqing

Intensity-modulated radiation therapy (IMRT) uses non-uniform beam intensities within a radiation field to provide patient-specific dose shaping, resulting in a dose distribution that conforms tightly to the planning target volume (PTV). Unavoidable geometric uncertainty arising from patient repositioning and internal organ motion can lead to lower conformality index (CI) during treatment delivery, a decrease in tumor control probability (TCP) and an increase in normal tissue complication probability (NTCP). The CI of the IMRT plan depends heavily on steep dose gradients between the PTV and organ at risk (OAR). Geometric uncertainties reduce the planned dose gradients and result in a less steep or "blurred" dose gradient. The blurred dose gradients can be maximized by constraining the dose objective function in the static IMRT plan or by reducing geometric uncertainty during treatment with corrective verification imaging. Internal organ motion and setup error were evaluated simultaneously for 118 individual patients with implanted fiducials and MV electronic portal imaging (EPI). A Gaussian probability density function (PDF) is reasonable for modeling geometric uncertainties as indicated by the 118 patients group. The Gaussian PDF is patient specific and group standard deviation (SD) should not be used for accurate treatment planning for individual patients. In addition, individual SD should not be determined or predicted from small imaging samples because of random nature of the fluctuations. Frequent verification imaging should be employed in situations where geometric uncertainties are expected. Cumulative PDF data can be used for re-planning to assess accuracy of delivered dose. Group data is useful for determining worst case discrepancy between planned and delivered dose. The margins for the PTV should ideally represent true geometric uncertainties. The measured geometric uncertainties were used in this thesis to assess PTV coverage, dose to OAR, equivalent uniform dose per fraction (EUDf) and NTCP. The dose distribution including geometric uncertainties was determined from integration of the convolution of the static dose gradient with the PDF. Integration of the convolution of the static dose and derivative of the PDF can also be used to determine the dose including geometric uncertainties although this method was not investigated in detail. Local maximum dose gradient (LMDG) was determined via optimization of dose objective function by manually adjusting DVH control points or selecting beam numbers and directions during IMRT treatment planning. Minimum SD (SDmin) is used when geometric uncertainty is corrected with verification imaging. Maximum SD (SDmax) is used when the geometric uncertainty is known to be large and difficult to manage. SDmax was 4.38 mm in anterior-posterior (AP) direction, 2.70 mm in left-right (LR) direction and 4.35 mm in superior-inferior (SI) direction; SDmin was 1.1 mm in all three directions if less than 2 mm threshold was used for uncorrected fractions in every direction. EUDf is a useful QA parameter for interpreting the biological impact of geometric uncertainties on the static dose distribution. The EUD f has been used as the basis for the time-course NTCP evaluation in the thesis. Relative NTCP values are useful for comparative QA checking by normalizing known complications (e.g. reported in the RTOG studies) to specific DVH control points. For prostate cancer patients, rectal complications were evaluated from specific RTOG clinical trials and detailed evaluation of the treatment techniques (e.g. dose prescription, DVH, number of beams, bean angles). Treatment plans that did not meet DVH constraints represented additional complication risk. Geometric uncertainties improved or worsened rectal NTCP depending on individual internal organ motion within patient.

False homozygous HLA genotyping results due to copy number neutral loss of heterozygosity in acquired aplastic anaemia.

PubMed

Heyrman, Bert; De Becker, Ann; Verheyden, Sonja; Demanet, Christian

2017-03-02

The aim of this case report is to draw attention on possible false human leucocyte antigen (HLA) genotyping in acquired aplastic anaemia prior to allogeneic haematopoietic stem cell transplantation. In acquired aplastic anaemia loss of heterozygosity (LOH) of chromosome 6p is known to occur in around 12%. We report false HLA genotyping results due to LOH and a coinciding steep rise in neutrophils following filgrastim stimulation in a patient with very severe aplastic anaemia. At diagnosis we obtained heterozygous results on peripheral blood. Failing to reach a partial response at 6 months with immune-suppressive therapy we repeated HLA genotyping, obtaining homozygous results. Repeated testing confirmed loss of HLA genotype heterozygosity. HLA genotyping on cells obtained by a buccal swab confirmed the previous HLA heterozygosity. A second course of filgrastim at the time of homozygous HLA genotyping resulted in a steep rise in neutrophils. Stopping filgrastim resulted in an equally steep drop. 2017 BMJ Publishing Group Ltd.

Vegetation response after post-fire mulching and native grass seeding

Treesearch

Penelope Morgan; Marshell Moy; Christine A. Droske; Leigh B. Lentile; Sarah A. Lewis; Peter R. Robichaud; Andrew T. Hudak

2014-01-01

Post-fire mulch and seeding treatments, often applied on steep, severely burned slopes immediately after large wildfires, are meant to reduce the potential of erosion and establishment of invasive plants, especially non-native plants, that could threaten values at risk. However, the effects of these treatments on native vegetation response post fire are little studied...

WE-D-BRE-01: A Sr-90 Irradiation Device for the Study of Cutaneous Radiation Injury

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

Dorand, JE; Bourland, JD; Burnett, LR

2014-06-15

Purpose: To determine dosimetric character for a custom-built Sr-90 beta irradiator designed for the study of Cutaneous Radiation Injury (CRI) in a porcine animal model. In the event of a radiological accident or terrorist event, Sr-90, a fission by-product, will likely be produced. CRI is a main concern due to the low energy and superficial penetration in tissue of beta particles from Sr-90. Seven 100 mCi plaque Sr-90 radiation sources within a custom-built irradiation device create a 40 mm diameter region of radiation-induced skin injury as part of a larger project to study the efficacy of a topical keratin-based productmore » in CRI healing. Methods: A custom-built mobile irradiation device was designed and implemented for in vivo irradiations. Gafchromic™ EBT3 radiochromic film and a PTW Markus chamber type 23343 were utilized for dosimetric characterization of the beta fluence at the surface produced by this device. Films were used to assess 2-dimensional dose distribution and percent depth dose characteristics of the radiation field. Ion chamber measurements provided dose rate data within the field. Results: The radiation field produced by the irradiation device is homogeneous with high uniformity (∼5%) and symmetry (∼3%) with a steep dose fall-off with depth from the surface. Dose rates were determined to be 3.8 Gy/min and 3.3 Gy/min for film and ion chamber measurements, respectively. A dose rate of 3.4 Gy/min was used to calculate irradiation times for in vivo irradiations. Conclusion: The custom-built irradiation device enables the use of seven Sr-90 beta sources in an array to deliver a 40 mm diameter area of homogeneous skin dose with a dose rate that is useful for research purposes and clinically relevant for the induction of CRI. Doses of 36 and 42 Gy successfully produce Grade III CRI and are used in the study of the efficacy of KeraStat™. This project has been funded in whole or in part with Federal funds from the Biomedical Advanced Research and Development Authority, Office of the Assistant Secretary for Preparedness and Response, Office of the Secretary, Department of Health and Human Services, under Contract No. HHSO100201200007C.« less

Neutrophil migration under spatially-varying chemoattractant gradient profiles.

PubMed

Halilovic, Iris; Wu, Jiandong; Alexander, Murray; Lin, Francis

2015-01-01

Chemotaxis plays an important role in biological processes such as cancer metastasis, embryogenesis, wound healing, and immune response. Neutrophils are the frontline defenders against invasion of foreign microorganisms into our bodies. To achieve this important immune function, a neutrophil can sense minute chemoattractant concentration differences across its cell body and effectively migrate toward the chemoattractant source. Furthermore, it has been demonstrated in various studies that neutrophils are highly sensitive to changes in the surrounding chemoattractant environments, suggesting the role of a chemotactic memory for processing the complex spatiotemporal chemical guiding signals. Using a microfluidic device, in the present study we characterized neutrophil migration under spatially varying profiles of interleukine-8 gradients, which consist of three spatially ordered regions of a shallow gradient, a steep gradient and a nearly saturated gradient. This design allowed us to examine how neutrophils migrate under different chemoattractant gradient profiles, and how the migratory response is affected when the cell moves from one gradient profile to another in a single experiment. Our results show robust neutrophil chemotaxis in the shallow and steep gradient, but not the saturated gradient. Furthermore, neutrophils display a transition from chemotaxis to flowtaxis when they migrate across the steep gradient interface, and the relative efficiency of this transition depends on the cell's chemotaxis history. Finally, some neutrophils were observed to adjust their morphology to different gradient profiles.

The photon fluence non-uniformity correction for air kerma near Cs-137 brachytherapy sources.

PubMed

Rodríguez, M L; deAlmeida, C E

2004-05-07

The use of brachytherapy sources in radiation oncology requires their proper calibration to guarantee the correctness of the dose delivered to the treatment volume of a patient. One of the elements to take into account in the dose calculation formalism is the non-uniformity of the photon fluence due to the beam divergence that causes a steep dose gradient near the source. The correction factors for this phenomenon have been usually evaluated by the two theories available, both of which were conceived only for point sources. This work presents the Monte Carlo assessment of the non-uniformity correction factors for a Cs-137 linear source and a Farmer-type ionization chamber. The results have clearly demonstrated that for linear sources there are some important differences among the values obtained from different calculation models, especially at short distances from the source. The use of experimental values for each specific source geometry is recommended in order to assess the non-uniformity factors for linear sources in clinical situations that require special dose calculations or when the correctness of treatment planning software is verified during the acceptance tests.

Topical Review: Polymer gel dosimetry

PubMed Central

Baldock, C; De Deene, Y; Doran, S; Ibbott, G; Jirasek, A; Lepage, M; McAuley, K B; Oldham, M; Schreiner, L J

2010-01-01

Polymer gel dosimeters are fabricated from radiation sensitive chemicals which, upon irradiation, polymerize as a function of the absorbed radiation dose. These gel dosimeters, with the capacity to uniquely record the radiation dose distribution in three-dimensions (3D), have specific advantages when compared to one-dimensional dosimeters, such as ion chambers, and two-dimensional dosimeters, such as film. These advantages are particularly significant in dosimetry situations where steep dose gradients exist such as in intensity-modulated radiation therapy (IMRT) and stereotactic radiosurgery. Polymer gel dosimeters also have specific advantages for brachytherapy dosimetry. Potential dosimetry applications include those for low-energy x-rays, high-linear energy transfer (LET) and proton therapy, radionuclide and boron capture neutron therapy dosimetries. These 3D dosimeters are radiologically soft-tissue equivalent with properties that may be modified depending on the application. The 3D radiation dose distribution in polymer gel dosimeters may be imaged using magnetic resonance imaging (MRI), optical-computerized tomography (optical-CT), x-ray CT or ultrasound. The fundamental science underpinning polymer gel dosimetry is reviewed along with the various evaluation techniques. Clinical dosimetry applications of polymer gel dosimetry are also presented. PMID:20150687

In vivo verification of particle therapy: how Compton camera configurations affect 3D image quality

NASA Astrophysics Data System (ADS)

Mackin, D.; Draeger, E.; Peterson, S.; Polf, J.; Beddar, S.

2017-05-01

The steep dose gradients enabled by the Bragg peaks of particle therapy beams are a double edged sword. They enable highly conformal dose distributions, but even small deviations from the planned beam range can cause overdosing of healthy tissue or under-dosing of the tumour. To reduce this risk, particle therapy treatment plans include margins large enough to account for all the sources of range uncertainty, which include patient setup errors, patient anatomy changes, and CT number to stopping power ratios. Any system that could verify the beam range in vivo, would allow reduced margins and more conformal dose distributions. Toward our goal developing such a system based on Compton camera (CC) imaging, we studied how three configurations (single camera, parallel opposed, and orthogonal) affect the quality of the 3D images. We found that single CC and parallel opposed configurations produced superior images in 2D. The increase in parallax produced by an orthogonal CC configuration was shown to be beneficial in producing artefact free 3D images.

A novel method for the evaluation of uncertainty in dose-volume histogram computation.

PubMed

Henríquez, Francisco Cutanda; Castrillón, Silvia Vargas

2008-03-15

Dose-volume histograms (DVHs) are a useful tool in state-of-the-art radiotherapy treatment planning, and it is essential to recognize their limitations. Even after a specific dose-calculation model is optimized, dose distributions computed by using treatment-planning systems are affected by several sources of uncertainty, such as algorithm limitations, measurement uncertainty in the data used to model the beam, and residual differences between measured and computed dose. This report presents a novel method to take them into account. To take into account the effect of associated uncertainties, a probabilistic approach using a new kind of histogram, a dose-expected volume histogram, is introduced. The expected value of the volume in the region of interest receiving an absorbed dose equal to or greater than a certain value is found by using the probability distribution of the dose at each point. A rectangular probability distribution is assumed for this point dose, and a formulation that accounts for uncertainties associated with point dose is presented for practical computations. This method is applied to a set of DVHs for different regions of interest, including 6 brain patients, 8 lung patients, 8 pelvis patients, and 6 prostate patients planned for intensity-modulated radiation therapy. Results show a greater effect on planning target volume coverage than in organs at risk. In cases of steep DVH gradients, such as planning target volumes, this new method shows the largest differences with the corresponding DVH; thus, the effect of the uncertainty is larger.

Using biological markets principles to examine patterns of grooming exchange in Macaca thibetana.

PubMed

Balasubramaniam, K N; Berman, C M; Ogawa, H; Li, J

2011-12-01

Biological markets principles offer testable hypotheses to explain variation in grooming exchange patterns among nonhuman primates. They predict that when within-group contest competition (WGC) is high and dominance hierarchies steep, grooming interchange with other "commodity" behaviors (such as agonistic support) should prevail. In contrast, when WGC is low and gradients shallow, market theory predicts that grooming reciprocity should prevail. We tested these predictions in a wild, provisioned Tibetan macaque (Macaca thibetana) group across six time periods during which the group had been subjected to varying degrees of range restriction. Data on female-female aggression, grooming, and support were collected using all-occurrences and focal animal sampling techniques, and analyzed using ANCOVA methods and correlation analyses. We found that hierarchical steepness varied significantly across periods, but did not correlate with two indirect indicators of WGC (group size and range restriction) in predicted directions. Contrary to expectations, we found a negative correlation between steepness and group size, perhaps because the responses of group members to external risks (i.e. prolonged and unavoidable exposure to humans) may have overshadowed the effects of WGC. As predicted, grooming reciprocity was significant in each period and negatively correlated with steepness, even after we controlled group size, kinship, rank differences, and proximity. In contrast, there was no evidence for grooming interchange with agonistic support or for a positive relationship between interchange and steepness. We hypothesize that stressful conditions and/or the presence of stable hierarchies during each period may have led to a greater market demand for grooming than support. We suggest that future studies testing these predictions consider more direct measures of WGC and commodities in addition to support, such as feeding tolerance and access to infants. © 2011 Wiley Periodicals, Inc.

Cell Blebbing in Confined Microfluidic Environments

PubMed Central

Ibo, Markela; Srivastava, Vasudha; Robinson, Douglas N.; Gagnon, Zachary R.

2016-01-01

Migrating cells can extend their leading edge by forming myosin-driven blebs and F-actin-driven pseudopods. When coerced to migrate in resistive environments, Dictyostelium cells switch from using predominately pseudopods to blebs. Bleb formation has been shown to be chemotactic and can be influenced by the direction of the chemotactic gradient. In this study, we determine the blebbing responses of developed cells of Dictyostelium discoideum to cAMP gradients of varying steepness produced in microfluidic channels with different confining heights, ranging between 1.7 μm and 3.8 μm. We show that microfluidic confinement height, gradient steepness, buffer osmolarity and Myosin II activity are important factors in determining whether cells migrate with blebs or with pseudopods. Dictyostelium cells were observed migrating within the confines of microfluidic gradient channels. When the cAMP gradient steepness is increased from 0.7 nM/μm to 20 nM/μm, cells switch from moving with a mixture of blebs and pseudopods to moving only using blebs when chemotaxing in channels with confinement heights less than 2.4 μm. Furthermore, the size of the blebs increases with gradient steepness and correlates with increases in myosin-II localization at the cell cortex. Reduction of intracellular pressure by high osmolarity buffer or inhibition of myosin-II by blebbistatin leads to a decrease in bleb formation and bleb size. Together, our data reveal that the protrusion type formed by migrating cells can be influenced by the channel height and the steepness of the cAMP gradient, and suggests that a combination of confinement-induced myosin-II localization and cAMP-regulated cortical contraction leads to increased intracellular fluid pressure and bleb formation. PMID:27706201

Influence of landscape position and transient water table on soil development and carbon distribution in a steep, headwater catchment

Treesearch

Scott W. Bailey; Patricia A. Brousseau; Kevin J. McGuire; Donald S. Ross

2014-01-01

Upland headwater catchments, such as those in the AppalachianMountain region, are typified by coarse textured soils, flashy hydrologic response, and low baseflow of streams, suggesting well drained soils and minimal groundwater storage. Model formulations of soil genesis, nutrient cycling, critical loads and rainfall/runoff response are typically based on vertical...

Entanglement between thermoregulation and nociception in the rat: the case of morphine

PubMed Central

El Bitar, Nabil; Pollin, Bernard; Karroum, Elias; Pincedé, Ivanne

2016-01-01

In thermoneutral conditions, rats display cyclic variations of the vasomotion of the tail and paws, the most widely used target organs in current acute or chronic animal models of pain. Systemic morphine elicits their vasoconstriction followed by hyperthermia in a naloxone-reversible and dose-dependent fashion. The dose-response curves were steep with ED50 in the 0.5–1 mg/kg range. Given the pivotal functional role of the rostral ventromedial medulla (RVM) in nociception and the rostral medullary raphe (rMR) in thermoregulation, two largely overlapping brain regions, the RVM/rMR was blocked by muscimol: it suppressed the effects of morphine. “On-” and “off-” neurons recorded in the RVM/rMR are activated and inhibited by thermal nociceptive stimuli, respectively. They are also implicated in regulating the cyclic variations of the vasomotion of the tail and paws seen in thermoneutral conditions. Morphine elicited abrupt inhibition and activation of the firing of on- and off-cells recorded in the RVM/rMR. By using a model that takes into account the power of the radiant heat source, initial skin temperature, core body temperature, and peripheral nerve conduction distance, one can argue that the morphine-induced increase of reaction time is mainly related to the morphine-induced vasoconstriction. This statement was confirmed by analyzing in psychophysical terms the tail-flick response to random variations of noxious radiant heat. Although the increase of a reaction time to radiant heat is generally interpreted in terms of analgesia, the present data question the validity of using such an approach to build a pain index. PMID:27605533

European and Mexican vs US diagnostic extracts of Bermuda grass and cat in skin testing.

PubMed

Larenas-Linnemann, Désirée; Cruz, Alfredo Arias; Gutierrez, Isabel Rojo; Rodriguez, Pablo; Shah-Hosseini, Kijawasch; Michels, Alexandra; Mösges, Ralph

2011-05-01

Laboratory testing of various diagnostic extracts has shown lower potencies for several European and Mexican extracts relative to the US Food and Drug Administration (FDA) reference (10,000 BAU/mL). Quantitative skin prick testing (QSPT) with Dermatophagoides pteronyssinus extracts have previously shown a similar picture. To compare European and Mexican Bermuda grass (BG) and cat diagnostic extracts against an FDA-validated extract using QSPT. Six diagnostic BG and cat extracts (1 reference FDA extract, 3 European extracts, 1 imported nonstandardized extract from the United States, and 1 Mexican extract) were tested with quadruplicate QSPT, as a concentrate and as 2 serial 2-fold dilutions, in cat and BG allergic individuals. BG showed good dose response in wheal size for the concentrate (1:2-1:4 dilutions; steep part of the curve). Cat showed poorer dose response. The Wilcoxon test for linked random samples was used to investigate whether the distribution of the reference differed from each of the test extracts to a statistically significant degree (2-sided asymptotic significance, α = .05). All BG and 2 cat extracts were statistically less potent than the 10,000 BAU/mL US reference. European BG extracts were 7,700, 4,100, and 1,600 BAU/mL, and cat extracts were 12,500, 4,400, and 5,100 BAU/mL. The potency of some diagnostic extracts of BG and cat used in Europe, Mexico, and the United States differs, with the US extracts being generally more potent. On the basis of provocation tests, optimal diagnostic concentrations should be determined. Similar comparisons using other manufacturers and therapeutic extracts might be interesting. Copyright © 2011 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Future possibilities in the prevention of breast cancer: Luteinizing hormone-releasing hormone agonists

PubMed Central

Spicer, Darcy V; Pike, Malcolm C

2000-01-01

The cyclic production of estrogen and progesterone by the premenopausal ovary accounts for the steep rise in breast cancer risk in premenopausal women. These hormones are breast cell mitogens. By reducing exposure to these ovarian hormones, agonists of luteinizing hormone-releasing hormone (LHRH) given to suppress ovarian function may prove useful in cancer prevention. To prevent deleterious effects of hypoestrogenemia, the addition of low-dose hormone replacement to the LHRH agonist appears necessary. Pilot data with such an approach indicates it is feasible and reduces mammographic densities. PMID:11250719

Poster - 36: Effect of Planning Target Volume Coverage on the Dose Delivered in Lung Radiotherapy

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

Dekker, Chris; Wierzbicki, Marcin

2016-08-15

Purpose: In lung radiotherapy, breathing motion may be encompassed by contouring the internal target volume (ITV). Remaining uncertainties are included in a geometrical expansion to the planning target volume (PTV). In IMRT, the treatment is then optimized until a desired PTV fraction is covered by the appropriate dose. The resulting beams often carry high fluence in the PTV margin to overcome low lung density and to generate steep dose gradients. During treatment, the high density tumour can enter the PTV margin, potentially increasing target dose. Thus, planning lung IMRT with a reduced PTV dose may still achieve the desired ITVmore » dose during treatment. Methods: A retrospective analysis was carried out with 25 IMRT plans prescribed to 63 Gy in 30 fractions. The plans were re-normalized to cover various fractions of the PTV by different isodose lines. For each case, the isocentre was moved using 125 shifts derived from all 3D combinations of 0 mm, (PTV margin - 1 mm), and PTV margin. After each shift, the dose was recomputed to approximate the delivered dose. Results and Conclusion: Our plans typically cover 95% of the PTV by 95% of the dose. Reducing the PTV covered to 94% did not significantly reduce the delivered ITV doses for (PTV margin - 1 mm) shifts. Target doses were reduced significantly for all other shifts and planning goals studied. Thus, a reduced planning goal will likely deliver the desired target dose as long as the ITV rarely enters the last mm of the PTV margin.« less

Continuous and Delayed Photohemolysis Sensitized With Methylene Blue and Iron Oxide Nanoparticles (Fe3O4)

NASA Astrophysics Data System (ADS)

AL-Akhras, M.-Ali; Aljarrah, Khaled; Albiss, Borhan; Alhaji Bala, Abba

2015-10-01

This research present the sensitization of methylene blue (MB), as a potential photodynamic therapy photo sensitizer which showed phototoxicity for many tumor cells in vitro incorporated with iron oxide nanoparticles (Fe3O4, IO-NP), which offer magnificent interaction both inside and outside the surface of biomolecules together with red blood cells (RBC's) with significant change in hemolysis process. The study investigated the sensitization of continuous photohemolysis (CPH) for MB and MB with IO-NP, delayed photohemolysis (DPH) at different irradiation temperature (Tirr). The photohemolysis rate for CPH at room temperature has a power dependence of 0.39 ± 0.05 with relative of steepness of 1.25 ± 0.02 and for different concentration of MB and power dependent of 0.15 ± 0.03 with relative steepness of 1.34 ± 0.01 for different MB and IO-NP. Logistic and Gompertz functions were applied as appropriate mathematical models to fit the collected experimental data for CPH and DPH respectively, and to calculate fractional photohemolysis rate with minimum errors. The Logistic function parameter; α, the hemolysis rate, increases with increasing concentrations of MB and decreases with increasing IO-NP concentrations in the presence of 6 μg/ml of MB. The parameter β the time required to reduce the maximum number of RBCs to one half of its value, decreases with increasing MB concentration and increases with increasing IO-NP concentrations in the presence of 6 pg/ml of MB. In DPH at different Tirr, the Gompertz parameter; a, fractional hemolysis ratio, is independent of temperature in both case MB and MB plus IO-NP, while the parameter; b, rate of fractional hemolysis change, increases with increasing Tirr, in both case MB and MB plus IO-NP. The apparent activation energy of colloid-osmotic hemolysis is 9.47±0.01 Kcal/mol with relative steepness of 1.31 ± 0.05 for different MB and 6.06±0.03 Kcal/mol with relative steepness of 1.41 ± 0.09 for MB with iron oxide. Our results suggest that Logistic equation is the best fit for the CPH and Gompertz function for the DPH. Both models predict also that the relative steepness is independent of the light dose, sensitizer and IO-NP concentrations.

Dosimetric audit in brachytherapy

PubMed Central

Bradley, D A; Nisbet, A

2014-01-01

Dosimetric audit is required for the improvement of patient safety in radiotherapy and to aid optimization of treatment. The reassurance that treatment is being delivered in line with accepted standards, that delivered doses are as prescribed and that quality improvement is enabled is as essential for brachytherapy as it is for the more commonly audited external beam radiotherapy. Dose measurement in brachytherapy is challenging owing to steep dose gradients and small scales, especially in the context of an audit. Several different approaches have been taken for audit measurement to date: thimble and well-type ionization chambers, thermoluminescent detectors, optically stimulated luminescence detectors, radiochromic film and alanine. In this work, we review all of the dosimetric brachytherapy audits that have been conducted in recent years, look at current audits in progress and propose required directions for brachytherapy dosimetric audit in the future. The concern over accurate source strength measurement may be essentially resolved with modern equipment and calibration methods, but brachytherapy is a rapidly developing field and dosimetric audit must keep pace. PMID:24807068

In vivo proton range verification: a review

NASA Astrophysics Data System (ADS)

Knopf, Antje-Christin; Lomax, Antony

2013-08-01

Protons are an interesting modality for radiotherapy because of their well defined range and favourable depth dose characteristics. On the other hand, these same characteristics lead to added uncertainties in their delivery. This is particularly the case at the distal end of proton dose distributions, where the dose gradient can be extremely steep. In practice however, this gradient is rarely used to spare critical normal tissues due to such worries about its exact position in the patient. Reasons for this uncertainty are inaccuracies and non-uniqueness of the calibration from CT Hounsfield units to proton stopping powers, imaging artefacts (e.g. due to metal implants) and anatomical changes of the patient during treatment. In order to improve the precision of proton therapy therefore, it would be extremely desirable to verify proton range in vivo, either prior to, during, or after therapy. In this review, we describe and compare state-of-the art in vivo proton range verification methods currently being proposed, developed or clinically implemented.

Verification of the grid size and angular increment effects in lung stereotactic body radiation therapy using the dynamic conformal arc technique

NASA Astrophysics Data System (ADS)

Park, Hae-Jin; Suh, Tae-Suk; Park, Ji-Yeon; Lee, Jeong-Woo; Kim, Mi-Hwa; Oh, Young-Taek; Chun, Mison; Noh, O. Kyu; Suh, Susie

2013-06-01

The dosimetric effects of variable grid size and angular increment were systematically evaluated in the measured dose distributions of dynamic conformal arc therapy (DCAT) for lung stereotactic body radiation therapy (SBRT). Dose variations with different grid sizes (2, 3, and 4 mm) and angular increments (2, 4, 6, and 10°) for spherical planning target volumes (PTVs) were verified in a thorax phantom by using EBT2 films. Although the doses for identical PTVs were predicted for the different grid sizes, the dose discrepancy was evaluated using one measured dose distribution with the gamma tool because the beam was delivered in the same set-up for DCAT. The dosimetric effect of the angular increment was verified by comparing the measured dose area histograms of organs at risk (OARs) at each angular increment. When the difference in the OAR doses is higher than the uncertainty of the film dosimetry, the error is regarded as the angular increment effect in discretely calculated doses. In the results, even when a 2-mm grid size was used with an elaborate dose calculation, 4-mm grid size led to a higher gamma pass ratio due to underdosage, a steep-dose descent gradient, and lower estimated PTV doses caused by the smoothing effect in the calculated dose distribution. An undulating dose distribution and a difference in the maximum contralateral lung dose of up to 14% were observed in dose calculation using a 10° angular increment. The DCAT can be effectively applied for an approximately spherical PTV in a relatively uniform geometry, which is less affected by inhomogeneous materials and differences in the beam path length.

A new understanding of inert gas narcosis

NASA Astrophysics Data System (ADS)

Meng, Zhang; Yi, Gao; Haiping, Fang

2016-01-01

Anesthetics are extremely important in modern surgery to greatly reduce the patient’s pain. The understanding of anesthesia at molecular level is the preliminary step for the application of anesthetics in clinic safely and effectively. Inert gases, with low chemical activity, have been found to cause anesthesia for centuries, but the mechanism is unclear yet. In this review, we first summarize the progress of theories about general anesthesia, especially for inert gas narcosis, and then propose a new hypothesis that the aggregated rather than the dispersed inert gas molecules are the key to trigger the narcosis to explain the steep dose-response relationship of anesthesia. Project supported by the Supercomputing Center of Chinese Academy of Sciences in Beijing, China, the Shanghai Supercomputer Center, China, the National Natural Science Foundation of China (Grant Nos. 21273268, 11290164, and 11175230), the Startup Funding from Shanghai Institute of Applied Physics, Chinese Academy of Sciences (Grant No. Y290011011), “Hundred People Project” from Chinese Academy of Sciences, and “Pu-jiang Rencai Project” from Science and Technology Commission of Shanghai Municipality, China (Grant No. 13PJ1410400).

Irradiation as a quarantine treatment for the solenopsis mealybug, Phenacoccus solenopsis

NASA Astrophysics Data System (ADS)

Huang, Fang; Li, Weidi; Li, Xiuqiong; Bei, Yawei; Lin, Wencai; Lu, Yaobin; Wang, Bingkui

2014-03-01

Phenacoccus solenopsis is an aggressively invasive species that targets agricultural and ornamental plants, thereby threatening the world cotton industry and other crops. P. solenopsis has been listed as a quarantine insect in Europe and China. The utilization of phytosanitary irradiation as a potential treatment for disinfesting agricultural commodities in trade has expanded rapidly in recent years. A reasonable dose of radiation to eliminate P. solenopsis needs to be determined, taking into account the side effects of radiation on agricultural products and the species-specific tolerance of the insect to radiation. We applied radiation ranging from 50 to 200 Gy to P. solenopsis to determine the optimal dose. Both the radiation dose and the developmental stage of the insect were independent variables. Higher doses of radiation or lesser mature insect stages provided more effective treatment. In nymphs, a radiation dose of 100 Gy caused extinction of the irradiated population by disrupting ovary development, while 150 Gy caused 100% mortality. In adults, all tested doses of irradiation did not affect longevity, but we were able to prevent reproduction with high (150 and 200 Gy) doses. In P. solenopsis, a 100 Gy dose of radiation could eliminate the irradiated population in two generations. The mortality curve showed a steep slope beyond 150 Gy; thus, if killing all of the insects in a shorter amount of time is necessary, 200 Gy may be a reasonable dose for the quarantine treatment of the solenopsis mealybug.

Differential Weight Procedure of the Conditional P.D.F. Approach for Estimating the Operating Characteristics of Discrete Item Responses.

ERIC Educational Resources Information Center

Samejima, Fumiko

A method is proposed that increases the accuracies of estimation of the operating characteristics of discrete item responses, especially when the true operating characteristic is represented by a steep curve, and also at the lower and upper ends of the ability distribution where the estimation tends to be inaccurate because of the smaller number…

Exploring the long-term response of undisturbed Mediterranean catchments to changes in atmospheric inputs through time series analysis.

PubMed

Bernal, S; Belillas, C; Ibáñez, J J; Àvila, A

2013-08-01

The aim of this study was to gain insights on the potential hydrological and biogeochemical mechanisms controlling the response of two nested Mediterranean catchments to long-term changes in atmospheric inorganic nitrogen and sulphate deposition. One catchment was steep and fully forested (TM9, 5.9 ha) and the other one had gentler slopes and heathlands in the upper part while side slopes were steep and forested (TM0, 205 ha). Both catchments were highly responsive to the 45% decline in sulphate concentration measured in atmospheric deposition during the 1980s and 1990s, with stream concentrations decreasing by 1.4 to 3.4 μeq L(-1) y(-1). Long-term changes in inorganic nitrogen in both, atmospheric deposition and stream water were small compared to sulphate. The quick response to changes in atmospheric inputs could be explained by the small residence time of water (4-5 months) in these catchments (inferred from chloride time series variance analysis), which was attributed to steep slopes and the role of macropore flow bypassing the soil matrix during wet periods. The estimated residence time for sulphate (1.5-3 months) was substantially lower than for chloride suggesting unaccounted sources of sulphate (i.e., dry deposition, or depletion of soil adsorbed sulphate). In both catchments, inorganic nitrogen concentration in stream water was strongly damped compared to precipitation and its residence time was of the order of decades, indicating that this essential nutrient was strongly retained in these catchments. Inorganic nitrogen concentration tended to be higher at TM0 than at TM9 which was attributed to the presence of nitrogen fixing species in the heathlands. Our results indicate that these Mediterranean catchments react rapidly to environmental changes, which make them especially vulnerable to changes in atmospheric deposition. Copyright © 2013 Elsevier B.V. All rights reserved.

Nixtamalized flour from quality protein maize (Zea mays L). optimization of alkaline processing.

PubMed

Milán-Carrillo, J; Gutiérrez-Dorado, R; Cuevas-Rodríguez, E O; Garzón-Tiznado, J A; Reyes-Moreno, C

2004-01-01

Quality of maize proteins is poor, they are deficient in the essential amino acids lysine and tryptophan. Recently, in Mexico were successfully developed nutritionally improved 26 new hybrids and cultivars called quality protein maize (QPM) which contain greater amounts of lysine and tryptophan. Alkaline cooking of maize with lime (nixtamalization) is the first step for producing several maize products (masa, tortillas, flours, snacks). Processors adjust nixtamalization variables based on experience. The objective of this work was to determine the best combination of nixtamalization process variables for producing nixtamalized maize flour (NMF) from QPM V-537 variety. Nixtamalization conditions were selected from factorial combinations of process variables: nixtamalization time (NT, 20-85 min), lime concentration (LC, 3.3-6.7 g Ca(OH)2/l, in distilled water), and steep time (ST, 8-16 hours). Nixtamalization temperature and ratio of grain to cooking medium were 85 degrees C and 1:3 (w/v), respectively. At the end of each cooking treatment the steeping started for the required time. Steeping was finished by draining the cooking liquor (nejayote). Nixtamal (alkaline-cooked maize kernels) was washed with running tap water. Wet nixtamal was dried (24 hours, 55 degrees C) and milled to pass through 80-US mesh screen to obtain NMF. Response surface methodology (RSM) was applied as optimization technique, over four response variables: In vitro protein digestibility (PD), total color difference (deltaE), water absorption index (WAI), and pH. Predictive models for response variables were developed as a function of process variables. Conventional graphical method was applied to obtain maximum PD, WAI and minimum deltaE, pH. Contour plots of each of the response variables were utilized applying superposition surface methodology, to obtain three contour plots for observation and selection of best combination of NT (31 min), LC (5.4 g Ca(OH)2/l), and ST (8.1 hours) for producing optimized NMF from QPM.

Mechanism of cassava tuber cell wall weakening by dilute sodium hydroxide steeping.

PubMed

Odoch, Martin; Buys, Elna M; Taylor, John R N

2017-08-01

Steeping of cassava root pieces in 0.75% NaOH in combination with wet milling was investigated to determine whether and how dilute NaOH modifies cassava cell walls. Gas chromatography data of cell wall constituent sugar composition and Fourier transform infrared (FTIR) data showed that NaOH steeping reduced the level of pectin in cassava cell walls. FTIR and wide-angle X-ray scattering spectroscopy also indicated that NaOH steeping combined with fine milling slightly reduced cellulose crystallinity. Scanning electron microscopy showed that NaOH steeping produced micropores in the cell walls and light microscopy revealed that NaOH steeping increased disaggregation of parenchyma cells. Steeping of ground cassava in NaOH resulted in a 12% decrease in large residue particles and approx. 4% greater starch yield with wet milling. Therefore dilute NaOH steeping can improve the effectiveness of wet milling in disintegrating cell walls through solubilisation of pectin, thereby reduced cell wall strength. Copyright © 2017 Elsevier Ltd. All rights reserved.

Integration of shallow gradients of Shh and Netrin-1 guides commissural axons.

PubMed

Sloan, Tyler F W; Qasaimeh, Mohammad A; Juncker, David; Yam, Patricia T; Charron, Frédéric

2015-03-01

During nervous system development, gradients of Sonic Hedgehog (Shh) and Netrin-1 attract growth cones of commissural axons toward the floor plate of the embryonic spinal cord. Mice defective for either Shh or Netrin-1 signaling have commissural axon guidance defects, suggesting that both Shh and Netrin-1 are required for correct axon guidance. However, how Shh and Netrin-1 collaborate to guide axons is not known. We first quantified the steepness of the Shh gradient in the spinal cord and found that it is mostly very shallow. We then developed an in vitro microfluidic guidance assay to simulate these shallow gradients. We found that axons of dissociated commissural neurons respond to steep but not shallow gradients of Shh or Netrin-1. However, when we presented axons with combined Shh and Netrin-1 gradients, they had heightened sensitivity to the guidance cues, turning in response to shallower gradients that were unable to guide axons when only one cue was present. Furthermore, these shallow gradients polarized growth cone Src-family kinase (SFK) activity only when Shh and Netrin-1 were combined, indicating that SFKs can integrate the two guidance cues. Together, our results indicate that Shh and Netrin-1 synergize to enable growth cones to sense shallow gradients in regions of the spinal cord where the steepness of a single guidance cue is insufficient to guide axons, and we identify a novel type of synergy that occurs when the steepness (and not the concentration) of a guidance cue is limiting.

Integration of Shallow Gradients of Shh and Netrin-1 Guides Commissural Axons

PubMed Central

Sloan, Tyler F. W.; Qasaimeh, Mohammad A.; Juncker, David; Yam, Patricia T.; Charron, Frédéric

2015-01-01

During nervous system development, gradients of Sonic Hedgehog (Shh) and Netrin-1 attract growth cones of commissural axons toward the floor plate of the embryonic spinal cord. Mice defective for either Shh or Netrin-1 signaling have commissural axon guidance defects, suggesting that both Shh and Netrin-1 are required for correct axon guidance. However, how Shh and Netrin-1 collaborate to guide axons is not known. We first quantified the steepness of the Shh gradient in the spinal cord and found that it is mostly very shallow. We then developed an in vitro microfluidic guidance assay to simulate these shallow gradients. We found that axons of dissociated commissural neurons respond to steep but not shallow gradients of Shh or Netrin-1. However, when we presented axons with combined Shh and Netrin-1 gradients, they had heightened sensitivity to the guidance cues, turning in response to shallower gradients that were unable to guide axons when only one cue was present. Furthermore, these shallow gradients polarized growth cone Src-family kinase (SFK) activity only when Shh and Netrin-1 were combined, indicating that SFKs can integrate the two guidance cues. Together, our results indicate that Shh and Netrin-1 synergize to enable growth cones to sense shallow gradients in regions of the spinal cord where the steepness of a single guidance cue is insufficient to guide axons, and we identify a novel type of synergy that occurs when the steepness (and not the concentration) of a guidance cue is limiting. PMID:25826604

Parotid Gland Function After Radiotherapy: The Combined Michigan and Utrecht Experience

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

Dijkema, Tim, E-mail: T.Dijkema@umcutrecht.n; Raaijmakers, Cornelis P.J.; Ten Haken, Randall K.

2010-10-01

Purpose: To analyze the combined and updated results from the University of Michigan and University Medical Center Utrecht on normal tissue complication probability (NTCP) of the parotid gland 1 year after radiotherapy (RT) for head-and-neck (HN) cancer. Patients and Methods: A total of 222 prospectively analyzed patients with various HN malignancies were treated with conventional and intensity-modulated RT. Stimulated individual parotid gland flow rates were measured before RT and 1 year after RT using Lashley cups at both centers. A flow ratio <25% of pretreatment was defined as a complication. The data were fitted to the Lyman-Kutcher-Burman model. Results: Amore » total of 384 parotid glands (Michigan: 157; Utrecht: 227 glands) was available for analysis 1 year after RT. Combined NTCP analysis based on mean dose resulted in a TD{sub 50} (uniform dose leading to 50% complication probability) of 39.9 Gy and m (steepness of the curve) of 0.40. The resulting NTCP curve had good qualitative agreement with the combined clinical data. Mean doses of 25-30 Gy were associated with 17-26% NTCP. Conclusions: A definite NTCP curve for parotid gland function 1 year after RT is presented, based on mean dose. No threshold dose was observed, and TD{sub 50} was equal to 40 Gy.« less

Integration of comprehensive women's health programmes into health systems: cervical cancer prevention, care and control in Rwanda.

PubMed

Binagwaho, Agnes; Ngabo, Fidele; Wagner, Claire M; Mugeni, Cathy; Gatera, Maurice; Nutt, Cameron T; Nsanzimana, Sabin

2013-09-01

Although it is highly preventable and treatable, cervical cancer is the most common and most deadly cancer among women in Rwanda. By mobilizing a diverse coalition of partnerships, Rwanda became the first country in Africa to develop and implement a national strategic plan for cervical cancer prevention, screening and treatment. Rwanda - a small, landlocked nation in East Africa with a population of 10.4 million - is well positioned to tackle a number of "high-burden" noncommunicable diseases. The country's integrated response to infectious diseases has resulted in steep declines in premature mortality over the past decade. In 2011-2012, Rwanda vaccinated 227,246 girls with all three doses of the human papillomavirus (HPV) vaccine. Among eligible girls, three-dose coverage rates of 93.2% and 96.6% were achieved in 2011 and 2012, respectively. The country has also initiated nationwide screening and treatment programmes that are based on visual inspection of the cervix with acetic acid, testing for HPV DNA, cryotherapy, the loop electrosurgical excision procedure and various advanced treatment options. Low-income countries should begin to address cervical cancer by integrating prevention, screening and treatment into routine women's health services. This requires political will, cross-sectoral collaboration and planning, innovative partnerships and robust monitoring and evaluation. With external support and adequate planning, high nationwide coverage rates for HPV vaccination and screening for cervical cancer can be achieved within a few years.

Response of six non-native invasive plant species to wildfires in the northern Rocky Mountains, USA

Treesearch

Dennis E. Ferguson; Christine L. Craig

2010-01-01

This paper presents early results on the response of six non-native invasive plant species to eight wildfires on six National Forests (NFs) in the northern Rocky Mountains, USA. Stratified random sampling was used to choose 224 stands based on burn severity, habitat type series, slope steepness, stand height, and stand density. Data for this report are from 219 stands...

The cardiovascular response to the AGS

NASA Technical Reports Server (NTRS)

Cardus, David; Mctaggart, Wesley G.

1993-01-01

This paper reports the preliminary results of experiments on human subjects conducted to study the cardiovascular response to various g-levels and exposure times using an artificial gravity simulator (AGS). The AGS is a short arm centrifuge consisting of a turntable, a traction system, a platform and four beds. Data collection hardware is part of the communication system. The AGS provides a steep acceleration gradient in subjects in the supine position.

Dose-dependent acute liver injury with hypersensitivity features in humans due to a novel microsomal prostaglandin E synthase 1 inhibitor.

PubMed

Jin, Yan; Regev, Arie; Kam, Jeanelle; Phipps, Krista; Smith, Claire; Henck, Judith; Campanale, Kristina; Hu, Leijun; Hall, D Greg; Yang, Xiao Yan; Nakano, Masako; McNearney, Terry Ann; Uetrecht, Jack; Landschulz, William

2018-01-01

LY3031207, a novel microsomal prostaglandin E synthase 1 inhibitor, was evaluated in a multiple ascending dose study after nonclinical toxicology studies and a single ascending dose study demonstrated an acceptable toxicity, safety and tolerability profile. Healthy subjects were randomized to receive LY3031207 (25, 75 and 275 mg), placebo or celecoxib (400 mg) once daily for 28 days. The safety, tolerability and pharmacokinetic and pharmacodynamic profiles of LY3031207 were evaluated. The study was terminated when two subjects experienced drug-induced liver injury (DILI) after they had received 225 mg LY3031207 for 19 days. Liver biopsy from these subjects revealed acute liver injury with eosinophilic infiltration. Four additional DILI cases were identified after LY3031207 dosing had been stopped. All six DILI cases shared unique presentations of hepatocellular injury with hypersensitivity features and demonstrated a steep dose-dependent trend. Prompt discontinuation of the study drug and supportive medical care resulted in full recovery. Metabolites from metabolic activation of the imidazole ring were observed in plasma and urine samples from all subjects randomized to LY3031207 dosing. This study emphasized the importance of careful safety monitoring and serious adverse events management in phase I trials. Metabolic activation of the imidazole ring may be involved in the development of hepatotoxicity of LY3031207. © 2017 The British Pharmacological Society.

A mother-child intervention program in adolescent mothers and their children to improve maternal sensitivity, child responsiveness and child development (the TeeMo study): study protocol for a randomized controlled trial.

PubMed

Firk, Christine; Dahmen, Brigitte; Lehmann, Christin; Niessen, Anke; Koslowski, Julia; Rauch, Geraldine; Schwarte, Reinhild; Stich, Kerstin; Konrad, Kerstin; Herpertz-Dahlmann, Beate

2015-05-27

Children of adolescent mothers present a high-risk group for child neglect and maltreatment. Previous findings suggest that early interventions can reduce maltreatment by improving the quality of mother-child interaction, particularly maternal sensitivity. The aim of the current study is to evaluate the effects of a mother-child intervention program using home visits and video-feedback regarding mother-child interaction (STEEP-b) plus psychiatric treatment of the mother in cases where mental illness is present compared with TAU (treatment as usual, that is, standardized support by the child welfare system) on enhancing maternal sensitivity and child responsiveness in adolescent, high-risk mothers. The second aim of the current project is to investigate behavioral and neural differences between adolescent and adult mothers at baseline and postintervention. This is a randomized controlled trial (RCT) with 120 high-risk adolescent mothers (<21 years old) and their 3- to 6-month-old children. Half of the participants will be randomized to receive STEEP-b in addition to their standard treatment for up to 12 to 18 sessions over 9 months. The other half will continue with treatment as usual. For further comparisons, 40 adult mothers with positive and negative rearing experiences (>25 years) will additionally be recruited to investigate behavioral and neural differences between the adolescent and adult group. Blind assessments will take place at T1 (pre-intervention), at the end of the 9-month intervention (T2, postintervention) and 6 months postintervention (T3, follow-up). Moderators of treatment outcomes and sociodemographic data will be assessed at T1. The primary outcome hypothesis is that STEEP-b added to treatment as usual will improve maternal sensitivity and child responsiveness compared with treatment as usual alone in high-risk adolescent mothers. The primary hypothesis will be evaluated at the end of the 9-month follow-up assessment based on the intention-to-treat principle. The trial is funded by the German Ministry for Research and Education (BMBF). Data collection started in October 2012. This is a randomized controlled trial that evaluates the effects of an early intervention program (STEEP-b) on the quality of mother-child interaction and child development in adolescent, high-risk mothers. DRKS00004409 (27 September 2012).

What Can Modern River Profiles Tell Us about Orogenic Processes and Orogen Evolution?

NASA Astrophysics Data System (ADS)

Whipple, K. X.

2008-12-01

Numerous lines of evidence from theory, numerical simulations, and physical experiments suggest that orogen evolution is strongly coupled to atmospheric processes through the interrelationships among climate, topography, and erosion rate. In terms of orogenic processes and orogen evolution, these relationships are most important at the regional scale (mean topographic gradient, mean relief above surrounding plains) largely because crustal deformation is most sensitive to erosional unloading averaged over sufficiently long wavelengths. For this reason, and because above moderate erosion rates (> 0.2 mm/yr) hillslope form becomes decoupled from erosion rate, attention has focused on the river network, and even on particularly large rivers. We now have data that demonstrates a monotonic relationship between erosion rate and the channel steepness index (slope normalized for differences in drainage area) in a variety of field settings. Consequently, study of modern river profiles can yield useful information on recent and on-going patterns of rock uplift. It is not yet possible, however, to quantitatively isolate expected climatic and lithologic influences on this relationship. A combination of field studies and theoretical analyses are beginning to reveal the timescale of landscape response, and thus the topographic memory of past conditions. At orogen scale, river profile response to a change in rock uplift rate is on the order of 1-10 Myr. Because of these long response times, the modern profiles of large rivers and their major tributaries can potentially preserve an interpretable record of rock uplift rates since the Miocene and are insensitive to short-term climatic fluctuations. Only significant increases in rock uplift rate, however, are likely to leave a clear topographic signature. Strategies have been developed to differentiate between temporal and spatial (tectonic, climatic, or lithologic) influences on channel profile form, especially where spatially distributed data on recent incision rates is available. A more difficult question is one of cause and effect. Only in some circumstances is it possible to determine whether rivers are steep in response to localized rock uplift or whether localized rock uplift occurs in response to rapidly incising steep rivers.

In Vivo Pharmacodynamic Target Assessment of Delafloxacin against Staphylococcus aureus, Streptococcus pneumoniae, and Klebsiella pneumoniae in a Murine Lung Infection Model.

PubMed

Lepak, Alexander J; Andes, David R

2016-08-01

Delafloxacin is a broad-spectrum anionic fluoroquinolone under development for the treatment of bacterial pneumonia. The goal of the study was to determine the pharmacokinetic/pharmacodynamic (PK/PD) targets in the murine lung infection model for Staphylococcus aureus, Streptococcus pneumoniae, and Klebsiella pneumoniae Four isolates of each species were utilized for in vivo studies: for S. aureus, one methicillin-susceptible and three methicillin-resistant isolates; S. pneumoniae, two penicillin-susceptible and two penicillin-resistant isolates; K. pneumoniae, one wild-type and three extended-spectrum beta-lactamase-producing isolates. MICs were determined using CLSI methods. A neutropenic murine lung infection model was utilized for all treatment studies, and drug dosing was by the subcutaneous route. Single-dose plasma pharmacokinetics was determined in the mouse model after administration of 2.5, 10, 40, and 160 mg/kg. For in vivo studies, 4-fold-increasing doses of delafloxacin (range, 0.03 to 160 mg/kg) were administered every 6 h (q6h) to infected mice. Treatment outcome was measured by determining organism burden in the lung (CFU counts) at the end of each experiment (24 h). The Hill equation for maximum effect (Emax) was used to model the dose-response data. The magnitude of the PK/PD index, the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC), associated with net stasis and 1-log kill endpoints was determined in the lung model for all isolates. MICs ranged from 0.004 to 1 mg/liter. Single-dose PK parameter ranges include the following: for maximum concentration of drug in serum (Cmax), 2 to 70.7 mg/liter; AUC from 0 h to infinity (AUC0-∞), 2.8 to 152 mg · h/liter; half-life (t1/2), 0.7 to 1 h. At the start of therapy mice had 6.3 ± 0.09 log10 CFU/lung. In control mice the organism burden increased 2.1 ± 0.44 log10 CFU/lung over the study period. There was a relatively steep dose-response relationship observed with escalating doses of delafloxacin. Maximal organism reductions ranged from 2 log10 to more than 4 log10 The median free-drug AUC/MIC magnitude associated with net stasis for each species group was 1.45, 0.56, and 40.3 for S. aureus, S. pneumoniae, and K. pneumoniae, respectively. AUC/MIC targets for the 1-log kill endpoint were 2- to 5-fold higher. Delafloxacin demonstrated in vitro and in vivo potency against a diverse group of pathogens, including those with phenotypic drug resistance to other classes. These results have potential relevance for clinical dose selection and evaluation of susceptibility breakpoints for delafloxacin for the treatment of lower respiratory tract infections involving these pathogens. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

In Vivo Pharmacodynamic Target Assessment of Delafloxacin against Staphylococcus aureus, Streptococcus pneumoniae, and Klebsiella pneumoniae in a Murine Lung Infection Model

PubMed Central

Lepak, Alexander J.

2016-01-01

Delafloxacin is a broad-spectrum anionic fluoroquinolone under development for the treatment of bacterial pneumonia. The goal of the study was to determine the pharmacokinetic/pharmacodynamic (PK/PD) targets in the murine lung infection model for Staphylococcus aureus, Streptococcus pneumoniae, and Klebsiella pneumoniae. Four isolates of each species were utilized for in vivo studies: for S. aureus, one methicillin-susceptible and three methicillin-resistant isolates; S. pneumoniae, two penicillin-susceptible and two penicillin-resistant isolates; K. pneumoniae, one wild-type and three extended-spectrum beta-lactamase-producing isolates. MICs were determined using CLSI methods. A neutropenic murine lung infection model was utilized for all treatment studies, and drug dosing was by the subcutaneous route. Single-dose plasma pharmacokinetics was determined in the mouse model after administration of 2.5, 10, 40, and 160 mg/kg. For in vivo studies, 4-fold-increasing doses of delafloxacin (range, 0.03 to 160 mg/kg) were administered every 6 h (q6h) to infected mice. Treatment outcome was measured by determining organism burden in the lung (CFU counts) at the end of each experiment (24 h). The Hill equation for maximum effect (Emax) was used to model the dose-response data. The magnitude of the PK/PD index, the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC), associated with net stasis and 1-log kill endpoints was determined in the lung model for all isolates. MICs ranged from 0.004 to 1 mg/liter. Single-dose PK parameter ranges include the following: for maximum concentration of drug in serum (Cmax), 2 to 70.7 mg/liter; AUC from 0 h to infinity (AUC0–∞), 2.8 to 152 mg · h/liter; half-life (t1/2), 0.7 to 1 h. At the start of therapy mice had 6.3 ± 0.09 log10 CFU/lung. In control mice the organism burden increased 2.1 ± 0.44 log10 CFU/lung over the study period. There was a relatively steep dose-response relationship observed with escalating doses of delafloxacin. Maximal organism reductions ranged from 2 log10 to more than 4 log10. The median free-drug AUC/MIC magnitude associated with net stasis for each species group was 1.45, 0.56, and 40.3 for S. aureus, S. pneumoniae, and K. pneumoniae, respectively. AUC/MIC targets for the 1-log kill endpoint were 2- to 5-fold higher. Delafloxacin demonstrated in vitro and in vivo potency against a diverse group of pathogens, including those with phenotypic drug resistance to other classes. These results have potential relevance for clinical dose selection and evaluation of susceptibility breakpoints for delafloxacin for the treatment of lower respiratory tract infections involving these pathogens. PMID:27216072

Topographic and ecological controls on root reinforcement

Treesearch

T.C. Hales; C.R. Ford; T. Hwang; J.M. Vose; L.E. Band

2009-01-01

Shallow landslides are a significant hazard in steep, soil-mantled landscapes. During intense rainfall events, the distribution of shallow landslides is controlled by variations in landscape gradient, the frictional and cohesive properties of soil and roots, and the subsurface hydrologic response. While gradients can be estimated from digital elevation models,...

Topographic and ecologic controls on root reinforcement

Treesearch

T.C. Hales; C.R. Ford; T. Hwang; J.M. Vose; L.E. Band

2009-01-01

Shallow landslides are a significant hazard in steep, soil-mantled landscapes. During intense rainfall events, the distribution of shallow landslides is controlled by variations in landscape gradient, the frictional and cohesive properties of soil and roots, and the subsurface hydrologic response. While gradients can be estimated from digital elevation models,...

Redefining the Speed Limit of Phase Change Memory Revealed by Time-resolved Steep Threshold-Switching Dynamics of AgInSbTe Devices

NASA Astrophysics Data System (ADS)

Shukla, Krishna Dayal; Saxena, Nishant; Durai, Suresh; Manivannan, Anbarasu

2016-11-01

Although phase-change memory (PCM) offers promising features for a ‘universal memory’ owing to high-speed and non-volatility, achieving fast electrical switching remains a key challenge. In this work, a correlation between the rate of applied voltage and the dynamics of threshold-switching is investigated at picosecond-timescale. A distinct characteristic feature of enabling a rapid threshold-switching at a critical voltage known as the threshold voltage as validated by an instantaneous response of steep current rise from an amorphous off to on state is achieved within 250 picoseconds and this is followed by a slower current rise leading to crystallization. Also, we demonstrate that the extraordinary nature of threshold-switching dynamics in AgInSbTe cells is independent to the rate of applied voltage unlike other chalcogenide-based phase change materials exhibiting the voltage dependent transient switching characteristics. Furthermore, numerical solutions of time-dependent conduction process validate the experimental results, which reveal the electronic nature of threshold-switching. These findings of steep threshold-switching of ‘sub-50 ps delay time’, opens up a new way for achieving high-speed non-volatile memory for mainstream computing.

Electronic brachytherapy—current status and future directions

PubMed Central

2015-01-01

In the past decade, electronic brachytherapy (EB) has emerged as an attractive modality for the treatment of skin lesions and intraoperative partial breast irradiation, as well as finding wider applications in intracavitary and interstitial sites. These miniature X-ray sources, which operate at low kilovoltage energies (<100 kV), have reduced shielding requirements and inherent portability, therefore can be used outside the traditional realms of the radiotherapy department. However, steep dose gradients and increased sensitivity to inhomogeneities challenge accurate dosimetry. Secondly, ease of use does not mitigate the need for close involvement by medical physics experts and consultant oncologists. Finally, further studies are needed to relate the more heterogeneous dose distributions to clinical outcomes. With these provisos, the practical convenience of EB strongly suggests that it will become an established option for selected patients, not only in radiotherapy departments but also in a range of operating theatres and clinics around the world. PMID:25748070

Fractal characterization and wettability of ion treated silicon surfaces

NASA Astrophysics Data System (ADS)

Yadav, R. P.; Kumar, Tanuj; Baranwal, V.; Vandana, Kumar, Manvendra; Priya, P. K.; Pandey, S. N.; Mittal, A. K.

2017-02-01

Fractal characterization of surface morphology can be useful as a tool for tailoring the wetting properties of solid surfaces. In this work, rippled surfaces of Si (100) are grown using 200 keV Ar+ ion beam irradiation at different ion doses. Relationship between fractal and wetting properties of these surfaces are explored. The height-height correlation function extracted from atomic force microscopic images, demonstrates an increase in roughness exponent with an increase in ion doses. A steep variation in contact angle values is found for low fractal dimensions. Roughness exponent and fractal dimensions are found correlated with the static water contact angle measurement. It is observed that after a crossover of the roughness exponent, the surface morphology has a rippled structure. Larger values of interface width indicate the larger ripples on the surface. The contact angle of water drops on such surfaces is observed to be lowest. Autocorrelation function is used for the measurement of ripple wavelength.

Risk of Skin Cancer from Space Radiation. Chapter 11

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Kim, Myung-Hee Y.; George, Kerry A.; Wu, Hong-Lu

2003-01-01

We review the methods for estimating the probability of increased incidence of skin cancers from space radiation exposure, and describe some of the individual factors that may contribute to risk projection models, including skin pigment, and synergistic effects of combined ionizing and UV exposure. The steep dose gradients from trapped electrons, protons, and heavy ions radiation during EVA and limitations in EVA dosimetry are important factors for projecting skin cancer risk of astronauts. We estimate that the probability of increased skin cancer risk varies more than 10-fold for individual astronauts and that the risk of skin cancer could exceed 1 % for future lunar base operations for astronauts with light skin color and hair. Limitations in physical dosimetry in estimating the distribution of dose at the skin suggest that new biodosimetry methods be developed for responding to accidental overexposure of the skin during future space missions.

Vascular responsiveness measured by tissue oxygen saturation reperfusion slope is sensitive to different occlusion durations and training status.

PubMed

McLay, Kaitlin M; Gilbertson, James E; Pogliaghi, Silvia; Paterson, Donald H; Murias, Juan M

2016-10-01

What is the central question of this study? Is the near-infrared spectroscopy-derived measure of tissue oxygen saturation (StO2) reperfusion slope sensitive to a range of ischaemic conditions, and do differences exist between trained and untrained individuals? What is the main finding and its importance? The StO2 reperfusion rate is sensitive to different occlusion durations, and changes in the reperfusion slope in response to a variety of ischaemic challenges can be used to detect differences between two groups. These data indicate that near-infrared spectroscopy-derived measures of StO2, specifically the reperfusion slope following a vascular occlusion, can be used as a sensitive measure of vascular responsiveness. The reperfusion rate of near-infrared spectroscopy-derived measures of tissue oxygen saturation (StO2) represents vascular responsiveness. This study examined whether the reperfusion slope of StO2 is sensitive to different ischaemic conditions (i.e. a dose-response relationship) and whether differences exist between two groups of different fitness levels. Nine healthy trained (T; age 25 ± 3 years; maximal oxygen uptake 63.4 ± 6.7 ml kg -1  min -1 ) and nine healthy untrained men (UT; age 21 ± 1 years; maximal oxygen uptake 46.6 ± 2.5 ml kg -1  min -1 ) performed a series of vascular occlusion tests of different durations (30 s, 1, 2, 3 and 5 min), each separated by 30 min. The StO2 was measured over the tibialis anterior using near-infrared spectroscopy, with the StO2 reperfusion slope calculated as the upslope during 10 s following cuff release. The reperfusion slope was steeper in T compared with UT at all occlusion durations (P < 0.05). For the T group, the reperfusion slopes for 30 s and 1 min occlusions were less than for all longer durations (P < 0.05). The reperfusion slope following 2 min occlusion was similar to that for 3 min (P > 0.05), but both were less steep than for 5 min of occlusion. In UT, the reperfusion slope at 30 s was smaller than for all longer occlusion durations (P < 0.05), and 1 min occlusion resulted in a reperfusion slope that was less steep than following 2 and 3 min (P < 0.05), albeit not different from 5 min (P > 0.05). The present study demonstrated that the reperfusion rate of StO2 is sensitive to different occlusion durations, and that changes in the reperfusion rate in response to a variety of ischaemic challenges can be used to detect differences in vascular responsiveness between trained and untrained groups. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

Drift and Behavior of E. coli Cells

NASA Astrophysics Data System (ADS)

Micali, Gabriele; Colin, Rémy; Sourjik, Victor; Endres, Robert G.

2017-12-01

Chemotaxis of the bacterium Escherichia coli is well understood in shallow chemical gradients, but its swimming behavior remains difficult to interpret in steep gradients. By focusing on single-cell trajectories from simulations, we investigated the dependence of the chemotactic drift velocity on attractant concentration in an exponential gradient. While maxima of the average drift velocity can be interpreted within analytical linear-response theory of chemotaxis in shallow gradients, limits in drift due to steep gradients and finite number of receptor-methylation sites for adaptation go beyond perturbation theory. For instance, we found a surprising pinning of the cells to the concentration in the gradient at which cells run out of methylation sites. To validate the positions of maximal drift, we recorded single-cell trajectories in carefully designed chemical gradients using microfluidics.

Autoimmunity: a decision theory model.

PubMed Central

Morris, J A

1987-01-01

Concepts from statistical decision theory were used to analyse the detection problem faced by the body's immune system in mounting immune responses to bacteria of the normal body flora. Given that these bacteria are potentially harmful, that there can be extensive cross reaction between bacterial antigens and host tissues, and that the decisions are made in uncertainty, there is a finite chance of error in immune response leading to autoimmune disease. A model of ageing in the immune system is proposed that is based on random decay in components of the decision process, leading to a steep age dependent increase in the probability of error. The age incidence of those autoimmune diseases which peak in early and middle life can be explained as the resultant of two processes: an exponentially falling curve of incidence of first contact with common bacteria, and a rapidly rising error function. Epidemiological data on the variation of incidence with social class, sibship order, climate and culture can be used to predict the likely site of carriage and mode of spread of the causative bacteria. Furthermore, those autoimmune diseases precipitated by common viral respiratory tract infections might represent reactions to nasopharyngeal bacterial overgrowth, and this theory can be tested using monoclonal antibodies to search the bacterial isolates for cross reacting antigens. If this model is correct then prevention of autoimmune disease by early exposure to low doses of bacteria might be possible. PMID:3818985

Advanced water remediation from ofloxacin by ionizing radiation

NASA Astrophysics Data System (ADS)

Esposito, Biagio R.; Capobianco, Massimo L.; Martelli, Alessandro; Navacchia, Maria Luisa; Pretali, Luca; Saracino, Michela; Zanelli, Alberto; Emmi, Salvatore S.

2017-12-01

The performances of remediation processes initiated by ionizing radiation on ofloxacin are investigated in ambient conditions. The effectiveness of the decomposition of ofloxacin has been assessed both by γ-rays and electron beam in various aqueous solutions differentiated by the dissolved gases (Air or oxygen saturated) and H2O2. By HPLC it is shown that ofloxacin is removed according to a first order process vs. dose in any system. O2 accelerates the decomposition rate, while H2O2 does not seem to enhance any oxidation effect. The simultaneous oxidative-reductive treatment (no additive) demonstrated to have better mineralizing performances than the fully oxidative one (H2O2 present). Mineralization by γ results to be more efficient than by EB. The Total Organic Carbon decrease was investigated in dependence of dose and of the •OH production rate. The latter parameter was changed over 7 orders of magnitude by controlling dose rate and/or by adding H2O2. A steep increase of acidity remarks the phases of fluorine-carbon bond break.

Significantly enhanced biomass production of a novel bio-therapeutic strain Lactobacillus plantarum (AS-14) by developing low cost media cultivation strategy.

PubMed

Manzoor, Asma; Qazi, Javed Iqbal; Haq, Ikram Ul; Mukhtar, Hamid; Rasool, Akhtar

2017-01-01

Probiotic bacteria are becoming an important tool for improving human health, controlling diseases and enhancing immune responses. The availability of a cost effective cultivation conditions has profound effect on the efficiency and role of probiotic bacteria. Therefore the current study was conducted with an objective to develop a low cost growth medium for enhancing the biomass production of a bio-therapeutic bacterial strain Lactobacillus plantarum AS-14. In this work the isolation of Lactobacillus plantarum AS-14 bacterial strain was carried out from brinjal using cheese whey as a main carbon source. Moreover, the effect of four other nutritional factors besides cheese whey was investigated on the enhanced cell mass production by using response surface methodology (RSM). The best culture medium contained 60 g/l cheese whey, 15 g/l glucose and 15 g/l corn steep liquor in addition to other minor ingredients and it resulted in maximum dry cell mass (15.41 g/l). The second-order polynomial regression model determined that the maximum cell mass production (16.02 g/l) would be obtained at temperature 40°C and pH 6.2. Comparative studies showed that cultivation using cheese whey and corn steep liquor with other components of the selected medium generated higher biomass with lower cost than that of De Man, Rogosa and Sharpe (MRS) medium under similar cultivation conditions (pH 6.2 and temperature 40°C). It is evident that the cell biomass of L. Plantarum AS-14 was enhanced by low cost cultivation conditions. Moreover, corn steep liquor and ammonium bisulphate were perceived as low-cost nitrogen sources in combination with other components to substitute yeast extract. Of all these factors, cheese whey, corn steep liquor, yeast extract and two operating conditions (temperature and pH) were found to be the most significant parameters. Thus the cost effective medium developed in this research might be used for large-scale commercial application where economics is quite likely important.

Maintaining a Sacred Trust: A School District's Responsibility

ERIC Educational Resources Information Center

Ruder, Robert

2011-01-01

Rich with the histories of families and steeped in traditions, schools often embrace all that is good within a community. In fact, the school is often where families, students, and staff choose to memorialize the achievements, contributions, and sacrifices of those who learned or worked within the school's classrooms and corridors. A school's…

Impacts of fire on hydrology and erosion in steep mountain big sagebrush communities

Treesearch

Frederick B. Pierson; Peter R. Robichaud; Kenneth E. Spaeth; Corey A. Moffet

2003-01-01

Wildfire is an important ecological process and management issue on western rangelands. Major unknowns associated with wildfire are its affects on vegetation and soil conditions that influence hydrologic processes including infiltration, surface runoff, erosion, sediment transport, and flooding. Post wildfire hydrologic response was studied in big sagebrush plant...

Flood disturbance in a forested mountain landscape: interactions of land use and floods.

Treesearch

F.J. Swanson; S.L. Johnson; S.V. Gregory; S.A. Acker

1998-01-01

Recent flooding in the Pacific Northwest vividly illustrates the complexity of watershed and ecosystem responses to floods, especially in steep forest landscapes. Flooding involves a sequence of interactions that begins with climatic drivers. These drivers, generally rain and snowmelt, interact with landscape conditions, such as vegetation pattern and topography, to...

Alerting Attention and Time Perception in Children.

ERIC Educational Resources Information Center

Droit-Volet, Sylvie

2003-01-01

Examined effects of a click signaling arrival of a visual stimulus to be timed on temporal discrimination in 3-, 5-, and 8-year-olds. Found that in all groups, the proportion of long responses increased with the stimulus duration, although the steepness of functions increased with age. Stimulus duration was judged longer with than without the…

A comparison of artifical and natural slope failures: the Santa Barbara earthquake of August 13, 1978.

USGS Publications Warehouse

Harp, E.L.; Keefer, D.K.; Wilson, R.C.

1980-01-01

The earthquake triggered rockfalls and rockslides from steep road cuts and coastal cliffs. The landslide reconnaissance survey which was carried out is described, with separate comments on each landslide site recorded. The general regional slope response to the earthquake is briefly considered. -R. House

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

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

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

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

Mixture toxicity of the anti-inflammatory drugs diclofenac, ibuprofen, naproxen, and acetylsalicylic acid.

PubMed

Cleuvers, Michael

2004-11-01

The ecotoxicity of the nonsteroidal anti-inflammatory drugs (NSAIDs) diclofenac, ibuprofen, naproxen, and acetylsalicylic acid (ASA) has been evaluated using acute Daphnia and algal tests. Toxicities were relatively low, with half-maximal effective concentration (EC50) values obtained using Daphnia in the range from 68 to 166 mg L(-1) and from 72 to 626 mg L(-1) in the algal test. Acute effects of these substances seem to be quite improbable. The quantitative structure-activity relationships (QSAR) approach showed that all substances act by nonpolar narcosis; thus, the higher the n-octanol/water partitioning coefficient (log Kow) of the substances, the higher is their toxicity. Mixture toxicity of the compounds could be accurately predicted using the concept of concentration addition. Toxicity of the mixture was considerable, even at concentrations at which the single substances showed no or only very slight effects, with some deviations in the Daphnia test, which could be explained by incompatibility of the very steep dose-response curves and the probit analysis of the data. Because pharmaceuticals in the aquatic environment occur usually as mixtures, an accurate prediction of the mixture toxicity is indispensable for environmental risk assessment.

Robot Would Climb Steep Terrain

NASA Technical Reports Server (NTRS)

Kennedy, Brett; Ganino, Anthony; Aghazarian, Hrand; Hogg, Robert; McHerny, Michael; Garrett, Michael

2007-01-01

This brief describes the steep terrain access robot (STAR) -- a walking robot that has been proposed for exploring steep terrain on remote planets. The STAR would be able to climb up or down on slopes as steep as vertical, and even beyond vertical to overhangs. Its system of walking mechanisms and controls would be to react forces and maintain stability. To enable the STAR to anchor itself in the terrain on steep slopes to maintain stability and react forces, it would be necessary to equip the tips of the walking legs with new ultrasonic/ sonic drill corers (USDCs) and to develop sensors and control algorithms to enable robust utilization of the USDCs.

Dosimetric characterizations of GZP6 60Co high dose rate brachytherapy sources: application of superimposition method

PubMed Central

Bahreyni Toossi, Mohammad Taghi; Ghorbani, Mahdi; Mowlavi, Ali Asghar; Meigooni, Ali Soleimani

2012-01-01

Background Dosimetric characteristics of a high dose rate (HDR) GZP6 Co-60 brachytherapy source have been evaluated following American Association of Physicists in MedicineTask Group 43U1 (AAPM TG-43U1) recommendations for their clinical applications. Materials and methods MCNP-4C and MCNPX Monte Carlo codes were utilized to calculate dose rate constant, two dimensional (2D) dose distribution, radial dose function and 2D anisotropy function of the source. These parameters of this source are compared with the available data for Ralstron 60Co and microSelectron192Ir sources. Besides, a superimposition method was developed to extend the obtained results for the GZP6 source No. 3 to other GZP6 sources. Results The simulated value for dose rate constant for GZP6 source was 1.104±0.03 cGyh-1U-1. The graphical and tabulated radial dose function and 2D anisotropy function of this source are presented here. The results of these investigations show that the dosimetric parameters of GZP6 source are comparable to those for the Ralstron source. While dose rate constant for the two 60Co sources are similar to that for the microSelectron192Ir source, there are differences between radial dose function and anisotropy functions. Radial dose function of the 192Ir source is less steep than both 60Co source models. In addition, the 60Co sources are showing more isotropic dose distribution than the 192Ir source. Conclusions The superimposition method is applicable to produce dose distributions for other source arrangements from the dose distribution of a single source. The calculated dosimetric quantities of this new source can be introduced as input data to the GZP6 treatment planning system (TPS) and to validate the performance of the TPS. PMID:23077455

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

Xu, Z; Baker, J; Hsia, A

Purpose: The commercially available Leipzig-style Cone for High Dose Rate (HDR) Brachytherapy has a steep depth dose curve and a non-uniform dose distribution. This work shows the performance of a Ring Surface Applicator created using a 3D printer that can generate a better dose distribution. Calculated doses were verified with film measurement. Methods: The water equivalent red-ABS plastic was used to print the Ring Surface Applicator which hosts three catheters: a center piece with a straight catheter and two concentric rings with diameters of 3.5 and 5.5 cm. Gafchromic EBT2 film, Epson Expression 10000 flatbed scanner, and the online softwaremore » at radiochromic.com were used to analyze the measured data. 10cm×10cm piece of film was sandwiched between two 15×10×5cm3 polystyrene phantoms. The applicator was positioned directly on top of the phantom. Measurement was done using dwell time and positions calculated by Eclipse BrachyVision treatment planning system (RTP). Results: Depth dose curve was generated from the plan and measurement. The results show that the measured and calculated depth dose were in agreement (<3%) from surface to 4mm depth. A discrepancy of 6% was observed at 5 mm depth, where the dose is typically prescribed to. For depths deeper than 5 mm, the measured doses were lower than those calculated by Eclipse BrachyVision. This can be attributed to a combination of simple calculation algorithm using TG-43 and the lack of inhomogeneity correction. Dose profiles at 5 mm depth were also generated from TPS calculation and measured with film. The measured and calculated profiles are similar. Consistent with the depth dose curve, the measured dose is lower than the calculated. Conclusion: Our results showed that the Ring Surface Applicator, printed using 3D printer, can generate more uniform dose distribution within the target volume and can be safely used in the clinic.« less

Ultrasensitivity by Molecular Titration in Spatially Propagating Enzymatic Reactions

PubMed Central

Semenov, Sergey N.; Markvoort, Albert J.; Gevers, Wouter B.L.; Piruska, Aigars; de Greef, Tom F.A.; Huck, Wilhelm T.S.

2013-01-01

Delineating design principles of biological systems by reconstitution of purified components offers a platform to gauge the influence of critical physicochemical parameters on minimal biological systems of reduced complexity. Here we unravel the effect of strong reversible inhibitors on the spatiotemporal propagation of enzymatic reactions in a confined environment in vitro. We use micropatterned, enzyme-laden agarose gels which are stamped on polyacrylamide films containing immobilized substrates and reversible inhibitors. Quantitative fluorescence imaging combined with detailed numerical simulations of the reaction-diffusion process reveal that a shallow gradient of enzyme is converted into a steep product gradient by addition of strong inhibitors, consistent with a mathematical model of molecular titration. The results confirm that ultrasensitive and threshold effects at the molecular level can convert a graded input signal to a steep spatial response at macroscopic length scales. PMID:23972857

Trajectories of diurnal cortisol in mothers of children with autism and other developmental disabilities: Relations to health and mental health

PubMed Central

Dykens, Elisabeth M.; Lambert, Warren

2014-01-01

This study used a stress biomarker, diurnal cortisol, to identify how elevated stress in mothers of children and adults with autism and other disabilities relates to their health and mental health. Based on semi-parametric, group-based trajectory analysis of 91 mothers, two distinctive cortisol trajectories emerged: blunted (63%) or steep (37%). Mothers in the blunted (versus steep) trajectory had higher stress levels, lower health ratings, and 89% of mothers of children with autism, and 53% with other disabilities, belonged to this trajectory. Atypical cortisol awakening responses and evening rises were differentially associated with anxiety, depression, health problems and employment status. Stress-reducing interventions are needed for parents of children with autism and other disabilities that include biomarkers as indices of risk or treatment outcome. PMID:23468069

Single-energy intensity modulated proton therapy

NASA Astrophysics Data System (ADS)

Farace, Paolo; Righetto, Roberto; Cianchetti, Marco

2015-09-01

In this note, an intensity modulated proton therapy (IMPT) technique, based on the use of high single-energy (SE-IMPT) pencil beams, is described. The method uses only the highest system energy (226 MeV) and only lateral penumbra to produce dose gradient, as in photon therapy. In the study, after a preliminary analysis of the width of proton pencil beam penumbras at different depths, SE-IMPT was compared with conventional IMPT in a phantom containing titanium inserts and in a patient, affected by a spinal chordoma with fixation rods. It was shown that SE-IMPT has the potential to produce a sharp dose gradient and that it is not affected by the uncertainties produced by metal implants crossed by the proton beams. Moreover, in the chordoma patient, target coverage and organ at risk sparing of the SE-IMPT plan resulted comparable to that of the less reliable conventional IMPT technique. Robustness analysis confirmed that SE-IMPT was not affected by range errors, which can drastically affect the IMPT plan. When accepting a low-dose spread as in modern photon techniques, SE-IMPT could be an option for the treatment of lesions (e.g. cervical bone tumours) where steep dose gradient could improve curability, and where range uncertainty, due for example to the presence of metal implants, hampers conventional IMPT.

Single-energy intensity modulated proton therapy.

PubMed

Farace, Paolo; Righetto, Roberto; Cianchetti, Marco

2015-10-07

In this note, an intensity modulated proton therapy (IMPT) technique, based on the use of high single-energy (SE-IMPT) pencil beams, is described.The method uses only the highest system energy (226 MeV) and only lateral penumbra to produce dose gradient, as in photon therapy. In the study, after a preliminary analysis of the width of proton pencil beam penumbras at different depths, SE-IMPT was compared with conventional IMPT in a phantom containing titanium inserts and in a patient, affected by a spinal chordoma with fixation rods.It was shown that SE-IMPT has the potential to produce a sharp dose gradient and that it is not affected by the uncertainties produced by metal implants crossed by the proton beams. Moreover, in the chordoma patient, target coverage and organ at risk sparing of the SE-IMPT plan resulted comparable to that of the less reliable conventional IMPT technique. Robustness analysis confirmed that SE-IMPT was not affected by range errors, which can drastically affect the IMPT plan.When accepting a low-dose spread as in modern photon techniques, SE-IMPT could be an option for the treatment of lesions (e.g. cervical bone tumours) where steep dose gradient could improve curability, and where range uncertainty, due for example to the presence of metal implants, hampers conventional IMPT.

The preclinical set-up at the ID17 biomedical beamline to achieve high local dose deposition using interlaced microbeams

NASA Astrophysics Data System (ADS)

Bräuer-Krisch, E.; Nemoz, C.; Brochard, Th; Berruyer, G.; Renier, M.; Pouyatos, B.; Serduc, R.

2013-03-01

Microbeam Radiation Therapy (MRT) uses spatially a fractionated "white beam" (energies 50-350 keV) irradiation from a Synchrotron Source. The typical microbeams used at ID17 are 25-100μm-thick, spaced by 200-400μm, and carry extremely high dose rates (up to about 16 kGy/s). These microbeams are well tolerated by biological tissue, i.e. up to several hundred of Gy in the peaks. When valley doses, caused by Compton scattering in between two microbeams, remain within a dose regime similar to conventional RT, a superior tumour control can be achieved with MRT than with conventional RT. The normal tissue tolerance of these microscopically small beams is outstanding and well documented in the literature. The hypothesis of a differential effect in particular on the vasculature of normal versus tumoral tissue might best be proven by using large animal models with spontaneous tumors instead of small laboratory animals with transplantable tumors, an ongoing project on ID17. An alternative approach to deposit a high dose, while preserving the feature of the spatial separation of these microbeams outside the target has opened up new applications in preclinical research. The instrumentation of this method to produce such interlaced beams is presented with an outlook on the challenges to build a treatment platform for human patients. Dose measurements using Gafchromic films exposed in interlaced geometries with their steep profiles highlight the potential to deposit radiotoxic doses in the vicinity of radiosensitive tissues.

Rehabilitation and Flood Management Planning in a Steep, Boulder-Bedded Stream

NASA Astrophysics Data System (ADS)

Caruso, Brian S.; Downs, Peter W.

2007-08-01

This study demonstrates the integration of rehabilitation and flood management planning in a steep, boulder-bedded stream in a coastal urban catchment on the South Island of New Zealand. The Water of Leith, the primary stream flowing through the city of Dunedin, is used as a case study. The catchment is steep, with a short time of concentration and rapid hydrologic response, and the lower stream reaches are highly channelized with floodplain encroachment, a high potential for debris flows, significant flood risks, and severely degraded aquatic habitat. Because the objectives for rehabilitation and flood management in urban catchments are often conflicting, a number of types of analyses at both the catchment and the reach scales and careful planning with stakeholder consultation were needed for successful rehabilitation efforts. This included modeling and analysis of catchment hydrology, fluvial geomorphologic assessment, analysis of water quality and aquatic ecology, hydraulic modeling and flood risk evaluation, detailed feasibility studies, and preliminary design to optimize multiple rehabilitation and flood management objectives. The study showed that all of these analyses were needed for integrated rehabilitation and flood management and that some incremental improvements in stream ecological health, aesthetics, and public recreational opportunities could be achieved in this challenging environment. These methods should be considered in a range of types of stream rehabilitation projects.

Divergent phenological response to hydroclimate variability in forested mountain watersheds

Treesearch

Taehee Hwang; Lawrence E. Band; Chelcy F. Miniat; Conghe Song; Paul V . Bolstad; James M. Vose; Jason P. Love

2014-01-01

Mountain watersheds are primary sources of freshwater, carbon sequestration, and other ecosystem services. There is significant interest in the effects of climate change and variability on these processes over short to long time scales. Much of the impact of hydroclimate variability in forest ecosystems is manifested in vegetation dynamics in space and time. In steep...

Tracking rainfall impulses through progressively larger drainage basins in steep forested terrain

Treesearch

R. R. Ziemer; R. M. Rice

1990-01-01

Abstract - The precision of timing devices in modern electronic data loggers makes it possible to study the routing of water through small drainage basins having rapid responses to hydrologic impulses. Storm hyetographs were measured using digital tipping bucket rain gauges and their routing was observed at headwater piezometers located mid-slope, above a swale, and...

Selenium impacts on fish: an insidious time bomb

Treesearch

A. Dennis Lemly

1999-01-01

A selenium time bomb situation is developing in the United States and elsewhere that may result in substantial impacts on fish populations. The selenium time bomb has three components: (1) high food-chain bioaccumulation; (2) steep toxic response curve for fish; and (3) insidious mode of toxicity. If the threshold for selenium toxicity is exceeded, the time bomb...

The role of bedrock groundwater in rainfall-runoff response at hillslope and catchment scales

Treesearch

C. Gabrielli; J.J. McDonnell; W.T. Jarvis

2012-01-01

Bedrock groundwater dynamics in headwater catchments are poorly understood and poorly characterized. Direct hydrometric measurements have been limited due to the logistical challenges associated with drilling through hard rock in steep, remote and often roadless terrain. We used a new portable bedrock drilling system to explore bedrock groundwater dynamics aimed at...

Effects of climatic gradients on genetic differentiation of Caragana on the Ordos Plateau, China

Treesearch

Jiuyan Yang; Samuel A. Cushman; Jie Yang; Mingbo Yang; Tiejun Bao

2013-01-01

The genus Caragana (Fabr.) in the Ordos Plateau of Inner Mongolia, China, provides a strong opportunity to investigate patterns of genetic differentiation along steep climatic gradients, and to identify the environmental factors most likely to be responsible for driving the radiation. This study used a factorial, multi-model approach to evaluate alternative hypotheses...

77 FR 27760 - Appalachian Power Company; Notice of Application for Amendment of License and Soliciting Comments...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-11

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 739-028] Appalachian Power... relating to the merits of an issue that may affect the responsibilities of a particular resource agency... located near a stream bed in the back of a cove with a steep slope and is classified as conservation...

A response to Annette Gough and Jesse Bazzul. Subverting subjectivity: an anti-neoliberal reformulation of science education for life

NASA Astrophysics Data System (ADS)

Levinson, Ralph

2017-12-01

In responding to Jesse Bazzul's and Annette Gough's articles I maintain that contemporary positivist science curricula cannot address the urgent issues of sustainability and biopower that confront us. Drawing on the writings and interpretations of Emmanuel Levinas I argue that contemplating the meaning of responsibility to the Other is a radically subversive activity and a means of moving from the neoliberal dominance of science education towards a science one steeped in social justice.

Post-fire geomorphic response in steep, forested landscapes: Oregon Coast Range, USA

NASA Astrophysics Data System (ADS)

Jackson, Molly; Roering, Joshua J.

2009-06-01

The role of fire in shaping steep, forested landscapes depends on a suite of hydrologic, biologic, and geological characteristics, including the propensity for hydrophobic soil layers to promote runoff erosion during subsequent rainfall events. In the Oregon Coast Range, several studies postulate that fire primarily modulates sediment production via root reinforcement and shallow landslide susceptibility, although few studies have documented post-fire geomorphic response. Here, we describe field observations and topographic analyses for three sites in the central Oregon Coast Range that burned in 1999, 2002, and 2003. The fires generated strongly hydrophobic soil layers that did not promote runoff erosion because the continuity of the layers was interrupted by pervasive discontinuities that facilitated rapid infiltration. At each of our sites, fire generated significant colluvial transport via dry ravel, consistent with other field-based studies in the western United States. Fire-driven dry ravel accumulation in low-order valleys of our Sulphur Creek site equated to a slope-averaged landscape lowering of 2.5 mm. Given Holocene estimates of fire frequency, these results suggest that fire may contribute 10-20% of total denudation across steep, dissected portions of the Oregon Coast Range. In addition, we documented more rapid decline of root strength at our sites than has been observed after timber harvest, suggesting that root strength was compromised prior to fire or that intense heat damaged roots in the shallow subsurface. Given that fire frequencies in the Pacific Northwest are predicted to increase with continued climate change, our findings highlight the importance of fire-induced dry ravel and post-fire debris flow activity in controlling sediment delivery to channels.

Effect of intra-fraction motion on the accumulated dose for free-breathing MR-guided stereotactic body radiation therapy of renal-cell carcinoma

NASA Astrophysics Data System (ADS)

Stemkens, Bjorn; Glitzner, Markus; Kontaxis, Charis; de Senneville, Baudouin Denis; Prins, Fieke M.; Crijns, Sjoerd P. M.; Kerkmeijer, Linda G. W.; Lagendijk, Jan J. W.; van den Berg, Cornelis A. T.; Tijssen, Rob H. N.

2017-09-01

Stereotactic body radiation therapy (SBRT) has shown great promise in increasing local control rates for renal-cell carcinoma (RCC). Characterized by steep dose gradients and high fraction doses, these hypo-fractionated treatments are, however, prone to dosimetric errors as a result of variations in intra-fraction respiratory-induced motion, such as drifts and amplitude alterations. This may lead to significant variations in the deposited dose. This study aims to develop a method for calculating the accumulated dose for MRI-guided SBRT of RCC in the presence of intra-fraction respiratory variations and determine the effect of such variations on the deposited dose. For this, RCC SBRT treatments were simulated while the underlying anatomy was moving, based on motion information from three motion models with increasing complexity: (1) STATIC, in which static anatomy was assumed, (2) AVG-RESP, in which 4D-MRI phase-volumes were time-weighted, and (3) PCA, a method that generates 3D volumes with sufficient spatio-temporal resolution to capture respiration and intra-fraction variations. Five RCC patients and two volunteers were included and treatments delivery was simulated, using motion derived from subject-specific MR imaging. Motion was most accurately estimated using the PCA method with root-mean-squared errors of 2.7, 2.4, 1.0 mm for STATIC, AVG-RESP and PCA, respectively. The heterogeneous patient group demonstrated relatively large dosimetric differences between the STATIC and AVG-RESP, and the PCA reconstructed dose maps, with hotspots up to 40% of the D99 and an underdosed GTV in three out of the five patients. This shows the potential importance of including intra-fraction motion variations in dose calculations.

Influence of steeping solution and storage temperature on the color change of garlic.

PubMed

Bae, Song Hwan; Lee, Seog-Won; Kim, Mi-Ryung; Kim, Jin Man; Suh, Hyung Joo

2010-01-01

The objective of this study was to investigate the browning of garlic under different steeping conditions and storage temperatures. The brown indices of steeped garlics showed lowest values (7.3 and 7) in 25% and 50% EtOH at 7 d of storage. The degree of browning of steeped garlics was lowest (10.2 in 25% EtOH and 10.4 in 50% EtOH) in the samples soaked for 8 h at 13 d of storage. As the storage temperature was increased from 10 to 40 degrees C, the brown indices of garlics revealed an increasing trend relative to storage time regardless of steeping treatment. Overall, the kinetic parameters showed relatively low R(2) and irregular reaction constants, but the k(o) values showed an increasing trend with temperature under a zero-order model. The highest polyphenol content within the garlic bulbs was seen in controls (without steeping treatment, 588.9 microg/g), than 0% EtOH (water, 392.5 microg/g), than 25% EtOH (211.3 microg/g), and finally 50% EtOH (155.6 microg/g). The polyphenol oxidase activity of garlic showed a similar trend to that of polyphenol content. However, the texture properties of garlics steeped with 25% and 50% did not change. The garlic color preferred by consumers is a creamy-white, but this is susceptible to enzymatic browning when pre-peeled and chopped. When garlic was steeped in the 25% and 50% alcohol, the browning of garlic was prevented during storage.

Patient specific quality control for Stereotactic Ablative Body Radiotherapy (SABR): it takes more than one phantom

NASA Astrophysics Data System (ADS)

Kron, T.; Ungureanu, E.; Antony, R.; Hardcastle, N.; Clements, N.; Ukath, J.; Fox, C.; Lonski, P.; Wanigaratne, D.; Haworth, A.

2017-01-01

Stereotactic Ablative Body Radiotherapy (SABR) is an extension of the concepts of Stereotactic Radiosurgery from intracranial procedures to extracranial targets. This brings with it new technological challenges for set-up of a SABR program and continuing quality assurance. Compared with intracranial procedures SABR requires consideration of motion and inhomogeneities and has to deal with a much larger variety of targets ranging from lung to liver, kidney and bone. To meet many of the challenges virtually all advances in modern radiotherapy, such as Intensity Modulated and Image Guided Radiation Therapy (IMRT and IGRT) are used. Considering the few fractions and high doses per fraction delivered to complex targets it is not surprising that patient specific quality control is considered essential for safe delivery. Given the variety of targets and clinical scenarios we employ different strategies for different patients to ensure that the most important aspects of the treatment are appropriately tested, be it steep dose gradients, inhomogeneities or the delivery of dose in the presence of motion. The current paper reviews the different approaches and phantoms utilised at Peter MacCallum Cancer Centre for SABR QA.

Morpho-dynamics of mountain streams: from laboratory experiments to field observations

NASA Astrophysics Data System (ADS)

Mettra, François; Lane, Stuart Nicholas; Heyman, Joris; Ancey, Christophe

2017-04-01

Due to the complexity of mountain stream evolution and its causes, it is judicious to conduct flume experiments to better understand the morpho-dynamics of steep river channels. A series of long-term experiments under steady conditions revealed the high internal variability of transport processes (including erosion and deposition events). In particular, high fluctuations over time of the sediment volume stored in the channel (or released from the channel) were observed for the steepest channel experiments at intermittent transport conditions. These conditions imply an autogenic regulation of the sediment transport process. When these were extended to non-steady conditions, repeated flood events suggested a hysteresis effect on sediment transport but where the forcing frequency (of the repeated floods) plays an important role in the response of the channel system. The results are compared with preliminary field observations from continuous measurements in Swiss Alpine rivers. Simple mechanisms of steep river channel behavior are proposed.

Optimizing MOS-gated thyristor using voltage-based equivalent circuit model for designing steep-subthreshold-slope PN-body-tied silicon-on-insulator FET

NASA Astrophysics Data System (ADS)

Ueda, Daiki; Takeuchi, Kiyoshi; Kobayashi, Masaharu; Hiramoto, Toshiro

2018-04-01

A new circuit model that provides a clear guide on designing a MOS-gated thyristor (MGT) is reported. MGT plays a significant role in achieving a steep subthreshold slope of a PN-body tied silicon-on-insulator (SOI) FET (PNBTFET), which is an SOI MOSFET merged with an MGT. The effects of design parameters on MGT and the proposed equivalent circuit model are examined to determine how to regulate the voltage response of MGT and how to suppress power dissipation. It is demonstrated that MGT with low threshold voltages, small hysteresis widths, and small power dissipation can be designed by tuning design parameters. The temperature dependence of MGT is also examined, and it is confirmed that hysteresis width decreases with the average threshold voltage kept nearly constant as temperature rises. The equivalent circuit model can be conveniently used to design low-power PNBTFET.

Evaluation of organic matter addition and incorporation on steep cut slopes : phase I, literature review and potential applicable equipment evaluation.

DOT National Transportation Integrated Search

2003-08-01

Erosion of steep highway cut slopes in Montana is the consequence of poor vegetation development in : nutrient-poor growth media resulting from highway construction where topsoil cannot physically be : replaced due to slope steepness. A literature re...

Evaluation of organic matter compost addition and incorporation on steep cut slopes. Phase II : test plot construction and performance monitoring

DOT National Transportation Integrated Search

2007-04-01

Erosion of steep highway cut slopes in Montana is often times the consequence of poor vegetation development in nutrient-poor growth media resulting from highway construction where topsoil cannot physically be replaced due to slope steepness. Topsoil...

Evaluation of organic matter addition and incorporation on steep cut slopes : phase II, test plot construction and performance monitoring.

DOT National Transportation Integrated Search

2007-04-01

Erosion of steep highway cut slopes in Montana is often times the consequence of poor vegetation development : in nutrient-poor growth media resulting from highway construction where topsoil cannot physically be replaced : due to slope steepness. Top...

Environmental impacts of forest road construction on mountainous terrain.

PubMed

Caliskan, Erhan

2013-03-15

Forest roads are the base infrastructure foundation of forestry operations. These roads entail a complex engineering effort because they can cause substantial environmental damage to forests and include a high-cost construction. This study was carried out in four sample sites of Giresun, Trabzon(2) and Artvin Forest Directorate, which is in the Black Sea region of Turkey. The areas have both steep terrain (30-50% gradient) and very steep terrain (51-80% gradient). Bulldozers and hydraulic excavators were determined to be the main machines for forest road construction, causing environmental damage and cross sections in mountainous areas.As a result of this study, the percent damage to forests was determined as follows: on steep terrain, 21% of trees were damaged by excavators and 33% of trees were damaged by bulldozers during forest road construction, and on very steep terrain, 27% of trees were damaged by excavators and 44% of trees were damaged by bulldozers during forest road construction. It was also determined that on steep terrain, when excavators were used, 12.23% less forest area was destroyed compared with when bulldozers were used and 16.13% less area was destroyed by excavators on very steep terrain. In order to reduce the environmental damage on the forest ecosystem, especially in steep terrains, hydraulic excavators should replace bulldozers in forest road construction activities.

Plasmodium falciparum: attenuation by irradiation

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

Waki, S.; Yonome, I.; Suzuki, M.

The effect of irradiation on the in vitro growth of Plasmodium falciparum was investigated. The cultured malarial parasites at selected stages of development were exposed to gamma rays and the sensitivity of each stage was determined. The stages most sensitive to irradiation were the ring forms and the early trophozoites; late trophozoites were relatively insensitive. The greatest resistance was shown when parasites were irradiated at a time of transition from the late trophozoite and schizont stages to young ring forms. The characteristics of radiosensitive variation in the parasite cycle resembled that of mammalian cells. Growth curves of parasites exposed tomore » doses of irradiation upto 150 gray had the same slope as nonirradiated controls but parasites which were exposed to 200 gray exhibited a growth curve which was less steep than that for parasites in other groups. Less than 10 organisms survived from the 10(6) parasites exposed to this high dose of irradiation; the possibility exists of obtaining radiation-attenuated P. falciparum.« less

Response Surface Methodology for Optimizing the Production of Biosurfactant by Candida tropicalis on Industrial Waste Substrates

PubMed Central

Almeida, Darne G.; Soares da Silva, Rita de Cássia F.; Luna, Juliana M.; Rufino, Raquel D.; Santos, Valdemir A.; Sarubbo, Leonie A.

2017-01-01

Biosurfactant production optimization by Candida tropicalis UCP0996 was studied combining central composite rotational design (CCRD) and response surface methodology (RSM). The factors selected for optimization of the culture conditions were sugarcane molasses, corn steep liquor, waste frying oil concentrations and inoculum size. The response variables were surface tension and biosurfactant yield. All factors studied were important within the ranges investigated. The two empirical forecast models developed through RSM were found to be adequate for describing biosurfactant production with regard to surface tension (R2 = 0.99833) and biosurfactant yield (R2 = 0.98927) and a very strong, negative, linear correlation was found between the two response variables studied (r = −0.95). The maximum reduction in surface tension and the highest biosurfactant yield were 29.98 mNm−1 and 4.19 gL−1, respectively, which were simultaneously obtained under the optimum conditions of 2.5% waste frying oil, 2.5%, corn steep liquor, 2.5% molasses, and 2% inoculum size. To validate the efficiency of the statistically optimized variables, biosurfactant production was also carried out in 2 and 50 L bioreactors, with yields of 5.87 and 7.36 gL−1, respectively. Finally, the biosurfactant was applied in motor oil dispersion, reaching up to 75% dispersion. Results demonstrated that the CCRD was suitable for identifying the optimum production conditions and that the new biosurfactant is a promising dispersant for application in the oil industry. PMID:28223971

Coping Strategies of International Chinese Undergraduates in Response to Academic Challenges in U.S. Colleges

ERIC Educational Resources Information Center

Heng, Tang

2018-01-01

Background/Context: One in three international students in the U.S. comes from China, propelled by a steep increase in undergraduate enrollment in U.S. colleges. This phenomenon has been accompanied by negative media discourse that portrays them as needy, passive, and unable to cope with their new educational demands. Purpose/Objective: Using a…

Pre- and postfire distribution of soil water repellency in a steep chaparral watershed

Treesearch

K. R. Hubbert; P. M. Wohlgemuth; H. K. Preisler

2008-01-01

The development and nature of water repellent soils and their spatial distribution on the landscape are not well understood relative to evaluating hillslope response to fire. Soil water repellency is particularly common in chaparral communities, due in part to the coarse-textured soils, and the high resin content of the organic litter. Objectives of this study were 1)...

Deep Inspiration Breath Hold—Based Radiation Therapy: A Clinical Review

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

Boda-Heggemann, Judit, E-mail: judit.boda-heggemann@umm.de; Knopf, Antje-Christin; Simeonova-Chergou, Anna

Several recent developments in linear accelerator–based radiation therapy (RT) such as fast multileaf collimators, accelerated intensity modulation paradigms like volumeric modulated arc therapy and flattening filter-free (FFF) high-dose-rate therapy have dramatically shortened the duration of treatment fractions. Deliverable photon dose distributions have approached physical complexity limits as a consequence of precise dose calculation algorithms and online 3-dimensional image guided patient positioning (image guided RT). Simultaneously, beam quality and treatment speed have continuously been improved in particle beam therapy, especially for scanned particle beams. Applying complex treatment plans with steep dose gradients requires strategies to mitigate and compensate for motion effectsmore » in general, particularly breathing motion. Intrafractional breathing-related motion results in uncertainties in dose delivery and thus in target coverage. As a consequence, generous margins have been used, which, in turn, increases exposure to organs at risk. Particle therapy, particularly with scanned beams, poses additional problems such as interplay effects and range uncertainties. Among advanced strategies to compensate breathing motion such as beam gating and tracking, deep inspiration breath hold (DIBH) gating is particularly advantageous in several respects, not only for hypofractionated, high single-dose stereotactic body RT of lung, liver, and upper abdominal lesions but also for normofractionated treatment of thoracic tumors such as lung cancer, mediastinal lymphomas, and breast cancer. This review provides an in-depth discussion of the rationale and technical implementation of DIBH gating for hypofractionated and normofractionated RT of intrathoracic and upper abdominal tumors in photon and proton RT.« less

Mercury Reduces Avian Reproductive Success and Imposes Selection: An Experimental Study with Adult- or Lifetime-Exposure in Zebra Finch

PubMed Central

Varian-Ramos, Claire W.; Swaddle, John P.; Cristol, Daniel A.

2014-01-01

Mercury is a global pollutant that biomagnifies in food webs, placing wildlife at risk of reduced reproductive fitness and survival. Songbirds are the most diverse branch of the avian evolutionary tree; many are suffering persistent and serious population declines and we know that songbirds are frequently exposed to mercury pollution. Our objective was to determine the effects of environmentally relevant doses of mercury on reproductive success of songbirds exposed throughout their lives or only as adults. The two modes of exposure simulated philopatric species versus dispersive species, and are particularly relevant because of the heightened mercury-sensitivity of developing nervous systems. We performed a dosing study with dietary methylmercury in a model songbird species, the zebra finch (Taeniopygia guttata), at doses from 0.3 – 2.4 parts per million. Birds were exposed to mercury either as adults only or throughout their lives. All doses of mercury reduced reproductive success, with the lowest dose reducing the number of independent offspring produced in one year by 16% and the highest dose, representing approximately half the lethal dose for this species, causing a 50% reduction. While mercury did not affect clutch size or survivorship, it had the most consistent effect on the proportion of chicks that fledged from the nest, regardless of mode of exposure. Among birds exposed as adults, mercury caused a steep increase in the latency to re-nest after loss of a clutch. Birds exposed for their entire lifetimes, which were necessarily the offspring of dosed parents, had up to 50% lower reproductive success than adult-exposed birds at low doses of methylmercury, but increased reproductive success at high doses, suggesting selection for mercury tolerance at the highest level of exposure. Our results indicate that mercury levels in prey items at contaminated sites pose a significant threat to populations of songbirds through reduced reproductive success. PMID:24759822

Dosimetric impact of daily setup variations during treatment of canine nasal tumors using intensity-modulated radiation therapy.

PubMed

Deveau, Michael A; Gutiérrez, Alonso N; Mackie, Thomas R; Tomé, Wolfgang A; Forrest, Lisa J

2010-01-01

Intensity-modulated radiation therapy (IMRT) can be employed to yield precise dose distributions that tightly conform to targets and reduce high doses to normal structures by generating steep dose gradients. Because of these sharp gradients, daily setup variations may have an adverse effect on clinical outcome such that an adjacent normal structure may be overdosed and/or the target may be underdosed. This study provides a detailed analysis of the impact of daily setup variations on optimized IMRT canine nasal tumor treatment plans when variations are not accounted for due to the lack of image guidance. Setup histories of ten patients with nasal tumors previously treated using helical tomotherapy were replanned retrospectively to study the impact of daily setup variations on IMRT dose distributions. Daily setup shifts were applied to IMRT plans on a fraction-by-fraction basis. Using mattress immobilization and laser alignment, mean setup error magnitude in any single dimension was at least 2.5 mm (0-10.0 mm). With inclusions of all three translational coordinates, mean composite offset vector was 5.9 +/- 3.3 mm. Due to variations, a loss of equivalent uniform dose for target volumes of up to 5.6% was noted which corresponded to a potential loss in tumor control probability of 39.5%. Overdosing of eyes and brain was noted by increases in mean normalized total dose and highest normalized dose given to 2% of the volume. Findings suggest that successful implementation of canine nasal IMRT requires daily image guidance to ensure accurate delivery of precise IMRT distributions when non-rigid immobilization techniques are utilized. Unrecognized geographical misses may result in tumor recurrence and/or radiation toxicities to the eyes and brain.

DOSIMETRIC IMPACT OF DAILY SETUP VARIATIONS DURING TREATMENT OF CANINE NASAL TUMORS USING INTENSITY-MODULATED RADIATION THERAPY

PubMed Central

Deveau, Michael A.; Gutiérrez, Alonso N.; Mackie, Thomas R.; Tomé, Wolfgang A.; Forrest, Lisa J.

2009-01-01

Intensity-modulated radiation therapy (IMRT) can be employed to yield precise dose distributions that tightly conform to targets and reduce high doses to normal structures by generating steep dose gradients. Because of these sharp gradients, daily setup variations may have an adverse effect on clinical outcome such that an adjacent normal structure may be overdosed and/or the target may be underdosed. This study provides a detailed analysis of the impact of daily setup variations on optimized IMRT canine nasal tumor treatment plans when variations are not accounted for due to the lack of image guidance. Setup histories of ten patients with nasal tumors previously treated using helical tomotherapy were replanned retrospectively to study the impact of daily setup variations on IMRT dose distributions. Daily setup shifts were applied to IMRT plans on a fraction-by-fraction basis. Using mattress immobilization and laser alignment, mean setup error magnitude in any single dimension was at least 2.5mm (0-10.0mm). With inclusions of all three translational coordinates, mean composite offset vector was 5.9±3.3mm. Due to variations, a loss of equivalent uniform dose (EUD) for target volumes of up to 5.6% was noted which corresponded to a potential loss in TCP of 39.5%. Overdosing of eyes and brain was noted by increases in mean normalized total dose (NTDmean) and highest normalized dose given to 2% of the volume (NTD2%). Findings suggest that successful implementation of canine nasal IMRT requires daily image guidance to ensure accurate delivery of precise IMRT distributions when non-rigid immobilization techniques are utilized. Unrecognized geographical misses may result in tumor recurrence and/or radiation toxicities to the eyes and brain. PMID:20166402

A silicon strip detector array for energy verification and quality assurance in heavy ion therapy.

PubMed

Debrot, Emily; Newall, Matthew; Guatelli, Susanna; Petasecca, Marco; Matsufuji, Naruhiro; Rosenfeld, Anatoly B

2018-02-01

The measurement of depth dose profiles for range and energy verification of heavy ion beams is an important aspect of quality assurance procedures for heavy ion therapy facilities. The steep dose gradients in the Bragg peak region of these profiles require the use of detectors with high spatial resolution. The aim of this work is to characterize a one dimensional monolithic silicon detector array called the "serial Dose Magnifying Glass" (sDMG) as an independent ion beam energy and range verification system used for quality assurance conducted for ion beams used in heavy ion therapy. The sDMG detector consists of two linear arrays of 128 silicon sensitive volumes each with an effective size of 2mm × 50μm × 100μm fabricated on a p-type substrate at a pitch of 200 μm along a single axis of detection. The detector was characterized for beam energy and range verification by measuring the response of the detector when irradiated with a 290 MeV/u 12 C ion broad beam incident along the single axis of the detector embedded in a PMMA phantom. The energy of the 12 C ion beam incident on the detector and the residual energy of an ion beam incident on the phantom was determined from the measured Bragg peak position in the sDMG. Ad hoc Monte Carlo simulations of the experimental setup were also performed to give further insight into the detector response. The relative response profiles along the single axis measured with the sDMG detector were found to have good agreement between experiment and simulation with the position of the Bragg peak determined to fall within 0.2 mm or 1.1% of the range in the detector for the two cases. The energy of the beam incident on the detector was found to vary less than 1% between experiment and simulation. The beam energy incident on the phantom was determined to be (280.9 ± 0.8) MeV/u from the experimental and (280.9 ± 0.2) MeV/u from the simulated profiles. These values coincide with the expected energy of 281 MeV/u. The sDMG detector response was studied experimentally and characterized using a Monte Carlo simulation. The sDMG detector was found to accurately determine the 12 C beam energy and is suited for fast energy and range verification quality assurance. It is proposed that the sDMG is also applicable for verification of treatment planning systems that rely on particle range. © 2017 American Association of Physicists in Medicine.

Alpine debris flows triggered by a 28 July 1999 thunderstorm in the central Front Range, Colorado

NASA Astrophysics Data System (ADS)

Godt, Jonathan W.; Coe, Jeffrey A.

2007-02-01

On 28 July 1999, about 480 alpine debris flows were triggered by an afternoon thunderstorm along the Continental Divide in Clear Creek and Summit counties in the central Front Range of Colorado. The thunderstorm produced about 43 mm of rain in 4 h, 35 mm of which fell in the first 2 h. Several debris flows triggered by the storm impacted Interstate Highway 70, U.S. Highway 6, and the Arapahoe Basin ski area. We mapped the debris flows from color aerial photography and inspected many of them in the field. Three processes initiated debris flows. The first process initiated 11% of the debris flows and involved the mobilization of shallow landslides in thick, often well vegetated, colluvium. The second process, which was responsible for 79% of the flows, was the transport of material eroded from steep unvegetated hillslopes via a system of coalescing rills. The third, which has been termed the "firehose effect," initiated 10% of the debris flows and occurred where overland flow became concentrated in steep bedrock channels and scoured debris from talus deposits and the heads of debris fans. These three processes initiated high on steep hillsides (> 30°) in catchments with small contributing areas (< 8000 m 2), however, shallow landslides occurred on slopes that were significantly less steep than either overland flow process. Based on field observations and examination of soils mapping of the northern part of the study area, we identified a relation between the degree of soil development and the process type that generated debris flows. In general, areas with greater soil development were less likely to generate runoff and therefore less likely to generate debris flows by the firehose effect or by rilling. The character of the surficial cover and the spatially variable hydrologic response to intense rainfall, rather than a threshold of contributing area and topographic slope, appears to control the initiation process in the high alpine of the Front Range. Because debris flows initiated by rilling and the firehose effect tend to increase in volume as they travel downslope, these debris flows are potentially more hazardous than those initiated by shallow landslides, which tend to deposit material along their paths.

Alpine debris flows triggered by a 28 July 1999 thunderstorm in the central Front Range, Colorado

USGS Publications Warehouse

Godt, J.W.; Coe, J.A.

2007-01-01

On 28 July 1999, about 480 alpine debris flows were triggered by an afternoon thunderstorm along the Continental Divide in Clear Creek and Summit counties in the central Front Range of Colorado. The thunderstorm produced about 43??mm of rain in 4??h, 35??mm of which fell in the first 2??h. Several debris flows triggered by the storm impacted Interstate Highway 70, U.S. Highway 6, and the Arapahoe Basin ski area. We mapped the debris flows from color aerial photography and inspected many of them in the field. Three processes initiated debris flows. The first process initiated 11% of the debris flows and involved the mobilization of shallow landslides in thick, often well vegetated, colluvium. The second process, which was responsible for 79% of the flows, was the transport of material eroded from steep unvegetated hillslopes via a system of coalescing rills. The third, which has been termed the "firehose effect," initiated 10% of the debris flows and occurred where overland flow became concentrated in steep bedrock channels and scoured debris from talus deposits and the heads of debris fans. These three processes initiated high on steep hillsides (> 30??) in catchments with small contributing areas (< 8000??m2), however, shallow landslides occurred on slopes that were significantly less steep than either overland flow process. Based on field observations and examination of soils mapping of the northern part of the study area, we identified a relation between the degree of soil development and the process type that generated debris flows. In general, areas with greater soil development were less likely to generate runoff and therefore less likely to generate debris flows by the firehose effect or by rilling. The character of the surficial cover and the spatially variable hydrologic response to intense rainfall, rather than a threshold of contributing area and topographic slope, appears to control the initiation process in the high alpine of the Front Range. Because debris flows initiated by rilling and the firehose effect tend to increase in volume as they travel downslope, these debris flows are potentially more hazardous than those initiated by shallow landslides, which tend to deposit material along their paths. ?? 2006 Elsevier B.V. All rights reserved.

Optimization of polyhydroxybutyrate production by Bacillus sp. CFR 256 with corn steep liquor as a nitrogen source.

PubMed

Vijayendra, S V N; Rastogi, N K; Shamala, T R; Anil Kumar, P K; Kshama, L; Joshi, G J

2007-06-01

Polyhydroxyalkanotes (PHAs), the eco-friendly biopolymers produced by many bacteria, are gaining importance in curtailing the environmental pollution by replacing the non-biodegradable plastics derived from petroleum. The present study was carried out to economize the polyhydroxybutyrate (PHB) production by optimizing the fermentation medium using corn steep liquor (CSL), a by-product of starch processing industry, as a cheap nitrogen source, by Bacillus sp. CFR 256. Response surface methodology (RSM) was used to optimize the fermentation medium using the variables such as corn steep liquor (5-25 g l(-1)), Na(2)HPO(4) 2H(2)O (2.2-6.2 g l(-1)), KH(2)PO(4) (0.5-2.5 g l(-1)), sucrose (5-55 g l(-1)) and inoculum concentration (1-25 ml l(-1)). Central composite rotatable design (CCRD) experiments were carried out to study the complex interactions of the variables.The optimum conditions for maximum PHB production were (g l(-1)): CSL-25, Na(2)HPO(4) 2H(2)O-2.2, KH(2)PO(4) - 0.5, sucrose - 55 and inoculum - 10 (ml l(-1)). After 72 h of fermentation, the amount of PHA produced was 8.20 g l(-1) (51.20% of dry cell biomass). It is the first report on optimization of fermentation medium using CSL as a nitrogen source, for PHB production by Bacillus sp.

Effects of controlled element dynamics on human feedforward behavior in ramp-tracking tasks.

PubMed

Laurense, Vincent A; Pool, Daan M; Damveld, Herman J; van Paassen, Marinus René M; Mulder, Max

2015-02-01

In real-life manual control tasks, human controllers are often required to follow a visible and predictable reference signal, enabling them to use feedforward control actions in conjunction with feedback actions that compensate for errors. Little is known about human control behavior in these situations. This paper investigates how humans adapt their feedforward control dynamics to the controlled element dynamics in a combined ramp-tracking and disturbance-rejection task. A human-in-the-loop experiment is performed with a pursuit display and vehicle-like controlled elements, ranging from a single integrator through second-order systems with a break frequency at either 3, 2, or 1 rad/s, to a double integrator. Because the potential benefits of feedforward control increase with steeper ramp segments in the target signal, three steepness levels are tested to investigate their possible effect on feedforward control with the various controlled elements. Analyses with four novel models of the operator, fitted to time-domain data, reveal feedforward control for all tested controlled elements and both (nonzero) tested levels of ramp steepness. For the range of controlled element dynamics investigated, it is found that humans adapt to these dynamics in their feedforward response, with a close to perfect inversion of the controlled element dynamics. No significant effects of ramp steepness on the feedforward model parameters are found.

Diffusion Profiles of Health Beneficial Components from Goji Berry (Lyceum barbarum) Marinated in Alcohol and Their Antioxidant Capacities as Affected by Alcohol Concentration and Steeping Time

PubMed Central

Song, Yang; Xu, Baojun

2013-01-01

The fruit (goji berry) of Lycium barbarum, a traditional Chinese medicine, has been widely used in health diets due to its potential role in the prevention of chronic diseases. One of the most popular applications of goji berry is to make goji wine in China by steeping goji berry in grain liquor. However, how the steeping process affects antioxidant capacities and phytochemicals of goji berry is not yet fully understood. Therefore, to provide scientific data for the utilization of goji berry in the nutraceutical industry, the diffusion rate of betaine, β-carotene, phenolic compounds in goji berry and their antioxidant capacities affected by alcohol concentration and steeping time were determined by UV-Visible spectrophotometer. The results showed that low alcohol concentration (15% or 25%) would promote the diffusion of betaine and increase antioxidant activity, while high concentration (55% or 65%) would generally increase the diffusion of flavonoids and reduce antioxidant activity. The steeping time had no significant effect on the diffusion of phenolic compounds and antioxidant activities. However, all goji berry wine steeped for 14 days with different alcohol concentrations exhibited the highest betaine concentration. Current findings provide useful information for the nutraceutical industries to choose proper steeping time and alcohol concentration to yield desired health promotion components from goji. PMID:28239094

The Occurrence of Ridge-and-Runnel Beach Morphology Associated with Deep-Water Wave Steepness on New York's Ocean Coast

NASA Astrophysics Data System (ADS)

Bokuniewicz, H.; Fallon, K.

2017-12-01

The occurrences of ridge-and-runnels were documented along the ocean shoreline of New York. These ephemeral beach morphologies represent the post-storm recovery period as sand eroded from the subaerial beach makes its way back on shore. Daily images from a camera in East Hampton, NY (40.964;-72.185) were examined to look for the occurrence and duration of ridge-and-runnel events between October 2010 to November 2012 and again from February 2014 to July 2016. Seventy-five ridge-and-runnel events were seen lasting between one to seven days, and representing about 16% of the time. Deep-water wave steepness has long been used as a parameter to determine beach erosion and accretion, because steep waves remove sand from the subaerial beach and deposit it as an offshore bar which remains until waves of low steepness return it. The time series of wave steepness (NOAA Buoy 44017) was found to be dominated by rapid increases to values of about 0.06 followed by gradual decays to about 0.012. Wave steepness is positively correlated to wind speed representing the passage of mesoscale weather systems. These cycles occurred about every five days; when ridge-and runnels occurred, they appeared, on average, 2.7 days after the peak in wave steepness.

Environmental impacts of forest road construction on mountainous terrain

PubMed Central

2013-01-01

Forest roads are the base infrastructure foundation of forestry operations. These roads entail a complex engineering effort because they can cause substantial environmental damage to forests and include a high-cost construction. This study was carried out in four sample sites of Giresun, Trabzon(2) and Artvin Forest Directorate, which is in the Black Sea region of Turkey. The areas have both steep terrain (30-50% gradient) and very steep terrain (51-80% gradient). Bulldozers and hydraulic excavators were determined to be the main machines for forest road construction, causing environmental damage and cross sections in mountainous areas. As a result of this study, the percent damage to forests was determined as follows: on steep terrain, 21% of trees were damaged by excavators and 33% of trees were damaged by bulldozers during forest road construction, and on very steep terrain, 27% of trees were damaged by excavators and 44% of trees were damaged by bulldozers during forest road construction. It was also determined that on steep terrain, when excavators were used, 12.23% less forest area was destroyed compared with when bulldozers were used and 16.13% less area was destroyed by excavators on very steep terrain. In order to reduce the environmental damage on the forest ecosystem, especially in steep terrains, hydraulic excavators should replace bulldozers in forest road construction activities. PMID:23497078

Derivation of an occupational exposure limit (OEL) for methylene chloride based on acute CNS effects and relative potency analysis.

PubMed

Storm, J E; Rozman, K K

1998-06-01

The Occupational Safety and Health Administration (OSHA) methylene chloride Permissible Exposure Level (PEL) or 25 ppm is quantitatively derived from mouse tumor results observed in a high-exposure National Toxicology Program bioassay. Because this approach depends on controversial interspecies and low-dose extrapolations, the PEL itself has stimulated heated debate. Here, an alternative safety assessment for methylene chloride is presented. It is based on an acute human lowest-observed-adverse-effect level (LOAEL) of 200 ppm for subtle central nervous system (CNS) depression. Steep, parallel exposure-response curves for anesthetic and subanesthetic CNS effects associated with compounds mechanistically and structurally related to methylene chloride are shown to support a safety factor of two to account for inter-individual variability in response. LOAEL/no-observed-adverse-effect ratios for subtle CNS effects associated with structurally related solvents are shown to support a safety factor range of two to four to account for uncertainty in identifying a subthreshold exposure level. Anesthetic relative potencies and anesthetic/subanesthetic effect level ratios are shown to be constant for the compounds evaluated, demonstrating that subanesthetic relative potencies are also constant. Relative potencies among similarly derived occupational exposure limits (OELs) for solvents structurally related to methylene chloride are therefore used to validate the derived methylene chloride OEL range of 25-50 ppm. Because this safety assessment is based on human (rather than rodent) data and empirical (rather than theoretical) exposure-response relationships and is supported by relative potency analysis, it is a defensible alternative to to the OSHA risk assessment and should positively contribute to the debate regarding the appropriate basis and value for a methylene chloride PEL.

Stochastic optimization of intensity modulated radiotherapy to account for uncertainties in patient sensitivity

NASA Astrophysics Data System (ADS)

Kåver, Gereon; Lind, Bengt K.; Löf, Johan; Liander, Anders; Brahme, Anders

1999-12-01

The aim of the present work is to better account for the known uncertainties in radiobiological response parameters when optimizing radiation therapy. The radiation sensitivity of a specific patient is usually unknown beyond the expectation value and possibly the standard deviation that may be derived from studies on groups of patients. Instead of trying to find the treatment with the highest possible probability of a desirable outcome for a patient of average sensitivity, it is more desirable to maximize the expectation value of the probability for the desirable outcome over the possible range of variation of the radiation sensitivity of the patient. Such a stochastic optimization will also have to consider the distribution function of the radiation sensitivity and the larger steepness of the response for the individual patient. The results of stochastic optimization are also compared with simpler methods such as using biological response `margins' to account for the range of sensitivity variation. By using stochastic optimization, the absolute gain will typically be of the order of a few per cent and the relative improvement compared with non-stochastic optimization is generally less than about 10 per cent. The extent of this gain varies with the level of interpatient variability as well as with the difficulty and complexity of the case studied. Although the dose changes are rather small (<5 Gy) there is a strong desire to make treatment plans more robust, and tolerant of the likely range of variation of the radiation sensitivity of each individual patient. When more accurate predictive assays of the radiation sensitivity for each patient become available, the need to consider the range of variations can be reduced considerably.

Shrub succession on eight mixed-severity wildfires in western Montana, northeastern Oregon, and northern Idaho

Treesearch

Dennis E. Ferguson; John C. Byrne

2016-01-01

The response of 28 shrub species to wildfire burn severity was assessed for 8 wildfires on 6 national forests in the northern Rocky Mountains, USA. Stratified random sampling was used to choose 224 stands based on burn severity, habitat type series, slope steepness, stand height, and stand density, which resulted in 896 plots measured at approximately 2-year intervals...

Marital and Family Characteristics of the Labor Force, March 1979. Special Labor Force Report 237.

ERIC Educational Resources Information Center

Johnson, Beverly L.

The rising number of multi-earner families has been one of the most important socioeconomic developments of the 1970s; since 1970, the number of such families has increased by more than 3 million. Almost exclusively responsible for the rising number of multi-earner families have been the steep annual increases in the number and proportion of…

Feeding corn grain steeped in citric acid modulates rumen fermentation and inflammatory responses in dairy goats.

PubMed

Shen, Y Z; Ding, L Y; Chen, L M; Xu, J H; Zhao, R; Yang, W Z; Wang, H R; Wang, M Z

2018-06-04

Cereal grains treated with organic acids were proved to increase ruminal resistant starch and can relieve the risk of ruminal acidosis. However, previous study mainly focussed on acid-treated barley, the effects of organic acid-treated corn is still unknown. The objectives of this study were to evaluate whether feeding ground corn steeped in citric acid (CA) would affect ruminal pH and fermentation patterns, milk production and innate immunity responses in dairy goats. Eight ruminally cannulated Saanen dairy goats were used in a crossover designed experiment. Each experimental period was 21 day long including 14 days for adaption to new diet and 7 days for sampling and data collection. The goats were fed high-grain diet contained 30% hay and 70% corn-based concentrate. The corn was steeped either in water (control) or in 0.5% (wt/vol) CA solution for 48 h. Goats fed CA diet showed improved ruminal pH status with greater mean and minimum ruminal pH, and shorter (P<0.05) duration of ruminal pH<5.6 and less area of ruminal pH<5.6, 5.8 and 6.0. Concentration of total volatile fatty acid and molar proportion of propionate were less but the molar proportion of acetate was greater (P<0.05) in goats fed the CA diet than the control diet. Concentration of ruminal lipopolysaccharide (LPS) was lower (P<0.05) and that of lactic acid also tended (P<0.10) to be lower in goats fed CA than the control. Although dry matter intake, actual milk yield, yield and content of milk protein and lactose were not affected, the milk fat content and 4% fat-corrected milk tended (P<0.10) to be greater in goats fed CA diet. For the inflammatory responses, peripheral LPS did not differ, whereas the concentration of LPS binding protein and serum amyloid A tended (P<0.10) to be less in goats fed CA diet. Similarly, goats fed CA diet had less (P<0.05) concentration of haptoglobin and tumour necrosis factor. These results indicated that feeding ground corn treated with CA effectively improved ruminal pH status, thus alleviated the risk of ruminal acidosis, reduced inflammatory response, and tend to improve milk yield and milk fat test.

Delineation of preventative landslide buffers along steep streamside slopes in northern California

Treesearch

Jason S. Woodward; David W. Lamphear; Matthew R. House

2012-01-01

Green Diamond Resource Co (GDRCo) applies tree retention buffers to steep slopes along fish bearing (Class I) and non-fish bearing (Class II) streams that are in addition to the standard riparian management zones associated with timber harvest plans. These Steep Streamside Slope (SSS) buffers were designed to reduce the amount of sediment delivering to watercourses as...

SU-E-T-196: Comparative Analysis of Surface Dose Measurements Using MOSFET Detector and Dose Predicted by Eclipse - AAA with Varying Dose Calculation Grid Size

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

Badkul, R; Nejaiman, S; Pokhrel, D

2015-06-15

Purpose: Skin dose can be the limiting factor and fairly common reason to interrupt the treatment, especially for treating head-and-neck with Intensity-modulated-radiation-therapy(IMRT) or Volumetrically-modulated - arc-therapy (VMAT) and breast with tangentially-directed-beams. Aim of this study was to investigate accuracy of near-surface dose predicted by Eclipse treatment-planning-system (TPS) using Anisotropic-Analytic Algorithm (AAA)with varying calculation grid-size and comparing with metal-oxide-semiconductor-field-effect-transistors(MOSFETs)measurements for a range of clinical-conditions (open-field,dynamic-wedge, physical-wedge, IMRT,VMAT). Methods: QUASAR™-Body-Phantom was used in this study with oval curved-surfaces to mimic breast, chest wall and head-and-neck sites.A CT-scan was obtained with five radio-opaque markers(ROM) placed on the surface of phantom to mimic themore » range of incident angles for measurements and dose prediction using 2mm slice thickness.At each ROM, small structure(1mmx2mm) were contoured to obtain mean-doses from TPS.Calculations were performed for open-field,dynamic-wedge,physical-wedge,IMRT and VMAT using Varian-21EX,6&15MV photons using twogrid-sizes:2.5mm and 1mm.Calibration checks were performed to ensure that MOSFETs response were within ±5%.Surface-doses were measured at five locations and compared with TPS calculations. Results: For 6MV: 2.5mm grid-size,mean calculated doses(MCD)were higher by 10%(±7.6),10%(±7.6),20%(±8.5),40%(±7.5),30%(±6.9) and for 1mm grid-size MCD were higher by 0%(±5.7),0%(±4.2),0%(±5.5),1.2%(±5.0),1.1% (±7.8) for open-field,dynamic-wedge,physical-wedge,IMRT,VMAT respectively.For 15MV: 2.5mm grid-size,MCD were higher by 30%(±14.6),30%(±14.6),30%(±14.0),40%(±11.0),30%(±3.5)and for 1mm grid-size MCD were higher by 10% (±10.6), 10%(±9.8),10%(±8.0),30%(±7.8),10%(±3.8) for open-field, dynamic-wedge, physical-wedge, IMRT, VMAT respectively.For 6MV, 86% and 56% of all measured values agreed better than ±20% for 1mm and 2.5mm grid-sizes respectively. For 18MV, 56% and 18% of all measured-values agreed better than ±20% for 1mm and 2.5mm grid-sizes respectively. Conclusion: Reliable Skin-dose calculations by TPS can be very difficult due to steep dose-gradient and inaccurate beam-modelling in buildup region.Our results showed that Eclipse over-estimates surface-dose.Impact of grid-size is also significant,surface-dose increased up to 40% from 1mm to 2.5mm,however, 1mm calculated-values closely agrees with measurements. Due to large uncertnities in skin-dose predictions from TPS, outmost caution must be exercised when skin dose is evaluated,a sufficiently smaller grid-size(1mm)can improve the accuracy and MOSFETs can be used for verification.« less

Potential Risk Assessment of Mountain Torrent Disasters on Sloping Fields in China

NASA Astrophysics Data System (ADS)

GAO, X.

2017-12-01

China's sloping fields have the problems of low production and serious soil erosion, and mountain torrent disasters will bring more serious soil and water loss to traditional extensive exploitation of sloping field resources. In this paper, China's sloping fields were classified into three grades, such as slightly steep, steep and very steep grade. According to the geological hazards prevention and control regulation, the historical data of China's mountain torrent disasters were spatially interpolated and divided into five classes, such as extremely low, low, middle, high and extremely high level. And the risk level map of mountain torrents was finished in ArcGIS. By using overlaying analysis on sloping fields and risk level map, the potential risk regionalization map of sloping fields in various slope grades was obtained finally. The results shows that the very steep and steep sloping fields are mainly distributed in the first or second stage terraces in China. With the increase of hazard risk level, the area of sloping fields decreases rapidly and the sloping fields in extremely low and low risk levels of mountain torrents reach 98.9%. With the increase of slope grade, the area of sloping fields in various risk levels also declines sharply. The sloping fields take up approximately 60 65% and 26 30% in slightly steep and steep grade areas separately at different risk level. The risk regionalization map can provide effective information for returning farmland to forests or grassland and reducing water and soil erosion of sloping fields in the future.

Hydraulic properties for interrill erosion on steep slopes using a portable rainfall simulator

NASA Astrophysics Data System (ADS)

Shin, Seung Sook; Hwang, Yoonhee; Deog Park, Sang; Yun, Minu; Park, Sangyeon

2017-04-01

The hydraulic parameters for sheet flow on steep slopes have been not frequently measured because the shallow flow depth and slow flow velocity are difficult to measure. In this study hydraulic values of sheet flow were analyzed to evaluate interrill erosion on steep slopes. A portable rainfall simulator was used to conduct interrill erosion test. The kinetic energy of rainfall simulator was obtained by disdrometer being capable of measuring the drop size distribution and velocity of falling raindrops. The sheet flow velocity was determined by the taken time for a dye transferring fixed points using video images. Surface runoff discharge and sediment yield increased with increase of rainfall intensity and kinetic energy and slope steepness. Especially sediment yield was strongly correlated with sheet flow velocity. The maximum velocity of sheet flow was 2.3cm/s under rainfall intensity of 126.8mm/h and slope steepness of 53.2%. The sheet flow was laminar and subcritical flow as the flow Reynolds number and Froude number are respectively the ranges of 10 22 and 0.05 0.25. The roughness coefficient (Manning's n) for sheet flow on steep slopes was relatively large compared to them on the gentle slope. Keywords: Sheet flow velocity; Rainfall simulator; Interrill erosion; Steep slope This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIP) (No. 2015R1C1A2A01055469).

Longitudinal Stream Profile Morphology and Patterns of Knickpoint Propagation in the Bighorn Range

NASA Astrophysics Data System (ADS)

Safran, E. B.; Anderson, R. S.; Riihimaki, C. A.; Armstrong, J.

2005-12-01

The northern U. S. Rocky Mountains and the adjacent sedimentary basins are in a transient state of response to regional, Late Cenozoic exhumation. Assembling the history of landscape change there requires interpreting the morphology and genesis of transient landforms such as knickpoints in longitudinal stream profiles. We used concavity and normalized channel steepness indices to quantify the longitudinal profile morphology of >75 streams draining the east side of the Bighorn Range and the adjacent Powder River Basin. Our analyses show that individual units in the range-margin sedimentary cover rock exert a strong influence on longitudinal profile morphology. In the Tongue River and Crazy Woman Creek drainages, more than 50% of the streams examined had knickpoints localized within a resistant, siliceous dolomite. Knickpoints on most streams with drainage areas greater than ~100 km2 at the range front have migrated headward into the gneissic and plutonic core of the range. In the Clear Creek drainage, where the lateral extent of sedimentary cover rock is more restricted than in the adjacent drainages, knickpoints do not align with any particular unit. River profiles in the Powder River Basin beyond 10-20 km from the range front exhibit concavities of ~0.3-0.6 and normalized channel steepness indices of 40-60 (using 0.45 as a reference concavity). All profiles analyzed that extend into the mountain range exhibit at least one reach with exceptionally high (>2) concavity and relatively high (100-600) normalized channel steepness index, highlighting zones of transient adjustment to local base-level drop in the basin. Headwater reaches of range-draining streams exhibit variable but moderate values of concavity (0.15-0.9) and normalized channel steepness index (20-100). The varied morphology of these reaches reflects their passage across a relict surface of low relief but also the effects of glaciation and/or the signature of the narrow summit spine that caps the range.

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

High dose rate brachytherapy for oral cancer

PubMed Central

YamazakI, Hideya; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Furukawa, Souhei; Koizumi, Masahiko; Ogawa, Kazuhiko

2013-01-01

Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer. PMID:23179377

High dose rate brachytherapy for oral cancer.

PubMed

Yamazaki, Hideya; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Furukawa, Souhei; Koizumi, Masahiko; Ogawa, Kazuhiko

2013-01-01

Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer.

Spectral characterization of the LANDSAT thematic mapper sensors

NASA Technical Reports Server (NTRS)

Markham, B. L.; Barker, J. L.

1983-01-01

Data collected on the spectral characteristics of the LANDSAT-4 and LANDSAT-4 backup thematic mapper instruments, the protoflight (TM/PF) and flight (TM/F) models, respectively, are presented and analyzed. Tests were conducted on the instruments and their components to determine compliance with two sets of spectral specifications: band-by-band spectral coverage and channel-by-channel within-band spectral matching. Spectral coverage specifications were placed on: (1) band edges--points at 50% of peak response, (2) band edge slopes--steepness of rise and fall-off of response, (3) spectral flatness--evenness of response between edges, and (4) spurious system response--ratio of out-of-band response to in-band response. Compliance with the spectral coverage specifications was determined by analysis of spectral measurements on the individual components contributing to the overall spectral response: filters, detectors, and optical surfaces.

Sediment discharge from highway construction near Port Carbon, Pennsylvania

USGS Publications Warehouse

Helm, Robert E.

1978-01-01

About 16,000 tons of suspended-sediment was discharged from the basin during the construction. The highway construction produced about 8,000 tons or 50 percent of the total sediment discharge. Steep slopes, the availability of fine coal wastes, coal-washing operations, and other land uses in the basin were responsible for most of the remaining sediment discharge. Seventy percent of the total suspended-sediment discharge occurred during eight storms.

Hillslope response to knickpoint migration in the Southern Appalachians: Implications for the evolution of post-orogenic landscapes

USGS Publications Warehouse

Wegmann, S.F.G.; Franke, K.L.; Hughes, S.; Lewis, R.Q.; Lyons, N.; Paris, P.; Ross, K.; Bauer, J.B.; Witt, A.C.

2011-01-01

The southern Appalachians represent a landscape characterized by locally high topographic relief, steep slopes, and frequent mass movement in the absence of significant tectonic forcing for at least the last 200 Ma. The fundamental processes responsible for landscape evolution in a post-orogenic landscape remain enigmatic. The non-glaciated Cullasaja River basin of south-western North Carolina, with uniform lithology, frequent debris flows, and the availability of high-resolution airborne lidar DEMs, is an ideal natural setting to study landscape evolution in a post-orogenic landscape through the lens of hillslope-channel coupling. This investigation is limited to channels with upslope contributing areas >2.7 km2, a conservative estimate of the transition from fluvial to debris-flow dominated channel processes. Values of normalized hypsometry, hypsometric integral, and mean slope vs elevation are used for 14 tributary basins and the Cullasaja basin as a whole to characterize landscape evolution following upstream knickpoint migration. Results highlight the existence of a transient spatial relationship between knickpoints present along the fluvial network of the Cullasaja basin and adjacent hillslopes. Metrics of topography (relief, slope gradient) and hillslope activity (landslide frequency) exhibit significant downstream increases below the current position of major knickpoints. The transient effect of knickpoint-driven channel incision on basin hillslopes is captured by measuring the relief, mean slope steepness, and mass movement frequency of tributary basins and comparing these results with the distance from major knickpoints along the Cullasaja River. A conceptual model of area-elevation and slope distributions is presented that may be representative of post-orogenic landscape evolution in analogous geologic settings. Importantly, the model explains how knickpoint migration and channel- hillslope coupling is an important factor in tectonically-inactive (i.e. post-orogenic) orogens for the maintenance of significant relief, steep slopes, and weathering-limited hillslopes. ?? 2011 John Wiley & Sons, Ltd.

Northern Drosophila montana flies show variation both within and between cline populations in the critical day length evoking reproductive diapause.

PubMed

Lankinen, Pekka; Tyukmaeva, Venera I; Hoikkala, Anneli

2013-08-01

Reproductive diapause, and its correct timing, plays an important role in the life cycle of many insect species living in a seasonally varying environment at high latitudes. In the present paper we have documented variation in the critical day length (CDL) for adult reproductive diapause and the steepness of photoperiodic response curves (PPRCs) in seven clinal populations of Drosophila montana in Finland between the latitudes 61 and 67°N, paying special attention to variation in these traits within and between cline populations. The isofemale lines representing these populations showed a sharp transition from 0% to 100% in females' diapause incidence in the shortening day lengths, indicated by steep PPRCs. The mean CDL showed a clear latitudinal cline decreasing by 1.6h from North to South regardless of the age of the lines, variation within the populations (i.e. among lines) in this trait being up to 3h. The steepness of the PPRCs correlated with the age of the line and this trait showed no clear latitudinal cline. Further studies on a large number of lines from one D. montana population confirmed that while maintaining the flies in diapause preventing conditions in the laboratory has no effect on CDL, older lines had steeper PPRCs. High variation in CDL within and between D. montana cline populations is likely to be heritable and provide a good potential for the evolution of photoperiodic responses. Information on genetic variation in life-history traits, such as diapause, is of utmost importance for predicting the ability of insects to survive in seasonally changing environmental conditions and to respond to long term changes in the length of the growing period e.g. by postponing the timing of diapause towards shorter day length and later calendar date. Copyright © 2013 Elsevier Ltd. All rights reserved.

Compensating effect of sap velocity for stand density leads to uniform hillslope-scale forest transpiration across a steep valley cross-section

NASA Astrophysics Data System (ADS)

Renner, Maik; Hassler, Sibylle; Blume, Theresa; Weiler, Markus; Hildebrandt, Anke; Guderle, Marcus; Schymanski, Stan; Kleidon, Axel

2016-04-01

Roberts (1983) found that forest transpiration is relatively uniform across different climatic conditions and suggested that forest transpiration is a conservative process compensating for environmental heterogeneity. Here we test this hypothesis at a steep valley cross-section composed of European Beech in the Attert basin in Luxemburg. We use sapflow, soil moisture, biometric and meteorological data from 6 sites along a transect to estimate site scale transpiration rates. Despite opposing hillslope orientation, different slope angles and forest stand structures, we estimated relatively similar transpiration responses to atmospheric demand and seasonal transpiration totals. This similarity is related to a negative correlation between sap velocity and site-average sapwood area. At the south facing sites with an old, even-aged stand structure and closed canopy layer, we observe significantly lower sap velocities but similar stand-average transpiration rates compared to the north-facing sites with open canopy structure, tall dominant trees and dense understorey. This suggests that plant hydraulic co-ordination allows for flexible responses to environmental conditions leading to similar transpiration rates close to the water and energy limits despite the apparent heterogeneity in exposition, stand density and soil moisture. References Roberts, J. (1983). Forest transpiration: A conservative hydrological process? Journal of Hydrology 66, 133-141.

Site characterization and site response in Port-au-Prince, Haiti

USGS Publications Warehouse

Hough, Susan E.; Yong, Alan K.; Altidor, Jean Robert; Anglade, Dieuseul; Given, Douglas D.; Mildor, Saint-Louis

2011-01-01

Waveform analysis of aftershocks of the Mw7.0 Haiti earthquake of 12 January 2010 reveals amplification of ground motions at sites within the Cul de Sac valley in which Port-au-Prince is situated. Relative to ground motions recorded at a hard-rock reference site, peak acceleration values are amplified by a factor of approximately 1.8 at sites on low-lying Mio-Pliocene deposits in central Port-au-Prince and by a factor of approximately 2.5–3 on a steep foothill ridge in the southern Port-au-Prince metropolitan region. The observed amplitude, predominant periods, variability, and polarization of amplification are consistent with predicted topographic amplification by a steep, narrow ridge. A swath of unusually high damage in this region corresponds with the extent of the ridge where high weak-motion amplifications are observed. We use ASTER (Advanced Spaceborne Thermal Emission and Reflection Radiometer) imagery to map local geomorphology, including characterization of both near-surface and of small-scale topographic structures that correspond to zones of inferred amplification.

The Steep Nekhoroshev's Theorem

NASA Astrophysics Data System (ADS)

Guzzo, M.; Chierchia, L.; Benettin, G.

2016-03-01

Revising Nekhoroshev's geometry of resonances, we provide a fully constructive and quantitative proof of Nekhoroshev's theorem for steep Hamiltonian systems proving, in particular, that the exponential stability exponent can be taken to be {1/(2nα_1\\cdotsα_{n-2}}) ({α_i}'s being Nekhoroshev's steepness indices and {n ≥ 3} the number of degrees of freedom). On the base of a heuristic argument, we conjecture that the new stability exponent is optimal.

Characteristics of the Roof Behaviors and Mine Pressure Manifestations During the Mining of Steep Coal Seam

NASA Astrophysics Data System (ADS)

Hong-Sheng, Tu; Shi-Hao, Tu; Cun, Zhang; Lei, Zhang; Xiao-Gang, Zhang

2017-12-01

A steep seam similar simulation system was developed based on the geological conditions of a steep coal seam in the Xintie Coal Mine. Basing on similar simulation, together with theoretical analysis and field measurement, an in-depth study was conducted to characterize the fracture and stability of the roof of steep working face and calculate the width of the region backfilled with gangue in the goaf. The results showed that, as mining progressed, the immediate roof of the steep face fell upon the goaf and backfilled its lower part due to gravity. As a result, the roof in the lower part had higher stability than the roof in the upper part of the working face. The deformation and fracture of main roof mainly occurred in the upper part of the working face; the fractured main roof then formed a "voussoir beam" structure in the strata's dip direction, which was subjected to the slip- and deformation-induced instability. The stability analysis indicated that, when the dip angle increased, the rock masses had greater capacity to withstand slip-induced instability but smaller capacity to withstand deformation-induced instability. Finally, the field measurement of the forces exerted on the hydraulic supports proved the characteristics of the roof's behaviors during the mining of a steep seam.

In vivo dose verification method in catheter based high dose rate brachytherapy.

PubMed

Jaselskė, Evelina; Adlienė, Diana; Rudžianskas, Viktoras; Urbonavičius, Benas Gabrielis; Inčiūra, Arturas

2017-12-01

In vivo dosimetry is a powerful tool for dose verification in radiotherapy. Its application in high dose rate (HDR) brachytherapy is usually limited to the estimation of gross errors, due to inability of the dosimetry system/ method to record non-uniform dose distribution in steep dose gradient fields close to the radioactive source. In vivo dose verification in interstitial catheter based HDR brachytherapy is crucial since the treatment is performed inserting radioactive source at the certain positions within the catheters that are pre-implanted into the tumour. We propose in vivo dose verification method for this type of brachytherapy treatment which is based on the comparison between experimentally measured and theoretical dose values calculated at well-defined locations corresponding dosemeter positions in the catheter. Dose measurements were performed using TLD 100-H rods (6 mm long, 1 mm diameter) inserted in a certain sequences into additionally pre-implanted dosimetry catheter. The adjustment of dosemeter positioning in the catheter was performed using reconstructed CT scans of patient with pre-implanted catheters. Doses to three Head&Neck and one Breast cancer patient have been measured during several randomly selected treatment fractions. It was found that the average experimental dose error varied from 4.02% to 12.93% during independent in vivo dosimetry control measurements for selected Head&Neck cancer patients and from 7.17% to 8.63% - for Breast cancer patient. Average experimental dose error was below the AAPM recommended margin of 20% and did not exceed the measurement uncertainty of 17.87% estimated for this type of dosemeters. Tendency of slightly increasing average dose error was observed in every following treatment fraction of the same patient. It was linked to the changes of theoretically estimated dosemeter positions due to the possible patient's organ movement between different treatment fractions, since catheter reconstruction was performed for the first treatment fraction only. These findings indicate potential for further average dose error reduction in catheter based brachytherapy by at least 2-3% in the case that catheter locations will be adjusted before each following treatment fraction, however it requires more detailed investigation. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

A Role of Erythrocytes in Adenosine Monophosphate Initiation of Hypometabolism in Mammals*

PubMed Central

Daniels, Isadora Susan; Zhang, Jianfa; O'Brien, William G.; Tao, Zhenyin; Miki, Tomoko; Zhao, Zhaoyang; Blackburn, Michael R.; Lee, Cheng Chi

2010-01-01

Biochemical and mechanistic aspects into how various hypometabolic states are initiated in mammals are poorly understood. Here, we show how a state of hypometabolism is initiated by 5′-AMP uptake by erythrocytes. Wild type, ecto-5′-nucleotidase-deficient, and adenosine receptor-deficient mice undergo 5′-AMP-induced hypometabolism in a similar fashion. Injection of 5′-AMP leads to two distinct declining phases of oxygen consumption (VO2). The phase I response displays a rapid and steep decline in VO2 that is independent of body temperature (Tb) and ambient temperature (Ta). It is followed by a phase II decline that is linked to Tb and moderated by Ta. Altering the dosages of 5′-AMP from 0.25- to 2-fold does not change the phase I response. For mice, a Ta of 15 °C is effective for induction of DH with the appropriate dose of 5′-AMP. Erythrocyte uptake of 5′-AMP leads to utilization of ATP to synthesize ADP. This is accompanied by increased glucose but decreased lactate levels, suggesting that glycolysis has slowed. Reduction in glycolysis is known to stimulate erythrocytes to increase intracellular levels of 2,3-bisphosphoglycerate, a potent allosteric inhibitor of hemoglobin's affinity for oxygen. Our studies showed that both 2,3-bisphosphoglycerate and deoxyhemoglobin levels rose following 5′-AMP administration and is in parallel with the phase I decline in VO2. In summary, our investigations reveal that 5′-AMP mediated hypometabolism is probably triggered by reduced oxygen transport by erythrocytes initiated by uptake of 5′-AMP. PMID:20430891

A role of erythrocytes in adenosine monophosphate initiation of hypometabolism in mammals.

PubMed

Daniels, Isadora Susan; Zhang, Jianfa; O'Brien, William G; Tao, Zhenyin; Miki, Tomoko; Zhao, Zhaoyang; Blackburn, Michael R; Lee, Cheng Chi

2010-07-02

Biochemical and mechanistic aspects into how various hypometabolic states are initiated in mammals are poorly understood. Here, we show how a state of hypometabolism is initiated by 5'-AMP uptake by erythrocytes. Wild type, ecto-5'-nucleotidase-deficient, and adenosine receptor-deficient mice undergo 5'-AMP-induced hypometabolism in a similar fashion. Injection of 5'-AMP leads to two distinct declining phases of oxygen consumption (VO(2)). The phase I response displays a rapid and steep decline in VO(2) that is independent of body temperature (T(b)) and ambient temperature (T(a)). It is followed by a phase II decline that is linked to T(b) and moderated by T(a). Altering the dosages of 5'-AMP from 0.25- to 2-fold does not change the phase I response. For mice, a T(a) of 15 degrees C is effective for induction of DH with the appropriate dose of 5'-AMP. Erythrocyte uptake of 5'-AMP leads to utilization of ATP to synthesize ADP. This is accompanied by increased glucose but decreased lactate levels, suggesting that glycolysis has slowed. Reduction in glycolysis is known to stimulate erythrocytes to increase intracellular levels of 2,3-bisphosphoglycerate, a potent allosteric inhibitor of hemoglobin's affinity for oxygen. Our studies showed that both 2,3-bisphosphoglycerate and deoxyhemoglobin levels rose following 5'-AMP administration and is in parallel with the phase I decline in VO(2). In summary, our investigations reveal that 5'-AMP mediated hypometabolism is probably triggered by reduced oxygen transport by erythrocytes initiated by uptake of 5'-AMP.

Phosgene

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

Bast, Cheryl B; Glass-Mattie, Dana F

2009-01-01

Inhalation is the most important route of exposure for phosgene. A latency period occurs before phosgene affects the target organ, the lungs. The odor threshold is between 0.5 and 1.5 ppm, and the odor has been described as similar to newly-mown hay. Toxic effects have been reported at concentrations below the threshold. On initial exposure, phosgene can undergo hydrolysis and form hydrogen chloride which can be slightly irritating to the upper respiratory tract and eyes; the amount formed is limited by the low water solubility of phosgene. Once inhaled to the lower respiratory tract, phosgene undergoes an acylation reaction withmore » amino, hydroxyl and sulfhydryl groups causing destruction of protein, lipids, and disruption of cellular functions. In response to this destruction, after a latency period of 1-24 hours, a breakdown in the blood-air barrier occurs and protein rich fluid accumulates in the lungs. Most commonly, death occurs within 48 hours after exposure from a progressive pulmonary edema and anoxia. At very high concentrations, death can occur from acute heart failure prior to the start of the pulmonary edema. Data on humans are limited to occupational exposures or accounts from the use of phosgene in World War I. Animal studies with phosgene show a steep dose-response curve for pulmonary edema and mortality. Animal studies also indicate little species variability as all species exposed developed similar clinical signs (dyspnea, pulmonary edema, labored breathing) and histopathological lesions in the lungs. While there are no chronic animal data, subchronic studies indicate little accumulation of phosgene or increased severity of lesions with continuous exposure.« less

Individual and joint toxicity of the herbicide S-metolachlor and a metabolite, deethylatrazine on aquatic crustaceans: Difference between ecological groups.

PubMed

Maazouzi, C; Coureau, C; Piscart, C; Saplairoles, M; Baran, N; Marmonier, P

2016-12-01

We studied the individual and joint acute toxicity of S-metolachlor (SMOC) and deethylatrazine (DEA - a metabolite of atrazine) on different non-target freshwater crustaceans. We used animals from different ecological groups: two amphipods from surface running water (Gammarus pulex and Gammarus cf. orinos), an isopod from surface stagnant water (Asellus aquaticus) and an amphipod living in groundwater (Niphargus rhenorhodanensis). Organisms were exposed to different levels of SMOC and DEA, alone or in binary mixture. Temperature effect on SMOC toxicity was assessed by exposing G. pulex and N. rhenorhodanensis to SMOC at 11 °C and 15 °C. Studying mortality as the biological endpoint, N. rhenorhodanensis was more resistant than surface water species towards SMOC and DEA. Among surface water species, G. pulex was the most sensitive while Gammarus cf. orinos and A. aquaticus showed similar responses to both compounds. Temperature increase did not change SMOC toxicity but modify the shape and steepness of the dose-response curve. We used a Model Deviation Ratio (MDR) approach to evaluate the predictability of Concentration Addition (CA) and Independent Action (IA) models to mixture toxicity. Results indicated either an additive or an antagonistic or a synergistic interaction depending on the concentrations combination and the test species. Our finding conclusively show the suitability of CA and IA in predicting mixture toxicities but results should be interpreted with caution according to ecological group of exposed species in risk assessment procedures. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dose-Response Calculator for ArcGIS

USGS Publications Warehouse

Hanser, Steven E.; Aldridge, Cameron L.; Leu, Matthias; Nielsen, Scott E.

2011-01-01

The Dose-Response Calculator for ArcGIS is a tool that extends the Environmental Systems Research Institute (ESRI) ArcGIS 10 Desktop application to aid with the visualization of relationships between two raster GIS datasets. A dose-response curve is a line graph commonly used in medical research to examine the effects of different dosage rates of a drug or chemical (for example, carcinogen) on an outcome of interest (for example, cell mutations) (Russell and others, 1982). Dose-response curves have recently been used in ecological studies to examine the influence of an explanatory dose variable (for example, percentage of habitat cover, distance to disturbance) on a predicted response (for example, survival, probability of occurrence, abundance) (Aldridge and others, 2008). These dose curves have been created by calculating the predicted response value from a statistical model at different levels of the explanatory dose variable while holding values of other explanatory variables constant. Curves (plots) developed using the Dose-Response Calculator overcome the need to hold variables constant by using values extracted from the predicted response surface of a spatially explicit statistical model fit in a GIS, which include the variation of all explanatory variables, to visualize the univariate response to the dose variable. Application of the Dose-Response Calculator can be extended beyond the assessment of statistical model predictions and may be used to visualize the relationship between any two raster GIS datasets (see example in tool instructions). This tool generates tabular data for use in further exploration of dose-response relationships and a graph of the dose-response curve.

The frequency of U-shaped dose responses in the toxicological literature.

PubMed

Calabrese, E J; Baldwin, L A

2001-08-01

Hormesis has been defined as a dose-response relationship in which there is a stimulatory response at low doses, but an inhibitory response at high doses, resulting in a U- or inverted U-shaped dose response. To assess the proportion of studies satisfying criteria for evidence of hormesis, a database was created from published toxicological literature using rigorous a priori entry and evaluative criteria. One percent (195 out of 20,285) of the published articles contained 668 dose-response relationships that met the entry criteria. Subsequent application of evaluative criteria revealed that 245 (37% of 668) dose-response relationships from 86 articles (0.4% of 20,285) satisfied requirements for evidence of hormesis. Quantitative evaluation of false-positive and false-negative responses indicated that the data were not very susceptible to such influences. A complementary analysis of all dose responses assessed by hypothesis testing or distributional analyses, where the units of comparison were treatment doses below the NOAEL, revealed that of 1089 doses below the NOAEL, 213 (19.5%) satisfied statistical significance or distributional data evaluative criteria for hormesis, 869 (80%) did not differ from the control, and 7 (0.6%) displayed evidence of false-positive values. The 32.5-fold (19.5% vs 0.6%) greater occurrence of hormetic responses than a response of similar magnitude in the opposite (negative) direction strongly supports the nonrandom nature of hormetic responses. This study, which provides the first documentation of a data-derived frequency of hormetic responses in the toxicologically oriented literature, indicates that when the study design satisfies a priori criteria (i.e., a well-defined NOAEL, > or = 2 doses below the NOAEL, and the end point measured has the capacity to display either stimulatory or inhibitory responses), hormesis is frequently encountered and is broadly represented according to agent, model, and end point. These findings have broad-based implications for study design, risk assessment methods, and the establishment of optimal drug doses and suggest important evolutionarily adaptive strategies for dose-response relationships.

The Model Averaging for Dichotomous Response Benchmark Dose (MADr-BMD) Tool

EPA Pesticide Factsheets

Providing quantal response models, which are also used in the U.S. EPA benchmark dose software suite, and generates a model-averaged dose response model to generate benchmark dose and benchmark dose lower bound estimates.

[Proton imaging applications for proton therapy: state of the art].

PubMed

Amblard, R; Floquet, V; Angellier, G; Hannoun-Lévi, J M; Hérault, J

2015-04-01

Proton therapy allows a highly precise tumour volume irradiation with a low dose delivered to the healthy tissues. The steep dose gradients observed and the high treatment conformity require a precise knowledge of the proton range in matter and the target volume position relative to the beam. Thus, proton imaging allows an improvement of the treatment accuracy, and thereby, in treatment quality. Initially suggested in 1963, radiographic imaging with proton is still not used in clinical routine. The principal difficulty is the lack of spatial resolution, induced by the multiple Coulomb scattering of protons with nuclei. Moreover, its realization for all clinical locations requires relatively high energies that are previously not considered for clinical routine. Abandoned for some time in favor of X-ray technologies, research into new imaging methods using protons is back in the news because of the increase of proton radiation therapy centers in the world. This article exhibits a non-exhaustive state of the art in proton imaging. Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Modeling Rabbit Responses to Single and Multiple Aerosol ...

EPA Pesticide Factsheets

Journal Article Survival models are developed here to predict response and time-to-response for mortality in rabbits following exposures to single or multiple aerosol doses of Bacillus anthracis spores. Hazard function models were developed for a multiple dose dataset to predict the probability of death through specifying dose-response functions and the time between exposure and the time-to-death (TTD). Among the models developed, the best-fitting survival model (baseline model) has an exponential dose-response model with a Weibull TTD distribution. Alternative models assessed employ different underlying dose-response functions and use the assumption that, in a multiple dose scenario, earlier doses affect the hazard functions of each subsequent dose. In addition, published mechanistic models are analyzed and compared with models developed in this paper. None of the alternative models that were assessed provided a statistically significant improvement in fit over the baseline model. The general approach utilizes simple empirical data analysis to develop parsimonious models with limited reliance on mechanistic assumptions. The baseline model predicts TTDs consistent with reported results from three independent high-dose rabbit datasets. More accurate survival models depend upon future development of dose-response datasets specifically designed to assess potential multiple dose effects on response and time-to-response. The process used in this paper to dev

Installation Restoration Program Preliminary Assessment Bear Creek Radio Relay Station, Alaska

DTIC Science & Technology

1989-04-01

Cryachrepts, very gravelly, hilly to steep - Histic Pergelic Cryaquepts, loamy, nearly to rolling association. This association is extensive on hilly...loam. On steep slopes, these soils are only 20 to 40 inches deep over bedrock. 3 Histic Pergelic Cryaquepts, loamy, nearly level to rolling, make up 25...usually 10 to 20 inches below the peaty surface. 3 Histic Pergelic Cryaquepts, very gravelly, hilly to steep, compose 10 percent of this association. These

Turbulence Simulation of Laboratory Wind-Wave Interaction in High Winds and Upscaling to Ocean Conditions

DTIC Science & Technology

2016-12-22

investigated air-sea fluxes characterized by strong air flow separation over a very steep wave field. We first investigated propagating steep wave...mechanisms for flow separation over rigid surfaces compared with unsteady surfaces with a boundary slip velocity. We investigated passive scalar fluxes. In...turbulent flow over steep stationary roughness, the primary mechanism for momentum flux is via pressure drag resulting from flow separation. However

Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor

PubMed Central

1994-01-01

Interleukin 15 (IL-15) is a novel cytokine that has recently been cloned and expressed. Whereas it has no sequence homology with IL-2, IL- 15 interacts with components of the IL-2 receptor (IL-2R). In the present study we performed a functional analysis of recombinant IL-15 on phenotypically and functionally distinct populations of highly purified human natural killer (NK) cells. The CD56bright subset of human NK cells constitutively expresses the high affinity IL-2R and exhibits a brisk proliferative response after the binding of picomolar amounts of IL-2. Using a proliferation assay, IL-15 demonstrated a very steep dose-response curve that was distinct from the dose-response curve for IL-2. The proliferative effects of IL-15 could be abrogated by anti-IL-2R beta (p75), but not by anti-IL-2R alpha (p55). The proliferative effects of IL-2 on CD56bright NK cells could be inhibited by both antibodies. CD56dim NK cells express the intermediate affinity IL-2R in the absence of the high affinity IL-2R. Activation of CD56dim NK cells by IL-15 was similar to that of IL-2 as measured by enhanced NK cytotoxic activity, antibody-dependent cellular cytotoxicity, and NK cell production of interferon gamma, tumor necrosis factor alpha, and granulocyte/macrophage colony-stimulating factor. The IL-15-enhanced NK cytotoxic activity could be completely blocked by anti-IL-2R beta monoclonal antibody. The binding of radiolabeled IL-2 and IL-15 to CD56dim NK cells was inhibited in the presence of anti-IL-2R beta. Scatchard analysis of radiolabeled IL-15 and IL-2 binding to NK- enriched human lymphocytes revealed the presence of high and intermediate affinity receptors for both ligands. IL-15 is a ligand that activates human NK cells through components of the IL-2R in a pattern that is similar but not identical to that of IL-2. Unlike IL-2, IL-15 is produced by activated monocytes/macrophages. The discovery of IL-15 may increase our understanding of how monocytes/macrophages participate in the regulation of NK cell function. PMID:7523571

Comparison of two dosing schedules for subcutaneous injections of low-dose anti-CD20 veltuzumab in relapsed immune thrombocytopenia

PubMed Central

Liebman, Howard A.; Saleh, Mansoor N.; Bussel, James B.; Negrea, O. George; Horne, Heather; Wegener, William A.; Goldenberg, David M.

2016-01-01

We compared two dosing schedules for subcutaneous injections of a low-dose humanized anti-CD20 antibody, veltuzumab, in immune thrombocytopenia. Fifty adults with primary immune thrombocytopenia, in whom one or more lines of standard therapy had failed and who had a platelet count <30×109/L but no major bleeding, initially received escalating 80, 160, or 320 mg doses of subcutaneous veltuzumab administered twice, 2 weeks apart; the last group received once-weekly doses of 320 mg for 4 weeks. In all dose groups, injection reactions were transient and mild to moderate; there were no other safety issues. Forty-seven response-evaluable patients had 23 (49%) objective responses (platelet counts ≥30×109/L and ≥2 × baseline) including 15 (32%) complete responses (platelets ≥100×109/L). Responses (including complete responses) and bleeding reduction occurred in all dose groups and were not dose-dependent. In contrast, response duration increased progressively with total dose, reaching a median of 2.7 years with the four once-weekly 320-mg doses. Among nine responders retreated at relapse, three at higher dose levels responded again, including one patient who was retreated four times. In all dose groups, B-cell depletion occurred after the first dose until recovery starting 12 to 16 weeks after treatment. Veltuzumab serum levels increased with dose group according to total dose administered, but terminal half-life and clearance were comparable. Human anti-veltuzumab antibody titers developed without apparent dose dependence in nine patients, of whom six responded including five who had complete responses. Subcutaneous veltuzumab was convenient, well-tolerated, and active, without causing significant safety concerns. Platelet responses and bleeding reduction occurred in all dose groups, and response durability appeared to improve with higher doses. Clinicaltrials.gov identifier: NCT00547066 PMID:27515248

Evaluation and implementation of triple‐channel radiochromic film dosimetry in brachytherapy

PubMed Central

Bradley, David; Nisbet, Andrew

2014-01-01

The measurement of dose distributions in clinical brachytherapy, for the purpose of quality control, commissioning or dosimetric audit, is challenging and requires development. Radiochromic film dosimetry with a commercial flatbed scanner may be suitable, but careful methodologies are required to control various sources of uncertainty. Triple‐channel dosimetry has recently been utilized in external beam radiotherapy to improve the accuracy of film dosimetry, but its use in brachytherapy, with characteristic high maximum doses, steep dose gradients, and small scales, has been less well researched. We investigate the use of advanced film dosimetry techniques for brachytherapy dosimetry, evaluating uncertainties and assessing the mitigation afforded by triple‐channel dosimetry. We present results on postirradiation film darkening, lateral scanner effect, film surface perturbation, film active layer thickness, film curling, and examples of the measurement of clinical brachytherapy dose distributions. The lateral scanner effect in brachytherapy film dosimetry can be very significant, up to 23% dose increase at 14 Gy, at ± 9 cm lateral from the scanner axis for simple single‐channel dosimetry. Triple‐channel dosimetry mitigates the effect, but still limits the useable width of a typical scanner to less than 8 cm at high dose levels to give dose uncertainty to within 1%. Triple‐channel dosimetry separates dose and dose‐independent signal components, and effectively removes disturbances caused by film thickness variation and surface perturbations in the examples considered in this work. The use of reference dose films scanned simultaneously with brachytherapy test films is recommended to account for scanner variations from calibration conditions. Postirradiation darkening, which is a continual logarithmic function with time, must be taken into account between the reference and test films. Finally, films must be flat when scanned to avoid the Callier‐like effects and to provide reliable dosimetric results. We have demonstrated that radiochromic film dosimetry with GAFCHROMIC EBT3 film and a commercial flatbed scanner is a viable method for brachytherapy dose distribution measurement, and uncertainties may be reduced with triple‐channel dosimetry and specific film scan and evaluation methodologies. PACS numbers: 87.55.Qr, 87.56.bg, 87.55.km PMID:25207417

Simultaneous integrated protection : A new concept for high-precision radiation therapy.

PubMed

Brunner, Thomas B; Nestle, Ursula; Adebahr, Sonja; Gkika, Eleni; Wiehle, Rolf; Baltas, Dimos; Grosu, Anca-Ligia

2016-12-01

Stereotactic radiotherapy near serial organs at risk (OAR) requires special caution. A novel intensity-modulated radiotherapy (IMRT) prescription concept termed simultaneous integrated protection (SIP) for quantifiable and comparable dose prescription to targets very close to OAR is described. An intersection volume of a planning risk volume (PRV) with the total planning target volume (PTV) defined the protection volume (PTV SIP ). The remainder of the PTV represented the dominant PTV (PTV dom ). Planning was performed using IMRT. Dose was prescribed to PTV dom according to ICRU in 3, 5, 8, or 12 fractions. Constraints to OARs were expressed as absolute and as equieffective doses at 2 Gy (EQD2). Dose to the gross risk volume of an OAR was to respect constraints. Violation of constraints to OAR triggered a planning iteration at increased fractionation. Dose to PTV SIP was required to be as high as possible within the constraints to avoid local relapse. SIP was applied in 6 patients with OAR being large airways (n = 2) or bowel (n = 4) in 3, 5, 8, and 12 fractions in 1, 3, 1, and 1 patients, respectively. PTVs were 14.5-84.9 ml and PTV SIP 1.8-3.9 ml (2.9-13.4 % of PTV). Safety of the plans was analyzed from the absolute dose-volume histogram (dose to ml). The steepness of dose fall-off could be determined by comparing the dose constraints to the PRVs with those to the OARs (Wilcoxon test p = 0.001). Constraints were respected for the corresponding OARs. All patients had local control at a median 9 month follow-up and toxicity was low. SIP results in a median dose of ≥100 % to PTV, to achieve high local control and low toxicity. Longer follow-up is required to verify results and a prospective clinical trial is currently testing this new approach in chest and abdomen stereotactic body radiotherapy.

Rainfall and sheet power model for interrill erosion in steep slope

NASA Astrophysics Data System (ADS)

Shin, Seung Sook; Deog Park, Sand; Nam, Myeong Jun

2015-04-01

The two-phase process of interrill erosion consist of the splash and detachment of individual particles from soil mass by impact of raindrops and the transport by erosive running water. Most experimental results showed that the effect of interaction between rainfall impact and surface runoff increases soil erosion in low or gentle slope. Especially, the combination of rain splash and sheet flow is the dominant runoff and erosion mechanism occurring on most steep hillslopes. In this study, a rainfall simulation was conducted to evaluate interrill erosion in steep slope with cover or non-cover. The kinetic energy of raindrops of rainfall simulator was measured by disdrometer used to measure the drop size distribution and velocity of falling raindrops and showed about 0.563 rate of that calculated from empirical equation between rainfall kinetic energy and rainfall intensity. Surface and subsurface runoff and sediment yield depended on rainfall intensity, gradient of slope, and existence of cover. Sediment from steep plots under rainfall simulator is greatly reduced by existence of the strip cover that the kinetic energy of raindrop approximates to zero. Soil erosion in steep slope with non-cover was nearly 4.93 times of that measured in plots with strip cover although runoff was only 1.82 times. The equation of a rainfall and sheet power was used to evaluate sediment yields in steep slope with cover or non-cover. The power model successfully explained physical processes for interrill erosion that combination of raindrop impact and sheet flow increases greatly soil erosion in steep slope. This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education, Science and Technology(No. 2013R1A1A3011962).

Environmentally Preferred Coatings for Steel

NASA Technical Reports Server (NTRS)

Kessel, Kurt R.

2016-01-01

NASA is responsible for a number of facilities and structures with metallic structural and nonstructural components in a highly corrosive environment. Metals require periodic maintenance activity to guard against the insidious effects of corrosion and thus ensure that structures meet or exceed design or performance life. The deleterious effects of corrosion result in steep costs, asset downtime affecting mission readiness, and safety risks to personnel. It is vital to reduce corrosion costs and risks in a sustainable manner.

Rock gabion, rock armoring, and culvert treatments contributing to and reducing erosion during post-wildfire flooding - Schultz Fire 2010

Treesearch

Daniel G. Neary; Karen A. Koestner; Ann Youberg

2011-01-01

The Schultz Fire burned 6,100 ha on the eastern slopes of the San Francisco Peaks of the Coconino National Forest in north-central Arizona. The fire burned between June 20th and 30th, 2010, across moderate to very steep ponderosa pine and mixed conifer watersheds. One of the Burned Area Emergency Response treatments on Coconino National Forest lands consisted of the...

Probabilistic assessment method of the non-monotonic dose-responses-Part I: Methodological approach.

PubMed

Chevillotte, Grégoire; Bernard, Audrey; Varret, Clémence; Ballet, Pascal; Bodin, Laurent; Roudot, Alain-Claude

2017-08-01

More and more studies aim to characterize non-monotonic dose response curves (NMDRCs). The greatest difficulty is to assess the statistical plausibility of NMDRCs from previously conducted dose response studies. This difficulty is linked to the fact that these studies present (i) few doses tested, (ii) a low sample size per dose, and (iii) the absence of any raw data. In this study, we propose a new methodological approach to probabilistically characterize NMDRCs. The methodology is composed of three main steps: (i) sampling from summary data to cover all the possibilities that may be presented by the responses measured by dose and to obtain a new raw database, (ii) statistical analysis of each sampled dose-response curve to characterize the slopes and their signs, and (iii) characterization of these dose-response curves according to the variation of the sign in the slope. This method allows characterizing all types of dose-response curves and can be applied both to continuous data and to discrete data. The aim of this study is to present the general principle of this probabilistic method which allows to assess the non-monotonic dose responses curves, and to present some results. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inactivation of tannins in milled sorghum grain through steeping in dilute NaOH solution.

PubMed

Adetunji, Adeoluwa I; Duodu, Kwaku G; Taylor, John R N

2015-05-15

Steeping milled sorghum in up to 0.4% NaOH was investigated as a method of tannin inactivation. NaOH steeping substantially reduced assayable total phenols and tannins in both Type III and Type II sorghums and with Type III sorghum caused a 60-80% reduction in α-amylase inhibition compared to a 20% reduction by water steeping. NaOH treatment also reduced starch liquefaction time and increased free amino nitrogen. Type II tannin sorghum did not inhibit α-amylase and consequently the NaOH treatment had no effect. HPLC and LC-MS of the tannin extracts indicated a general trend of increasing proanthocyanidin/procyanidin size with increasing NaOH concentration and steeping time, coupled with a reduction in total area of peaks resolved. These show that the NaOH treatment forms highly polymerised tannin compounds, too large to assay and to interact with the α-amylase. NaOH pre-treatment of Type III sorghums could enable their utilisation in bioethanol production. Copyright © 2014 Elsevier Ltd. All rights reserved.

Post-wildfire landscape change and erosional processes from repeat terrestrial lidar in a steep headwater catchment, Chiricahua Mountains, Arizona, USA

NASA Astrophysics Data System (ADS)

DeLong, Stephen B.; Youberg, Ann M.; DeLong, Whitney M.; Murphy, Brendan P.

2018-01-01

Flooding and erosion after wildfires present increasing hazard as climate warms, semi-arid lands become drier, population increases, and the urban interface encroaches farther into wildlands. We quantify post-wildfire erosion in a steep, initially unchannelized, 7.5 ha headwater catchment following the 2011 Horseshoe 2 Fire in the Chiricahua Mountains of southeastern Arizona. Using time-lapse cameras, rain gauges, and repeat surveys by terrestrial laser scanner, we quantify the response of a burned landscape to subsequent precipitation events. Repeat surveys provide detailed pre-and post-rainfall measurements of landscape form associated with a range of weather events. The first post-fire precipitation led to sediment delivery equivalent to 0.017 m of erosion from hillslopes and 0.12 m of erosion from colluvial hollows. Volumetrically, 69% of sediment yield was generated from hillslope erosion and 31% was generated from gully channel establishment in colluvial hollows. Processes on hillslopes included erosion by extensive shallow overland flow, formation of rills and gullies, and generation of sediment-laden flows and possibly debris flows. Subsequent smaller rain events caused ongoing hillslope erosion and local deposition and erosion in gullies. Winter freeze-thaw led to soil expansion, likely related to frost-heaving, causing a net centimeter-scale elevation increase across soil-mantled slopes. By characterizing landscape form, the properties of near-surface materials, and measuring both precipitation and landscape change, we can improve our empirical understanding of landscape response to environmental forcing. This detailed approach to studying landscape response to wildfires may be useful in the improvement of predictive models of flood, debris flow and sedimentation hazards used in post-wildfire response assessments and land management, and may help improve process-based models of landscape evolution.

Post-wildfire landscape change and erosional processes from repeat terrestrial lidar in a steep headwater catchment, Chiricahua Mountains, Arizona, USA

USGS Publications Warehouse

DeLong, Stephen B.; Youberg, Ann M.; DeLong, Whitney M.; Murphy, Brendan P.

2018-01-01

Flooding and erosion after wildfires present increasing hazard as climate warms, semi-arid lands become drier, population increases, and the urban interface encroaches farther into wildlands. We quantify post-wildfire erosion in a steep, initially unchannelized, 7.5 ha headwater catchment following the 2011 Horseshoe 2 Fire in the Chiricahua Mountains of southeastern Arizona. Using time-lapse cameras, rain gauges, and repeat surveys by terrestrial laser scanner, we quantify the response of a burned landscape to subsequent precipitation events. Repeat surveys provide detailed pre-and post-rainfall measurements of landscape form associated with a range of weather events. The first post-fire precipitation led to sediment delivery equivalent to 0.017 m of erosion from hillslopes and 0.12 m of erosion from colluvial hollows. Volumetrically, 69% of sediment yield was generated from hillslope erosion and 31% was generated from gully channel establishment in colluvial hollows. Processes on hillslopes included erosion by extensive shallow overland flow, formation of rills and gullies, and generation of sediment-laden flows and possibly debris flows. Subsequent smaller rain events caused ongoing hillslope erosion and local deposition and erosion in gullies. Winter freeze-thaw led to soil expansion, likely related to frost-heaving, causing a net centimeter-scale elevation increase across soil-mantled slopes. By characterizing landscape form, the properties of near-surface materials, and measuring both precipitation and landscape change, we can improve our empirical understanding of landscape response to environmental forcing. This detailed approach to studying landscape response to wildfires may be useful in the improvement of predictive models of flood, debris flow and sedimentation hazards used in post-wildfire response assessments and land management, and may help improve process-based models of landscape evolution.

Plasma response measurements of non-axisymmetric magnetic perturbations on DIII-D via soft x-ray imaging

DOE PAGES

Shafer, Morgan W.; Unterberg, Ezekial A.; Wingen, Andreas; ...

2014-12-29

Recent observations on DIII-D have advanced the understanding of plasma response to applied resonant magnetic perturbations (RMPs) in both H-mode and L-mode plasmas. Three distinct 3D features localized in minor radius are imaged via filtered soft x-ray emission: (i) the formation of lobes extending from the unperturbed separatrix in the X-point region at the plasma boundary, (ii) helical kink-like perturbations in the steep-gradient region inside the separatrix, and (iii) amplified islands in the core of a low-rotation L-mode plasma. In this study, these measurements are used to test and to validate plasma response models, which are crucial for providing predictivemore » capability of edge-localized mode control. In particular, vacuum and two-fluid resistive magnetohydrodynamic(MHD) responses are tested in the regions of these measurements. At the plasma boundary in H-mode discharges with n = 3 RMPs applied, measurements compare well to vacuum-field calculations that predict lobe structures. Yet in the steep-gradient region, measurements agree better with calculations from the linear resistive two-fluid MHD code, M3D-C1. Relative to the vacuum fields, the resistive two-fluid MHD calculations show a reduction in the pitch-resonant components of the normal magnetic field (screening), and amplification of non-resonant components associated with ideal kink modes. However, the calculations still over-predict the amplitude of the measuredperturbation by a factor of 4. In a slowly rotating L-mode plasma with n = 1 RMPs, core islands are observed amplified from vacuum predictions. Finally, these results indicate that while the vacuum approach describes measurements in the edge region well, it is important to include effects of extended MHD in the pedestal and deeper in the plasma core.« less

Nonmonotonic Dose-Response Curves and Endocrine-Disrupting Chemicals: Fact or Falderal?**

EPA Science Inventory

Nonmonotonic Dose-Response Curves and Endocrine-Disrupting Chemicals: Fact or Falderal? The shape of the dose response curve in the low dose region has been debated since the 1940s, originally focusing on linear no threshold (LNT) versus threshold responses for cancer and noncanc...

A MULTIMODEL APPROACH FOR CALCULATING BENCHMARK DOSE

EPA Science Inventory

A Multimodel Approach for Calculating Benchmark Dose
Ramon I. Garcia and R. Woodrow Setzer

In the assessment of dose response, a number of plausible dose- response models may give fits that are consistent with the data. If no dose response formulation had been speci...

Simple steep-axis marking technique using a corneal analyzer.

PubMed

Ng, Alex L K; Chan, Tommy C Y; Jhanji, Vishal; Cheng, George P M

2017-02-01

We describe a simple steep-axis marking technique that uses a corneal analyzer (OPD III scan) during arcuate keratotomy in femtosecond laser-assisted cataract surgery. The technique requires a single reference mark at the limbus, which does not have to be on the horizontal axis. Using the corneal analyzer, the angle between the steep axis and the reference line between the reference mark and the center of the cornea can be determined. The angle from the reference mark is used intraoperatively to locate the steep axis. This eliminates the potential error from different head positions during keratometry measurement and during traditional marking under the slitlamp. The marking technique can also be applied to toric intraocular lens implantation during cataract surgery. Copyright © 2017 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

The use of mode of action information in risk assessment: quantitative key events/dose-response framework for modeling the dose-response for key events.

PubMed

Simon, Ted W; Simons, S Stoney; Preston, R Julian; Boobis, Alan R; Cohen, Samuel M; Doerrer, Nancy G; Fenner-Crisp, Penelope A; McMullin, Tami S; McQueen, Charlene A; Rowlands, J Craig

2014-08-01

The HESI RISK21 project formed the Dose-Response/Mode-of-Action Subteam to develop strategies for using all available data (in vitro, in vivo, and in silico) to advance the next-generation of chemical risk assessments. A goal of the Subteam is to enhance the existing Mode of Action/Human Relevance Framework and Key Events/Dose Response Framework (KEDRF) to make the best use of quantitative dose-response and timing information for Key Events (KEs). The resulting Quantitative Key Events/Dose-Response Framework (Q-KEDRF) provides a structured quantitative approach for systematic examination of the dose-response and timing of KEs resulting from a dose of a bioactive agent that causes a potential adverse outcome. Two concepts are described as aids to increasing the understanding of mode of action-Associative Events and Modulating Factors. These concepts are illustrated in two case studies; 1) cholinesterase inhibition by the pesticide chlorpyrifos, which illustrates the necessity of considering quantitative dose-response information when assessing the effect of a Modulating Factor, that is, enzyme polymorphisms in humans, and 2) estrogen-induced uterotrophic responses in rodents, which demonstrate how quantitative dose-response modeling for KE, the understanding of temporal relationships between KEs and a counterfactual examination of hypothesized KEs can determine whether they are Associative Events or true KEs.

Dynamic gamma knife radiosurgery

NASA Astrophysics Data System (ADS)

Luan, Shuang; Swanson, Nathan; Chen, Zhe; Ma, Lijun

2009-03-01

Gamma knife has been the treatment of choice for various brain tumors and functional disorders. Current gamma knife radiosurgery is planned in a 'ball-packing' approach and delivered in a 'step-and-shoot' manner, i.e. it aims to 'pack' the different sized spherical high-dose volumes (called 'shots') into a tumor volume. We have developed a dynamic scheme for gamma knife radiosurgery based on the concept of 'dose-painting' to take advantage of the new robotic patient positioning system on the latest Gamma Knife C™ and Perfexion™ units. In our scheme, the spherical high dose volume created by the gamma knife unit will be viewed as a 3D spherical 'paintbrush', and treatment planning reduces to finding the best route of this 'paintbrush' to 'paint' a 3D tumor volume. Under our dose-painting concept, gamma knife radiosurgery becomes dynamic, where the patient moves continuously under the robotic positioning system. We have implemented a fully automatic dynamic gamma knife radiosurgery treatment planning system, where the inverse planning problem is solved as a traveling salesman problem combined with constrained least-square optimizations. We have also carried out experimental studies of dynamic gamma knife radiosurgery and showed the following. (1) Dynamic gamma knife radiosurgery is ideally suited for fully automatic inverse planning, where high quality radiosurgery plans can be obtained in minutes of computation. (2) Dynamic radiosurgery plans are more conformal than step-and-shoot plans and can maintain a steep dose gradient (around 13% per mm) between the target tumor volume and the surrounding critical structures. (3) It is possible to prescribe multiple isodose lines with dynamic gamma knife radiosurgery, so that the treatment can cover the periphery of the target volume while escalating the dose for high tumor burden regions. (4) With dynamic gamma knife radiosurgery, one can obtain a family of plans representing a tradeoff between the delivery time and the dose distributions, thus giving the clinician one more dimension of flexibility of choosing a plan based on the clinical situations.

Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

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

Appelt, Ane L., E-mail: ane.lindegaard.appelt@slb.regionsyddanmark.dk; University of Southern Denmark, Odense; Ploen, John

2013-01-01

Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from themore » histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D{sub 50,i}, and the normalized dose-response gradient, {gamma}{sub 50,i}. Results: A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D{sub 50,TRG1} = 92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), {gamma}{sub 50,TRG1} = 0.982 (CI 0.533-1.429), and for major response (TRG1-2) D{sub 50,TRG1} and {sub 2} = 72.1 Gy (CI 65.3-94.0 Gy), {gamma}{sub 50,TRG1} and {sub 2} = 0.770 (CI 0.338-1.201). Tumor size and N category both had a significant effect on the dose-response relationships. Conclusions: This study demonstrated a significant dose-response relationship for tumor regression after preoperative CRT for locally advanced rectal cancer for tumor dose levels in the range of 50.4-70 Gy, which is higher than the dose range usually considered.« less

A study on comparison of Gafchromic EBT2 film response under single and cumulative exposure conditions

PubMed Central

Ganapathy, K.; Kurup, P.G.G.; Murali, V.; Muthukumaran, M.; Velmurugan, J.

2013-01-01

Gafchromic films are used as dosimeter for in vivo and in phantom dose measurements. The dose response of Gafchromic EBT2 film under single and repeated exposure conditions is compared in this study to analyze the usability of Gafchromic EBT2 films in cumulative dose measurements. The post-irradiation change in response of the film is studied for up to 4 days after irradiation. The effect of repeated exposure to scanner light on the response of the film is also studied. To check usability of Gafchromic EBT2 films in cumulative dose measurements, three EBT2 films were exposed to a daily fraction dose of 100 cGy, 150 cGy and 200 cGy, respectively, for 4 days. The dose response of the films exposed to cumulative irradiation was compared with the dose measured from films exposed to the same dose but in a single exposure. It is observed that the post-irradiation darkening of the film does not saturate and continue to take place even 4 days after irradiation. The dose measured from the EBT2 films after 4 days from irradiation was around 2% higher than the dose measured from the same films at 24 hours post-irradiation. It was also observed that the repeated exposure to scanner light does not produce any significant change in the film response. The dose response of films exposed to cumulative irradiation agrees with the dose response of films exposed to the same dose in a single irradiation with less than 3% difference. Gafchromic EBT2 films can be used to measure the cumulative dose delivered over multiple fractions, when the delivered dose is uniform across the film. PMID:24672151

Separating snow, clean and debris covered ice in the Upper Indus Basin, Hindukush-Karakoram-Himalayas, using Landsat images between 1998 and 2002

NASA Astrophysics Data System (ADS)

Khan, Asif; Naz, Bibi S.; Bowling, Laura C.

2015-02-01

The Hindukush Karakoram Himalayan mountains contain some of the largest glaciers of the world, and supply melt water from perennial snow and glaciers to the Upper Indus Basin (UIB) upstream of Tarbela dam, which constitutes greater than 80% of the annual flows, and caters to the needs of millions of people in the Indus Basin. It is therefore important to study the response of perennial snow and glaciers in the UIB under changing climatic conditions, using improved hydrological modeling, glacier mass balance, and observations of glacier responses. However, the available glacier inventories and datasets only provide total perennial-snow and glacier cover areas, despite the fact that snow, clean ice and debris covered ice have different melt rates and densities. This distinction is vital for improved hydrological modeling and mass balance studies. This study, therefore, presents a separated perennial snow and glacier inventory (perennial snow-cover on steep slopes, perennial snow-covered ice, clean and debris covered ice) based on a semi-automated method that combines Landsat images and surface slope information in a supervised maximum likelihood classification to map distinct glacier zones, followed by manual post processing. The accuracy of the presented inventory falls well within the accuracy limits of available snow and glacier inventory products. For the entire UIB, estimates of perennial and/or seasonal snow on steep slopes, snow-covered ice, clean and debris covered ice zones are 7238 ± 724, 5226 ± 522, 4695 ± 469 and 2126 ± 212 km2 respectively. Thus total snow and glacier cover is 19,285 ± 1928 km2, out of which 12,075 ± 1207 km2 is glacier cover (excluding steep slope snow-cover). Equilibrium Line Altitude (ELA) estimates based on the Snow Line Elevation (SLE) in various watersheds range between 4800 and 5500 m, while the Accumulation Area Ratio (AAR) ranges between 7% and 80%. 0 °C isotherms during peak ablation months (July and August) range between ∼ 5500 and 6200 m in various watersheds. These outputs can be used as input to hydrological models, to estimate spatially-variable degree day factors for hydrological modeling, to separate glacier and snow-melt contributions in river flows, and to study glacier mass balance, and glacier responses to changing climate.

Inhibition linearizes firing rate responses in human motor units: implications for the role of persistent inward currents.

PubMed

Revill, Ann L; Fuglevand, Andrew J

2017-01-01

Motor neurons are the output neurons of the central nervous system and are responsible for controlling muscle contraction. When initially activated during voluntary contraction, firing rates of motor neurons increase steeply but then level out at modest rates. Activation of an intrinsic source of excitatory current at recruitment onset may underlie the initial steep increase in firing rate in motor neurons. We attempted to disable this intrinsic excitatory current by artificially activating an inhibitory reflex. When motor neuron activity was recorded while the inhibitory reflex was engaged, firing rates no longer increased steeply, suggesting that the intrinsic excitatory current was probably responsible for the initial sharp rise in motor neuron firing rate. During graded isometric contractions, motor unit (MU) firing rates increase steeply upon recruitment but then level off at modest rates even though muscle force continues to increase. The mechanisms underlying such firing behaviour are not known although activation of persistent inward currents (PICs) might be involved. PICs are intrinsic, voltage-dependent currents that activate strongly when motor neurons (MNs) are first recruited. Such activation might cause a sharp escalation in depolarizing current and underlie the steep initial rise in MU firing rate. Because PICs can be disabled with synaptic inhibition, we hypothesized that artificial activation of an inhibitory pathway might curb this initial steep rise in firing rate. To test this, human subjects performed slow triangular ramp contractions of the ankle dorsiflexors in the absence and presence of tonic synaptic inhibition delivered to tibialis anterior (TA) MNs by sural nerve stimulation. Firing rate profiles (expressed as a function of contraction force) of TA MUs recorded during these tasks were compared for control and stimulation conditions. Under control conditions, during the ascending phase of the triangular contractions, 93% of the firing rate profiles were best fitted by rising exponential functions. With stimulation, however, firing rate profiles were best fitted with linear functions or with less steeply rising exponentials. Firing rate profiles for the descending phases of the contractions were best fitted with linear functions for both control and stimulation conditions. These results seem consistent with the idea that PICs contribute to non-linear firing rate profiles during ascending but not descending phases of contractions. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

The hormesis database: the occurrence of hormetic dose responses in the toxicological literature.

PubMed

Calabrese, Edward J; Blain, Robyn B

2011-10-01

In 2005 we published an assessment of dose responses that satisfied a priori evaluative criteria for inclusion within the relational retrieval hormesis database (Calabrese and Blain, 2005). The database included information on study characteristics (e.g., biological model, gender, age and other relevant aspects, number of doses, dose distribution/range, quantitative features of the dose response, temporal features/repeat measures, and physical/chemical properties of the agents). The 2005 article covered information for about 5000 dose responses; the present article has been expanded to cover approximately 9000 dose responses. This assessment extends and strengthens the conclusion of the 2005 paper that the hormesis concept is broadly generalizable, being independent of biological model, endpoint measured and chemical class/physical agent. It also confirmed the definable quantitative features of hormetic dose responses in which the strong majority of dose responses display maximum stimulation less than twice that of the control group and a stimulatory width that is within approximately 10-20-fold of the estimated toxicological or pharmacological threshold. The remarkable consistency of the quantitative features of the hormetic dose response suggests that hormesis may provide an estimate of biological plasticity that is broadly generalized across plant, microbial and animal (invertebrate and vertebrate) models. Copyright © 2011 Elsevier Inc. All rights reserved.

DOSE-RESPONSE BEHAVIOR OF ANDROGENIC AND ANTIANDROGENIC CHEMICALS: IMPLICATIONS FOR LOW-DOSE EXTRAPOLATION AND CUMULATIVE TOXICITY

EPA Science Inventory

DOSE-RESPONSE BEHAVIOR OF ANDROGENIC AND ANTIANDROGENIC CHEMICALS: IMPLICATIONS FOR LOW-DOSE EXTRAPOLATION AND CUMULATIVE TOXICITY. LE Gray Jr, C Wolf, J Furr, M Price, C Lambright, VS Wilson and J Ostby. USEPA, ORD, NHEERL, EB, RTD, RTP, NC, USA.
Dose-response behavior of a...

[The older patient with malignant diseases].

PubMed

Buske, C; Hiddemann, W

2007-11-01

Most malignancies show a steep increase of incidence with growing age. Because of this age specific incidence and the general aging of the population in western industrial countries the number of elderly cancer patients continuously and rapidly increases. Despite this development elderly cancer patients are currently underrepresented in clinical trials. This is caused in part by the lack of a common definition of the elderly patient and by the fact that a part of the elderly patients suffers from co-morbidities, not allowing a more dose intense treatment in these patients. It is one of the key current challenges to compensate this deficit and to develop therapeutic concepts specifically for the elderly patients, taking the individual somatic, but also social situation and finally the quality and perspective of life of the elderly patient into account.

Investigation of dose characteristics in three-dimensional MAGAT-type polymer gel dosimetry with MSE MR imaging

NASA Astrophysics Data System (ADS)

Lee, Jason J. S.; Tsai, Chia-Jung; Lo, Man-Kuok; Huang, Yung-Hui; Chen, Chien-Chuan; Wu, Jay; Tyan, Yeu-Sheng; Wu, Tung-Hsin

2008-05-01

A new type of normoxic polymer gel dosimeter, named MAGAT responses well to absorbed dose even when manufacturing in the presence of normal levels of oxygen. The aim of this study was to evaluate dose response, diffusion effect and cumulated dose response under multiple fractional irradiations of the MAGAT gel dosimeter using Multiple Spin-Echo (MSE) Magnetic Resonance (MR) sequence. Dose response was performed by irradiating MAGAT-gel-filled testing vials with a 6 MV linear accelerator and a linear relationship was present with doses from 0 to 6 Gy, but gradually, a bi-exponential function result was obtained with given doses up to 20 Gy. No significant difference in dose response was present between single and cumulated doses (p > 0.05). For study of diffusion effect, edge sharpness of the R2 map imaging between two split doses was smaller than 1 cm of dose profile penumbra between 20% and 80%. In conclusion, the MAGAT polymer gel dosimeter with MSE MR imaging is a promising method for dose verification in clinical radiation therapy practice.

Electronic stethoscope with frequency shaping and infrasonic recording capabilities.

PubMed

Gordon, E S; Lagerwerff, J M

1976-03-01

A small electronic stethoscope with variable frequency response characteristics has been developed for aerospace and research applications. The system includes a specially designed piezoelectric pickup and amplifier with an overall frequency response from 0.7 to 5,000 HZ (-3 dB points) and selective bass and treble boost or cut of up to 15 dB. A steep slope, high pass filter can be switched in for ordinary clinical auscultation without overload distortion from strong infrasonic signal inputs. A commercial stethoscope-type headset, selected for best overall response, is used which can adequately handle up to 100 mW of audio power delivered from the amplifier. The active components of the amplifier consist of only four opamp-type integrated circuits.

10 CFR 960.5-2-7 - Transportation.

Code of Federal Regulations, 2011 CFR

2011-01-01

... of sharp curves or steep grades and are not likely to be affected by landslides or rock slides. (v... highways and railroads such that steep grades, sharp switchbacks, rivers, lakes, landslides, rock slides...

A steep peripheral ring in irregular cornea topography, real or an instrument error?

PubMed

Galindo-Ferreiro, Alicia; Galvez-Ruiz, Alberto; Schellini, Silvana A; Galindo-Alonso, Julio

2016-01-01

To demonstrate that the steep peripheral ring (red zone) on corneal topography after myopic laser in situ keratomileusis (LASIK) could possibly due to instrument error and not always to a real increase in corneal curvature. A spherical model for the corneal surface and modifying topography software was used to analyze the cause of an error due to instrument design. This study involved modification of the software of a commercially available topographer. A small modification of the topography image results in a red zone on the corneal topography color map. Corneal modeling indicates that the red zone could be an artifact due to an instrument-induced error. The steep curvature changes after LASIK, signified by the red zone, could be also an error due to the plotting algorithms of the corneal topographer, besides a steep curvature change.

Insect density-plant density relationships: a modified view of insect responses to resource concentrations.

PubMed

Andersson, Petter; Löfstedt, Christer; Hambäck, Peter A

2013-12-01

Habitat area is an important predictor of spatial variation in animal densities. However, the area often correlates with the quantity of resources within habitats, complicating our understanding of the factors shaping animal distributions. We addressed this problem by investigating densities of insect herbivores in habitat patches with a constant area but varying numbers of plants. Using a mathematical model, predictions of scale-dependent immigration and emigration rates for insects into patches with different densities of host plants were derived. Moreover, a field experiment was conducted where the scaling properties of odour-mediated attraction in relation to the number of odour sources were estimated, in order to derive a prediction of immigration rates of olfactory searchers. The theoretical model predicted that we should expect immigration rates of contact and visual searchers to be determined by patch area, with a steep scaling coefficient, μ = -1. The field experiment suggested that olfactory searchers should show a less steep scaling coefficient, with μ ≈ -0.5. A parameter estimation and analysis of published data revealed a correspondence between observations and predictions, and density-variation among groups could largely be explained by search behaviour. Aphids showed scaling coefficients corresponding to the prediction for contact/visual searchers, whereas moths, flies and beetles corresponded to the prediction for olfactory searchers. As density responses varied considerably among groups, and variation could be explained by a certain trait, we conclude that a general theory of insect responses to habitat heterogeneity should be based on shared traits, rather than a general prediction for all species.

Intrinsic disorder as a generalizable strategy for the rational design of highly responsive, allosterically cooperative receptors.

PubMed

Simon, Anna J; Vallée-Bélisle, Alexis; Ricci, Francesco; Plaxco, Kevin W

2014-10-21

Control over the sensitivity with which biomolecular receptors respond to small changes in the concentration of their target ligand is critical for the proper function of many cellular processes. Such control could likewise be of utility in artificial biotechnologies, such as biosensors, genetic logic gates, and "smart" materials, in which highly responsive behavior is of value. In nature, the control of molecular responsiveness is often achieved using "Hill-type" cooperativity, a mechanism in which sequential binding events on a multivalent receptor are coupled such that the first enhances the affinity of the next, producing a steep, higher-order dependence on target concentration. Here, we use an intrinsic-disorder-based mechanism that can be implemented without requiring detailed structural knowledge to rationally introduce this potentially useful property into several normally noncooperative biomolecules. To do so, we fabricate a tandem repeat of the receptor that is destabilized (unfolded) via the introduction of a long, unstructured loop. The first binding event requires the energetically unfavorable closing of this loop, reducing its affinity relative to that of the second binding event, which, in contrast occurs at a preformed site. Using this approach, we have rationally introduced cooperativity into three unrelated DNA aptamers, achieving in the best of these a Hill coefficient experimentally indistinguishable from the theoretically expected maximum. The extent of cooperativity and thus the steepness of the binding transition are, moreover, well modeled as simple functions of the energetic cost of binding-induced folding, speaking to the quantitative nature of this design strategy.

Does perceived steepness deter stair climbing when an alternative is available?

PubMed

Eves, Frank F; Thorpe, Susannah K S; Lewis, Amanda; Taylor-Covill, Guy A H

2014-06-01

Perception of hill slant is exaggerated in explicit awareness. Proffitt (Perspectives on Psychological Science 1:110-122, 2006) argued that explicit perception of the slant of a climb allows individuals to plan locomotion in keeping with their available locomotor resources, yet no behavioral evidence supports this contention. Pedestrians in a built environment can often avoid climbing stairs, the man-made equivalent of steep hills, by choosing an adjacent escalator. Stair climbing is avoided more by women, the old, and the overweight than by their comparators. Two studies tested perceived steepness of the stairs as a cue that promotes this avoidance. In the first study, participants estimated the steepness of a staircase in a train station (n = 269). Sex, age, height, and weight were recorded. Women, older individuals, and those who were heavier and shorter reported the staircase as steeper than did their comparison groups. In a follow-up study in a shopping mall, pedestrians were recruited from those who chose the stairs and those who avoided them, with the samples stratified for sex, age, and weight status. Participants (n = 229) estimated the steepness of a life-sized image of the stairs they had just encountered, presented on the wall of a vacant shop in the mall. Pedestrians who avoided stair climbing by choosing the escalator reported the stairs as steeper even when demographic differences were controlled. Perceived steepness may to be a contextual cue that pedestrians use to avoid stair climbing when an alternative is available.

THE DEPRESSANT EFFECT OF CONTINUOUS COBALT-60 RADIATION ON THE SECONDARY TETANUS ANTITOXIN RESPONSE IN MICE

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

Stoner, R.D.; Hale, W.M.

1958-05-01

The radiosensitivity of the secondary tetanus antitoxin response in mice was demonstrated after rather low doses of continuous gamma -radiation given at a dose rate of 4 rep/hr. Accumulated doses of 48 to 288 rep depressed antitoxin formation. Comparable doses of acute gamma radiation did not depress antitoxin production. Acute doses of 350 to 650 rep sharply depressed the secondary antibody response, however. Extended periods of continuous gamma -radiation from 10 to 28 days to accumulated doses of 960 to 2688 rep markedly depressed the secondary antibody response. An accumulated dose of 2688 rep was needed to depress antitoxin formationmore » to the level observed after an acute dose of 650 rep. When the secondary stimulus of fluid tetanus toxoid was given prior to 10 days of continuous exposure to an accumulated dose of 860 rep, the secondary antibody respense was not depressed. Irradiated mice recovered the ability to produce a normal secondary antitoxin response during the second week after an accumulated dose of 1248 rep. The secondary antitoxin response was depressed in mice given long-continued gamma -radiation at a dose rate of 1 rep/hr. (auth)« less

Investigation of vacuum pumping on the dose response of the MAGAS normoxic polymer gel dosimeter.

PubMed

Venning, A J; Mather, M L; Baldock, C

2005-06-01

The effect of vacuum pumping on the dose response of the MAGAS polymer gel dosimeter has been investigated. A delay of several days post-manufacture before irradiation was previously necessary due to the slow oxygen scavenging of ascorbic acid. The MAGAS polymer gel dosimeter was vacuum pumped before gelation to remove dissolved oxygen. The MAGAS polymer gel dosimeter was poured into glass screw-top vials, which were irradiated at various times, post-manufacture to a range of doses. Magnetic resonance imaging techniques were used to determine the R2-dose response and R2-dose sensitivity of the MAGAS polymer gel. The results were compared with a control batch of MAGAS polymer gel that was not vacuum pumped. It was shown that vacuum pumping on the MAGAS polymer gel solution immediately prior to sealing in glass screw-top vials initially increases the R2-dose response and R2-dose sensitivity of the dosimeter. An increase in the R2-dose response and R2-dose sensitivity was observed with increasing time between manufacture and irradiation. Over the range of post-manufacture irradiation times investigated, the greatest R2-dose response and R2-dose sensitivity occurred at 96 hours.

Response of the South China Sea to Forcing by Tropical Cyclone Ernie (1996)

DTIC Science & Technology

1998-03-01

complicated. Wide continental shelves appear in the northwest and southwest of the basin and steep slopes in the central portion, framing a deep, bowl...bottom topography of the SCS basin provides a favorable condition for the formation of anticyclonic eddies in the central SCS during the spring. From...cyclone is produced. This cyclonic wind stress then generates Ekman upwelling in the central basin and the formation of a cold pool. Again, through

Study of Chemotaxis and Cell–Cell Interactions in Cancer with Microfluidic Devices

PubMed Central

Sai, Jiqing; Rogers, Matthew; Hockemeyer, Kathryn; Wikswo, John P.; Richmond, Ann

2017-01-01

Microfluidic devices have very broad applications in biological assays from simple chemotaxis assays to much more complicated 3D bioreactors. In this chapter, we describe the design and methods for performing chemotaxis assays using simple microfluidic chemotaxis chambers. With these devices, using real-time video microscopy we can examine the chemotactic responses of neutrophil-like cells under conditions of varying gradient steepness or flow rate and then utilize software programs to calculate the speed and angles of cell migration as gradient steepness and flow are varied. Considering the shearing force generated on the cells by the constant flow that is required to produce and maintain a stable gradient, the trajectories of the cell migration will reflect the net result of both shear force generated by flow and the chemotactic force resulting from the chemokine gradient. Moreover, the effects of mutations in chemokine receptors or the presence of inhibitors of intracellular signals required for gradient sensing can be evaluated in real time. We also describe a method to monitor intracellular signals required for cells to alter cell polarity in response to an abrupt switch in gradient direction. Lastly, we demonstrate an in vitro method for studying the interactions of human cancer cells with human endothelial cells, fibroblasts, and leukocytes, as well as environmental chemokines and cytokines, using 3D microbioreactors that mimic the in vivo microenvironment. PMID:26921940

Quantifying Quaternary Deformation in the Eastern Cordillera of the Colombian Andes Using Cosmogenic Nuclide Geochronology and Fluvial Geomorphology

NASA Astrophysics Data System (ADS)

Dalman, E.; Taylor, M. H.; Veloza-fajardo, G.; Mora, A.

2014-12-01

Northwest South America is actively deforming through the interaction between the Nazca, South American, and Caribbean plates. Though the Colombian Andes are well studied, much uncertainty remains in the rate of Quaternary deformation along the east directed frontal thrust faults hundreds of kilometers in board from the subduction zones. The eastern foothills of the Eastern Cordillera (EC) preserve deformed landforms, allowing us to quantify incision rates. Using 10Be in-situ terrestrial cosmogenic nuclide (TCN) geochronology, we dated 2 deformed fluvial terraces in the hanging wall of the Guaicaramo thrust fault. From the 10Be concentration and terrace profile relative to local base level, we calculated incision rates. We present a reconstructed slip history of the Guaicaramo thrust fault and its Quaternary slip rate. Furthermore, to quantify the regional Quaternary deformation, we look at the fluvial response to tectonic uplift. Approximately 20 streams along the eastern foothills of the Eastern Cordillera (EC) were studied using a digital elevation model (DEM). From the DEM, longitudinal profiles were created and normalized channel steepness (Ksn) values calculated from plots of drainage area vs. slope. Knickpoints in the longitudinal profiles can record transient perturbations or differential uplift. Calculated Ksn values indicate that the EC is experiencing high rates of uplift, with the highest mean Ksn values occurring in the Cocuy region. Mean channel steepness values along strike of the foothills are related to increasing uplift rates from south to north. In contrast, we suggest that high channel steepness values in the south appear to be controlled by high rates of annual precipitation.

Dose-response relationships for carcinogens: a review.

PubMed Central

Zeise, L; Wilson, R; Crouch, E A

1987-01-01

We review the experimental evidence for various shapes of dose-response relationships for carcinogens and summarize those experiments that give the most information on relatively low doses. A brief review of some models is given to illustrate the shapes of dose-response curve expected from them. Our major interest is in the use of dose-response relationships to estimate risks to humans at low doses, and so we pay special attention to experimentally observed and theoretically expected nonlinearities. There are few experimental examples of nonlinear dose-response relations in humans, but this may simply be due to the limitations in the data. The several examples in rodents, even though for high dose data, suggest that nonlinearity is common. In some cases such nonlinearities may be rationalized on the basis of the pharmacokinetics of the test compound or its metabolites. PMID:3311725

Kinetic characterization of glucose aerodehydrogenase from Aspergillus niger EMS-150-F after optimizing the dose of mutagen for enhanced production of enzyme

PubMed Central

Umbreen, Huma; Zia, Muhammad Anjum; Rasul, Samreen

2013-01-01

In the present study enhanced production of glucose aerodehydrogenase from Aspergillus niger has been achieved after optimizing the dose of chemical mutagen ethyl methane sulfonate (EMS) that has not been reported earlier. Different doses of mutagen were applied and a strain was developed basing upon the best production. The selected strain Aspergillus niger EMS-150-F was optimized for nutrient requirements in order to produce enzyme through fermentation and the results showed the best yield at 2% corn steep liquor (CSL), 36 hours fermentation time, pH 5, 30°C temperature, 0.3% KH2PO4, 0.3% urea and 0.06% CaCO3. The enzyme was then purified and resulted in 57.88 fold purification with 52.12% recovery. On kinetic characterization, the enzyme showed optimum activity at pH 6 and temperature 30°C. The Michaelis-Menton constants (Km, Vmax, Kcat and Kcat/Km) were 20 mM, 45.87 U mL−1, 1118.81 s−1 and 55.94 s−1 mM−1, respectively. The enzyme was found to be thermaly stable and the enthalpy and free energy showed an increase with increase in temperature and ΔS* was highly negative proving the enzyme from A. niger EMS-150-F resistant to temperature and showing a very little disorderliness. PMID:24688499

Use of corn steep liquor as an economical nitrogen source for biosuccinic acid production by Actinobacillus succinogenes

NASA Astrophysics Data System (ADS)

Tan, J. P.; Jahim, J. M.; Wu, T. Y.; Harun, S.; Mumtaz, T.

2016-06-01

Expensive raw materials are the driving force that leads to the shifting of the petroleum-based succinic acid production into bio-based succinic acid production by microorganisms. Cost of fermentation medium is among the main factors contributing to the total production cost of bio-succinic acid. After carbon source, nitrogen source is the second largest component of the fermentation medium, the cost of which has been overlooked for the past years. The current study aimed at replacing yeast extract- a costly nitrogen source with corn steep liquor for economical production of bio-succinic acid by Actinobacillus succinogenes 130Z. In this study, a final succinic acid concentration of 20.6 g/L was obtained from the use of corn steep liquor as the nitrogen source, which was comparable with the use of yeast extract as the nitrogen source that had a final succinate concentration of 21.4 g/l. In terms of economical wise, corn steep liquor was priced at 200 /ton, which was one fifth of the cost of yeast extract at 1000 /ton. Therefore, corn steep liquor can be considered as a potential nitrogen source in biochemical industries instead of the costly yeast extract.

Effect of steeping temperature on antioxidant and inhibitory activities of green tea extracts against α-amylase, α-glucosidase and intestinal glucose uptake.

PubMed

Liu, Shuyuan; Ai, Zeyi; Qu, Fengfeng; Chen, Yuqiong; Ni, Dejiang

2017-11-01

The objective of the present study was to evaluate the effect of steeping temperature on the biological activities of green tea, including the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging capacity, α-glucosidase and α-amylase inhibitory activities, and glucose uptake inhibitory activity in Caco-2 cells. Results showed that, with increasing extraction temperature, the polyphenol content increased, which contributed to enhance antioxidant activity and inhibitory effects on α-glucosidase and α-amylase. Green tea steeped at 100°C showed the highest DPPH radical-scavenging activity and inhibitory effects on α-glucosidase and α-amylase activities with EC 50 or IC 50 values of 6.15μg/mL, 0.09mg/mL, and 6.31mg/mL, respectively. However, the inhibitory potential on glucose uptake did not show an upward trend with increasing extraction temperature. Green tea steeped at 60°C had significantly stronger glucose uptake inhibitory activity (p<0.05). The integrated data suggested that steeping temperature should be considered when evaluating the biological activities of green tea. Copyright © 2017 Elsevier Ltd. All rights reserved.

A swinging seesaw as a novel model mechanism for time-dependent hormesis under dose-dependent stimulatory and inhibitory effects: A case study on the toxicity of antibacterial chemicals to Aliivibrio fischeri.

PubMed

Sun, Haoyu; Calabrese, Edward J; Zheng, Min; Wang, Dali; Pan, Yongzheng; Lin, Zhifen; Liu, Ying

2018-08-01

Hormesis occurs frequently in broadly ranging biological areas (e.g. plant biology, microbiology, biogerontology), toxicology, pharmacology and medicine. While numerous mechanisms (e.g. receptor and pathway mediated pathway responses) account for stimulatory and inhibitory features of hormetic dose responses, the vast majority emphasizes the inclusion of many doses but only one timepoint or use of a single optimized dose that is assessed over a broad range of timepoints. In this paper, a toxicity study was designed using a large number of properly spaced doses with responses determined over a large number of timepoints, which could help us reveal the underlying mechanism of hormesis. We present the results of a dose-time-response study on hormesis using five antibacterial chemicals on the bioluminescence of Aliivibrio fischeri, measuring expression of protein mRNA based on quorum sensing, simulating bioluminescent reaction and analyzing toxic actions of test chemicals. The findings show dose-time-dependent responses conforming to the hormetic dose-response model, while revealing unique response dynamics between agent induced stimulatory and inhibitory effects within bacterial growth phase dynamics. These dynamic dose-time features reveal a type of biological seesaw model that integrates stimulatory and inhibitory responses within unique growth phase, dose and time features, which has faultlessly explained the time-dependent hormetic phenomenon induced by five antibacterial chemicals (characterized by low-dose stimulation and high-dose inhibition). This study offers advances in understanding cellular dynamics, the biological integration of diverse and opposing responses and their role in evolutionary adaptive strategies to chemicals, which can provide new insight into the mechanistic investigation of hormesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Biphasic dose responses in biology, toxicology and medicine: accounting for their generalizability and quantitative features.

PubMed

Calabrese, Edward J

2013-11-01

The most common quantitative feature of the hormetic-biphasic dose response is its modest stimulatory response which at maximum is only 30-60% greater than control values, an observation that is consistently independent of biological model, level of organization (i.e., cell, organ or individual), endpoint measured, chemical/physical agent studied, or mechanism. This quantitative feature suggests an underlying "upstream" mechanism common across biological systems, therefore basic and general. Hormetic dose response relationships represent an estimate of the peak performance of integrative biological processes that are allometrically based. Hormetic responses reflect both direct stimulatory or overcompensation responses to damage induced by relatively low doses of chemical or physical agents. The integration of the hormetic dose response within an allometric framework provides, for the first time, an explanation for both the generality and the quantitative features of the hormetic dose response. Copyright © 2013 Elsevier Ltd. All rights reserved.

SU-E-T-137: The Response of TLD-100 in Mixed Fields of Photons and Electrons.

PubMed

Lawless, M; Junell, S; Hammer, C; DeWerd, L

2012-06-01

Thermoluminescent dosimeters are used routinely for dosimetric measurements of photon and electron fields. However, no work has been published characterizing TLDs for use in combined photon and electron fields. This work investigates the response of TLD-100 (LiF:Mg,Ti) in mixed fields of photon and electron beam qualities. TLDs were irradiated in a 6 MV photon beam, 6 MeV electron beam, and a NIST traceable cobalt-60 beam. TLDs were also irradiated in a mixed field of the electron and photon beams. All irradiations were normalized to absorbed dose to water as defined in the AAPM TG-51 report. The average response per dose (nC/Gy) for each linac beam quality was normalized to the average response per dose of the TLDs irradiated by the cobalt-60 standard.Irradiations were performed in a water tank and a Virtual Water™ phantom. Two TLD dose calibration curves for determining absorbed dose to water were generated using photon and electron field TLD response data. These individual beam quality dose calibration curves were applied to the TLDs irradiated in the mixed field. The TLD response in the mixed field was less sensitive than the response in the photon field and more sensitive than the response in the electron field. TLD determination of dose in the mixed field using the dose calibration curve generated by TLDs irradiated by photons resulted in an underestimation of the delivered dose, while the use of a dose calibration curve generated using electrons resulted in an overestimation of the delivered dose. The relative response of TLD-100 in mixed fields fell consistently between the photon nd electron relative responses. When using TLD-100 in mixed fields, the user must account for this intermediate response to avoid an over- or underestimation of the dose due to calibration in a single photon or electron field. © 2012 American Association of Physicists in Medicine.

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

NASA Astrophysics Data System (ADS)

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

2007-09-01

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

Biphasic and triphasic dose responses in zebrafish embryos to low-dose 150 kV X-rays with different levels of hardness.

PubMed

Kong, Eva Yi; Cheng, Shuk Han; Yu, Kwan Ngok

2016-07-01

The in vivo low-dose responses of zebrafish (Danio rerio) embryos to 150 kV X-rays with different levels of hardness were examined through the number of apoptotic events revealed at 24 h post fertilization by vital dye acridine orange staining. Our results suggested that a triphasic dose response was likely a common phenomenon in living organisms irradiated by X-rays, which comprised an ultra-low-dose inhibition, low-dose stimulation and high-dose inhibition. Our results also suggested that the hormetic zone (or the stimulation zone) was shifted towards lower doses with application of filters. The non-detection of a triphasic dose response in previous experiments could likely be attributed to the use of hard X-rays, which shifted the hormetic zone into an unmonitored ultra-low-dose region. In such cases where the subhormetic zone was missed, a biphasic dose response would be reported instead. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Dose Response Data for Hormonally Active Chemicals ...

EPA Pesticide Factsheets

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

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

PubMed

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

2009-06-01

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

The occurrence of hormetic dose responses in the toxicological literature, the hormesis database: an overview

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

Calabrese, Edward J.; Blain, Robyn

A relational retrieval database has been developed compiling toxicological studies assessing the occurrence of hormetic dose responses and their quantitative characteristics. This database permits an evaluation of these studies over numerous parameters, including study design and dose-response features and physical/chemical properties of the agents. The database contains approximately 5600 dose-response relationships satisfying evaluative criteria for hormesis across over approximately 900 agents from a broadly diversified spectrum of chemical classes and physical agents. The assessment reveals that hormetic dose-response relationships occur in males and females of numerous animal models in all principal age groups as well as across species displaying amore » broad range of differential susceptibilities to toxic agents. The biological models are extensive, including plants, viruses, bacteria, fungi, insects, fish, birds, rodents, and primates, including humans. The spectrum of endpoints displaying hormetic dose responses is also broad being inclusive of growth, longevity, numerous metabolic parameters, disease incidences (including cancer), various performance endpoints such as cognitive functions, immune responses among others. Quantitative features of the hormetic dose response reveal that the vast majority of cases display a maximum stimulatory response less than two-fold greater than the control while the width of the stimulatory response is typically less than 100-fold in dose range immediately contiguous with the toxicological NO(A)EL. The database also contains a quantitative evaluation component that differentiates among the various dose responses concerning the strength of the evidence supporting a hormetic conclusion based on study design features, magnitude of the stimulatory response, statistical significance, and reproducibility of findings.« less

The occurrence of hormetic dose responses in the toxicological literature, the hormesis database: an overview.

PubMed

Calabrese, Edward J; Blain, Robyn

2005-02-01

A relational retrieval database has been developed compiling toxicological studies assessing the occurrence of hormetic dose responses and their quantitative characteristics. This database permits an evaluation of these studies over numerous parameters, including study design and dose-response features and physical/chemical properties of the agents. The database contains approximately 5600 dose-response relationships satisfying evaluative criteria for hormesis across over approximately 900 agents from a broadly diversified spectrum of chemical classes and physical agents. The assessment reveals that hormetic dose-response relationships occur in males and females of numerous animal models in all principal age groups as well as across species displaying a broad range of differential susceptibilities to toxic agents. The biological models are extensive, including plants, viruses, bacteria, fungi, insects, fish, birds, rodents, and primates, including humans. The spectrum of endpoints displaying hormetic dose responses is also broad being inclusive of growth, longevity, numerous metabolic parameters, disease incidences (including cancer), various performance endpoints such as cognitive functions, immune responses among others. Quantitative features of the hormetic dose response reveal that the vast majority of cases display a maximum stimulatory response less than two-fold greater than the control while the width of the stimulatory response is typically less than 100-fold in dose range immediately contiguous with the toxicological NO(A)EL. The database also contains a quantitative evaluation component that differentiates among the various dose responses concerning the strength of the evidence supporting a hormetic conclusion based on study design features, magnitude of the stimulatory response, statistical significance, and reproducibility of findings.

Orexinergic Neurotransmission in Temperature Responses to Methamphetamine and Stress: Mathematical Modeling as a Data Assimilation Approach

PubMed Central

Behrouzvaziri, Abolhassan; Fu, Daniel; Tan, Patrick; Yoo, Yeonjoo; Zaretskaia, Maria V.; Rusyniak, Daniel E.; Molkov, Yaroslav I.; Zaretsky, Dmitry V.

2015-01-01

Experimental Data Orexinergic neurotransmission is involved in mediating temperature responses to methamphetamine (Meth). In experiments in rats, SB-334867 (SB), an antagonist of orexin receptors (OX1R), at a dose of 10 mg/kg decreases late temperature responses (t>60 min) to an intermediate dose of Meth (5 mg/kg). A higher dose of SB (30 mg/kg) attenuates temperature responses to low dose (1 mg/kg) of Meth and to stress. In contrast, it significantly exaggerates early responses (t<60 min) to intermediate and high doses (5 and 10 mg/kg) of Meth. As pretreatment with SB also inhibits temperature response to the stress of injection, traditional statistical analysis of temperature responses is difficult. Mathematical Modeling We have developed a mathematical model that explains the complexity of temperature responses to Meth as the interplay between excitatory and inhibitory nodes. We have extended the developed model to include the stress of manipulations and the effects of SB. Stress is synergistic with Meth on the action on excitatory node. Orexin receptors mediate an activation of on both excitatory and inhibitory nodes by low doses of Meth, but not on the node activated by high doses (HD). Exaggeration of early responses to high doses of Meth involves disinhibition: low dose of SB decreases tonic inhibition of HD and lowers the activation threshold, while the higher dose suppresses the inhibitory component. Using a modeling approach to data assimilation appears efficient in separating individual components of complex response with statistical analysis unachievable by traditional data processing methods. PMID:25993564

Industrial vitamin B12 production by Pseudomonas denitrificans using maltose syrup and corn steep liquor as the cost-effective fermentation substrates.

PubMed

Xia, Wei; Chen, Wei; Peng, Wei-Fu; Li, Kun-Tai

2015-06-01

The aerobic Pseudomonas denitrificans is widely used for industrial and commercial vitamin B12 fermentation, due to its higher productivity compared to the anaerobic vitamin B12-producing microorganisms. This paper aimed to develop a cost-effective fermentation medium for industrial vitamin B12 production by P. denitrificans in 120,000-l fermenter. It was found that maltose syrup (a low-cost syrup from corn starch by means of enzymatic or acid hydrolysis) and corn steep liquor (CSL, a by-product of starch industry) were greatly applicable to vitamin B12 production by P. denitrificans. Under the optimal fermentation medium performed by response surface methodology, 198.27 ± 4.60 mg/l of vitamin B12 yield was obtained in 120,000-l fermenter, which was close to the fermentation with the refined sucrose (198.80 mg/l) and was obviously higher than that obtained under beet molasses utilization (181.75 mg/l). Therefore, maltose syrups and CSL were the efficient and economical substrates for industrial vitamin B12 fermentation by P. denitrificans.

The forecast of coastal recession in the eastern gulf of Finland for the twenty-first century

NASA Astrophysics Data System (ADS)

Leont'yev, I. O.; Ryabchuk, D. V.; Sergeev, A. Yu.; Kovaleva, O. A.

2015-05-01

The evolution of a significant part of the coast in the study area is determined by extreme storm surges eroding the upper part of dunes and inducing coastal recession. In order to forecast the recession a special method using numerical modelling of storm-induced changes in the coastal profiles based on the CROSS-P model is used. The response of the shoreline profile to sea-level rise is estimated using the Bruun rule. Three types of future coastal evolution are distinguished depending on slope of an active part of the profile. It is shown that if the most probable patterns of storm activity and sea level rise occur then the relatively steep coasts in an area from Komarovo to Solnechnoe will retreat by 302-40 meters. Recession of less steep coasts (Ushkovo, south Kotlin, and Petrodvorets) is expected to be 10-20 meters, whereas the extremely gently dipping coasts (in the vicinity of Sestroretsk and near the northern end of the St. Petersburg Flood Protection Complex (FPC)) will retreat by 50-100 m.

Statistical strategies for averaging EC50 from multiple dose-response experiments.

PubMed

Jiang, Xiaoqi; Kopp-Schneider, Annette

2015-11-01

In most dose-response studies, repeated experiments are conducted to determine the EC50 value for a chemical, requiring averaging EC50 estimates from a series of experiments. Two statistical strategies, the mixed-effect modeling and the meta-analysis approach, can be applied to estimate average behavior of EC50 values over all experiments by considering the variabilities within and among experiments. We investigated these two strategies in two common cases of multiple dose-response experiments in (a) complete and explicit dose-response relationships are observed in all experiments and in (b) only in a subset of experiments. In case (a), the meta-analysis strategy is a simple and robust method to average EC50 estimates. In case (b), all experimental data sets can be first screened using the dose-response screening plot, which allows visualization and comparison of multiple dose-response experimental results. As long as more than three experiments provide information about complete dose-response relationships, the experiments that cover incomplete relationships can be excluded from the meta-analysis strategy of averaging EC50 estimates. If there are only two experiments containing complete dose-response information, the mixed-effects model approach is suggested. We subsequently provided a web application for non-statisticians to implement the proposed meta-analysis strategy of averaging EC50 estimates from multiple dose-response experiments.

FIRE: an open-software suite for real-time 2D/3D image registration for image guided radiotherapy research

NASA Astrophysics Data System (ADS)

Furtado, H.; Gendrin, C.; Spoerk, J.; Steiner, E.; Underwood, T.; Kuenzler, T.; Georg, D.; Birkfellner, W.

2016-03-01

Radiotherapy treatments have changed at a tremendously rapid pace. Dose delivered to the tumor has escalated while organs at risk (OARs) are better spared. The impact of moving tumors during dose delivery has become higher due to very steep dose gradients. Intra-fractional tumor motion has to be managed adequately to reduce errors in dose delivery. For tumors with large motion such as tumors in the lung, tracking is an approach that can reduce position uncertainty. Tumor tracking approaches range from purely image intensity based techniques to motion estimation based on surrogate tracking. Research efforts are often based on custom designed software platforms which take too much time and effort to develop. To address this challenge we have developed an open software platform especially focusing on tumor motion management. FLIRT is a freely available open-source software platform. The core method for tumor tracking is purely intensity based 2D/3D registration. The platform is written in C++ using the Qt framework for the user interface. The performance critical methods are implemented on the graphics processor using the CUDA extension. One registration can be as fast as 90ms (11Hz). This is suitable to track tumors moving due to respiration (~0.3Hz) or heartbeat (~1Hz). Apart from focusing on high performance, the platform is designed to be flexible and easy to use. Current use cases range from tracking feasibility studies, patient positioning and method validation. Such a framework has the potential of enabling the research community to rapidly perform patient studies or try new methods.

Choice between delayed food and immediate opioids in rats: treatment effects and individual differences.

PubMed

Panlilio, Leigh V; Secci, Maria E; Schindler, Charles W; Bradberry, Charles W

2017-11-01

Addiction involves maladaptive choice behavior in which immediate drug effects are valued more than delayed nondrug rewards. To model this behavior and extend our earlier work with the prescription opioid oxycodone, we allowed rats to choose between immediate intravenous delivery of the short-acting opioid remifentanil and delayed delivery of highly palatable food pellets. Treatment drugs were tested on a baseline where remifentanil was preferred over food. Treatment with a high dose of the opioid antagonist naltrexone decreased but did not reverse the preference for remifentanil. Treatment with the serotonin 5-HT 2C agonist lorcaserin decreased remifentanil and food self-administration nonselectively. Across conditions in which the alternative to delayed food was either a moderate dose of oxycodone, a moderate or high dose of remifentanil, a smaller more immediate delivery of food, or timeout with no primary reinforcement, choice was determined by both the length of the delay and the nature of the alternative option. Delayed food was discounted most steeply when the alternative was a high dose of remifentanil, which was preferred over food when food was delayed by 30 s or more. Within-subject comparisons showed no evidence for trait-like impulsivity or sensitivity to delay across these conditions. Choice was determined more by the current contingencies of reinforcement than by innate individual differences. This finding suggests that people might develop steep delay-discounting functions because of the contingencies in their environment, and it supports the use of contingency management to enhance the relative value of delayed nondrug reinforcers.

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 comparison of different treatment modalities for stereotactic radiotherapy.

PubMed

Hsu, Shih-Ming; Lai, Yuan-Chun; Jeng, Chien-Chung; Tseng, Chia-Ying

2017-09-16

The modalities for performing stereotactic radiotherapy (SRT) on the brain include the cone-based linear accelerator (linac), the flattening filter-free (FFF) volumetric modulated arc therapy (VMAT) linac, and tomotherapy. In this study, the cone-based linac, FFF-VMAT linac, and tomotherapy modalities were evaluated by measuring the differences in doses delivered during brain SRT and experimentally assessing the accuracy of the output radiation doses through clinical measurements. We employed a homemade acrylic dosimetry phantom representing the head, within which a thermoluminescent dosimeter (TLD) and radiochromic EBT3 film were installed. Using the conformity/gradient index (CGI) and Paddick methods, the quality of the doses delivered by the various SRT modalities was evaluated. The quality indicators included the uniformity, conformity, and gradient indices. TLDs and EBT3 films were used to experimentally assess the accuracy of the SRT dose output. The dose homogeneity indices of all the treatment modalities were lower than 1.25. The cone-based linac had the best conformity for all tumors, regardless of the tumor location and size, followed by the FFF-VMAT linac; tomography was the worst-performing treatment modality in this regard. The cone-based linac had the best gradient, regardless of the tumor location and size, whereas the FFF-VMAT linac had a better gradient than tomotherapy for a large tumor diameter (28 mm). The TLD and EBT3 measurements of the dose at the center of tumors indicated that the average difference between the measurements and the calculated dose was generally less than 4%. When the 3% 3-mm gamma passing rate metric was used, the average passing rates of all three treatment modalities exceeded 98%. Regarding the dose, the cone-based linac had the best conformity and steepest dose gradient for tumors of different sizes and distances from the brainstem. The results of this study suggest that SRT should be performed using the cone-based linac on tumors that require treatment plans with a steep dose gradient, even as the tumor is slightly irregular, we should also consider using a high dose gradient of the cone base to treat and protect the normal tissue. If normal tissues require special protection exist at positions that are superior or inferior to the tumor, we can consider using tomotherapy or Cone base with couch at 0° for treatment.

Reconstruction and analysis of erythemal UV radiation time series from Hradec Králové (Czech Republic) over the past 50 years

NASA Astrophysics Data System (ADS)

Čížková, Klára; Láska, Kamil; Metelka, Ladislav; Staněk, Martin

2018-02-01

This paper evaluates the variability of erythemal ultraviolet (EUV) radiation from Hradec Králové (Czech Republic) in the period 1964-2013. The EUV radiation time series was reconstructed using a radiative transfer model and additional empirical relationships, with the final root mean square error of 9.9 %. The reconstructed time series documented the increase in EUV radiation doses in the 1980s and the 1990s (up to 15 % per decade), which was linked to the steep decline in total ozone (10 % per decade). The changes in cloud cover were the major factor affecting the EUV radiation doses especially in the 1960s, 1970s, and at the beginning of the new millennium. The mean annual EUV radiation doses in the decade 2004-2013 declined by 5 %. The factors affecting the EUV radiation doses differed also according to the chosen integration period (daily, monthly, and annually): solar zenith angle was the most important for daily doses, cloud cover, and surface UV albedo for their monthly means, and the annual means of EUV radiation doses were most influenced by total ozone column. The number of days with very high EUV radiation doses increased by 22 % per decade, the increase was statistically significant in all seasons except autumn. The occurrence of the days with very high EUV doses was influenced mostly by low total ozone column (82 % of days), clear-sky or partly cloudy conditions (74 % of days) and by increased surface albedo (19 % of days). The principal component analysis documented that the occurrence of days with very high EUV radiation doses was much affected by the positive phase of North Atlantic Oscillation with an Azores High promontory reaching over central Europe. In the stratosphere, a strong Arctic circumpolar vortex and the meridional inflow of ozone-poor air from the southwest were favorable for the occurrence of days with very high EUV radiation doses. This is the first analysis of the relationship between the high EUV radiation doses and macroscale circulation patterns, and therefore more attention should be given also to other dynamical variables that may affect the solar UV radiation on the Earth surface.

Historical Contingencies in Microbial Responses to Drought

NASA Astrophysics Data System (ADS)

Hawkes, C.; Waring, B.; Rocca, J.; Kivlin, S.; Giauque, H.; Averill, C.

2014-12-01

Although water is a primary controller of microbial function and we expect climate change to alter water availability in the future, our understanding of how microbial communities respond to a change in moisture and what that means for soil carbon cycling remain poorly understood. In part, this uncertainty arises from a lack of understanding of microbial response mechanisms and how those lead to aggregate soil function. Environmental tracking would be facilitated if microbial communities respond to new climatic conditions via rapid physiological acclimatization, shifts in community composition, or adaptation. In contrast, historical contingencies could be created by dispersal limitation or local adaptation to previous conditions. To address environmental tracking vs. legacies, we examined how soil microbial communities were affected by precipitation at multiple scales and asked whether rainfall was a primary driver of the observed responses. We leveraged a local steep rainfall gradient with field surveys, lab incubations, reciprocal transplants, and rainfall manipulations to approach this problem. Across a steep rainfall gradient, we found that soil microbial communities were strongly associated with historical rainfall, with two-thirds of the variation in community composition explained by mean annual precipitation. In 12-month experimental lab manipulations of soil moisture, soil functional responses were constrained by historical rainfall, with greater activity in soils subjected to their original moisture condition. The constraints of historical rainfall held even after 18 months in reciprocal transplant common gardens along the rainfall gradient and with manipulated dispersal of regional microbial communities. Yet, when water was manipulated at a single site over 4 years, legacies did not develop. Overall, these findings are consistent with long-term rainfall acting as a strong habitat filter and resulting in a legacy of both microbial community composition and physiological capacity that can affect soil carbon cycling. Placing the ecological and evolutionary dynamics of microbial communities in the context of historical and future environmental variation may thus provide us with a framework for improving prediction of ecosystem responses to climate change.

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

Hobbs, R; Le, Y; Armour, E

Purpose: Dose-response studies in radiation therapy are typically using single response values for tumors across ensembles of tumors. Using the high dose rate (HDR) treatment plan dose grid and pre- and post-therapy FDG-PET images, we look for correlations between voxelized dose and FDG uptake response in individual tumors. Methods: Fifteen patients were treated for localized rectal cancer using 192Ir HDR brachytherapy in conjunction with surgery. FDG-PET images were acquired before HDR therapy and 6–8 weeks after treatment (prior to surgery). Treatment planning was done on a commercial workstation and the dose grid was calculated. The two PETs and the treatmentmore » dose grid were registered to each other using non-rigid registration. The difference in PET SUV values before and after HDR was plotted versus absorbed radiation dose for each voxel. The voxels were then separated into bins for every 400 cGy of absorbed dose and the bin average values plotted similarly. Results: Individual voxel doses did not correlate with PET response; however, when group into tumor subregions corresponding to dose bins, eighty percent of the patients showed a significant positive correlation (R2 > 0) between PET uptake difference in the targeted region and the absorbed dose. Conclusion: By considering larger ensembles of voxels, such as organ average absorbed dose or the dose bins considered here, valuable information may be obtained. The dose-response correlations as measured by FDG-PET difference potentially underlines the importance of FDG-PET as a measure of response, as well as the value of voxelized information.« less

Steep cut slope composting : field trials and evaluation.

DOT National Transportation Integrated Search

2011-04-01

Three different depths of compost and five compost retention techniques were tested to determine : their efficacy and cost effectiveness for increasing the establishment of native grass seedings and decreasing : erosion on steep roadside cut slopes i...

Compost for steep slope erosion.

DOT National Transportation Integrated Search

2008-06-01

This study was initiated to develop guidelines for maintenance erosion control measures for steep slopes. The study focused on evaluating and monitoring KY-31 fescue germination rates using two media treatments 1) 100 percent by weight compost and 2)...

Sensitive periods of amygdala development: the role of maltreatment in preadolescence.

PubMed

Pechtel, Pia; Lyons-Ruth, Karlen; Anderson, Carl M; Teicher, Martin H

2014-08-15

The amygdala is vulnerable to stress-dependent disruptions in neural development. Animal models have shown that stress increases dendritic arborization leading to larger amygdala volumes. Human studies of early stress and amygdala volume, however, remain inconclusive. This study compared amygdala volume in adults with childhood maltreatment to that in healthy controls. Eighteen participants from a longitudinal cohort and 33 cross-sectional controls (17 M/34 F, 25.5±3.1 years) completed a structural magnetic resonance imagining scan and the Maltreatment and Abuse Chronology of Exposure scale. Random forest regression with conditional trees was used to assess relative importance of exposure to adversity at each age on amygdala, thalamic or caudate volume. Severity of exposure to adversity across age accounted for 27% of the variance in right amygdala volume. Peak sensitivity occurred at 10-11 years of age, and importance of exposure at this time was highly significant based on permutation tests (p=0.003). The regression model showed that exposure during this sensitive period resulted in steep dose-response function with maximal response to even modest levels of exposure. Subjects in the highest exposure quartile (MACE-11, range=11-54) had a 9.1% greater right amygdala volume than subjects in the lowest exposure quartile (MACE-11, ≤3.5). No associations emerged between age of exposure and volume of the left amygdala or bilateral caudate or thalamus. Severity of adversity experienced at age 10-11 contributed to larger right but not left amygdala volume in adulthood. Results provide preliminary evidence that the amygdala may have a developmental sensitive period in preadolescence. Copyright © 2014 Elsevier Inc. All rights reserved.

SU-G-BRB-14: Uncertainty of Radiochromic Film Based Relative Dose Measurements

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

Devic, S; Tomic, N; DeBlois, F

2016-06-15

Purpose: Due to inherently non-linear dose response, measurement of relative dose distribution with radiochromic film requires measurement of absolute dose using a calibration curve following previously established reference dosimetry protocol. On the other hand, a functional form that converts the inherently non-linear dose response curve of the radiochromic film dosimetry system into linear one has been proposed recently [Devic et al, Med. Phys. 39 4850–4857 (2012)]. However, there is a question what would be the uncertainty of such measured relative dose. Methods: If the relative dose distribution is determined going through the reference dosimetry system (conversion of the response bymore » using calibration curve into absolute dose) the total uncertainty of such determined relative dose will be calculated by summing in quadrature total uncertainties of doses measured at a given and at the reference point. On the other hand, if the relative dose is determined using linearization method, the new response variable is calculated as ζ=a(netOD)n/ln(netOD). In this case, the total uncertainty in relative dose will be calculated by summing in quadrature uncertainties for a new response function (σζ) for a given and the reference point. Results: Except at very low doses, where the measurement uncertainty dominates, the total relative dose uncertainty is less than 1% for the linear response method as compared to almost 2% uncertainty level for the reference dosimetry method. The result is not surprising having in mind that the total uncertainty of the reference dose method is dominated by the fitting uncertainty, which is mitigated in the case of linearization method. Conclusion: Linearization of the radiochromic film dose response provides a convenient and a more precise method for relative dose measurements as it does not require reference dosimetry and creation of calibration curve. However, the linearity of the newly introduced function must be verified. Dave Lewis is inventor and runs a consulting company for radiochromic films.« less

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

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

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

2014-08-15

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

The Role of High Dose Interleukin-2 in the Era of Targeted Therapy.

PubMed

Gills, Jessie; Parker, William P; Pate, Scott; Niu, Sida; Van Veldhuizen, Peter; Mirza, Moben; Holzbeierlein, Jeffery M; Lee, Eugene K

2017-09-01

We assessed survival outcomes following high dose interleukin-2 in a contemporary cohort of patients during the era of targeted agents. We retrospectively reviewed the records of patients with metastatic renal cell carcinoma treated with high dose interleukin-2 between July 2007 and September 2014. Clinicopathological data were abstracted and patient response to therapy was based on RECIST (Response Evaluation Criteria In Solid Tumors), version 1.1 criteria. The Kaplan-Meier method was used to estimate progression-free and overall survival in the entire cohort, the response to high dose interleukin-2 in regard to previous targeted agent therapy and the response to the targeted agent in relation to the response to high dose interleukin-2. We identified 92 patients, of whom 87 had documentation of a response to high dose interleukin-2. Median overall survival was 34.4 months from the initiation of high dose interleukin-2 therapy in the entire cohort. Patients who received targeted therapy before high dose interleukin-2 had overall survival (median 34.4 and 30.0 months, p = 0.88) and progression-free survival (median 1.5 and 1.7 months, p = 0.8) similar to those in patients who received no prior therapy, respectively. Additionally, patients with a complete or partial response to high dose interleukin-2 had similar outcomes for subsequent targeted agents compared to patients whose best response was stable or progressive disease (median overall survival 30.1 vs 25.4 months, p = 0.4). Our data demonstrate that patient responses to high dose interleukin-2 and to targeted agents before and after receiving high dose interleukin-2 are independent. As such, carefully selected patients should be offered high dose interleukin-2 for the possibility of a complete and durable response without the fear of limiting the treatment benefit of targeted agents. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Dose Response Data for Hormonally Active Chemicals: Estrogens, Antiandrogens and Androgens

EPA Science Inventory

The shape of the dose response curve in the low dose region has been debated since the late 1940s. The debate originally focused on linear no threshold (LNT) vs threshold responses in the low dose range for cancer and noncancer related effects. For noncancer effects the defaul...

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

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

Ballangrud, A; Kuo, L; Happersett, L

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

Validation of measurement‐guided 3D VMAT dose reconstruction on a heterogeneous anthropomorphic phantom

PubMed Central

Opp, Daniel; Nelms, Benjamin E.; Zhang, Geoffrey; Stevens, Craig

2013-01-01

3DVH software (Sun Nuclear Corp., Melbourne, FL) is capable of generating a volumetric patient VMAT dose by applying a volumetric perturbation algorithm based on comparing measurement‐guided dose reconstruction and TPS‐calculated dose to a cylindrical phantom. The primary purpose of this paper is to validate this dose reconstruction on an anthropomorphic heterogeneous thoracic phantom by direct comparison to independent measurements. The dosimetric insert to the phantom is novel, and thus the secondary goal is to demonstrate how it can be used for the hidden target end‐to‐end testing of VMAT treatments in lung. A dosimetric insert contains a 4 cm diameter unit‐density spherical target located inside the right lung (0.21g/cm3 density). It has 26 slots arranged in two orthogonal directions, milled to hold optically stimulated luminescent dosimeters (OSLDs). Dose profiles in three cardinal orthogonal directions were obtained for five VMAT plans with varying degrees of modulation. After appropriate OSLD corrections were applied, 3DVH measurement‐guided VMAT dose reconstruction agreed 100% with the measurements in the unit density target sphere at 3%/3 mm level (composite analysis) for all profile points for the four less‐modulated VMAT plans, and for 96% of the points in the highly modulated C‐shape plan (from TG‐119). For this latter plan, while 3DVH shows acceptable agreement with independent measurements in the unit density target, in the lung disagreement with experiment is relatively high for both the TPS calculation and 3DVH reconstruction. For the four plans excluding the C‐shape, 3%/3mm overall composite analysis passing rates for 3DVH against independent measurement ranged from 93% to 100%. The C‐shape plan was deliberately chosen as a stress test of the algorithm. The dosimetric spatial alignment hidden target test demonstrated the average distance to agreement between the measured and TPS profiles in the steep dose gradient area at the edge of the 2 cm target to be 1.0±0.7,0.3±0.3, and 0.3±0.3mm for the IEC X, Y, and Z directions, respectively. PACS number: 87.55Qr PMID:23835381

SU-G-BRC-14: Multi-Lesion, Multi-Rx, Brain Radiosurgery with Novel Single Isocenter Technique

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

Honig, N; Alani, S; Schlocker, A

Purpose: There is a strong trend to treat multiple brain metastases with radiosurgery rather than whole brain irradiation. This feasibility study investigates a novel planning technique for radio-surgical treatment of multiple brain lesions with differing dose prescriptions, a single isocenter, and dynamic conformal arcs. The novel technique will be compared to the well-established single-isocenter volumetric modulated arc therapy (VMAT) technique commonly used for treating brain lesions. Methods: Six patients with metastatic brain lesions were selected for a prospective treatment planning study to evaluate Interdigitating MLC Dynamic Conformal Arc (IMDCA) technique. Arcs were planned for simultaneous irradiation to maximize beam deliverymore » efficiency. To accommodate varying PTV dose prescriptions, selected arcs were re-irradiated in reverse. Beam weights were adjusted until all prescription constraints were met. The number of lesions ranged between 2 to 4 (mode = 3). For comparison, SRS VMAT plans were generated utilizing an established single-isocenter, 3 arc planning template. All plans were compared by means of Paddick conformity index (PCI), RTOG Conformity Index (RCI), gradient index (GI), and the normal brain volume receiving 10% (V10) of the highest prescription dose. The monitor units and delivery time were tabulated for each plan. Results: IMDCA achieved conformal plans (PCI = 0.72±0.03, RCI = 1.33±0.03) with steep dose fall-off (GI = 3.79±0.03) on average for all of the plans evaluated. The VMAT plans had slightly better conformity (PCI = 0.85 ± 0.03, RCI = 1.13 ± 0.03) than IMDCA, but overall worse GI (4.29 ± 0.06). IMDCA plans had lower V10% values, required 50% fewer MUs, and had 34% shorter beam delivery time on average compared to VMAT plans. Conclusion: IMDCA plans with varying dose prescriptions for multiple lesions, had comparable dosimetric coverage as VMAT plans, but were obtained with significantly lower integral dose, fewer monitor units, and quicker delivery time.« less

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

The dose-response of salvage radiotherapy following radical prostatectomy: A systematic review and meta-analysis.

PubMed

King, Christopher R

2016-11-01

To date neither the optimal radiotherapy dose nor the existence of a dose-response has been established for salvage RT (SRT). A systematic review from 1996 to 2015 and meta-analysis was performed to identify the pathologic, clinical and treatment factors associated with relapse-free survival (RFS) after SRT (uniformly defined as a PSA>0.2ng/mL or rising above post-SRT nadir). A sigmoidal dose-response curve was objectively fitted and a non-parametric statistical test used to determine significance. 71 studies (10,034 patients) satisfied the meta-analysis criteria. SRT dose (p=0.0001), PSA prior to SRT (p=0.0009), ECE+ (p=0.039) and SV+ (p=0.046) had significant associations with RFS. Statistical analyses confirmed the independence of SRT dose-response. Omission of series with ADT did not alter results. Dose-response is well fit by a sigmoidal curve (p=0.0001) with a TCD 50 of 65.8Gy, with a dose of 70Gy achieving 58.4% RFS vs. 38.5% for 60Gy. A 2.0% [95% CI 1.1-3.2] improvement in RFS is achieved for each Gy. The SRT dose-response remarkably parallels that for definitive RT of localized disease. This study provides level 2a evidence for dose-escalated SRT>70Gy. The presence of an SRT dose-response for microscopic disease supports the hypothesis that prostate cancer is inherently radio-resistant. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

K-band observations of boxy bulges - I. Morphology and surface brightness profiles

NASA Astrophysics Data System (ADS)

Bureau, M.; Aronica, G.; Athanassoula, E.; Dettmar, R.-J.; Bosma, A.; Freeman, K. C.

2006-08-01

In this first paper of a series on the structure of boxy and peanut-shaped (B/PS) bulges, Kn-band observations of a sample of 30 edge-on spiral galaxies are described and discussed. Kn-band observations best trace the dominant luminous galactic mass and are minimally affected by dust. Images, unsharp-masked images, as well as major-axis and vertically summed surface brightness profiles are presented and discussed. Galaxies with a B/PS bulge tend to have a more complex morphology than galaxies with other bulge types, more often showing centred or off-centred X structures, secondary maxima along the major-axis and spiral-like structures. While probably not uniquely related to bars, those features are observed in three-dimensional N-body simulations of barred discs and may trace the main bar orbit families. The surface brightness profiles of galaxies with a B/PS bulge are also more complex, typically containing three or more clearly separated regions, including a shallow or flat intermediate region (Freeman Type II profiles). The breaks in the profiles offer evidence for bar-driven transfer of angular momentum and radial redistribution of material. The profiles further suggest a rapid variation of the scaleheight of the disc material, contrary to conventional wisdom but again as expected from the vertical resonances and instabilities present in barred discs. Interestingly, the steep inner region of the surface brightness profiles is often shorter than the isophotally thick part of the galaxies, itself always shorter than the flat intermediate region of the profiles. The steep inner region is also much more prominent along the major-axis than in the vertically summed profiles. Similarly to other recent work but contrary to the standard `bulge + disc' model (where the bulge is both thick and steep), we thus propose that galaxies with a B/PS bulge are composed of a thin concentrated disc (a disc-like bulge) contained within a partially thick bar (the B/PS bulge), itself contained within a thin outer disc. The inner disc likely formed secularly through bar-driven processes and is responsible for the steep inner region of the surface brightness profiles, traditionally associated with a classic bulge, while the bar is responsible for the flat intermediate region of the surface brightness profiles and the thick complex morphological structures observed. Those components are strongly coupled dynamically and are formed mostly of the same (disc) material, shaped by the weak but relentless action of the bar resonances. Any competing formation scenario for galaxies with a B/PS bulge, which represent at least 45 per cent of the local disc galaxy population, must explain equally well and self-consistently the above morphological and photometric properties, the complex gas and stellar kinematics observed, and the correlations between them.

Fewer Doses of HPV Vaccine Result in Immune Response Similar to Three-Dose Regimen

MedlinePlus

... Releases NCI News Note Fewer doses of HPV vaccine result in immune response similar to three-dose ... that two doses of a human papillomavirus (HPV) vaccine, trademarked as Cervarix, resulted in similar serum antibody ...

A randomized, first-in-human, healthy volunteer trial of BIVV009, a humanized antibody for the specific inhibition of the classical complement pathway.

PubMed

Bartko, Johann; Schoergenhofer, Christian; Schwameis, Michael; Firbas, Christa; Beliveau, Martin; Chang, Colin; Marier, Jean-Francois; Nix, Darrell; Gilbert, James C; Panicker, Sandip; Jilma, Bernd

2018-05-08

Aberrant activation of the classical complement pathway is the common underlying pathophysiology of orphan diseases such as bullous pemphigoid, antibody-mediated rejection of organ transplants, cold agglutinin disease and warm autoimmune haemolytic anaemia. Therapeutic options for these complement-mediated disorders are limited and BIVV009, a humanized monoclonal antibody directed against complement factor C1s, may be potentially useful for inhibition of the classical complement pathway. A phase-1, first-in-human, double-blind, randomized, placebo-controlled, dose-escalation trial of single and multiple doses of BIVV009 or placebo was conducted in 64 volunteers to evaluate safety, tolerability, pharmacokinetic, and pharmacodynamic profiles. Single and multiple infusions of BIVV009 were well tolerated without any safety concerns. BIVV009 exhibited a steep concentration-effect relationship with a Hill coefficient of 2.4, and an IC90 of 15.5 µg/mL. This study establishes the foundation for using BIVV009 as a highly selective inhibitor of the classical complement pathway in different diseases. This article is protected by copyright. All rights reserved. © 2018 American Society for Clinical Pharmacology and Therapeutics.

Cranial Stereotactic Radiosurgery: Current Status of the Initial Paradigm Shifter

PubMed Central

Sheehan, Jason P.; Yen, Chun-Po; Lee, Cheng-Chia; Loeffler, Jay S.

2014-01-01

The concept of stereotactic radiosurgery (SRS) was first described by Lars Leksell in 1951. It was proposed as a noninvasive alternative to open neurosurgical approaches to manage a variety of conditions. In the following decades, SRS emerged as a unique discipline involving a collegial partnership among neurosurgeons, radiation oncologists, and medical physicists. SRS relies on the precisely guided delivery of high-dose ionizing radiation to an intracranial target. The focused convergence of multiple beams yields a potent therapeutic effect on the target and a steep dose fall-off to surrounding structures, thereby minimizing the risk of collateral damage. SRS is typically administered in a single session but can be given in as many as five sessions or fractions. By providing an ablative effect noninvasively, SRS has altered the treatment paradigms for benign and malignant intracranial tumors, functional disorders, and vascular malformations. Literature on extensive intracranial radiosurgery has unequivocally demonstrated the favorable benefit-to-risk profile that SRS affords for appropriately selected patients. In a departure from conventional radiotherapeutic strategies, radiosurgical principles have recently been extended to extracranial indications such as lung, spine, and liver tumors. The paradigm shift resulting from radiosurgery continues to alter the landscape of related fields. PMID:25113762

Continuous Toxicological Dose-Response Relationships Are Pretty Homogeneous (Society for Risk Analysis Annual Meeting)

EPA Science Inventory

Dose-response relationships for a wide range of in vivo and in vitro continuous datasets are well-described by a four-parameter exponential or Hill model, based on a recent analysis of multiple historical dose-response datasets, mostly with more than five dose groups (Slob and Se...

Nonmonotonic dose response curves (NMDRCs) are common after Estrogen or Androgen signaling pathway disruption. Fact or Falderal?##

EPA Science Inventory

Nonmonotonic dose response curves (NMDRCs) are common after Estrogen or Androgen signaling pathway disruption. Fact or Falderal? Leon Earl Gray Jr, USEPA, ORD, NHEERL, TAD, RTB. RTP, NC, USA The shape of the dose response curve in the low dose region has been debated since th...

Dose-Response for Multiple Biomarkers of Exposure and Genotoxic Effect Following Repeated Treatment of Rats with the Alkylating Agents, MMS and MNU.

PubMed

Ji, Zhiying; LeBaron, Matthew J; Schisler, Melissa R; Zhang, Fagen; Bartels, Michael J; Gollapudi, B Bhaskar; Pottenger, Lynn H

2016-05-01

The nature of the dose-response relationship for various in vivo endpoints of exposure and effect were investigated using the alkylating agents, methyl methanesulfonate (MMS) and methylnitrosourea (MNU). Six male F344 rats/group were dosed orally with 0, 0.5, 1, 5, 25 or 50mg/kg bw/day (mkd) of MMS, or 0, 0.01, 0.1, 1, 5, 10, 25 or 50 mkd of MNU, for 4 consecutive days and sacrificed 24h after the last dose. The dose-responses for multiple biomarkers of exposure and genotoxic effect were investigated. In MMS-treated rats, the hemoglobin adduct level, a systemic exposure biomarker, increased linearly with dose (r (2) = 0.9990, P < 0.05), indicating the systemic availability of MMS; however, the N7MeG DNA adduct, a target exposure biomarker, exhibited a non-linear dose-response in blood and liver tissues. Blood reticulocyte micronuclei (MN), a genotoxic effect biomarker, exhibited a clear no-observed-genotoxic-effect-level (NOGEL) of 5 mkd as a point of departure (PoD) for MMS. Two separate dose-response models, the Lutz and Lutz model and the stepwise approach using PROC REG both supported a bilinear/threshold dose-response for MN induction. Liver gene expression, a mechanistic endpoint, also exhibited a bilinear dose-response. Similarly, in MNU-treated rats, hepatic DNA adducts, gene expression changes and MN all exhibited clear PoDs, with a NOGEL of 1 mkd for MN induction, although dose-response modeling of the MNU-induced MN data showed a better statistical fit for a linear dose-response. In summary, these results provide in vivo data that support the existence of clear non-linear dose-responses for a number of biologically significant events along the pathway for genotoxicity induced by DNA-reactive agents. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effect of aerosol fenoterol on the severity of bronchial hyperreactivity in patients with asthma.

PubMed Central

Salome, C M; Schoeffel, R E; Yan, K; Woolcock, A J

1983-01-01

Beta adrenergic agents given by aerosol decrease the responsiveness of the airways to histamine and methacholine in subjects with asthma, causing a shift of the dose response curve to the right. To find out whether the shift is related to the dose of beta adrenergic agent given and to determine the duration of the reduced responsiveness, eight subjects with asthma were given histamine inhalation tests after inhaled saline and after increasing doses of inhaled fenoterol on different days. The histamine inhalation tests were repeated at hourly intervals for five hours after a selected dose of fenoterol. Fenoterol caused a dose related shift to the right of the histamine dose response curve in each subject and in some the dose response relationship reached the "non-symptomatic range." The shift in the dose response curve was short lived and had returned towards the control position within three hours in all subjects. There was no change in shape of the curves at the time of maximal shift. The results show that inhaled fenoterol greatly reduces the airway responsiveness to histamine, but up to 400 micrograms of fenoterol every four to five hours may be needed to keep the responsiveness of the airways in the non-symptomatic range. PMID:6648868

Steep cut slope composting : field trials and evaluation : project summary report.

DOT National Transportation Integrated Search

2011-04-01

This project is a continuation of earlier work performed by Montana State University (Jennings et al. 2007) evaluating compost application on, and incorporation into, soils on steep cut slopes for the Montana Department of Transportation (MDT). The e...

Short-term estradiol replacement in postmenopausal women selectively mutes somatostatin's dose-dependent inhibition of fasting growth hormone secretion.

PubMed

Bray, M J; Vick, T M; Shah, N; Anderson, S M; Rice, L W; Iranmanesh, A; Evans, W S; Veldhuis, J D

2001-07-01

How estradiol stimulates pulsatile GH secretion in the human is not well understood. Here, we test the clinical hypothesis that estradiol stimulates GH secretion, in part, by opposing somatostatin's inhibition of GH release. To this end, 13 estrogen-withdrawn postmenopausal women received placebo or 1 mg micronized estradiol-17beta orally, twice daily for 14 days, in a prospectively randomized, patient-blinded, within-subject cross-over design. For each intervention, the dose-dependent suppressive actions of somatostatin were evaluated by infusing 0 (saline), 3, 10, 30, 100, or 300 microg/1.73 m(2).h somatostatin-14 continuously, iv, for 3 h, on separate mornings, in the fasting state, 48 h apart. Blood was sampled at 10-min intervals for 2 h before, for 3 h concurrently with, and for 1 h after each infusion. Serum GH concentrations were quantitated in an ultrasensitive chemiluminescence-based assay (detection threshold, 0.005 microg/L). In the estrogen-deficient milieu, constant iv somatostatin infusions inhibited steady-state serum GH concentrations (valley mean during the last 60 min of the infusion interval) in a dose-dependent manner (P < 10(-4) interventional effect). Maximally effective doses of somatostatin reduced the latter by 89 +/- 6.1% (mean +/- SEM) below the subject-specific preinfusion baseline. Estrogen administration increased the serum estradiol concentration from 12 +/- 1 to 245 +/- 35 pg/mL [42 +/- 4 to 920 +/- 110 pmol/L] (P < 10(-4)); decreased serum concentrations of LH (P = 0.018), FSH (P < 10(-4)), and insulin-like growth factor-I (P = 0.003); and elevated the fasting (6-h mean) serum GH concentration from 0.41 +/- 0.07 to 0.87 +/- 0.27 (P = 0.011). Estradiol supplementation did not alter somatostatin's maximal suppression of GH by 89 +/- 4.7% (P < 10(-4) below subject-specific preinfusion baseline), thus signifying unchanging somatostatin efficacy. In contrast, estradiol replacement significantly elevated the half-maximally inhibitory dose of infused somatostatin by 13.5-fold, from 0.43 (0.38-0.48, 95% group statistical confidence intervals) (placebo) to 6.0 (5.2-7.0) (estradiol) microg/1.73 m(2)/h (P < 10(-4)), denoting muting of somatostatin's inhibitory potency. The latter inference was confirmed by a concomitant 4-fold decrease in the exponential steepness of the somatostatin inhibitory dose-response function; viz., mean 1.42 (1.49 to 1.33) (placebo) vs. 0.34 (0.62 to 0.26) (estradiol) slope units (P < 10(-4)). The foregoing effects were specific, because estrogen did not alter somatostatin's dose-dependent enhancement (P < 10(-4)) of the orderliness of GH release patterns, as quantitated via the approximate entropy regularity statistic. In summary, short-term replacement of estradiol to midfollicular phase levels in postmenopausal women selectively reduces the potency, but not the efficacy, of somatostatin's dose-dependent inhibition of GH release. Estrogen supplementation does not modify somatostatin's reciprocal enhancement of the quantifiable orderliness (approximate entropy) of the GH secretory process. Accordingly, we postulate that estradiol can facilitate pulsatile GH secretion, in part, by opposing the repressive actions of somatostatin.

Statistics of peak overpressure and shock steepness for linear and nonlinear N-wave propagation in a kinematic turbulence.

PubMed

Yuldashev, Petr V; Ollivier, Sébastien; Karzova, Maria M; Khokhlova, Vera A; Blanc-Benon, Philippe

2017-12-01

Linear and nonlinear propagation of high amplitude acoustic pulses through a turbulent layer in air is investigated using a two-dimensional KZK-type (Khokhlov-Zabolotskaya-Kuznetsov) equation. Initial waves are symmetrical N-waves with shock fronts of finite width. A modified von Kármán spectrum model is used to generate random wind velocity fluctuations associated with the turbulence. Physical parameters in simulations correspond to previous laboratory scale experiments where N-waves with 1.4 cm wavelength propagated through a turbulence layer with the outer scale of about 16 cm. Mean value and standard deviation of peak overpressure and shock steepness, as well as cumulative probabilities to observe amplified peak overpressure and shock steepness, are analyzed. Nonlinear propagation effects are shown to enhance pressure level in random foci for moderate initial amplitudes of N-waves thus increasing the probability to observe highly peaked waveforms. Saturation of the pressure level is observed for stronger nonlinear effects. It is shown that in the linear propagation regime, the turbulence mainly leads to the smearing of shock fronts, thus decreasing the probability to observe high values of steepness, whereas nonlinear effects dramatically increase the probability to observe steep shocks.

The assessment of environmentally sensitive forest road construction in Calabrian pine forest areas of Turkey.

PubMed

Tunay, Metin

2006-07-01

Forest road construction by bulldozers in Calabrian Pine (Pinus brutia Ten.) forests on mountainous terrain of Turkey causes considerable damage to the environment and the forest standing alongside the road. This situation obliges a study of environmentally sound road construction in Turkey. This study was carried out in 4 sample sites of Antalya Forest Directorate in steep (34-50% gradient) and very steep terrain (51-70% gradient) conditions with bulldozer and excavator machine and direct damages to forest during road construction was determined, including forest area losses and damages to downhill trees in mountainous areas. It was determined that in steep terrain when excavators were used, less forest area (22.16%) was destroyed compared to bulldozers and 26.54% less area in very steep terrain. The proportion of damage on trees where bulldozer worked was nearly twofold higher than excavator was used. The results of this research show that the environmentally sensitive techniques applied for the road construction projects are considerably superior to the traditional use of bulldozers on steep slopes. The environmentally sound forest road construction by use of excavator must be considered an appropriate and reliable solution for mountainous terrain where areas of sensitive forest ecosystems are to be opened up.

Response of TLD-100 in mixed fields of photons and electrons

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

Lawless, Michael J.; Junell, Stephanie; Hammer, Cliff

Purpose: Thermoluminescent dosimeters (TLDs) are routinely used for dosimetric measurements of high energy photon and electron fields. However, TLD response in combined fields of photon and electron beam qualities has not been characterized. This work investigates the response of TLD-100 (LiF:Mg,Ti) to sequential irradiation by high-energy photon and electron beam qualities. Methods: TLDs were irradiated to a known dose by a linear accelerator with a 6 MV photon beam, a 6 MeV electron beam, and a NIST-traceable {sup 60}Co beam. TLDs were also irradiated in a mixed field of the 6 MeV electron beam and the 6 MV photon beam.more » The average TLD response per unit dose of the TLDs for each linac beam quality was normalized to the average response per unit dose of the TLDs irradiated by the {sup 60}Co beam. Irradiations were performed in water and in a Virtual Water Trade-Mark-Sign phantom. The 6 MV photon beam and 6 MeV electron beam were used to create dose calibration curves relating TLD response to absorbed dose to water, which were applied to the TLDs irradiated in the mixed field. Results: TLD relative response per unit dose in the mixed field was less sensitive than the relative response in the photon field and more sensitive than the relative response in the electron field. Application of the photon dose calibration curve to the TLDs irradiated in a mixed field resulted in an underestimation of the delivered dose, while application of the electron dose calibration curve resulted in an overestimation of the dose. Conclusions: The relative response of TLD-100 in mixed fields fell between the relative response in the photon-only and electron-only fields. TLD-100 dosimetry of mixed fields must account for this intermediate response to minimize the estimation errors associated with calibration factors obtained from a single beam quality.« less

Response of TLD-100 in mixed fields of photons and electrons.

PubMed

Lawless, Michael J; Junell, Stephanie; Hammer, Cliff; DeWerd, Larry A

2013-01-01

Thermoluminescent dosimeters (TLDs) are routinely used for dosimetric measurements of high energy photon and electron fields. However, TLD response in combined fields of photon and electron beam qualities has not been characterized. This work investigates the response of TLD-100 (LiF:Mg,Ti) to sequential irradiation by high-energy photon and electron beam qualities. TLDs were irradiated to a known dose by a linear accelerator with a 6 MV photon beam, a 6 MeV electron beam, and a NIST-traceable (60)Co beam. TLDs were also irradiated in a mixed field of the 6 MeV electron beam and the 6 MV photon beam. The average TLD response per unit dose of the TLDs for each linac beam quality was normalized to the average response per unit dose of the TLDs irradiated by the (60)Co beam. Irradiations were performed in water and in a Virtual Water™ phantom. The 6 MV photon beam and 6 MeV electron beam were used to create dose calibration curves relating TLD response to absorbed dose to water, which were applied to the TLDs irradiated in the mixed field. TLD relative response per unit dose in the mixed field was less sensitive than the relative response in the photon field and more sensitive than the relative response in the electron field. Application of the photon dose calibration curve to the TLDs irradiated in a mixed field resulted in an underestimation of the delivered dose, while application of the electron dose calibration curve resulted in an overestimation of the dose. The relative response of TLD-100 in mixed fields fell between the relative response in the photon-only and electron-only fields. TLD-100 dosimetry of mixed fields must account for this intermediate response to minimize the estimation errors associated with calibration factors obtained from a single beam quality.

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

PubMed

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

2017-02-01

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

Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses

PubMed Central

Colborn, Theo; Hayes, Tyrone B.; Heindel, Jerrold J.; Jacobs, David R.; Lee, Duk-Hee; Shioda, Toshi; Soto, Ana M.; vom Saal, Frederick S.; Welshons, Wade V.; Zoeller, R. Thomas

2012-01-01

For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from the cell culture, animal, and epidemiology literature. We illustrate that nonmonotonic responses and low-dose effects are remarkably common in studies of natural hormones and EDCs. Whether low doses of EDCs influence certain human disorders is no longer conjecture, because epidemiological studies show that environmental exposures to EDCs are associated with human diseases and disabilities. We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health. PMID:22419778

Statistical analysis of nonmonotonic dose-response relationships: research design and analysis of nasal cell proliferation in rats exposed to formaldehyde.

PubMed

Gaylor, David W; Lutz, Werner K; Conolly, Rory B

2004-01-01

Statistical analyses of nonmonotonic dose-response curves are proposed, experimental designs to detect low-dose effects of J-shaped curves are suggested, and sample sizes are provided. For quantal data such as cancer incidence rates, much larger numbers of animals are required than for continuous data such as biomarker measurements. For example, 155 animals per dose group are required to have at least an 80% chance of detecting a decrease from a 20% incidence in controls to an incidence of 10% at a low dose. For a continuous measurement, only 14 animals per group are required to have at least an 80% chance of detecting a change of the mean by one standard deviation of the control group. Experimental designs based on three dose groups plus controls are discussed to detect nonmonotonicity or to estimate the zero equivalent dose (ZED), i.e., the dose that produces a response equal to the average response in the controls. Cell proliferation data in the nasal respiratory epithelium of rats exposed to formaldehyde by inhalation are used to illustrate the statistical procedures. Statistically significant departures from a monotonic dose response were obtained for time-weighted average labeling indices with an estimated ZED at a formaldehyde dose of 5.4 ppm, with a lower 95% confidence limit of 2.7 ppm. It is concluded that demonstration of a statistically significant bi-phasic dose-response curve, together with estimation of the resulting ZED, could serve as a point-of departure in establishing a reference dose for low-dose risk assessment.

Improved numerical modelling of morphodynamics of rivers with steep banks

USDA-ARS?s Scientific Manuscript database

The flow and sediment transport processes near steep streambanks, which are commonly found in meandering, braided, and anastomosing stream systems, exhibit complex patterns. The interactions between bed and bank morphologic adjustment, and their governing processes are still not well understood. Inc...

Felling and bunching small timber on steep slopes.

Treesearch

Rodger A. Arola; Edwin S. Miyata; John A. Sturos; Helmuth M. Steinhilb

1981-01-01

Discusses the results of a field test of the unique Menzi Muck machine for felling and bunching small trees on steep slopes. Includes the analysis of a detailed time study to determine the productivity, costs, and economic feasibility of this unusual machine.

Interrill soil erosion processes on steep slopes

USDA-ARS?s Scientific Manuscript database

To date interrill erosion processes and regimes are not fully understood. The objectives are to 1) identify the erosion regimes and limiting processes between detachment and transport on steep slopes, 2) characterize the interactive effects between rainfall intensity and flow depth on sediment trans...

Nonmonotonic dose response curves (NMDRCs) are common after Estrogen or Androgen signaling pathway disruption. Fact or Falderal? ###SETAC

EPA Science Inventory

The shape of the dose response curve in the low dose region has been debated since the late 1940s. The debate originally focused on linear no threshold (LNT) vs threshold responses in the low dose range for cancer and noncancer related effects. Recently, claims have arisen tha...

Object preference by walking fruit flies, Drosophila melanogaster, is mediated by vision and graviperception

PubMed Central

Robie, Alice A.; Straw, Andrew D.; Dickinson, Michael H.

2010-01-01

Walking fruit flies, Drosophila melanogaster, use visual information to orient towards salient objects in their environment, presumably as a search strategy for finding food, shelter or other resources. Less is known, however, about the role of vision or other sensory modalities such as mechanoreception in the evaluation of objects once they have been reached. To study the role of vision and mechanoreception in exploration behavior, we developed a large arena in which we could track individual fruit flies as they walked through either simple or more topologically complex landscapes. When exploring a simple, flat environment lacking three-dimensional objects, flies used visual cues from the distant background to stabilize their walking trajectories. When exploring an arena containing an array of cones, differing in geometry, flies actively oriented towards, climbed onto, and explored the objects, spending most of their time on the tallest, steepest object. A fly's behavioral response to the geometry of an object depended upon the intrinsic properties of each object and not a relative assessment to other nearby objects. Furthermore, the preference was not due to a greater attraction towards tall, steep objects, but rather a change in locomotor behavior once a fly reached and explored the surface. Specifically, flies are much more likely to stop walking for long periods when they are perched on tall, steep objects. Both the vision system and the antennal chordotonal organs (Johnston's organs) provide sufficient information about the geometry of an object to elicit the observed change in locomotor behavior. Only when both these sensory systems were impaired did flies not show the behavioral preference for the tall, steep objects. PMID:20581279

Rainfall-Runoff and Slope Failure in a Steep, Tropical Landscape

NASA Astrophysics Data System (ADS)

Deane, J.; Freyberg, D. L.

2016-12-01

Tropical forests are often located on short, steep slopes with pronounced heterogeneity in vegetation over small distances. Further, they are distinguished from their temperate counterparts by a thinner organic horizon, and large interannual and subseasonal variability in precipitation. However, hydrologic processes in tropical watersheds are difficult to quantify and study because of data scarcity, accessibility difficulties and complex topography. As a result, there has been little work on disentangling the effects of spatial and temporal heterogeneity on flow generation and slope failure on tropical hillslopes. In this work we analyze the connections between terrain properties, subsurface formation, land cover, and precipitation variability in changing water table dynamics at the interface between a thin soil mantle and underlying bedrock. We have developed a fully distributed integrated hydrologic model at two different scales: 1) a 100 m idealized hillslope (1 m model grid size) representative of physiographic regions on tropical islands and 2) a 48 sq. km tropical island watershed in Trinidad and Tobago (30 m model grid size) using ParFlow.CLM. Additionally, we couple Parflow to an infinite slope stability module to investigate the initiation of rainfall induced landslides under different precipitation scenarios. The characteristic hillslopes are used to used to generalize the near subsurface response of a soil-saprolite aquifer to a range of landscape properties. In particular, we investigate the role of mean slope, soil properties and road cuts in altering the partitioning of runoff and infiltration, and increasing slope stability. Moving from the idealized models to the steep tropical watershed, we evaluate the effects of different land cover and precipitation scenarios—consistent with climate change projections—on flooding and hillslope failure incidence.

Animal and human dose-response models for Brucella species.

PubMed

Teske, Sondra S; Huang, Yin; Tamrakar, Sushil B; Bartrand, Timothy A; Weir, Mark H; Haas, Charles N

2011-10-01

Human Brucellosis is one of the most common zoonotic diseases worldwide. Disease transmission often occurs through the handling of domestic livestock, as well as ingestion of unpasteurized milk and cheese, but can have enhanced infectivity if aerosolized. Because there is no human vaccine available, rising concerns about the threat of Brucellosis to human health and its inclusion in the Center for Disease Control's Category B Bioterrorism/Select Agent List make a better understanding of the dose-response relationship of this microbe necessary. Through an extensive peer-reviewed literature search, candidate dose-response data were appraised so as to surpass certain standards for quality. The statistical programming language, "R," was used to compute the maximum likelihood estimation to fit two models, the exponential and the approximate beta-Poisson (widely used for quantitative risk assessment) to dose-response data. Dose-response models were generated for prevalent species of Brucella: Br. suis, Br. melitensis, and Br. abortus. Dose-response models were created for aerosolized Br. suis exposure to guinea pigs from pooled studies. A parallel model for guinea pigs inoculated through both aerosol and subcutaneous routes with Br. melitensis showed that the median infectious dose corresponded to a 30 colony-forming units (CFU) dose of Br. suis, much less than the N(50) dose of about 94 CFU for Br. melitensis organisms. When Br. melitensis was tested subcutaneously on mice, the N(50) dose was higher, 1,840 CFU. A dose-response model was constructed from pooled data for mice, rhesus macaques, and humans inoculated through three routes (subcutaneously/aerosol/intradermally) with Br. melitensis. © 2011 Society for Risk Analysis.

Structural phylogeny by profile extraction and multiple superimposition using electrostatic congruence as a discriminator

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

Chakraborty, Sandeep; Rao, Basuthkar J.; Baker, Nathan A.

2013-04-01

Phylogenetic analysis of proteins using multiple sequence alignment (MSA) assumes an underlying evolutionary relationship in these proteins which occasionally remains undetected due to considerable sequence divergence. Structural alignment programs have been developed to unravel such fuzzy relationships. However, none of these structure based methods have used electrostatic properties to discriminate between spatially equivalent residues. We present a methodology for MSA of a set of related proteins with known structures using electrostatic properties as an additional discriminator (STEEP). STEEP first extracts a profile, then generates a multiple structural superimposition providing a consolidated spatial framework for comparing residues and finally emits themore » MSA. Residues that are aligned differently by including or excluding electrostatic properties can be targeted by directed evolution experiments to transform the enzymatic properties of one protein into another. We have compared STEEP results to those obtained from a MSA program (ClustalW) and a structural alignment method (MUSTANG) for chymotrypsin serine proteases. Subsequently, we used PhyML to generate phylogenetic trees for the serine and metallo-β-lactamase superfamilies from the STEEP generated MSA, and corroborated the accepted relationships in these superfamilies. We have observed that STEEP acts as a functional classifier when electrostatic congruence is used as a discriminator, and thus identifies potential targets for directed evolution experiments. In summary, STEEP is unique among phylogenetic methods for its ability to use electrostatic congruence to specify mutations that might be the source of the functional divergence in a protein family. Based on our results, we also hypothesize that the active site and its close vicinity contains enough information to infer the correct phylogeny for related proteins.« less

Comparative transcriptome analysis of rice seedlings induced by different doses of heavy ion radiation

NASA Astrophysics Data System (ADS)

Zhao, Qian; Sun, Yeqing; Wang, Wei

2016-07-01

Highly ionizing radiation (HZE) in space is considered as a main factor causing biological effects on plant seeds. To investigate the different effects on genome-wide gene expression of low-dose and high-dose ion radiation, we carried out ground-base carbon particle HZE experiments with different cumulative doses (0Gy, 0.2Gy, 2Gy) to rice seeds and then performed comparative transcriptome analysis of the rice seedlings. We identified a total of 2551 and 1464 differentially expressed genes (DEGs) in low-dose and high-dose radiation groups, respectively. Gene ontology analyses indicated that low-dose and high-dose ion radiation both led to multiple physiological and biochemical activities changes in rice. By Gene Ontology analyses, the results showed that only one process-oxidation reduction process was enriched in the biological process category after high-dose ion radiation, while more processes such as response to biotic stimulus, heme binding, tetrapyrrole binding, oxidoreductase activity, catalytic activity and oxidoreductase activity were significantly enriched after low-dose ion radiation. The results indicated that the rice plants only focused on the process of oxidation reduction to response to high-dose ion radiation, whereas it was a coordination of multiple biological processes to response to low-dose ion radiation. To elucidate the transcriptional regulation of radiation stress-responsive genes, we identified several DEGs-encoding TFs. AP2/EREBP, bHLH, C2H2, MYB and WRKY TF families were altered significantly in response to ion radiation. Mapman analysis speculated that the biological effects on rice seedlings caused by the radiation stress might share similar mechanisms with the biotic stress. Our findings highlight important alterations in the expression of radiation response genes, metabolic pathways, and TF-encoding genes in rice seedlings exposed to low-dose and high-dose ion radiation.

Dose-response relationships and extrapolation in toxicology - Mechanistic and statistical considerations

EPA Science Inventory

Controversy on toxicological dose-response relationships and low-dose extrapolation of respective risks is often the consequence of misleading data presentation, lack of differentiation between types of response variables, and diverging mechanistic interpretation. In this chapter...

WE-D-BRE-06: Quantification of Dose-Response for High Grade Esophagtis Patients Using a Novel Voxel-To-Voxel Method

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

Niedzielski, J; Martel, M; Tucker, S

2014-06-15

Purpose: Radiation induces an inflammatory response in the esophagus, discernible on CT studies. This work objectively quantifies the voxel esophageal radiation-response for patients with acute esophagitis. This knowledge is an important first-step towards predicting the effect of complex dose distributions on patient esophagitis symptoms. Methods: A previously validated voxel-based methodology of quantifying radiation esophagitis severity was used to identify the voxel dose-response for 18 NSCLC patients with severe esophagitis (CTCAE grading criteria, grade2 or higher). The response is quantified as percent voxel volume change for a given dose. During treatment (6–8 weeks), patients had weekly 4DCT studies and esophagitis scoring.more » Planning CT esophageal contours were deformed to each weekly CT using a demons DIR algorithm. An algorithm using the Jacobian Map from the DIR of the planning CT to all weekly CTs was used to quantify voxel-volume change, along with corresponding delivered voxel dose, to the planning voxel. Dose for each voxel for each time-point was calculated on each previous weekly CT image, and accumulated using DIR. Thus, for each voxel, the volume-change and delivered dose was calculated for each time-point. The data was binned according to when the volume-change first increased by a threshold volume (10%–100%, in 10% increments), and the average delivered dose calculated for each bin. Results: The average dose resulting in a voxel volume increase of 10–100% was 21.6 to 45.9Gy, respectively. The mean population dose to give a 50% volume increase was 36.3±4.4Gy, (range:29.8 to 43.5Gy). The average week of 50% response was 4.1 (range:4.9 to 2.8 weeks). All 18 patients showed similar dose to first response curves, showing a common trend in the initial inflammatoryresponse. Conclusion: We extracted the dose-response curve of the esophagus on a voxel-to-voxel level. This may be useful for estimating the esophagus response (and patient symptoms) to complicated dose distributions.« less

PREDICTING THE RISKS OF NEUROTOXIC VOLATILE ORGANIC COMPOUNDS BASED ON TARGET TISSUE DOSE.

EPA Science Inventory

Quantitative exposure-dose-response models relate the external exposure of a substance to the dose in the target tissue, and then relate the target tissue dose to production of adverse outcomes. We developed exposure-dose-response models to describe the affects of acute exposure...

Effective superelevation for large trucks on sharp curves and steep grades

DOT National Transportation Integrated Search

2002-10-01

This project was undertaken to identify the particular problems faced by trucks on sharp curves on steep grades, such as rebuilt switchback curves on mountainous two-lane, two-way roads and the high speed downgrade curves found on West Virginia's lim...

30 CFR 785.15 - Steep slope mining.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Steep slope mining. 785.15 Section 785.15 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR SURFACE COAL MINING AND RECLAMATION OPERATIONS PERMITS AND COAL EXPLORATION SYSTEMS UNDER REGULATORY PROGRAMS...

30 CFR 785.15 - Steep slope mining.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Steep slope mining. 785.15 Section 785.15 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR SURFACE COAL MINING AND RECLAMATION OPERATIONS PERMITS AND COAL EXPLORATION SYSTEMS UNDER REGULATORY PROGRAMS...

When what we need influences what we see: choice of energetic replenishment is linked with perceived steepness.

PubMed

Taylor-Covill, Guy A H; Eves, Frank F

2014-06-01

The apparent steepness of the locomotor challenge presented by hills and staircases is overestimated in explicit awareness. Experimental evidence suggests the visual system may rescale our conscious experience of steepness in line with available energy resources. Skeptics of this "embodied" view argue that such findings reflect experimental demand. This article tested whether perceived steepness was related to resource choices in the built environment. Travelers in a station estimated the slant angle of a 6.45 m staircase (23.4°) either before (N = 302) or after (N = 109) choosing from a selection of consumable items containing differing levels of energetic resources. Participants unknowingly allocated themselves to a quasi-experimental group based on the energetic resources provided by the item they chose. Consistent with a resource based model, individuals that chose items with a greater energy density, or more rapidly available energy, estimated the staircase as steeper than those opting for items that provided less energetic resources. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Physicochemical properties of nixtamalized corn flours with and without germ.

PubMed

Vega Rojas, Lineth J; Rojas Molina, Isela; Gutiérrez Cortez, Elsa; Rincón Londoño, Natalia; Acosta Osorio, Andrés A; Del Real López, Alicia; Rodríguez García, Mario E

2017-04-01

This research studied the influence of the germ components on the physicochemical properties of cooked corn and nixtamalized corn flours as a function of the calcium hydroxide content (from 0 to 2.1 w/w) and steeping time (between 0 and 9h). A linear relationship was found between calcium content in germ and steeping time used during nixtamalization process. X-ray diffraction analysis showed that calcium carbonate is formed into the germ structure to 2.1 w/w of calcium hydroxide and 9h steeping time. The presence of the germ improves the development of peak viscosity in flours, and it is related to the increases in calcium concentration in germ and the formation of amylose-lipid complexes. No significant changes were observed in palmitic, stearic, oleic and linoleic acids of corn oil. The levels of further corn oil deterioration were 2.1 w/w of calcium hydroxide concentration and 9h of steeping time. Copyright © 2016 Elsevier Ltd. All rights reserved.

The stratigraphy of the Steep Rock Group, N.W. Ontario, with evidence of a major unconformity

NASA Technical Reports Server (NTRS)

Wilks, M. E.; Nisbet, E. G.

1986-01-01

The Steep Rock Group is exposed 6 km north of Atikokan, 200 km west of Thunder Bay. It is situated on the southern margin of the Wabigoon Belt of the Archaean Superior Province, N. W. Ontario. Reinvestigation of the geology of the Group has shown that the Group lies unconformably on the Tonalite Complex to the east. This unconformity has been previously suspected, from regional and ine mapping but no conclusive outcrop evidence for its existence has as yet been published. The strike of the group, comprised of Basal Conglomerate, Carbonate Member, Ore Zone and Ashrock is generally north-northwest dipping steeply to the southwest. Of the 7 contacts between the Steep Rock Group and the Tonalite Complex, 3 expose the unconformity (The Headland, S. Roberts Pit, Trueman Point), and 4 are faulted. These three outcrops demonstrate unequivocally that the Steep Rock group was laid down unconformably on the underlying Tonalite Complex, which is circa 3 Ga old.

Distinguishing between tectonic and lithologic controls on bedrock channel longitudinal profiles using cosmogenic 10Be erosion rates and channel steepness index

USGS Publications Warehouse

Cyr, Andrew J.; Granger, Darryl E.; Olivetti, Valerio; Molin, Paola

2014-01-01

Knickpoints in fluvial channel longitudinal profiles and channel steepness index values derived from digital elevation data can be used to detect tectonic structures and infer spatial patterns of uplift. However, changes in lithologic resistance to channel incision can also influence the morphology of longitudinal profiles. We compare the spatial patterns of both channel steepness index and cosmogenic 10Be-determined erosion rates from four landscapes in Italy, where the geology and tectonics are well constrained, to four theoretical predictions of channel morphologies, which can be interpreted as the result of primarily tectonic or lithologic controls. These data indicate that longitudinal profile forms controlled by unsteady or nonuniform tectonics can be distinguished from those controlled by nonuniform lithologic resistance. In each landscape the distribution of channel steepness index and erosion rates is consistent with model predictions and demonstrates that cosmogenic nuclide methods can be applied to distinguish between these two controlling factors.

Kasner solutions, climbing scalars and big-bang singularity

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

Condeescu, Cezar; Dudas, Emilian, E-mail: cezar.condeescu@roma2.infn.it, E-mail: emilian.dudas@cpht.polytechnique.fr

We elaborate on a recently discovered phenomenon where a scalar field close to big-bang is forced to climb a steep potential by its dynamics. We analyze the phenomenon in more general terms by writing the leading order equations of motion near the singularity. We formulate the conditions for climbing to exist in the case of several scalars and after inclusion of higher-derivative corrections and we apply our results to some models of moduli stabilization. We analyze an example with steep stabilizing potential and notice again a related critical behavior: for a potential steepness above a critical value, going backwards towardsmore » big-bang, the scalar undergoes wilder oscillations, with the steep potential pushing it back at every passage and not allowing the scalar to escape to infinity. Whereas it was pointed out earlier that there are possible implications of the climbing phase to CMB, we point out here another potential application, to the issue of initial conditions in inflation.« less

Polymer gel dosimeters with reduced toxicity: a preliminary investigation of the NMR and optical dose response using different monomers

NASA Astrophysics Data System (ADS)

Senden, R. J.; DeJean, P.; McAuley, K. B.; Schreiner, L. J.

2006-07-01

In this work, three new polymer gel dosimeter recipes were investigated that may be more suitable for widespread applications than polyacrylamide gel dosimeters, since the extremely toxic acrylamide has been replaced with the less harmful monomers N-isopropylacrylamide (NIPAM), diacetone acrylamide and N-vinylformamide. The new gel dosimeters studied contained gelatin (5 wt%), monomer (3 wt%), N,N'-methylene-bis-acrylamide crosslinker (3 wt%) and tetrakis (hydroxymethyl) phosphonium chloride antioxidant (10 mM). The NMR response (R2) of the dosimeters was analysed for conditions of varying dose, dose rate, time post-irradiation, and temperature during irradiation and scanning. It was shown that the dose-response behaviour of the NIPAM/Bis gel dosimeter is comparable to that of normoxic polyacrylamide gel (PAGAT) in terms of high dose-sensitivity and low dependence on dose rate and irradiation temperature, within the ranges considered. The dose-response (R2) of NIPAM/Bis appears to be linear over a greater dose range than the PAGAT gel dosimeter. The effects of time post-irradiation (temporal instability) and temperature during NMR scanning on the R2 response were more significant for NIPAM/Bis dosimeters. Diacetone acrylamide and N-vinylformamide gel dosimeters possessed considerably lower dose-sensitivities. The optical dose-response, measured in terms of the attenuation coefficient for each polymer gel dosimeter, showed potential for the use of optical imaging techniques in future studies.

Geotechnical properties of cemented sands in steep slopes

USGS Publications Warehouse

Collins, B.D.; Sitar, N.

2009-01-01

An investigation into the geotechnical properties specific to assessing the stability of weakly and moderately cemented sand cliffs is presented. A case study from eroding coastal cliffs located in central California provides both the data and impetus for this study. Herein, weakly cemented sand is defined as having an unconfined compressive strength (UCS) of less than 100 kPa, and moderately cemented sand is defined as having UCS between 100 and 400 kPa. Testing shows that both materials fail in a brittle fashion and can be modeled effectively using linear Mohr-Coulomb strength parameters, although for weakly cemented sands, curvature of the failure envelope is more evident with decreasing friction and increasing cohesion at higher confinement. Triaxial tests performed to simulate the evolving stress state of an eroding cliff, using a reduction in confinement-type stress path, result in an order of magnitude decrease in strain at failure and a more brittle response. Tests aimed at examining the influence of wetting on steep slopes show that a 60% decrease in UCS, a 50% drop in cohesion, and 80% decrease in the tensile strength occurs in moderately cemented sand upon introduction to water. In weakly cemented sands, all compressive, cohesive, and tensile strength is lost upon wetting and saturation. The results indicate that particular attention must be given to the relative level of cementation, the effects of groundwater or surficial seepage, and the small-scale strain response when performing geotechnical slope stability analyses on these materials. ?? 2009 ASCE.

Design considerations and analysis planning of a phase 2a proof of concept study in rheumatoid arthritis in the presence of possible non-monotonicity.

PubMed

Liu, Feng; Walters, Stephen J; Julious, Steven A

2017-10-02

It is important to quantify the dose response for a drug in phase 2a clinical trials so the optimal doses can then be selected for subsequent late phase trials. In a phase 2a clinical trial of new lead drug being developed for the treatment of rheumatoid arthritis (RA), a U-shaped dose response curve was observed. In the light of this result further research was undertaken to design an efficient phase 2a proof of concept (PoC) trial for a follow-on compound using the lessons learnt from the lead compound. The planned analysis for the Phase 2a trial for GSK123456 was a Bayesian Emax model which assumes the dose-response relationship follows a monotonic sigmoid "S" shaped curve. This model was found to be suboptimal to model the U-shaped dose response observed in the data from this trial and alternatives approaches were needed to be considered for the next compound for which a Normal dynamic linear model (NDLM) is proposed. This paper compares the statistical properties of the Bayesian Emax model and NDLM model and both models are evaluated using simulation in the context of adaptive Phase 2a PoC design under a variety of assumed dose response curves: linear, Emax model, U-shaped model, and flat response. It is shown that the NDLM method is flexible and can handle a wide variety of dose-responses, including monotonic and non-monotonic relationships. In comparison to the NDLM model the Emax model excelled with higher probability of selecting ED90 and smaller average sample size, when the true dose response followed Emax like curve. In addition, the type I error, probability of incorrectly concluding a drug may work when it does not, is inflated with the Bayesian NDLM model in all scenarios which would represent a development risk to pharmaceutical company. The bias, which is the difference between the estimated effect from the Emax and NDLM models and the simulated value, is comparable if the true dose response follows a placebo like curve, an Emax like curve, or log linear shape curve under fixed dose allocation, no adaptive allocation, half adaptive and adaptive scenarios. The bias though is significantly increased for the Emax model if the true dose response follows a U-shaped curve. In most cases the Bayesian Emax model works effectively and efficiently, with low bias and good probability of success in case of monotonic dose response. However, if there is a belief that the dose response could be non-monotonic then the NDLM is the superior model to assess the dose response.

European Academy of Allergy and Clinical Immunology task force report on 'dose-response relationship in allergen-specific immunotherapy'.

PubMed

Calderón, M A; Larenas, D; Kleine-Tebbe, J; Jacobsen, L; Passalacqua, G; Eng, P A; Varga, E M; Valovirta, E; Moreno, C; Malling, H J; Alvarez-Cuesta, E; Durham, S; Demoly, P

2011-10-01

For a century, allergen-specific immunotherapy (SIT) has proven to be an effective treatment for allergic rhinitis, asthma, and insect sting allergy. However, as allergen doses are frequently adapted to the individual patient, there are few data on dose-response relationship in SIT. Allergen products for SIT are being increasingly required to conform to regulatory requirements for human medicines, which include the need to demonstrate dose-dependent effects. This report, produced by a Task Force of the EAACI Immunotherapy Interest Group, evaluates the currently available data on dose-response relationships in SIT and aims to provide recommendations for the design of future studies. Fifteen dose-ranging studies fulfilled the inclusion criteria and twelve reported a dose-response relationship for clinical efficacy. Several studies also reported a dose-response relationship for immunological and safety endpoints. Due to the use of different reference materials and methodologies for the determination of allergen content, variations in study design, and choice of endpoints, no comparisons could be made between studies and, as a consequence, no general dosing recommendations can be made. Despite recently introduced guidelines on the standardization of allergen preparations and study design, the Task Force identified a need for universally accepted standards for the measurement of allergen content in SIT preparations, dosing protocols, and selection of clinical endpoints to enable dose-response effects to be compared across studies. © 2011 John Wiley & Sons A/S.

A single dose of inactivated hepatitis A vaccine promotes HAV-specific memory cellular response similar to that induced by a natural infection.

PubMed

Melgaço, Juliana Gil; Morgado, Lucas Nóbrega; Santiago, Marta Almeida; Oliveira, Jaqueline Mendes de; Lewis-Ximenez, Lia Laura; Hasselmann, Bárbara; Cruz, Oswaldo Gonçalves; Pinto, Marcelo Alves; Vitral, Claudia Lamarca

2015-07-31

Based on current studies on the effects of single dose vaccines on antibody production, Latin American countries have adopted a single dose vaccine program. However, no data are available on the activation of cellular response to a single dose of hepatitis A. Our study investigated the functional reactivity of the memory cell phenotype after hepatitis A virus (HAV) stimulation through administration of the first or second dose of HAV vaccine and compared the response to that of a baseline group to an initial natural infection. Proliferation assays showed that the first vaccine dose induced HAV-specific cellular response; this response was similar to that induced by a second dose or an initial natural infection. Thus, from the first dose to the second dose, increase in the frequencies of classical memory B cells, TCD8 cells, and central memory TCD4 and TCD8 cells were observed. Regarding cytokine production, increased IL-6, IL-10, TNF, and IFNγ levels were observed after vaccination. Our findings suggest that a single dose of HAV vaccine promotes HAV-specific memory cell response similar to that induced by a natural infection. The HAV-specific T cell immunity induced by primary vaccination persisted independently of the protective plasma antibody level. In addition, our results suggest that a single dose immunization system could serve as an alternative strategy for the prevention of hepatitis A in developing countries. Copyright © 2015 Elsevier Ltd. All rights reserved.

A review: Development of a microdose model for analysis of adaptive response and bystander dose response behavior.

PubMed

Leonard, Bobby E

2008-02-27

Prior work has provided incremental phases to a microdosimetry modeling program to describe the dose response behavior of the radio-protective adaptive response effect. We have here consolidated these prior works (Leonard 2000, 2005, 2007a, 2007b, 2007c) to provide a composite, comprehensive Microdose Model that is also herein modified to include the bystander effect. The nomenclature for the model is also standardized for the benefit of the experimental cellular radio-biologist. It extends the prior work to explicitly encompass separately the analysis of experimental data that is 1.) only dose dependent and reflecting only adaptive response radio-protection, 2.) both dose and dose-rate dependent data and reflecting only adaptive response radio-protection for spontaneous and challenge dose damage, 3.) only dose dependent data and reflecting both bystander deleterious damage and adaptive response radio-protection (AR-BE model). The Appendix cites the various applications of the model. Here we have used the Microdose Model to analyze the, much more human risk significant, Elmore et al (2006) data for the dose and dose rate influence on the adaptive response radio-protective behavior of HeLa x Skin cells for naturally occurring, spontaneous chromosome damage from a Brachytherapy type (125)I photon radiation source. We have also applied the AR-BE Microdose Model to the Chromosome inversion data of Hooker et al (2004) reflecting both low LET bystander and adaptive response effects. The micro-beam facility data of Miller et al (1999), Nagasawa and Little (1999) and Zhou et al (2003) is also examined. For the Zhou et al (2003) data, we use the AR-BE model to estimate the threshold for adaptive response reduction of the bystander effect. The mammogram and diagnostic X-ray induction of AR and protective BE are observed. We show that bystander damage is reduced in the similar manner as spontaneous and challenge dose damage as shown by the Azzam et al (1996) data. We cite primary unresolved questions regarding adaptive response behavior and bystander behavior. The five features of major significance provided by the Microdose Model so far are 1. Single Specific Energy Hits initiate Adaptive Response. 2. Mammogram and diagnostic X-rays induce a protective Bystander Effect as well as Adaptive Response radio-protection. 3. For mammogram X-rays the Adaptive Response protection is retained at high primer dose levels. 4. The dose range of the AR protection depends on the value of the Specific Energy per Hit, 1 >. 5. Alpha particle induced deleterious Bystander damage is modulated by low LET radiation.

Three-dimensional geometry and tectonostratigraphy of the Pennine zone, Central Alps, Switzerland and Northern Italy

NASA Astrophysics Data System (ADS)

Maxelon, Michael; Mancktelow, Neil S.

2005-08-01

Continental collision during Alpine orogenesis entailed a polyphase deformation history (D 1-D 5) in the Pennine zone of the Central Alps. The regional tectonostratigraphy was basically developed during D 1 and D 2, characterised by isoclinal, typically north-closing recumbent anticlines, separated by pinched-in synclines, on the scale of tens of kilometres. Later deformation phases (D 3 and D 4) warped the stack into wavy to open folds. Exhumation of this zone resulted locally in later vertical shortening and folding of already steep fabrics (D 5). Three-dimensional models of the nappe pile were constructed, based on geostatistical assessment of the regional foliation field and considering the abundant structural field data. These models indicate the existence of five principal tectonostratigraphic levels developed during D 1 and thus equivalent to nappe units s. str.: the Gotthard, the Leventina-Antigorio, the Maggia-Simano (and probably the Monte Leone as well as the Composite Lepontine Series), Lebendun-Soja and Adula-Cima Lunga levels. All these tectonic units formed part of the passive continental margin of Europe prior to the onset of the Alpine orogenesis. Individual isoclinal post-nappe folds reflect relative displacements on the order of 40 km or more. The most prominent D 2 post-nappe structure is the Wandfluhhorn Fold, structurally equivalent to the northern closure of the Leventina-Lucomagno Antiform. The Lebendun and Monte Leone folds are of similar magnitudes and also affect the whole nappe pile, whereas the smaller Mogno and Molare synforms only refold the Maggia-Simano nappe internally. Principal D 3 and D 4 structures are the tight Mergoscia Synform directly north of the Insubric Fault between Bellinzona and Locarno (Southern Steep Belt), the Maggia Steep Zone, forming the steep western limb of the Campo Tencia Synform and subdividing the Lepontine dome into the Simplon and Ticino subdomes, the Chiéra Synform steepening the dominant foliation in the north (Northern Steep Belt) and the Vanzone and Claro Antiforms steepening the dominant foliation in the south (Southern Steep Belt). The current geometry of the Northern and Southern Steep Belts reflects an interplay between D 4 and D 3, involving both fold interference and reactivation/tightening.

Dose-response characteristics of an amorphous silicon EPID.

PubMed

Winkler, Peter; Hefner, Alfred; Georg, Dietmar

2005-10-01

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

Dose-response-a challenge for allelopathy?

PubMed

Belz, Regina G; Hurle, Karl; Duke, Stephen O

2005-04-01

The response of an organism to a chemical depends, among other things, on the dose. Nonlinear dose-response relationships occur across a broad range of research fields, and are a well established tool to describe the basic mechanisms of phytotoxicity. The responses of plants to allelochemicals as biosynthesized phytotoxins, relate as well to nonlinearity and, thus, allelopathic effects can be adequately quantified by nonlinear mathematical modeling. The current paper applies the concept of nonlinearity to assorted aspects of allelopathy within several bioassays and reveals their analysis by nonlinear regression models. Procedures for a valid comparison of effective doses between different allelopathic interactions are presented for both, inhibitory and stimulatory effects. The dose-response applications measure and compare the responses produced by pure allelochemicals [scopoletin (7-hydroxy-6-methoxy-2H-1-benzopyran-2-one); DIBOA (2,4-dihydroxy-2H-1,4-benzoxaxin-3(4H)-one); BOA (benzoxazolin-2(3H)-one); MBOA (6-methoxy-benzoxazolin-2(3H)-one)], involved in allelopathy of grain crops, to demonstrate how some general principles of dose responses also relate to allelopathy. Hereupon, dose-response applications with living donor plants demonstrate the validity of these principles for density-dependent phytotoxicity of allelochemicals produced and released by living plants (Avena sativa L., Secale cereale L., Triticum L. spp.), and reveal the use of such experiments for initial considerations about basic principles of allelopathy. Results confirm that nonlinearity applies to allelopathy, and the study of allelopathic effects in dose-response experiments allows for new and challenging insights into allelopathic interactions.

The Effects of Low Dose Irradiation on Inflammatory Response Proteins in a 3D Reconstituted Human Skin Tissue Model

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

Varnum, Susan M.; Springer, David L.; Chaffee, Mary E.

Skin responses to moderate and high doses of ionizing radiation include the induction of DNA repair, apoptosis, and stress response pathways. Additionally, numerous studies indicate that radiation exposure leads to inflammatory responses in skin cells and tissue. However, the inflammatory response of skin tissue to low dose radiation (<10 cGy) is poorly understood. In order to address this, we have utilized a reconstituted human skin tissue model (MatTek EpiDerm FT) and assessed changes in 23 cytokines twenty-four and forty eight hours following treatment of skin with either 3 or 10 cGy low-dose of radiation. Three cytokines, IFN-γ, IL-2, MIP-1α, weremore » significantly altered in response to low dose radiation. In contrast, seven cytokines were significantly altered in response to a high radiation dose of 200 cGy (IL-2, IL-10, IL-13, IFN-γ, MIP-1α, TNF α, and VEGF) or the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (G-CSF, GM-CSF, IL-1α, IL-8, MIP-1α, MIP-1β, RANTES). Additionally, radiation induced inflammation appears to have a distinct cytokine response relative to the non-radiation induced stressor, TPA. Overall, these results indicate that there are subtle changes in the inflammatory protein levels following exposure to low dose radiation and this response is a sub-set of what is seen following a high dose in a human skin tissue model.« less

PHYSIOLOCIGALLY BASED PHARMACOKINETIC (PBPK) MODELING AND MODE OF ACTION IN DOSE-RESPONSE ASSESSMENT

EPA Science Inventory

PHYSIOLOGICALLY BASED PHARMACOKINETIC (PBPK) MODELING AND MODE OF ACTION IN DOSE-RESPONSE ASSESSMENT. Barton HA. Experimental Toxicology Division, National Health and Environmental Effects Laboratory, ORD, U.S. EPA
Dose-response analysis requires quantitatively linking infor...

A distributed lag approach to fitting non-linear dose-response models in particulate matter air pollution time series investigations.

PubMed

Roberts, Steven; Martin, Michael A

2007-06-01

The majority of studies that have investigated the relationship between particulate matter (PM) air pollution and mortality have assumed a linear dose-response relationship and have used either a single-day's PM or a 2- or 3-day moving average of PM as the measure of PM exposure. Both of these modeling choices have come under scrutiny in the literature, the linear assumption because it does not allow for non-linearities in the dose-response relationship, and the use of the single- or multi-day moving average PM measure because it does not allow for differential PM-mortality effects spread over time. These two problems have been dealt with on a piecemeal basis with non-linear dose-response models used in some studies and distributed lag models (DLMs) used in others. In this paper, we propose a method for investigating the shape of the PM-mortality dose-response relationship that combines a non-linear dose-response model with a DLM. This combined model will be shown to produce satisfactory estimates of the PM-mortality dose-response relationship in situations where non-linear dose response models and DLMs alone do not; that is, the combined model did not systemically underestimate or overestimate the effect of PM on mortality. The combined model is applied to ten cities in the US and a pooled dose-response model formed. When fitted with a change-point value of 60 microg/m(3), the pooled model provides evidence for a positive association between PM and mortality. The combined model produced larger estimates for the effect of PM on mortality than when using a non-linear dose-response model or a DLM in isolation. For the combined model, the estimated percentage increase in mortality for PM concentrations of 25 and 75 microg/m(3) were 3.3% and 5.4%, respectively. In contrast, the corresponding values from a DLM used in isolation were 1.2% and 3.5%, respectively.

The effects of a selective 5-HT2 receptor antagonist (ICI 170,809) on platelet aggregation and pupillary responses in healthy volunteers.

PubMed Central

Millson, D S; Jessup, C L; Swaisland, A; Haworth, S; Rushton, A; Harry, J D

1992-01-01

1. ICI 170,809 (2-(2-dimethylamino-2-methylpropylthio)-3-phenylquinoline hydrochloride) is a potent 5-hydroxytryptamine (5-HT) type 2 postsynaptic receptor antagonist. 2. Effects of ICI 170,809 as single oral doses (3, 7, 15 and 30 mg) or placebo were studied on the duration of antagonism for the ex vivo platelet aggregatory response to 5-HT and to the pupillary light constrictor response in eight healthy male volunteers. 3. Pupillary dark adapted responses to a 0.5 s light stimulus were measured using a portable infrared pupillometer, for up to 24 h after dosing. 4. The in vitro platelet 5-HT aggregation response was reduced by ICI 170,809, with depression of the dose-response curve to 5-HT at all concentrations of 5-HT and with no evidence for a parallel shift. 5. The ex vivo platelet 5-HT response demonstrated a dose related significant (P less than 0.02) decrease in aggregation reaching a maximum at 2 h after dosing with the effect persisting for at least 8 h after dosing with the 7 and 15 mg doses. 6. Resting pupil diameter (RPD), and light induced pupillary responses in the dark adapted pupil, showed a significant (P less than 0.01) dose related reduction with significant (P less than 0.05) effects still present with the 15 and 30 mg doses at 8 h after dosing. 7. We conclude that, changes in both ex vivo platelet aggregation to 5-HT and dark adapted pupil size, are significantly correlated (P less than 0.0001) with log plasma concentrations (ng ml-1) of ICI 170,809, enabling the assessment of 5-HT2-receptor antagonism in man. PMID:1576048

Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework.

PubMed

Calabrese, Edward J; Bachmann, Kenneth A; Bailer, A John; Bolger, P Michael; Borak, Jonathan; Cai, Lu; Cedergreen, Nina; Cherian, M George; Chiueh, Chuang C; Clarkson, Thomas W; Cook, Ralph R; Diamond, David M; Doolittle, David J; Dorato, Michael A; Duke, Stephen O; Feinendegen, Ludwig; Gardner, Donald E; Hart, Ronald W; Hastings, Kenneth L; Hayes, A Wallace; Hoffmann, George R; Ives, John A; Jaworowski, Zbigniew; Johnson, Thomas E; Jonas, Wayne B; Kaminski, Norbert E; Keller, John G; Klaunig, James E; Knudsen, Thomas B; Kozumbo, Walter J; Lettieri, Teresa; Liu, Shu-Zheng; Maisseu, Andre; Maynard, Kenneth I; Masoro, Edward J; McClellan, Roger O; Mehendale, Harihara M; Mothersill, Carmel; Newlin, David B; Nigg, Herbert N; Oehme, Frederick W; Phalen, Robert F; Philbert, Martin A; Rattan, Suresh I S; Riviere, Jim E; Rodricks, Joseph; Sapolsky, Robert M; Scott, Bobby R; Seymour, Colin; Sinclair, David A; Smith-Sonneborn, Joan; Snow, Elizabeth T; Spear, Linda; Stevenson, Donald E; Thomas, Yolene; Tubiana, Maurice; Williams, Gary M; Mattson, Mark P

2007-07-01

Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose-response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines.

Thermoluminescent dosimetry in electron beams: energy dependence.

PubMed

Robar, V; Zankowski, C; Olivares Pla, M; Podgorsak, E B

1996-05-01

The response of thermoluminescent dosimeters to electron irradiations depends on the radiation dose, mean electron energy at the position of the dosimeter in phantom, and the size of the dosimeter. In this paper the semi-empirical expression proposed by Holt et al. [Phys. Med. Biol. 20, 559-570 (1975)] is combined with the calculated electron dose fraction to determine the thermoluminescent dosimetry (TLD) response as a function of the mean electron energy and the dosimeter size. The electron and photon dose fractions, defined as the relative contributions of electrons and bremsstrahlung photons to the total dose for a clinical electron beam, are calculated with Monte Carlo techniques using EGS4. Agreement between the calculated and measured TLD response is very good. We show that the considerable reduction in TLD response per unit dose at low electron energies, i.e., at large depths in phantom, is offset by an ever-increasing relative contribution of bremsstrahlung photons to the total dose of clinical electron beams. This renders the TLD sufficiently reliable for dose measurements over the entire electron depth dose distribution despite the dependence of the TLD response on electron beam energy.

Dose-responses for mortality from cerebrovascular and heart diseases in atomic bomb survivors: 1950-2003.

PubMed

Schöllnberger, Helmut; Eidemüller, Markus; Cullings, Harry M; Simonetto, Cristoforo; Neff, Frauke; Kaiser, Jan Christian

2018-03-01

The scientific community faces important discussions on the validity of the linear no-threshold (LNT) model for radiation-associated cardiovascular diseases at low and moderate doses. In the present study, mortalities from cerebrovascular diseases (CeVD) and heart diseases from the latest data on atomic bomb survivors were analyzed. The analysis was performed with several radio-biologically motivated linear and nonlinear dose-response models. For each detrimental health outcome one set of models was identified that all fitted the data about equally well. This set was used for multi-model inference (MMI), a statistical method of superposing different models to allow risk estimates to be based on several plausible dose-response models rather than just relying on a single model of choice. MMI provides a more accurate determination of the dose response and a more comprehensive characterization of uncertainties. It was found that for CeVD, the dose-response curve from MMI is located below the linear no-threshold model at low and medium doses (0-1.4 Gy). At higher doses MMI predicts a higher risk compared to the LNT model. A sublinear dose-response was also found for heart diseases (0-3 Gy). The analyses provide no conclusive answer to the question whether there is a radiation risk below 0.75 Gy for CeVD and 2.6 Gy for heart diseases. MMI suggests that the dose-response curves for CeVD and heart diseases in the Lifespan Study are sublinear at low and moderate doses. This has relevance for radiotherapy treatment planning and for international radiation protection practices in general.

Measurement of Posterior Corneal Astigmatism by the IOLMaster 700.

PubMed

LaHood, Benjamin R; Goggin, Michael

2018-05-01

To provide the first description of posterior corneal astigmatism as measured by the IOLMaster 700 (Carl Zeiss Meditec, Jena, Germany) and assess how its characteristics compare to previous measurements from other devices. A total of 1,098 routine IOLMaster 700 biometric measurements were analyzed to provide magnitudes and orientation of steep and flat axes of anterior and posterior corneal astigmatism. Subgroup analysis was conducted to assess correlation of posterior corneal astigmatism characteristics to anterior corneal astigmatism and describe the distribution of posterior corneal astigmatism with age. Mean posterior corneal astigmatism was 0.24 ± 0.15 diopters (D). The steep axis of posterior corneal astigmatism was vertically oriented in 73.32% of measurements. Correlation between the magnitude of anterior and posterior corneal astigmatism was greatest when the steep axis of the anterior corneal astigmatism was oriented vertically (r = 0.68, P < .0001). Vertical orientation of the steep axis of anterior corneal astigmatism became less common as age increased, whereas for posterior corneal astigmatism it remained by far the most common orientation. This first description of posterior corneal astigmatism measurement by the IOLMaster 700 found the average magnitude of posterior corneal astigmatism and proportion of vertical orientation of steep axis was lower than previous estimates. The IOLMaster 700 appears capable of providing enhanced biometric measurement for individualized surgical planning. [J Refract Surg. 2018;34(5):331-336.]. Copyright 2018, SLACK Incorporated.

Germination conditions affect physicochemical properties of germinated brown rice flour.

PubMed

Charoenthaikij, Phantipha; Jangchud, Kamolwan; Jangchud, Anuvat; Piyachomkwan, Kuakoon; Tungtrakul, Patcharee; Prinyawiwatkul, Witoon

2009-01-01

Germinated brown rice has been reported to be nutritious due to increased free gamma-aminobutyric acid (GABA). The physicochemical properties of brown rice (BR) and glutinous brown rice (GNBR) after germination as affected by different steeping times (24, 36, 48, and 72 h depending on the rice variety) and pHs of steeping water (3, 5, 7, and as-is) were determined and compared to those of the nongerminated one (control). As the steeping time increased or pH of steeping water decreased, germinated brown rice flours (GBRF) from both BR and GNBR had greater reducing sugar, free GABA and alpha-amylase activity; while the total starch and viscosity were lower than their respective controls. GBRFs from both BR and GNBR prepared after 24-h steeping time at pH 3 contained a high content of free GABA at 32.70 and 30.69 mg/100 g flour, respectively. The peak viscosity of GBRF obtained from both BR and GNBR (7.42 to 228.22 and 4.42 to 58.67 RVU, respectively) was significantly lower than that of their controls (255.46 and 190.17 RVU, respectively). The principal component analysis indicated that the important variables for discriminating among GBRFs, explained by the first 2 components at 89.82% of total explained variance, were the pasting profiles, alpha-amylase activity, and free GABA.

SU-E-J-274: Responses of Medulloblastoma Cells to Radiation Dosimetric Parameters in Intensity-Modulated Radiation Therapy

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

Park, J; Molecular Imaging Program at Stanford, Stanford, CA; Bio-X Program, Stanford, CA

2015-06-15

Purpose: To evaluate radiation responses of the medulloblastoma cell line Daoy in intensity-modulated radiation therapy (IMRT), quantitative variations to variable radiation dosimetic parameters were tracked by bioluminescent images (BLIs). Methods: The luciferase and green fluorescent protein positive Daoy cells were cultured on dishes. The medulloblastoma cells irradiated to different dose rate, interval of fractionated doses, field margin and misalignment, and dose uniformity in IMRT were monitored using bioluminescent images. The cultured cells were placed into a dedicated acrylic phantom to deliver intensity-modulated fluences and calculate accurate predicted dose distribution. The radiation with dose rate from 0.5 Gy/min to 15 Gy/minmore » was irradiated by adjusting monitor unit per minute and source-to-surface distances. The intervals of fractionated dose delivery were changed considering the repair time of double strand breaks (DSB) revealed by straining of gamma-H2AX.The effect of non-uniform doses on the cells were visualized by registering dose distributions and BLIs. The viability according to dosimetric parameters was correlated with bioluminescent intensities for cross-check of radiation responses. Results: The DSB and cell responses due to the first fractionated dose delivery significantly affected final tumor control rather than other parameters. The missing tumor volumes due to the smaller field margin than the tumor periphery or field misalignment caused relapse of cell responses on BLIs. The dose rate and gradient had effect on initial responses but could not bring out the distinguishable killing effect on cancer cells. Conclusion: Visualized and quantified bioluminescent images were useful to correlate the dose distributions with spatial radiation effects on cells. This would derive the effective combination of dose delivery parameters and fractionation. Radiation responses in particular IMRT configuration could be reflected to image based-dose re-optimization.« less

Comparison of dose response functions for EBT3 model GafChromic™ film dosimetry system.

PubMed

Aldelaijan, Saad; Devic, Slobodan

2018-05-01

Different dose response functions of EBT3 model GafChromic™ film dosimetry system have been compared in terms of sensitivity as well as uncertainty vs. error analysis. We also made an assessment of the necessity of scanning film pieces before and after irradiation. Pieces of EBT3 film model were irradiated to different dose values in Solid Water (SW) phantom. Based on images scanned in both reflection and transmission mode before and after irradiation, twelve different response functions were calculated. For every response function, a reference radiochromic film dosimetry system was established by generating calibration curve and by performing the error vs. uncertainty analysis. Response functions using pixel values from the green channel demonstrated the highest sensitivity in both transmission and reflection mode. All functions were successfully fitted with rational functional form, and provided an overall one-sigma uncertainty of better than 2% for doses above 2 Gy. Use of pre-scanned images to calculate response functions resulted in negligible improvement in dose measurement accuracy. Although reflection scanning mode provides higher sensitivity and could lead to a more widespread use of radiochromic film dosimetry, it has fairly limited dose range and slightly increased uncertainty when compared to transmission scan based response functions. Double-scanning technique, either in transmission or reflection mode, shows negligible improvement in dose accuracy as well as a negligible increase in dose uncertainty. Normalized pixel value of the images scanned in transmission mode shows linear response in a dose range of up to 11 Gy. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Radiotherapeutic management of medulloblastoma in a pediatric patient with ataxia telangiectasia

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

Hart, R.M.; Kimler, B.F.; Evans, R.G.

1987-08-01

Ataxia telangiectasia (AT) is a genetic disorder with a predisposition to malignancy. Cells from patients with AT demonstrate an increased sensitivity to ionizing radiation which creates a problem when these patients require treatment for their malignant disease. An eleven-year-old boy with a previous diagnosis of AT was seen in consultation following partial resection of medulloblastoma in the posterior fossa. To estimate how much the conventional radiation dose might have to be reduced, we compared the radiosensitivity of bone marrow myeloid progenitor cells from this patient to that of cells from the marrow of normal individuals, using colony formation in anmore » agar culture assay system as the endpoint (CFU-Cs). Neither radiation dose-survival curve exhibited a shoulder--each displayed an extrapolation number of 0.99. The survival curve of normal cells displayed a steep slope with a D0 of 0.98 Gy (0.83-1.19 Gy, 95% confidence limits); the slope for the AT cells was considerably steeper with a value for D0 of 0.32 Gy (0.29-0.35 Gy). The ratio of D0's indicated that these AT cells were approximately 3X more radiosensitive than normal cells. Based on this, the daily dose was reduced from 1.8 to 0.6 Gy and the radiation was restricted to 25 treatments to the posterior fossa rather than the conventional cranio-spinal treatment. An additional 5 treatments at 1.0 Gy per day were given to the whole brain. The patient's skin responded to these reduced fraction sizes and doses to a similar degree as normal patients' skin following a standard schedule and the patient is doing well nine months after initiation of treatment.« less

A Unified Probabilistic Framework for Dose-Response Assessment of Human Health Effects.

PubMed

Chiu, Weihsueh A; Slob, Wout

2015-12-01

When chemical health hazards have been identified, probabilistic dose-response assessment ("hazard characterization") quantifies uncertainty and/or variability in toxicity as a function of human exposure. Existing probabilistic approaches differ for different types of endpoints or modes-of-action, lacking a unifying framework. We developed a unified framework for probabilistic dose-response assessment. We established a framework based on four principles: a) individual and population dose responses are distinct; b) dose-response relationships for all (including quantal) endpoints can be recast as relating to an underlying continuous measure of response at the individual level; c) for effects relevant to humans, "effect metrics" can be specified to define "toxicologically equivalent" sizes for this underlying individual response; and d) dose-response assessment requires making adjustments and accounting for uncertainty and variability. We then derived a step-by-step probabilistic approach for dose-response assessment of animal toxicology data similar to how nonprobabilistic reference doses are derived, illustrating the approach with example non-cancer and cancer datasets. Probabilistically derived exposure limits are based on estimating a "target human dose" (HDMI), which requires risk management-informed choices for the magnitude (M) of individual effect being protected against, the remaining incidence (I) of individuals with effects ≥ M in the population, and the percent confidence. In the example datasets, probabilistically derived 90% confidence intervals for HDMI values span a 40- to 60-fold range, where I = 1% of the population experiences ≥ M = 1%-10% effect sizes. Although some implementation challenges remain, this unified probabilistic framework can provide substantially more complete and transparent characterization of chemical hazards and support better-informed risk management decisions.

SU-F-T-329: Characteristic Study of a Rado-Photoluminescenct Glass Dosimeter with Accumulated Dose

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

Kim, D; Chung, W; Chung, M

Purpose: This study investigated the effect of accumulated dose on radiophotoluminescent glass dosimeter in megavoltage photon. Methods: 45 commercially-available radio-photoluminescence glass dosimeters (RPLGD; GD-302M, Asahi Techno Glass Co., Shizuoka, JAPAN) were irradiated to 10 × 10 cm{sup 2} open-field with 6, 10 and 15 MV photon beams at 100 cm of source to surface distance and dose maximum depths. Each energy has consists of five groups which is consists of three detectors. A group #1 and #2 was irradiated about 1 Gy to 100 Gy, and estimated the integral dose response with and without annealing procedure. A group #3 wasmore » read the dose after irradiated 10 Gy of dose by 10 times repeatedly to estimate the fading effect of RPLGD. A group #4 and #5 was produced same ways with different irradiation dose such as 50 Gy for group #4 and 100 Gy for group #5. Results: From the results of group #1 and #2, an annealed detector shows linear response to integral dose but other detectors without the annealing process, has supra linearity for integral dose especially close to 100 Gy dose. For group #3, #4 and #5, the dose response of repeated irradiation, the dose response was decreased about 15%, 12% and 7% for 6 MV, 10 MV and 15MV. Conclusion: It was found that RPLGD response to accumulated dose was supra linear and this respond was altered with amount of accumulated dose to the RPLGD. In addition, the fading effect need to be concern with RPLGD.« less

Dose response and repair kinetics of gamma-H2AX foci induced by in vitro irradiation of whole blood and T-lymphocytes with X- and gamma-radiation.

PubMed

Beels, Laurence; Werbrouck, Joke; Thierens, Hubert

2010-09-01

Dose response and repair kinetics of phosphorylated histone H2A isoform X (gamma-H2AX) foci in T-lymphocytes were investigated in the low-dose range after in vitro irradiation of whole blood and T-lymphocytes with 100 kVp X-rays and (60)Co gamma-rays. Whole blood or isolated T-lymphocytes were irradiated in vitro and gamma-H2AX foci were scored. Dose response was determined in the 0-500 mGy dose range. Foci kinetics were studied at doses of 5 and 200 mGy up to 24 h post-irradiation. After X-irradiation, the dose response for whole blood shows a biphasic behaviour with a low-dose hypersensitivity, which is less pronounced for isolated T-lymphocytes. In contrast, gamma-radiation shows a linear dose response for both irradiation conditions. Concerning repair kinetics, delayed repair was found after X-ray whole blood irradiation (5 and 200 mGy) with 40% of the foci persisting 24 h post-irradiation. This number of foci is reduced to 10% after irradiation of isolated T-lymphocytes with 200 mGy X-rays. On the contrary, gamma-H2AX foci are reduced to background levels 24 h post-irradiation with 200 mGy (60)Co gamma-rays. gamma-H2AX foci response and repair kinetics depend on irradiation conditions and radiation quality, possibly linked to Bystander response.

Contrasting effects of low versus high ascorbate doses on blood pressure responses to oral nitrite in L-NAME-induced hypertension.

PubMed

Pinheiro, Lucas C; Ferreira, Graziele C; Vilalva, Kelvin H; Toledo, José C; Tanus-Santos, Jose E

2018-04-01

Nitrite reduces blood pressure (BP) in both clinical and experimental hypertension. This effect is attributable to the formation of nitric oxide (NO) and other NO-related species, which may be improved by ascorbate or other antioxidants. However, the BP responses to oral nitrite result, at least in part, of increased gastric S-nitrosothiol formation. This study tested the hypothesis that ascorbate may destroy S-nitrosothiols and therefore not all doses of ascorbate enhance the BP responses to oral nitrite. We assessed the BP responses to oral sodim nitrite (0.2 mmol/kg) in L-NAME hypertensive rats pretreated with ascorbate (0, 0.02, 0.2, or 2 mmol/kg). Plasma and gastric wall concentrations of nitrite and nitroso compounds concentrations were determined using an ozone-based reductive chemiluminescence assay. Nitrate concentrations were determined using the Griess reaction. Free thiol concentrations were determined by a colorimetric assay. The BP responses to nitrite exhibited a bell-shape profile as they were not modified by ascorbate 0.02 mmol/l, whereas the 0.2 mmol/kg dose enhanced and the 2 mmol/kg dose attenuated BP responses. In parallel with BP responses, nitrite-induced increases in plasma nitrite and RSNO species were not modified by ascorbate 0.02 mmol/l, whereas the 0.2 mmol/kg dose enhanced and the 2 mmol/kg dose attenuated them. Similar experiments were carried out with an equimolar dose of S-nitrosogluthathione. Ascorbate dose-dependently impaired the BP responses to S-nitrosogluthathione, and the corresponding increases in plasma RSNO, but not in plasma nitrite concentrations. This is the first study to show that while ascorbate dose-dependently impairs the BP responses to oral S-nitrosogluthathione, there are contrasting effects when low versus high ascorbate doses are compared with respect to its effects on the blood pressure responses to oral nitrite administration. Our findings may have special implications to patients taking ascorbate, as high doses of this vitamin may impair protective mechanisms associated with nitrite or nitrate from dietary sources. Copyright © 2018 Elsevier Inc. All rights reserved.

ENDOCRINE ACTIVE SUBSTANCES AND DOSE-RESPONSE FOR INDIVIDUALS AND POPULATIONS

EPA Science Inventory

Endocrine Active Substances and Dose-Response for Individuals and Populations
Hugh A. Barton

Abstract for IUPAC-SCOPE article

Dose-response characteristics for endocrine disruption have been major focuses in efforts to understand potential impacts on human and ec...

EVALUATING QUANTITATIVE FORMULAS FOR DOSE-RESPONSE ASSESSMENT OF CHEMICAL MIXTURES

EPA Science Inventory

Risk assessment formulas are often distinguished from dose-response models by being rough but necessary. The evaluation of these rough formulas is described here, using the example of mixture risk assessment. Two conditions make the dose-response part of mixture risk assessment d...

Analysis of Transcriptomic Dose Response Data in the ...

EPA Pesticide Factsheets

Slide presentation at the HESI-HEALTH Canada-McGill Workshop on Transcriptomic Dose Response Data in the Context of Chemical Risk Assessment Slide presentation at the HESI-HEALTH Canada-McGill Workshop on Transcriptomic Dose Response Data in the Context of Chemical Risk Assessment

Contour Planting: A Strategy to Reduce Soil Erosion on Steep Slopes

USDA-ARS?s Scientific Manuscript database

Practices that combine GPS-based guidance for terrain contouring and tillage for runoff detention have potential to increase water infiltration and reduce runoff. The objective of this study was to investigate contour planting as a means to reduce soil erosion on steep slopes of the Columbia Platea...

Light sheet microscopy reveals more gradual light attenuation in light green versus dark green soybean leaves

USDA-ARS?s Scientific Manuscript database

Light wavelengths preferentially absorbed by chlorophyll (chl) often display steep absorption gradients. This oversaturates photosynthesis in upper chloroplasts and deprives lower chloroplasts of blue and red light, causing a steep gradient in carbon fixation. Reducing chl content could create a mor...

Functional toxicity and tolerance patterns of bioavailable Pd(II), Pt(II), and Rh(III) on suspended Saccharomyces cerevisiae cells assayed in tandem by a respirometric biosensor.

PubMed

Frazzoli, Chiara; Dragone, Roberto; Mantovani, Alberto; Massimi, Cristiana; Campanella, Luigi

2007-12-01

Toxicological implications of exposure to bioavailable platinum group metals, here Pd, Pt, and Rh, are still to be clarified. This study obtained by a biosensor-based method preliminary information on potential effects on cellular metabolism as well as on possible tolerance mechanisms. Aerobic respiration was taken as the toxicological end point to perform tandem tests, namely functional toxicity test and tolerance test. Cells were suspended in the absence of essential constituents for growth. The dose-response curves obtained by exposure (2 h) to the metals (nanogram per gram range) suggested the same mechanisms of action, with Rh showing the greatest curve steepness and the lowest EC50 value. Conservative (95% lower confidence interval) EC10 values were 187, 85 and 51 ng g(-1) for Pt, Pd, and Rh respectively. Tolerance patterns were tested during the same runs. The full tolerance obtained after 12 h of exposure to each metal suggested mitochondrial inhibition of aerobic respiration as a target effect. The hazard rating of the metals in the tolerance test changed in the Rh EC50 range, where Rh showed the lowest toxicity. The observed tolerance might suggest a protective mechanism such as metallothionein induction at concentrations around the EC50 values. The performance of the bioassay was satisfactory, in terms of the limit of detection, repeatability, reproducibility, roboustness, sensibility, and stability; the method's critical uncertainty sources were identified for improvements.

Flow cytometric estimation on cytotoxic activity of leaf extracts from seashore plants in subtropical Japan: isolation, quantification and cytotoxic action of (-)-deoxypodophyllotoxin.

PubMed

Masuda, Toshiya; Oyama, Yasuo; Yonemori, Shigetomo; Takeda, Yoshio; Yamazaki, Yuko; Mizuguchi, Shinichi; Nakata, Mami; Tanaka, Tomochika; Chikahisa, Lumi; Inaba, Yuzuru; Okada, Yoshihiko

2002-06-01

The cytotoxic activity of methanol extracts of leaves collected from 39 seashore plants in Iriomote Island, subtropical Japan was examined on human leukaemia cells (K562 cells) using a flow cytometer with two fluorescent probes, ethidium bromide and annexin V-FITC. Five extracts (10 microg/mL) from Hernandia nymphaeaefolia, Cerbera manghas, Pongamia pinnata, Morus australis var. glabra and Thespesia populnea greatly inhibited the growth of K562 cells. When the concentration was decreased to 1 microg/mL, only one extract from H. nymphaeaefolia still inhibited the cell growth. A cytotoxic compound was isolated from the leaves by bioassay-guided fractionation and was identified as (-)-deoxypodophyllotoxin (DPT). The fresh leaves of H. nymphaeaefolia contained a remarkably high amount of DPT (0.21 +/- 0.07% of fresh leaf weight), being clarified by a quantitative HPLC analysis. DPT at 70-80 pM started to inhibit the growth of K562 cells in an all-or-none fashion and at 100 pM or more it produced complete inhibition in all cases. Therefore, the slope of the dose-response curve was very steep. DPT at 100 pM or more decreased the cell viability to 50%-60% and increased the number of cells undergoing apoptosis (annexin V-positive cells). The results indicate that DPT contributes to the cytotoxic action of the extract from the leaves of H. nymphaeaefolia on K562 cells. Copyright 2002 John Wiley & Sons, Ltd.

Interpretation of the margin of exposure for genotoxic carcinogens - elicitation of expert knowledge about the form of the dose response curve at human relevant exposures.

PubMed

Boobis, Alan; Flari, Villie; Gosling, John Paul; Hart, Andy; Craig, Peter; Rushton, Lesley; Idahosa-Taylor, Ehi

2013-07-01

The general approach to risk assessment of genotoxic carcinogens has been to advise reduction of exposure to "as low as reasonably achievable/practicable" (ALARA/P). However, whilst this remains the preferred risk management option, it does not provide guidance on the urgency or extent of risk management actions necessary. To address this, the "Margin of Exposure" (MOE) approach has been proposed. The MOE is the ratio between the point of departure for carcinogenesis and estimated human exposure. However, interpretation of the MOE requires implicit or explicit consideration of the shape of the dose-response curve at human relevant exposures. In a structured elicitation exercise, we captured expert opinion on available scientific evidence for low dose-response relationships for genotoxic carcinogens. This allowed assessment of: available evidence for the nature of dose-response relationships at human relevant exposures; the generality of judgments about such dose-response relationships; uncertainties affecting judgments on the nature of such dose-response relationships; and whether this last should differ for different classes of genotoxic carcinogens. Elicitation results reflected the variability in experts' views on the form of the dose-response curve for low dose exposure and major sources of uncertainty affecting the assumption of a linear relationship. Copyright © 2013 Elsevier Ltd. All rights reserved.

Investigation of J-shaped dose-responses induced by exposure to the alkylating agent N-methyl-N-nitrosourea.

PubMed

Chapman, Katherine E; Hoffmann, George R; Doak, Shareen H; Jenkins, Gareth J S

2017-07-01

Hormesis is defined as a biphasic dose-response where biological effects of low doses of a stressor demonstrate the opposite effect to high-dose effects of the same stressor. Hormetic, or J-shaped, dose-response relationships are relatively rarely observed in toxicology, resulting in a limited understanding and even some skepticism of the concept. Low dose-response studies for genotoxicity endpoints have been performed at Swansea University for over a decade. However, no statistically significant decreases below control genotoxicity levels have been detected until recently. A hormetic-style dose-response following a 24h exposure to the alkylating agent N-methyl-N-nitrosourea (MNU) was observed in a previous study for HPRT mutagenesis in the human lymphoblastoid cell line AHH-1. A second recent study demonstrated a J-shaped dose-response for the induction of micronuclei by MNU in a 24h treatment in a similar test system. Following mechanistic investigations, it was hypothesized that p53 may be responsible for the observed hormetic phenomenon. As genotoxic carcinogens are a major causative factor of many cancers, consideration of hormesis in carcinogenesis could be important in safety assessment. The data examined here offer possible insights into hormesis, including its estimated prevalence, underlying mechanisms and lack of generalizability. Copyright © 2017 Elsevier B.V. All rights reserved.

Using machine learning to model dose-response relationships.

PubMed

Linden, Ariel; Yarnold, Paul R; Nallamothu, Brahmajee K

2016-12-01

Establishing the relationship between various doses of an exposure and a response variable is integral to many studies in health care. Linear parametric models, widely used for estimating dose-response relationships, have several limitations. This paper employs the optimal discriminant analysis (ODA) machine-learning algorithm to determine the degree to which exposure dose can be distinguished based on the distribution of the response variable. By framing the dose-response relationship as a classification problem, machine learning can provide the same functionality as conventional models, but can additionally make individual-level predictions, which may be helpful in practical applications like establishing responsiveness to prescribed drug regimens. Using data from a study measuring the responses of blood flow in the forearm to the intra-arterial administration of isoproterenol (separately for 9 black and 13 white men, and pooled), we compare the results estimated from a generalized estimating equations (GEE) model with those estimated using ODA. Generalized estimating equations and ODA both identified many statistically significant dose-response relationships, separately by race and for pooled data. Post hoc comparisons between doses indicated ODA (based on exact P values) was consistently more conservative than GEE (based on estimated P values). Compared with ODA, GEE produced twice as many instances of paradoxical confounding (findings from analysis of pooled data that are inconsistent with findings from analyses stratified by race). Given its unique advantages and greater analytic flexibility, maximum-accuracy machine-learning methods like ODA should be considered as the primary analytic approach in dose-response applications. © 2016 John Wiley & Sons, Ltd.

Single- and Multilayered Nanostructures via Laser-Induced Block Copolymer Self-Assembly

NASA Astrophysics Data System (ADS)

Majewski, Pawel; Yager, Kevin; Rahman, Atikur; Black, Charles

We present a novel method of accelerated self-assembly of block copolymer thin films utilizing laser light, called Laser Zone Annealing (LZA). In our approach, steep temperature transients are induced in block copolymer films by rastering narrowly focused laser line over the light-absorbing substrate. Extremely steep temperature gradients accelerate the process of self-assembly by several orders-of-magnitude compared to conventional oven annealing, and, when coupled to photo-thermal shearing, lead to global alignment of block copolymer domains assessed by GISXAS diffraction studies and real-space SEM imaging. We demonstrate monolithic alignment of various block-copolymer thin films including PS-b-PMMA, PS-b-PEO, PS-b-P2VP, PS-b-PI and observe different responsiveness to the shearing rate depending on the characteristic relaxation timescale of the particular material. Subsequently, we use the aligned polymeric films as templates for synthesis of single- and multi-layered arrays of inorganic, metallic or semiconducting nanowires and nanomeshes and investigate their anisotropic electro-optical properties. Research carried out in part at the Center for Functional Nanomaterials, Brookhaven National Laboratory, which is supported by the U.S. Department of Energy, Office of Basic Energy Sciences, under Contract No. DE-AC02-98CH10886.

Climate change and the northern Russian treeline zone.

PubMed

MacDonald, G M; Kremenetski, K V; Beilman, D W

2008-07-12

The Russian treeline is a dynamic ecotone typified by steep gradients in summer temperature and regionally variable gradients in albedo and heat flux. The location of the treeline is largely controlled by summer temperatures and growing season length. Temperatures have responded strongly to twentieth-century global warming and will display a magnified response to future warming. Dendroecological studies indicate enhanced conifer recruitment during the twentieth century. However, conifers have not yet recolonized many areas where trees were present during the Medieval Warm period (ca AD 800-1,300) or the Holocene Thermal Maximum (HTM; ca 10,000-3,000 years ago). Reconstruction of tree distributions during the HTM suggests that the future position of the treeline due to global warming may approximate its former Holocene maximum position. An increased dominance of evergreen tree species in the northern Siberian forests may be an important difference between past and future conditions. Based on the slow rates of treeline expansion observed during the twentieth century, the presence of steep climatic gradients associated with the current Arctic coastline and the prevalence of organic soils, it is possible that rates of treeline expansion will be regionally variable and transient forest communities with species abundances different from today's may develop.

Sensitivity of the immature rat uterotrophic assay to mixtures of estrogens.

PubMed Central

Tinwell, Helen; Ashby, John

2004-01-01

We have evaluated whether mixtures of estrogens, present in the mix at doses that are individually inactive in the immature rat uterotrophic assay, can give a uterotrophic response. Seven chemicals were evaluated: nonylphenol, bisphenol A (BPA), methoxychlor, genistein (GEN), estradiol, diethylstilbestrol, and ethinyl estradiol. Dose responses in the uterotrophic assay were constructed for each chemical. The first series of experiments involved evaluating binary mixtures of BPA and GEN at dose levels that gave moderate uterotrophic responses when tested individually. The mixtures generally showed an intermediate or reduced uterotrophic effect compared with when the components of the mixture were tested alone at the dose used in the mixture. The next series of experiments used a multicomponent (complex) mixture of all seven chemicals evaluated at doses that gave either weakly positive or inactive uterotrophic responses when tested individually in the assay. Doses that were nominally equi-uterotrophic ranged over approximately six orders of magnitude for the seven chemicals. Doses of agents that gave a weak uterotrophic response when tested individually gave a marginally enhanced positive response in the assay when tested combined as a mixture. Doses of agents that gave a negative uterotrophic response when tested individually gave a positive response when tested as a mixture. These data indicate that a variety of different estrogen receptor (ER) agonists, present individually at subeffective doses, can act simultaneously to evoke an ER-regulated response. However, translating these findings into the process of environmental hazard assessment will be difficult. The simple addition of the observed, or predicted, activities for the components of a mixture is confirmed here to be inappropriate and to overestimate the actual effect induced by the mixture. Equally, isobole analysis is only suitable for two- or three-component mixtures, and concentration addition requires access to dose-response data and EC50 values (concentration giving 50% of the maximum response) for the individual components of the mixture--requirements that will rarely be fulfilled for complex environmental samples. Given these uncertainties, we conclude that it may be most expedient to select and bioassay whole environmental mixtures of potential concern. PMID:15064164

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

Wyrobek, A. J.; Manohar, C. F.; Nelson, D. O.

We investigated the low dose dependency of the transcriptional response of human cells to characterize the shape and biological functions associated with the dose response curve and to identify common and conserved functions of low dose expressed genes across cells and tissues. Human lymphoblastoid (HL) cells from two unrelated individuals were exposed to graded doses of radiation spanning the range of 1-10 cGy were analyzed by transcriptome profiling, qPCR and bioinformatics, in comparison to sham irradiated samples. A set of {approx}80 genes showed consistent responses in both cell lines; these genes were associated with homeostasis mechanisms (e.g., membrane signaling, moleculemore » transport), subcellular locations (e.g., Golgi, and endoplasmic reticulum), and involved diverse signal transduction pathways. The majority of radiation-modulated genes had plateau-like responses across 1-10 cGy, some with suggestive evidence that transcription was modulated at doses below 1 cGy. MYC, FOS and TP53 were the major network nodes of the low-dose response in HL cells. Comparison our low dose expression findings in HL cells with those of prior studies in mouse brain after whole body exposure, in human keratinocyte cultures, and in endothelial cells cultures, indicates that certain components of the low dose radiation response are broadly conserved across cell types and tissues, independent of proliferation status.« less

Enhancement of phototropic response to a range of light doses in Triticum aestivum coleoptiles in clinostat-simulated microgravity

NASA Technical Reports Server (NTRS)

Heathcote, D. G.; Bircher, B. W.; Brown, A. H. (Principal Investigator)

1987-01-01

The phototropic dose-response relationship has been determined for Triticum aestivum cv. Broom coleoptiles growing on a purpose-built clinostat apparatus providing gravity compensation by rotation about a horizontal axis at 2 rev min-1. These data are compared with data sets obtained with the clinostat axis vertical and stationary, as a 1 g control, and rotating vertically to examine clinostat effects other than gravity compensation. Triticum at 1 g follows the well-established pattern of other cereal coleoptiles with a first positive curvature at low doses, followed by an indifferent response region, and a second positive response at progressively increasing doses. However, these response regions lie at higher dose levels than reported for Avena. There is no significant difference between the responses observed with the clinostat axis vertical in the rotating and stationary modes, but gravity compensation by horizontal rotation increases the magnitude of first and second positive curvatures some threefold at 100 min after stimulation. The indifferent response is replaced by a significant curvature towards the light source, but remains apparent as a reduced curvature response at these dose levels.

Surgical Responses of Medial Rectus Muscle Recession in Thyroid Eye Disease-Related Esotropia

PubMed Central

Lyu, In Jeong; Lee, Ju-Yeun; Kong, Mingui; Park, Kyung-Ah; Oh, Sei Yeul

2016-01-01

We evaluate the surgical outcomes and surgical responses of medial rectus muscle (MR) recession patients with thyroid eye disease (TED)-related esotropia (ET). The surgical dose-response curves 1 week postoperatively and at the final visit were analyzed. Univariable and multivariable linear regression analyses were applied to investigate factors influencing surgical dose-response. A total of 43 patients with TED-related ET that underwent MR recession were included. The final success rate was 86.0% and the rate of undercorrection was 14.0%. The surgical dose-response curves of TED-related ET showed a gentle slope compared with those of standard surgical tables. In the univariable model, simultaneous vertical rectus muscle recession was the only significant factor influencing surgical dose-response of MR recession in TED-related ET (β = -0.397, P = 0.044). In a model adjusted for age, sex, type of surgery, and preoperative horizontal angle of deviation, simultaneous vertical rectus muscle recession showed marginal significance (β = -0.389, P = 0.064). The surgical dose-response curve of TED-related ET was unique. Simultaneous vertical rectus muscle recession was associated with increased surgical dose-response in TED-related ET. PMID:26796354

Phosphoprotein profiles of candidate markers for early cellular responses to low-dose γ-radiation in normal human fibroblast cells

PubMed Central

Yim, Ji-Hye; Yun, Jung Mi; Kim, Ji Young; Lee, In Kyung; Nam, Seon Young

2017-01-01

Abstract Ionizing radiation causes biological damage that leads to severe health effects. However, the effects and subsequent health implications caused by exposure to low-dose radiation are unclear. The objective of this study was to determine phosphoprotein profiles in normal human fibroblast cell lines in response to low-dose and high-dose γ-radiation. We examined the cellular response in MRC-5 cells 0.5 h after exposure to 0.05 or 2 Gy. Using 1318 antibodies by antibody array, we observed ≥1.3-fold increases in a number of identified phosphoproteins in cells subjected to low-dose (0.05 Gy) and high-dose (2 Gy) radiation, suggesting that both radiation levels stimulate distinct signaling pathways. Low-dose radiation induced nucleic acid–binding transcription factor activity, developmental processes, and multicellular organismal processes. By contrast, high-dose radiation stimulated apoptotic processes, cell adhesion and regulation, and cellular organization and biogenesis. We found that phospho-BTK (Tyr550) and phospho-Gab2 (Tyr643) protein levels at 0.5 h after treatment were higher in cells subjected to low-dose radiation than in cells treated with high-dose radiation. We also determined that the phosphorylation of BTK and Gab2 in response to ionizing radiation was regulated in a dose-dependent manner in MRC-5 and NHDF cells. Our study provides new insights into the biological responses to low-dose γ-radiation and identifies potential candidate markers for monitoring exposure to low-dose ionizing radiation. PMID:28122968

A Review: Development of a Microdose Model for Analysis of Adaptive Response and Bystander Dose Response Behavior

PubMed Central

Leonard, Bobby E.

2008-01-01

Prior work has provided incremental phases to a microdosimetry modeling program to describe the dose response behavior of the radio-protective adaptive response effect. We have here consolidated these prior works (Leonard 2000, 2005, 2007a, 2007b, 2007c) to provide a composite, comprehensive Microdose Model that is also herein modified to include the bystander effect. The nomenclature for the model is also standardized for the benefit of the experimental cellular radio-biologist. It extends the prior work to explicitly encompass separately the analysis of experimental data that is 1.) only dose dependent and reflecting only adaptive response radio-protection, 2.) both dose and dose-rate dependent data and reflecting only adaptive response radio-protection for spontaneous and challenge dose damage, 3.) only dose dependent data and reflecting both bystander deleterious damage and adaptive response radio-protection (AR-BE model). The Appendix cites the various applications of the model. Here we have used the Microdose Model to analyze the, much more human risk significant, Elmore et al (2006) data for the dose and dose rate influence on the adaptive response radio-protective behavior of HeLa x Skin cells for naturally occurring, spontaneous chromosome damage from a Brachytherapy type 125I photon radiation source. We have also applied the AR-BE Microdose Model to the Chromosome inversion data of Hooker et al (2004) reflecting both low LET bystander and adaptive response effects. The micro-beam facility data of Miller et al (1999), Nagasawa and Little (1999) and Zhou et al (2003) is also examined. For the Zhou et al (2003) data, we use the AR-BE model to estimate the threshold for adaptive response reduction of the bystander effect. The mammogram and diagnostic X-ray induction of AR and protective BE are observed. We show that bystander damage is reduced in the similar manner as spontaneous and challenge dose damage as shown by the Azzam et al (1996) data. We cite primary unresolved questions regarding adaptive response behavior and bystander behavior. The five features of major significance provided by the Microdose Model so far are 1.) Single Specific Energy Hits initiate Adaptive Response, 2.) Mammogram and diagnostic X-rays induce a protective Bystander Effect as well as Adaptive Response radio-protection. 3.) For mammogram X-rays the Adaptive Response protection is retained at high primer dose levels. 4.) The dose range of the AR protection depends on the value of the Specific Energy per Hit, . 5.) Alpha particle induced deleterious Bystander damage is modulated by low LET radiation. PMID:18648579

Regional radiation dose-response modeling of functional liver in hepatocellular carcinoma patients with longitudinal sulfur colloid SPECT/CT: a proof of concept.

PubMed

Price, Ryan G; Apisarnthanarax, Smith; Schaub, Stephanie K; Nyflot, Matthew J; Chapman, Tobias R; Matesan, Manuela; Vesselle, Hubert J; Bowen, Stephen R

2018-06-19

We report on patient-specific quantitative changes in longitudinal sulfur colloid SPECT/CT as a function of regional radiation dose distributions to normal liver in a cohort of hepatocellular carcinoma patients. Dose-response thresholds and slopes varied with baseline liver function metrics, and extreme values were found in patients with fatal hepatotoxicity. Dose-response modeling of normal liver in individual HCC patients has potential to characterize in vivo radiosensitivity, identify high risk subgroups, and personalize treatment planning dose constraints. Hepatotoxicity risk in hepatocellular carcinoma (HCC) patients is modulated by radiation dose delivered to normal liver tissue, but reported dose-response data are limited. Our prior work established baseline [ 99m Tc]sulfur colloid (SC) SPECT/CT liver function imaging biomarkers that predict clinical outcomes. We conducted a proof-of-concept investigation with longitudinal SC SPECT/CT to characterize patient-specific radiation dose-response relationships as surrogates for liver radiosensitivity. SC SPECT/CT images of 15 HCC patients with variable Child-Pugh status (8 CP-A, 7 CP-B/C) were acquired in treatment position prior to and 1 month (nominal) after SBRT (n=6) or proton therapy (n=9). Localized rigid registrations between pre/post-treatment CT to planning CT scans were performed, and transformations were applied to pre/post-treatment SC SPECT images. Radiotherapy doses were converted to EQD2 α/β=3 and Gy (RBE), and binned in 5 GyEQD2 increments within tumor-subtracted livers. Mean dose and percent change (%ΔSC) between pre- and post-treatment SPECT uptake, normalized to regions receiving < 5 GyEQD2, were calculated in each binned dose region. Dose-response data were parameterized by sigmoid functions (double exponential) consisting of maximum reduction (%ΔSC max ), dose midpoint (D mid ), and dose-response slope (α mid ) parameters. Individual patient sigmoid dose-response curves had high goodness-of-fit (median R 2 = 0.96, range 0.76-0.99). Large inter-patient variability was observed, with median (range) in %ΔSC max of 44% (20-75%), D mid of 13 Gy (4-27 GyEQD2), and α mid of 0.11 GyEQD2 -1 (0.04-0.29 GyEQD2 -1 ), respectively. Eight of 15 patients had %ΔSC max = 20-45%, while 7/15 had %ΔSC max = 60-75%, with subgroups made up of variable baseline liver function status and radiation treatment modality. Fatal hepatotoxicity occurred in patients (2/15) with low TLF (< 0.12) and low D mid (< 7 GyEQD2). Longitudinal SC SPECT/CT imaging revealed patient-specific variations in dose-response, and may identify patients with poor baseline liver function and increased sensitivity to radiation therapy. Validation of this regional liver dose-response modeling concept as a surrogate for patient-specific radiosensitivity has potential to guide HCC therapy regimen selection and planning constraints. Copyright © 2018 Elsevier Inc. All rights reserved.

BY HOW MUCH DO SHAPES OF TOXICOLOGICAL DOSE-RESPONSE RELATIONSHIPS VARY? (SOT)

EPA Science Inventory

A re-analysis of a large number of historical dose-response data for continuous endpoints showed that the shapes of the dose-response relationships were surprisingly homogenous. The datasets were selected on the sole criterion that they were expected to provide relatively good in...

NEUROTOXIC EFFECTS OF ENVIRONMENTAL AGENTS: DATA GAPS THAT CHALLENGE DOSE-RESPONSE ESTIMATION

EPA Science Inventory

Neurotoxic effects of environmental agents: Data gaps that challenge dose-response estimation
S Gutter*, P Mendola+, SG Selevan**, D Rice** (*UNC Chapel Hill; +US EPA, NHEERL; **US EPA, NCEA)

Dose-response estimation is a critical feature of risk assessment. It can be...

Estimation of dose-response models for discrete and continuous data in weed science

USDA-ARS?s Scientific Manuscript database

Dose-response analysis is widely used in biological sciences and has application to a variety of risk assessment, bioassay, and calibration problems. In weed science, dose-response methodologies have typically relied on least squares estimation under an assumption of normality. Advances in computati...

USE OF MECHANISTIC DATA TO HELP DEFINE DOSE-RESPONSE CURVES

EPA Science Inventory

Use of Mechanistic Data to Help Define Dose-Response Curves

The cancer risk assessment process described by the U.S. EPA necessitates a description of the dose-response curve for tumors in humans at low (environmental) exposures. This description can either be a default l...

Development of noise dose/visitor response relationships for the national parks overflight rule : Bryce Canyon National Park Study

DOT National Transportation Integrated Search

1998-07-01

This research was conducted in support of the National Parks Overflight Rule (National Rule). The foundation of the research program for the National Rule is the performance of noise dose/visitor response (dose-response) studies in several National P...

An Adaptive Staggered Dose Design for a Normal Endpoint.

PubMed

Wu, Joseph; Menon, Sandeep; Chang, Mark

2015-01-01

In a clinical trial where several doses are compared to a control, a multi-stage design that combines both the selection of the best dose and the confirmation of this selected dose is desirable. An example is the two-stage drop-the-losers or pick-the-winner design, where inferior doses are dropped after interim analysis. Selection of target dose(s) can be based on ranking of observed effects, hypothesis testing with adjustment for multiplicity, or other criteria at interim stages. A number of methods have been proposed and have made significant gains in trial efficiency. However, many of these designs started off with all doses with equal allocation and did not consider prioritizing the doses using existing dose-response information. We propose an adaptive staggered dose procedure that allows explicit prioritization of doses and applies error spending scheme that favors doses with assumed better responses. This design starts off with only a subset of the doses and adaptively adds new doses depending on interim results. Using simulation, we have shown that this design performs better in terms of increased statistical power than the drop-the-losers design given strong prior information of dose response.

Dynamics of Cellular Responses to Radiation

PubMed Central

Wodarz, Dominik; Sorace, Ron; Komarova, Natalia L.

2014-01-01

Understanding the consequences of exposure to low dose ionizing radiation is an important public health concern. While the risk of low dose radiation has been estimated by extrapolation from data at higher doses according to the linear non-threshold model, it has become clear that cellular responses can be very different at low compared to high radiation doses. Important phenomena in this respect include radioadaptive responses as well as low-dose hyper-radiosensitivity (HRS) and increased radioresistance (IRR). With radioadaptive responses, low dose exposure can protect against subsequent challenges, and two mechanisms have been suggested: an intracellular mechanism, inducing cellular changes as a result of the priming radiation, and induction of a protected state by inter-cellular communication. We use mathematical models to examine the effect of these mechanisms on cellular responses to low dose radiation. We find that the intracellular mechanism can account for the occurrence of radioadaptive responses. Interestingly, the same mechanism can also explain the existence of the HRS and IRR phenomena, and successfully describe experimentally observed dose-response relationships for a variety of cell types. This indicates that different, seemingly unrelated, low dose phenomena might be connected and driven by common core processes. With respect to the inter-cellular communication mechanism, we find that it can also account for the occurrence of radioadaptive responses, indicating redundancy in this respect. The model, however, also suggests that the communication mechanism can be vital for the long term survival of cell populations that are continuously exposed to relatively low levels of radiation, which cannot be achieved with the intracellular mechanism in our model. Experimental tests to address our model predictions are proposed. PMID:24722167

TH-C-19A-01: Analytic Design Method to Make a 2D Planar, Segmented Ion Chamber Water-Equivalent for Proton Dose Measurements

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

Harris, W; Hollebeek, R; Teo, B

2014-06-15

Purpose: Quality Assurance (QA) measurements of proton therapy fields must accurately measure steep longitudinal dose gradients as well as characterize the dose distribution laterally. Currently, available devices for two-dimensional field measurements perturb the dose distribution such that routine QA measurements performed at multiple depths require multiple field deliveries and are time consuming. Methods: A design procedure for a two-dimensional detector array is introduced whereby the proton energy loss and scatter are adjusted so that the downstream dose distribution is maintained to be equivalent to that which would occur in uniform water. Starting with the design for an existing, functional two-dimensionalmore » segmented ion chamber prototype, a compensating material is introduced downstream of the detector to simultaneously equate the energy loss and lateral scatter in the detector assembly to the values in water. An analytic formalism and procedure is demonstrated to calculate the properties of the compensating material in the general case of multiple layers of arbitrary material. The resulting design is validated with Monte Carlo simulations. Results: With respect to the specific prototype design considered, the results indicate that a graphite compensating layer of the proper dimensions can yield proton beam range perturbation less than 0.1mm and beam sigma perturbation less than 2% across the energy range of therapeutic proton beams. Conclusion: We have shown that, for a 2D gas-filled detector array, a graphite-compensating layer can balance the energy loss and multiple Coulomb scattering relative to uniform water. We have demonstrated an analytic formalism and procedure to determine a compensating material in the general case of multiple layers of arbitrary material. This work was supported by the US Army Medical Research and Materiel Command under Contract Agreement No. DAMD17-W81XWH-04-2-0022. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the US Army.« less

Inverse treatment planning for spinal robotic radiosurgery: an international multi-institutional benchmark trial.

PubMed

Blanck, Oliver; Wang, Lei; Baus, Wolfgang; Grimm, Jimm; Lacornerie, Thomas; Nilsson, Joakim; Luchkovskyi, Sergii; Cano, Isabel Palazon; Shou, Zhenyu; Ayadi, Myriam; Treuer, Harald; Viard, Romain; Siebert, Frank-Andre; Chan, Mark K H; Hildebrandt, Guido; Dunst, Jürgen; Imhoff, Detlef; Wurster, Stefan; Wolff, Robert; Romanelli, Pantaleo; Lartigau, Eric; Semrau, Robert; Soltys, Scott G; Schweikard, Achim

2016-05-08

Stereotactic radiosurgery (SRS) is the accurate, conformal delivery of high-dose radiation to well-defined targets while minimizing normal structure doses via steep dose gradients. While inverse treatment planning (ITP) with computerized optimization algorithms are routine, many aspects of the planning process remain user-dependent. We performed an international, multi-institutional benchmark trial to study planning variability and to analyze preferable ITP practice for spinal robotic radiosurgery. 10 SRS treatment plans were generated for a complex-shaped spinal metastasis with 21 Gy in 3 fractions and tight constraints for spinal cord (V14Gy < 2 cc, V18Gy < 0.1 cc) and target (coverage > 95%). The resulting plans were rated on a scale from 1 to 4 (excellent-poor) in five categories (constraint compliance, optimization goals, low-dose regions, ITP complexity, and clinical acceptability) by a blinded review panel. Additionally, the plans were mathemati-cally rated based on plan indices (critical structure and target doses, conformity, monitor units, normal tissue complication probability, and treatment time) and compared to the human rankings. The treatment plans and the reviewers' rankings varied substantially among the participating centers. The average mean overall rank was 2.4 (1.2-4.0) and 8/10 plans were rated excellent in at least one category by at least one reviewer. The mathematical rankings agreed with the mean overall human rankings in 9/10 cases pointing toward the possibility for sole mathematical plan quality comparison. The final rankings revealed that a plan with a well-balanced trade-off among all planning objectives was preferred for treatment by most par-ticipants, reviewers, and the mathematical ranking system. Furthermore, this plan was generated with simple planning techniques. Our multi-institutional planning study found wide variability in ITP approaches for spinal robotic radiosurgery. The participants', reviewers', and mathematical match on preferable treatment plans and ITP techniques indicate that agreement on treatment planning and plan quality can be reached for spinal robotic radiosurgery.

Sci-Fri PM: Radiation Therapy, Planning, Imaging, and Special Techniques - 02: Feasibility of using multileaf collimation for stereotactic radiosurgery of arteriovenous malformation

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

Lee, Young; Ruschin, Mark

SRS using linac and cones offers steep dose fall-off but a tradeoff exists between conformality and treatment time, which depends on the number of isocentres. Purpose of this study is to quantify planning metrics between cones- and MLC-based SRS for arteriovenous malformation(AVM). Seven AVM cases treated with cones were re-planned with MLC on Pinnacle treatment planning system. Planning target volume(PTV) was created with 1mm uniform margin to the AVM to account for MLC positional variation. Clinically-planned prescription dose(15–25Gy) was used. Four plans were generated per case:non-coplanar VMAT(ncV), single-arc VMAT(saV), non-coplanar IMRT(ncI), non-coplanar conformal(ncC). Plans were compared for conformity(CI), heterogeneity(HI) andmore » gradient(GI) indices and brain doses. Estimated treatment times and monitor units(MU) were compared. Cone-based plans required 2–6 isocentres. Though CI-RTOG was similar for plans(median=0.98), CI-Paddick was most favourable for ncV(median=0.86) and worst for cones(0.54). HI for MLC plans(median=1.19–1.27) were lower than cone-based plans(1.43). GI was similar for all plans. For 2/7 ncC had brainstem maximum dose>16.7Gy and therefore were clinically unacceptable. Brain V12Gy,V10Gy,V2Gy were lowest in the cones plan. ncV brain V12Gy,V10Gy,V2Gy were lowest of all MLC-based plans studied. Treatment MUs were similar for MLC-based plans and up to 70% lower than clinically delivered plans. ncV showed best conformality in this study. Of the MLC-based plans, ncV also showed lowest normal tissue dose with reasonable treatment time.« less

Study of the Genes and Mechanism Involved in the Radioadaptive Response

NASA Technical Reports Server (NTRS)

Dasgupta, Pushan R.

2009-01-01

The radioadaptive response is a phenomenon where exposure to a prior low dose of radiation reduces the level of damage induced by a subsequent high radiation dose. The molecular mechanism behind this is still not well understood. Learning more about the radioadaptive response is critical for long duration spaceflight since astronauts are exposed to low levels of cosmic radiation. The micronucleus assay was used to measure the level of damage caused by radiation. Although cells which were not washed with phosphate buffered saline (PBS) after a low priming dose of 5cGy did not show adaptation to the challenge dose, washing the cells with PBS and giving the cells fresh media after the low dose did allow radioadaptation to occur. This is consistent with the results of a previous publication by another research group. In the present study, genes involved in DNA damage signaling and the oxidative stress response were studied using RT PCR techniques in order to look at changes in expression level after the low dose with or without washing. Our preliminary results indicate that upregulation of oxidative stress response genes ANGPTL7, NCF2, TTN, and SRXN1 may be involved in the radioadaptive response. The low dose of radiation alone was found to activate the oxidative stress response genes GPR156 and MTL5, whereas, washing the cells alone caused relatively robust upregulation of the oxidative stress response genes DUSP1 and PTGS2. Washing after the priming dose showed some changes in the expression level of several DNA damage signaling genes. In addition, we studied whether washing the cells after the priming dose has an effect on the level of nitric oxide in both the media and cells, since nitric oxide levels are known to increase in the media of the cells after a high dose of radiation only if the cells were already exposed to a low priming dose. Based on this preliminary study, we propose that washing the cells after priming exposure actually eliminates some factor secreted by the cells that inhibits radioadaptation leading to the upregulation of some genes which initiates the response.

The c-Abl signaling network in the radioadaptive response

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

Chi-Min, Yuan

2014-01-28

The radioadaptive response, or radiation hormesis, i.e. a low dose of radiation can protect cells and organisms from the effects of a subsequent higher dose, is a widely recognized phenomenon. Mechanisms underlying such radiation hormesis, however, remain largely unclear. Preliminary studies indicate an important role of c-Abl signaling in mediating the radioadaptive response. We propose to investigate how c-Abl regulates the crosstalk between p53 and NFκB in response to low doses irradiation. We found in our recent study that low dose IR induces a reciprocal p53 suppression and NFκB activation, which induces HIF-a and subsequently a metabolic reprogramming resulting inmore » a transition from oxidative phosphorylation to glycolysis. Of importance is that this glycolytic switch is essential for the radioadaptive response. This low-dose radiationinduced HIF1α activation was in sharp contrast with the high-dose IR-induced p53 activation and HIF1α inhibition. HIF1α and p53 seem to play distinct roles in mediating the radiation dose-dependent metabolic response. The induction of HIF1α-mediated glycolysis is restricted to a low dose range of radiation, which may have important implications in assessing the level of radiation exposure and its potential health risk. Our results support a dose-dependent metabolic response to IR. When IR doses are below the threshold of causing detectable DNA damage (<0.2Gy) and thus little p53 activation, HIF1α is induced resulting in induction of glycolysis and increased radiation resistance. When the radiation dose reaches levels eliciting DNA damage, p53 is activated and diminishes the activity of HIF1α and glycolysis, leading to the induction of cell death. Our work challenges the LNT model of radiation exposure risk and provides a metabolic mechanism of radioadaptive response. The study supports a need for determining the p53 and HIF1α activity as a potential reliable biological readout of radiation exposure in humans. The exquisite sensitivity of cellular metabolism to low doses of radiation could also serve as a valuable biomarker for estimating the health effects of low-level radiation exposure.« less

Induction of chromosomal aberrations at fluences of less than one HZE particle per cell nucleus.

PubMed

Hada, Megumi; Chappell, Lori J; Wang, Minli; George, Kerry A; Cucinotta, Francis A

2014-10-01

The assumption of a linear dose response used to describe the biological effects of high-LET radiation is fundamental in radiation protection methodologies. We investigated the dose response for chromosomal aberrations for exposures corresponding to less than one particle traversal per cell nucleus by high-energy charged (HZE) nuclei. Human fibroblast and lymphocyte cells were irradiated with several low doses of <0.1 Gy, and several higher doses of up to 1 Gy with oxygen (77 keV/μm), silicon (99 keV/μm) or Fe (175 keV/μm), Fe (195 keV/μm) or Fe (240 keV/μm) particles. Chromosomal aberrations at first mitosis were scored using fluorescence in situ hybridization (FISH) with chromosome specific paints for chromosomes 1, 2 and 4 and DAPI staining of background chromosomes. Nonlinear regression models were used to evaluate possible linear and nonlinear dose-response models based on these data. Dose responses for simple exchanges for human fibroblasts irradiated under confluent culture conditions were best fit by nonlinear models motivated by a nontargeted effect (NTE). The best fits for dose response data for human lymphocytes irradiated in blood tubes were a linear response model for all particles. Our results suggest that simple exchanges in normal human fibroblasts have an important NTE contribution at low-particle fluence. The current and prior experimental studies provide important evidence against the linear dose response assumption used in radiation protection for HZE particles and other high-LET radiation at the relevant range of low doses.

Impact of plasma response on plasma displacements in DIII-D during application of external 3D perturbations

DOE PAGES

Wingen, Andreas; Ferraro, Nathaniel M.; Shafer, Morgan W.; ...

2014-05-23

The effects of applied non-axisymmetric resonant magnetic perturbations (RMPs) are predicted without and with self-consistent plasma response by modeling of the magnetic field structure and two-fluid MHD simulations, respectively. A synthetic diagnostic is used to simulate soft X-ray (SXR) emission within the steep gradient region of the pedestal, 0.98 > ψ > 0.94. The entire pedestal and edge region is characterized by large changes in plasma rotation and current density. Those parameters are expected to strongly affect the plasma response to RMPs. The M3D-C1 code takes into account this response self-consistently. The plasma response is investigated in detail and usedmore » in the forward modeling of the simulated local SXR emission, within the framework of the synthetic diagnostic. The resulting synthetic emission is compared to measured SXR data. The latter clearly shows helical m = 11 ± 1 displacements around the 11/3 rational surface of sizes up to 5 cm, which change with the poloidal angle. The synthetic emission with plasma response is used to explain the nature of the measured displacements. Different approaches are tested. One approach is based on the magnetic field structure to simulate local emission, which shows additional structures at the separatrix, that are caused by the lobes. Especially without plasma response, almost only separatrix structures are generated while no significant displacements are found further inside. Another approach to model local emission uses the fluid quantities electron density and temperature, as calculated by M3D-C1. Compared to the previous approach, based on the magnetic field structure, the emission simulated by the fluid approach with plasma response shows better agreement with the measured SXR data. To be specific, it has comparable displacements in the steep gradient region and no lobe structures at all. The helical displacements around the 11/3 surface are identified to be directly related to the kink response, caused by non-resonant amplification of various poloidal RMP modes due to plasma response. Regarding the latter, the role of different plasma parameters is investigated, but it appears that the electron rotation plays a key role in the formation of screening and resonant amplification, while the kinking appears to be sensitive to the edge current density. As a result, it is also hypothesised that the strength of the kink response is also correlated to edge-localized-mode (ELM) stability.« less

Modulating intracellular acidification by regulating the incubation time of proton caged compounds.

PubMed

Carbone, Marilena; Sabbatella, Gianfranco; Antonaroli, Simonetta; Orlando, Viviana; Biagioni, Stefano; Nucara, Alessandro

2016-09-01

A proton caged compound, the 1-(2-nitrophenyl)- ethylhexadecyl sulfonate (HDNS), was dosed into HEK-293 at different incubation times. Samples were irradiated with filtered UV light for inducing photolysis of the HDNS and then probed by infrared spectroscopy. The intracellular acidification reaction can be followed by monitoring the consequent CO2 peak intensity variation. The total CO2 produced is similar for all the samples, hence it is only a function of the initial HDNS concentration. The way it is achieved, though, is different for the different incubation times and follows kinetics, which results in a combination of a linear CO2 increase and a steep CO2 increase followed by a decay. This is interpreted in terms of confinement of the HDNS into intracellular vesicles of variable average size and sensitive to UV light when they reach critical dimensions.

The forest ecosystem of southeast Alaska: 5. Soil mass movement.

Treesearch

Douglas N. Swanston

1974-01-01

Research in southeast Alaska has identified soil mass movement as the dominant erosion process, with debris avalanches and debris flows the most frequent events on characteristically steep, forested slopes. Periodically high soil water levels and steep slopes are controlling factors. Bedrock structure and the rooting characteristics of trees and other vegetation exert...

Does WEPP meet the specificity of soil erosion in steep mountain regions?

USDA-ARS?s Scientific Manuscript database

We chose the USDA-ARS-WEPP model (Water Erosion Prediction Project) to describe the soil erosion in the Urseren valley (Central Switzerland) as it seems to be one of the most promising models for steep mountain environments. Crucial model parameters were determined in the field (slope, plant species...

It's time to look at yarding problems on steep slopes.

Treesearch

Robert H. Ruth

1960-01-01

In many parts of the Pacific Northwest, logging operations are moving into rugged terrain as access roads probe deeper into the back country. Because of this trend, it's time to look more carefully at steep slopes and decide on the best possible management practices consistent with maximum protection against erosion.

Riparian hydraulic gradient and stream-groundwater exchange dynamics in steep headwater valleys

Treesearch

T.J. Voltz; M.N. Gooseff; A.S. Ward; K. Singha; M. Fitzgerald; T. Wagener

2013-01-01

Patterns of riparian hydraulic gradients and stream-groundwater exchange in headwater catchments provide the hydrologic context for important ecological processes. Although the controls are relatively well understood, their dynamics during periods of hydrologic change is not. We investigate riparian hydraulic gradients over three different time scales in two steep,...

Slope, Rate of Change, and Steepness: Do Students Understand These Concepts?

ERIC Educational Resources Information Center

Teuscher, Dawn; Reys, Robert E.

2010-01-01

How do mathematics teachers introduce the concepts of slope, rate of change, and steepness in their classrooms? Do students understand these concepts as interchangeable or regard them as three different ideas? In this article, the authors report the results of a study of high school Advanced Placement (AP) Calculus students who displayed…

[Use of flour from sunflower oil cake in the biosynthesis of antigungal antibiotics].

PubMed

Sukharevich, V M; Shvetsova, N N; Prodan, S I; Malkov, M A

1977-04-01

The possibility of replacing soybean meal and corn-steep liquor by food wastes of the oilpress industry and the meal of the sunflower oil cake in particular is discussed as applied to the fermentation media for production of antifungal antibiotics, such as levorin, mycoheptin, amphotericin. The studies showed that replacement of soybean meal by sunflower oil cake meal with simultaneous increasing of the amount of carbohydrates in the medium increased the levorin levels by 60--70 per cent as compared to the media used at present. When soybean meal and corn-steep liquor were simultaneously replaced by sunflower oil cake meal in amounts of 3--4 per cent the levels of mycoheptin in the fermentation broth increased by 30--65 per cent respectively. Replacement of soybean meal and corn-steep liquor by 3 per cent of sunflow oil cake meal in the medium used presently increased the amphotericin levels by 27 percent as compared to the control. Therefore, sunflower oil cake meal is a substitute of full value for soybean meal and corn-steep liquor in the fermentation media for production of antifungal antibiotics.

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

PubMed Central

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

2018-01-01

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

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

PubMed

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

2018-01-01

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

A Four-Step and Four-Criteria Approach for Evaluating Evidence of Dose Addition in Chemical Mixture Toxicity

EPA Science Inventory

Dose addition is the most frequently-used component-based approach for predicting dose response for a mixture of toxicologically-similar chemicals and for statistical evaluation of whether the mixture response is consistent with dose additivity and therefore predictable from the ...

Dose-response relationship between hand-transmitted vibration and hand-arm vibration syndrome in a tropical environment.

PubMed

Su, Anselm Ting; Maeda, Setsuo; Fukumoto, Jin; Darus, Azlan; Hoe, Victor C W; Miyai, Nobuyuki; Isahak, Marzuki; Takemura, Shigeki; Bulgiba, Awang; Yoshimasu, Kouichi; Miyashita, Kazuhisa

2013-07-01

The dose-response relationship for hand-transmitted vibration has been investigated extensively in temperate environments. Since the clinical features of hand-arm vibration syndrome (HAVS) differ between the temperate and tropical environment, we conducted this study to investigate the dose-response relationship of HAVS in a tropical environment. A total of 173 male construction, forestry and automobile manufacturing plant workers in Malaysia were recruited into this study between August 2011 and 2012. The participants were interviewed for history of vibration exposure and HAVS symptoms, followed by hand functions evaluation and vibration measurement. Three types of vibration doses-lifetime vibration dose (LVD), total operating time (TOT) and cumulative exposure index (CEI)-were calculated and its log values were regressed against the symptoms of HAVS. The correlation between each vibration exposure dose and the hand function evaluation results was obtained. The adjusted prevalence ratio for finger tingling and numbness was 3.34 (95% CI 1.27 to 8.98) for subjects with lnLVD≥20 ln m(2) s(-4) against those <16 ln m(2) s(-4). Similar dose-response pattern was found for CEI but not for TOT. No subject reported white finger. The prevalence of finger coldness did not increase with any of the vibration doses. Vibrotactile perception thresholds correlated moderately with lnLVD and lnCEI. The dose-response relationship of HAVS in a tropical environment is valid for finger tingling and numbness. The LVD and CEI are more useful than TOT when evaluating the dose-response pattern of a heterogeneous group of vibratory tools workers.

Dose-Response—A Challenge for Allelopathy?

PubMed Central

Belz, Regina G.; Hurle, Karl; Duke, Stephen O.

2005-01-01

The response of an organism to a chemical depends, among other things, on the dose. Nonlinear dose-response relationships occur across a broad range of research fields, and are a well established tool to describe the basic mechanisms of phytotoxicity. The responses of plants to allelochemicals as biosynthesized phytotoxins, relate as well to nonlinearity and, thus, allelopathic effects can be adequately quantified by nonlinear mathematical modeling. The current paper applies the concept of nonlinearity to assorted aspects of allelopathy within several bioassays and reveals their analysis by nonlinear regression models. Procedures for a valid comparison of effective doses between different allelopathic interactions are presented for both, inhibitory and stimulatory effects. The dose-response applications measure and compare the responses produced by pure allelochemicals [scopoletin (7-hydroxy-6-methoxy-2H-1-benzopyran-2-one); DIBOA (2,4-dihydroxy-2H-1,4-benzoxaxin-3(4H)-one); BOA (benzoxazolin-2(3H)-one); MBOA (6-methoxy-benzoxazolin-2(3H)-one)], involved in allelopathy of grain crops, to demonstrate how some general principles of dose responses also relate to allelopathy. Hereupon, dose-response applications with living donor plants demonstrate the validity of these principles for density-dependent phytotoxicity of allelochemicals produced and released by living plants (Avena sativa L., Secale cereale L., Triticum L. spp.), and reveal the use of such experiments for initial considerations about basic principles of allelopathy. Results confirm that nonlinearity applies to allelopathy, and the study of allelopathic effects in dose-response experiments allows for new and challenging insights into allelopathic interactions. PMID:19330161

Mechanisms and biological importance of photon-induced bystander responses: do they have an impact on low-dose radiation responses

PubMed Central

Tomita, Masanori; Maeda, Munetoshi

2015-01-01

Abstract Elucidating the biological effect of low linear energy transfer (LET), low-dose and/or low-dose-rate ionizing radiation is essential in ensuring radiation safety. Over the past two decades, non-targeted effects, which are not only a direct consequence of radiation-induced initial lesions produced in cellular DNA but also of intra- and inter-cellular communications involving both targeted and non-targeted cells, have been reported and are currently defining a new paradigm in radiation biology. These effects include radiation-induced adaptive response, low-dose hypersensitivity, genomic instability, and radiation-induced bystander response (RIBR). RIBR is generally defined as a cellular response that is induced in non-irradiated cells that receive bystander signals from directly irradiated cells. RIBR could thus play an important biological role in low-dose irradiation conditions. However, this suggestion was mainly based on findings obtained using high-LET charged-particle radiations. The human population (especially the Japanese, who are exposed to lower doses of radon than the world average) is more frequently exposed to low-LET photons (X-rays or γ-rays) than to high-LET charged-particle radiation on a daily basis. There are currently a growing number of reports describing a distinguishing feature between photon-induced bystander response and high-LET RIBR. In particular, photon-induced bystander response is strongly influenced by irradiation dose, the irradiated region of the targeted cells, and p53 status. The present review focuses on the photon-induced bystander response, and discusses its impact on the low-dose radiation effect. PMID:25361549

QMRA for Drinking Water: 2. The Effect of Pathogen Clustering in Single-Hit Dose-Response Models.

PubMed

Nilsen, Vegard; Wyller, John

2016-01-01

Spatial and/or temporal clustering of pathogens will invalidate the commonly used assumption of Poisson-distributed pathogen counts (doses) in quantitative microbial risk assessment. In this work, the theoretically predicted effect of spatial clustering in conventional "single-hit" dose-response models is investigated by employing the stuttering Poisson distribution, a very general family of count distributions that naturally models pathogen clustering and contains the Poisson and negative binomial distributions as special cases. The analysis is facilitated by formulating the dose-response models in terms of probability generating functions. It is shown formally that the theoretical single-hit risk obtained with a stuttering Poisson distribution is lower than that obtained with a Poisson distribution, assuming identical mean doses. A similar result holds for mixed Poisson distributions. Numerical examples indicate that the theoretical single-hit risk is fairly insensitive to moderate clustering, though the effect tends to be more pronounced for low mean doses. Furthermore, using Jensen's inequality, an upper bound on risk is derived that tends to better approximate the exact theoretical single-hit risk for highly overdispersed dose distributions. The bound holds with any dose distribution (characterized by its mean and zero inflation index) and any conditional dose-response model that is concave in the dose variable. Its application is exemplified with published data from Norovirus feeding trials, for which some of the administered doses were prepared from an inoculum of aggregated viruses. The potential implications of clustering for dose-response assessment as well as practical risk characterization are discussed. © 2016 Society for Risk Analysis.

Peficitinib, an Oral Janus Kinase Inhibitor, in Moderate-to-Severe Ulcerative Colitis: Results From a Randomized, Phase 2 Study.

PubMed

Sands, Bruce E; Sandborn, William J; Feagan, Brian G; Lichtenstein, Gary R; Zhang, Hongyan; Strauss, Richard; Szapary, Philippe; Johanns, Jewel; Panes, Julian; Vermeire, Severine; O'Brien, Christopher D; Yang, Zijiang; Bertelsen, Kirk; Marano, Colleen

2018-06-15

Janus kinase (JAK) inhibitors have shown efficacy in ulcerative colitis (UC). We studied the dose-response, efficacy, and safety of peficitinib, an oral JAK inhibitor, in patients with moderate-to-severe UC. In this Phase 2b, dose-ranging trial, we evaluated peficitinib at 25mg once daily (qd), 75mg qd, 150mg qd, and 75mg twice daily versus placebo for efficacy and safety in 219 patients with moderate-to-severe UC. The primary outcome was peficitinib dose-response at Week 8 with response assessed using Mayo score change from baseline. Secondary endpoints were clinical response, clinical remission, mucosal healing, change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ), and normalization of inflammatory biomarkers at Week 8; other secondary endpoints were treatment response through Week 16 and through Week 32 for patients in clinical response at Week 8. Safety was assessed through Week 36 or 4 weeks after the last dose. A statistically significant peficitinib dose-response was not demonstrated at Week 8, although a numerically greater proportion of patients receiving peficitinib ≥75mg qd achieved clinical response, remission, and mucosal healing at Week 8, supported by IBDQ improvement and inflammatory biomarker normalization. Treatment-emergent adverse event (TEAE) rates reported through Week 8 and the final safety visit were higher in the combined peficitinib group than placebo; patients receiving doses of ≥75mg qd peficitinib reported TEAEs more frequently. While no dose-response in patients with moderate-to-severe UC was demonstrated with peficitinib, evidence of efficacy was suggested at doses ≥75mg qd. The safety profile of peficitinib was consistent with current information. ClinicalTrials.gov NCT01959282.

Antibody Secreting Cell Responses following Vaccination with Bivalent Oral Cholera Vaccine among Haitian Adults.

PubMed

Matias, Wilfredo R; Falkard, Brie; Charles, Richelle C; Mayo-Smith, Leslie M; Teng, Jessica E; Xu, Peng; Kováč, Pavol; Ryan, Edward T; Qadri, Firdausi; Franke, Molly F; Ivers, Louise C; Harris, Jason B

2016-06-01

The bivalent whole-cell (BivWC) oral cholera vaccine (Shanchol) is effective in preventing cholera. However, evaluations of immune responses following vaccination with BivWC have been limited. To determine whether BivWC induces significant mucosal immune responses, we measured V. cholerae O1 antigen-specific antibody secreting cell (ASC) responses following vaccination. We enrolled 24 Haitian adults in this study, and administered doses of oral BivWC vaccine 14 days apart (day 0 and day 14). We drew blood at baseline, and 7 days following each vaccine dose (day 7 and 21). Peripheral blood mononuclear cells (PBMCs) were isolated, and ASCs were enumerated using an ELISPOT assay. Significant increases in Ogawa (6.9 cells per million PBMCs) and Inaba (9.5 cells per million PBMCs) OSP-specific IgA ASCs were detected 7 days following the first dose (P < 0.001), but not the second dose. The magnitude of V. cholerae-specific ASC responses did not appear to be associated with recent exposure to cholera. ASC responses measured against the whole lipolysaccharide (LPS) antigen and the OSP moiety of LPS were equivalent, suggesting that all or nearly all of the LPS response targets the OSP moiety. Immunization with the BivWC oral cholera vaccine induced ASC responses among a cohort of healthy adults in Haiti after a single dose. The second dose of vaccine resulted in minimal ASC responses over baseline, suggesting that the current dosing schedule may not be optimal for boosting mucosal immune responses to V. cholerae antigens for adults in a cholera-endemic area.

Influence of Terraced area DEM Resolution on RUSLE LS Factor

NASA Astrophysics Data System (ADS)

Zhang, Hongming; Baartman, Jantiene E. M.; Yang, Xiaomei; Gai, Lingtong; Geissen, Viollette

2017-04-01

Topography has a large impact on the erosion of soil by water. Slope steepness and slope length are combined (the LS factor) in the universal soil-loss equation (USLE) and its revised version (RUSLE) for predicting soil erosion. The LS factor is usually extracted from a digital elevation model (DEM). The grid size of the DEM will thus influence the LS factor and the subsequent calculation of soil loss. Terracing is considered as a support practice factor (P) in the USLE/RUSLE equations, which is multiplied with the other USLE/RUSLE factors. However, as terraces change the slope length and steepness, they also affect the LS factor. The effect of DEM grid size on the LS factor has not been investigated for a terraced area. We obtained a high-resolution DEM by unmanned aerial vehicles (UAVs) photogrammetry, from which the slope steepness, slope length, and LS factor were extracted. The changes in these parameters at various DEM resolutions were then analysed. The DEM produced detailed LS-factor maps, particularly for low LS factors. High (small valleys, gullies, and terrace ridges) and low (flats and terrace fields) spatial frequencies were both sensitive to changes in resolution, so the areas of higher and lower slope steepness both decreased with increasing grid size. Average slope steepness decreased and average slope length increased with grid size. Slope length, however, had a larger effect than slope steepness on the LS factor as the grid size varied. The LS factor increased when the grid size increased from 0.5 to 30-m and increased significantly at grid sizes >5-m. The LS factor was increasingly overestimated as grid size decreased. The LS factor decreased from grid sizes of 30 to 100-m, because the details of the terraced terrain were gradually lost, but the factor was still overestimated.

Egalitarian despots: hierarchy steepness, reciprocity and the grooming-trade model in wild chimpanzees, Pan troglodytes.

PubMed

Kaburu, Stefano S K; Newton-Fisher, Nicholas E

2015-01-01

Biological market theory models the action of natural selection as a marketplace in which animals are viewed as traders with commodities to offer and exchange. Studies of female Old World monkeys have suggested that grooming might be employed as a commodity to be reciprocated or traded for alternative services, yet previous tests of this grooming-trade model in wild adult male chimpanzees have yielded mixed results. Here we provide the strongest test of the model to date for male chimpanzees: we use data drawn from two social groups (communities) of chimpanzees from different populations and give explicit consideration to variation in dominance hierarchy steepness, as such variation results in differing conditions for biological markets. First, analysis of data from published accounts of other chimpanzee communities, together with our own data, showed that hierarchy steepness varied considerably within and across communities and that the number of adult males in a community aged 20-30 years predicted hierarchy steepness. The two communities in which we tested predictions of the grooming-trade model lay at opposite extremes of this distribution. Second, in accord with the grooming-trade model, we found evidence that male chimpanzees trade grooming for agonistic support where hierarchies are steep (despotic) and consequent effective support is a rank-related commodity, but not where hierarchies are shallow (egalitarian). However, we also found that grooming was reciprocated regardless of hierarchy steepness. Our findings also hint at the possibility of agonistic competition, or at least exclusion, in relation to grooming opportunities compromising the free market envisioned by biological market theory. Our results build on previous findings across chimpanzee communities to emphasize the importance of reciprocal grooming exchanges among adult male chimpanzees, which can be understood in a biological markets framework if grooming by or with particular individuals is a valuable commodity.

Egalitarian despots: hierarchy steepness, reciprocity and the grooming-trade model in wild chimpanzees, Pan troglodytes

PubMed Central

Kaburu, Stefano S. K.; Newton-Fisher, Nicholas E.

2014-01-01

Biological market theory models the action of natural selection as a marketplace in which animals are viewed as traders with commodities to offer and exchange. Studies of female Old World monkeys have suggested that grooming might be employed as a commodity to be reciprocated or traded for alternative services, yet previous tests of this grooming-trade model in wild adult male chimpanzees have yielded mixed results. Here we provide the strongest test of the model to date for male chimpanzees: we use data drawn from two social groups (communities) of chimpanzees from different populations and give explicit consideration to variation in dominance hierarchy steepness, as such variation results in differing conditions for biological markets. First, analysis of data from published accounts of other chimpanzee communities, together with our own data, showed that hierarchy steepness varied considerably within and across communities and that the number of adult males in a community aged 20–30 years predicted hierarchy steepness. The two communities in which we tested predictions of the grooming-trade model lay at opposite extremes of this distribution. Second, in accord with the grooming-trade model, we found evidence that male chimpanzees trade grooming for agonistic support where hierarchies are steep (despotic) and consequent effective support is a rank-related commodity, but not where hierarchies are shallow (egalitarian). However, we also found that grooming was reciprocated regardless of hierarchy steepness. Our findings also hint at the possibility of agonistic competition, or at least exclusion, in relation to grooming opportunities compromising the free market envisioned by biological market theory. Our results build on previous findings across chimpanzee communities to emphasize the importance of reciprocal grooming exchanges among adult male chimpanzees, which can be understood in a biological markets framework if grooming by or with particular individuals is a valuable commodity. PMID:25580017

NONMONOTONIC DOSE RESPONSE CURVES (NMDRCS) ARE COMMON AFTER ESTROGEN OR ANDROGEN SIGNALING PATHWAY DISRUPTION. FACT OR FALDERAL?

EPA Science Inventory

ABSTRACT BODY: The shape of the dose response curve in the low dose region has been debated since the 1940s, originally focusing on linear no threshold (LNT) versus threshold responses for cancer and noncancer effects. Recently, it has been claimed that endocrine disrupters (EDCs...

Hierarchical dose response of E. coli O157:H7 from human outbreaks incorporating heterogeneity in exposure.

PubMed

Teunis, P F M; Ogden, I D; Strachan, N J C

2008-06-01

The infectivity of pathogenic microorganisms is a key factor in the transmission of an infectious disease in a susceptible population. Microbial infectivity is generally estimated from dose-response studies in human volunteers. This can only be done with mildly pathogenic organisms. Here a hierarchical Beta-Poisson dose-response model is developed utilizing data from human outbreaks. On the lowest level each outbreak is modelled separately and these are then combined at a second level to produce a group dose-response relation. The distribution of foodborne pathogens often shows strong heterogeneity and this is incorporated by introducing an additional parameter to the dose-response model, accounting for the degree of overdispersion relative to Poisson distribution. It was found that heterogeneity considerably influences the shape of the dose-response relationship and increases uncertainty in predicted risk. This uncertainty is greater than previously reported surrogate and outbreak models using a single level of analysis. Monte Carlo parameter samples (alpha, beta of the Beta-Poisson model) can be readily incorporated in risk assessment models built using tools such as S-plus and @ Risk.

Effect of corn bran and steep inclusion in finishing diets on diet digestibility, cattle performance, and nutrient mass balance.

PubMed

Sayer, K M; Buckner, C D; Erickson, G E; Klopfenstein, T J; Macken, C N; Loy, T W

2013-08-01

One metabolism trial and 2 finishing trials were conducted to evaluate the effects of adding corn bran and steep liquor (steep) in replacement of dry-rolled corn (DRC) on diet digestibility, cattle performance, and nutrient mass balance in open feedlot pens. The metabolism trial (Exp. 1) used 8 ruminally cannulated heifers in a 4 × 4 Latin square design and the 2 finishing trials used 128 steer calves fed for 167 d (Exp. 2) and 256 yearling steers fed for 126 d (Exp. 3). Dietary treatments for all trials included a DRC-based control (CON), 30% corn bran (30/0), 30% corn bran plus 15% steep (30/15), and 45% corn bran plus 15% steep (45/15), in which by-products replaced DRC and molasses in the diet (DM basis). Diets were not isonitrogenous or isoenergetic. In the metabolism trial, feeding the by-product diets produced greater rumen pH (5.95) than CON (5.76; P < 0.01). Total tract DM and OM digestibility were greater for heifers fed CON than the by-product diets (P < 0.01). Dry matter and NDF ruminal disappearance (%/h) of corn bran were numerically less for cattle fed the CON diet than the by-product diets (2.36 vs. 2.84 and 0.72 vs. 1.66, respectively). In the performance trials, steers fed the by-product diets consumed more DM (P = 0.06) and G:F was either similar for all diets in Exp. 2 (P = 0.56) or less for cattle fed 30/0 than the other diets in Exp. 3 (P = 0.05). Percent N loss was reduced in Exp. 2 by including corn bran in diets compared with CON (P < 0.01). However, in Exp. 3, no differences in percent N loss were detected among treatments (P = 0.16), but more N was removed in the manure from pens where steers were fed by-products (P = 0.01). Although steep did not improve diet digestibility, it was beneficial in maintaining cattle performance in the feedlot studies. Feeding corn bran in combination with steep increased manure N removed and N in compost, but decreased percent N lost during the winter months only.

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

NASA Technical Reports Server (NTRS)

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

1999-01-01

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

Extensional Fault Evolution and its Flexural Isostatic Response During Iberia-Newfoundland Rifted Margin Formation

NASA Astrophysics Data System (ADS)

Gómez-Romeu, J.; Kusznir, N.; Manatschal, G.; Roberts, A.

2017-12-01

During the formation of magma-poor rifted margins, upper lithosphere thinning and stretching is achieved by extensional faulting, however, there is still debate and uncertainty how faults evolve during rifting leading to breakup. Seismic data provides an image of the present-day structural and stratigraphic configuration and thus initial fault geometry is unknown. To understand the geometric evolution of extensional faults at rifted margins it is extremely important to also consider the flexural response of the lithosphere produced by fault displacement resulting in footwall uplift and hangingwall subsidence. We investigate how the flexural isostatic response to extensional faulting controls the structural development of rifted margins. To achieve our aim, we use a kinematic forward model (RIFTER) which incorporates the flexural isostatic response to extensional faulting, crustal thinning, lithosphere thermal loads, sedimentation and erosion. Inputs for RIFTER are derived from seismic reflection interpretation and outputs of RIFTER are the prediction of the structural and stratigraphic consequences of recursive sequential faulting and sedimentation. Using RIFTER we model the simultaneous tectonic development of the Iberia-Newfoundland conjugate rifted margins along the ISE01-SCREECH1 and TGS/LG12-SCREECH2 seismic lines. We quantitatively test and calibrate the model against observed target data restored to breakup time. Two quantitative methods are used to obtain this target data: (i) gravity anomaly inversion which predicts Moho depth and continental lithosphere thinning and (ii) reverse post-rift subsidence modelling to give water and Moho depths at breakup time. We show that extensional faulting occurs on steep ( 60°) normal faults in both proximal and distal parts of rifted margins. Extensional faults together with their flexural isostatic response produce not only sub-horizontal exhumed footwall surfaces (i.e. the rolling hinge model) and highly rotated (60° or more) pre- and syn-rift stratigraphy, but also extensional allochthons underlain by apparent horizontal detachments. These detachment faults were never active in this sub-horizontal geometry; they were only active as steep faults which were isostatically rotated to their present sub-horizontal position.

Induction of Chromosomal Aberrations at Fluences of Less Than One HZE Particle per Cell Nucleus

NASA Technical Reports Server (NTRS)

Hada, Megumi; Chappell, Lori J.; Wang, Minli; George, Kerry A.; Cucinotta, Francis A.

2014-01-01

The assumption of a linear dose response used to describe the biological effects of high LET radiation is fundamental in radiation protection methodologies. We investigated the dose response for chromosomal aberrations for exposures corresponding to less than one particle traversal per cell nucleus by high energy and charge (HZE) nuclei. Human fibroblast and lymphocyte cells where irradiated with several low doses of <0.1 Gy, and several higher doses of up to 1 Gy with O (77 keV/ (long-s)m), Si (99 keV/ (long-s)m), Fe (175 keV/ (long-s)m), Fe (195 keV/ (long-s)m) or Fe (240 keV/ (long-s)m) particles. Chromosomal aberrations at first mitosis were scored using fluorescence in situ hybridization (FISH) with chromosome specific paints for chromosomes 1, 2 and 4 and DAPI staining of background chromosomes. Non-linear regression models were used to evaluate possible linear and non-linear dose response models based on these data. Dose responses for simple exchanges for human fibroblast irradiated under confluent culture conditions were best fit by non-linear models motivated by a non-targeted effect (NTE). Best fits for the dose response data for human lymphocytes irradiated in blood tubes were a NTE model for O and a linear response model fit best for Si and Fe particles. Additional evidence for NTE were found in low dose experiments measuring gamma-H2AX foci, a marker of double strand breaks (DSB), and split-dose experiments with human fibroblasts. Our results suggest that simple exchanges in normal human fibroblasts have an important NTE contribution at low particle fluence. The current and prior experimental studies provide important evidence against the linear dose response assumption used in radiation protection for HZE particles and other high LET radiation at the relevant range of low doses.

Factors modifying the response of large animals to low-intensity radiation exposure

NASA Technical Reports Server (NTRS)

Page, N. P.; Still, E. T.

1972-01-01

In assessing the biological response to space radiation, two of the most important modifying factors are dose protraction and dose distribution to the body. Studies are reported in which sheep and swine were used to compare the hematology and lethality response resulting from radiation exposure encountered in a variety of forms, including acute (high dose-rate), chronic (low dose-rate), combinations of acute and chronic, and whether received as a continuous or as fractionated exposure. While sheep and swine are basically similar in response to acute radiation, their sensitivity to chronic irradiation is markedly different. Sheep remain relatively sensitive as the radiation exposure is protracted while swine are more resistant and capable of surviving extremely large doses of chronic irradiation. This response to chronic irradiation correlated well with changes in radiosensitivity and recovery following an acute, sublethal exposure.

Platelet response to increased aspirin dose in patients with persistent platelet aggregation while treated with aspirin 81 mg.

PubMed

Gengo, Fran; Westphal, Erica S; Rainka, Michelle M; Janda, Maria; Robson, Matthew J; Hourihane, J Maurice; Bates, Vernice

2016-04-01

This study demonstrates that patients who are taking 81 mg of aspirin and are nonresponsive benefit from a dose of 162 mg or greater vs a different antiplatelet therapy. We identified 100 patients who were nonresponsive to aspirin 81 mg via whole blood aggregometry and observed how many patients became responsive at a dose of 162 mg or greater. Platelet nonresponsiveness was defined as >10 Ω of resistance to collagen 1 µg/mL and/or an ohms ratio of collagen 1 µg/mL to collagen 5 µg/mL >0.5 and/or >6 Ω to arachidonate. Borderline response was defined as an improvement in 1 but not both of the above criteria. Of the initial 100 patients who were nonresponsive to an aspirin dose of 81 mg, 79% became responsive at a dose of 162 mg or >162 mg. Only 6% did not respond to any increase in dose. We believe that patients treated with low-dose aspirin who have significant risk for secondary vascular events should be individually assessed to determine their antiplatelet response. Those found to have persistent platelet aggregation despite treatment with 81 mg of aspirin have a higher likelihood of obtaining an adequate antiplatelet response at a higher aspirin dose. © 2015, The American College of Clinical Pharmacology.

Ceruletide intravenous dose-response study by a simplified scintigraphic technique

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

Krishnamurthy, G.T.; Turner, F.E.; Mangham, D.

1985-04-01

The intravenous dose response of a ceruletide diethylamine (ceruletide) was established by a simplified scintigraphic technique where multiple graded doses were given sequentially on a single occasion. The gallbladder volume was presented nongeometrically by /sup 99m/Tc-IDA counts. The mean latent period, ejection period, and ejection rate were similar for all four groups of subjects given 1-20 ng/kg of ceruletide. The ejection fractions were similar to the values when the identical dose of ceruletide was administered sequentially either before or after another dose. A dose of 5 ng/kg produced the most physiologic type of emptying. Intravenous doses of 10 ng/kg andmore » larger caused adverse reactions in 42% of the total doses in the form of abdominal pain, nausea, systolic and diastolic hypotension, or bradycardia. It is concluded that the dose response of a cholecystokininlike agent (ceruletide) can be established reliably by a scintigraphic technique where multiple graded doses are given on a single occasion.« less

Analyzing the dose-dependence of the Saccharomyces cerevisiae global transcriptional response to methyl methanesulfonate and ionizing radiation.

PubMed

Benton, Michael G; Somasundaram, Swetha; Glasner, Jeremy D; Palecek, Sean P

2006-12-01

One of the most crucial tasks for a cell to ensure its long term survival is preserving the integrity of its genetic heritage via maintenance of DNA structure and sequence. While the DNA damage response in the yeast Saccharomyces cerevisiae, a model eukaryotic organism, has been extensively studied, much remains to be elucidated about how the organism senses and responds to different types and doses of DNA damage. We have measured the global transcriptional response of S. cerevisiae to multiple doses of two representative DNA damaging agents, methyl methanesulfonate (MMS) and gamma radiation. Hierarchical clustering of genes with a statistically significant change in transcription illustrated the differences in the cellular responses to MMS and gamma radiation. Overall, MMS produced a larger transcriptional response than gamma radiation, and many of the genes modulated in response to MMS are involved in protein and translational regulation. Several clusters of coregulated genes whose responses varied with DNA damaging agent dose were identified. Perhaps the most interesting cluster contained four genes exhibiting biphasic induction in response to MMS dose. All of the genes (DUN1, RNR2, RNR4, and HUG1) are involved in the Mec1p kinase pathway known to respond to MMS, presumably due to stalled DNA replication forks. The biphasic responses of these genes suggest that the pathway is induced at lower levels as MMS dose increases. The genes in this cluster with a threefold or greater transcriptional response to gamma radiation all showed an increased induction with increasing gamma radiation dosage. Analyzing genome-wide transcriptional changes to multiple doses of external stresses enabled the identification of cellular responses that are modulated by magnitude of the stress, providing insights into how a cell deals with genotoxicity.

Cranial stereotactic radiosurgery: current status of the initial paradigm shifter.

PubMed

Sheehan, Jason P; Yen, Chun-Po; Lee, Cheng-Chia; Loeffler, Jay S

2014-09-10

The concept of stereotactic radiosurgery (SRS) was first described by Lars Leksell in 1951. It was proposed as a noninvasive alternative to open neurosurgical approaches to manage a variety of conditions. In the following decades, SRS emerged as a unique discipline involving a collegial partnership among neurosurgeons, radiation oncologists, and medical physicists. SRS relies on the precisely guided delivery of high-dose ionizing radiation to an intracranial target. The focused convergence of multiple beams yields a potent therapeutic effect on the target and a steep dose fall-off to surrounding structures, thereby minimizing the risk of collateral damage. SRS is typically administered in a single session but can be given in as many as five sessions or fractions. By providing an ablative effect noninvasively, SRS has altered the treatment paradigms for benign and malignant intracranial tumors, functional disorders, and vascular malformations. Literature on extensive intracranial radiosurgery has unequivocally demonstrated the favorable benefit-to-risk profile that SRS affords for appropriately selected patients. In a departure from conventional radiotherapeutic strategies, radiosurgical principles have recently been extended to extracranial indications such as lung, spine, and liver tumors. The paradigm shift resulting from radiosurgery continues to alter the landscape of related fields. © 2014 by American Society of Clinical Oncology.

Method to determine the position-dependant metal correction factor for dose-rate equivalent laser testing of semiconductor devices

DOEpatents

Horn, Kevin M.

2013-07-09

A method reconstructs the charge collection from regions beneath opaque metallization of a semiconductor device, as determined from focused laser charge collection response images, and thereby derives a dose-rate dependent correction factor for subsequent broad-area, dose-rate equivalent, laser measurements. The position- and dose-rate dependencies of the charge-collection magnitude of the device are determined empirically and can be combined with a digital reconstruction methodology to derive an accurate metal-correction factor that permits subsequent absolute dose-rate response measurements to be derived from laser measurements alone. Broad-area laser dose-rate testing can thereby be used to accurately determine the peak transient current, dose-rate response of semiconductor devices to penetrating electron, gamma- and x-ray irradiation.

The effect of pre-dose on thermally and optically stimulated luminescence from α-Al2O3:C,Mg and α-Al2O3:C.

PubMed

Kalita, J M; Chithambo, M L

2018-06-15

We report the effect of pre-dose on the thermoluminescence (TL) and optically stimulated luminescence (OSL) dose response of α-Al 2 O 3 :C,Mg and α-Al 2 O 3 :C. Before any luminescence measurement, the samples were irradiated with different doses, namely 100, 500 and 1000 Gy to populate the deep electron traps. This is the pre-dose. The results from TL and OSL studies are compared with results from samples used without any pre-measurement dose. The TL glow curves and OSL decay curves of α-Al 2 O 3 :C,Mg recorded after pre-doses of 100, 500 and 1000 Gy are identical to those from a sample used without any pre-dose. Further, the TL and OSL dose response of all α-Al 2 O 3 :C,Mg samples are similar regardless of pre-dose. In comparison, the TL glow curves and OSL decay curves of α-Al 2 O 3 :C are influenced by pre-dose. We conclude that the differences in the TL and OSL dose response of various pre-dosed samples of α-Al 2 O 3 :C are due to the concentration of charge in the deep traps. On the other hand, owing to the lower concentration of such deep traps in α-Al 2 O 3 :C,Mg, the TL or OSL dose responses are not affected by pre-dose in this material. Copyright © 2018 Elsevier Ltd. All rights reserved.

Methylphenidate has nonlinear dose effects on cued response inhibition in adults but not adolescents

PubMed Central

Simon, Nicholas W.; Moghaddam, Bita

2016-01-01

Ongoing development of the dopamine system during adolescence may provide a partial mechanism for behavioral and psychiatric vulnerabilities. Despite early evidence for a hyperactive adolescent dopaminergic system, recent data suggest that adolescent dopamine may be functionally hypoactive compared to in adults. While this distinction has been established in response to dopaminergic drugs and natural rewards, little is known about age-related differences in cognitive efficacy of dopaminergic drugs. Using a recently established Cued Response Inhibition Task, we tested the effects of acute systemic methylphenidate, commonly known as Ritalin, on response inhibition and response initiation in adolescent and adults rats. First, we replicated previous data that adolescents are able to inhibit a response to a cue on par with adults, but are slower to produce a rewarded response after a stop cue. Next, we observed that methylphenidate modulated response inhibition in adult rats, with low dose (0.3 mg/kg) improving inhibition, and high dose (3 mg/kg) impairing performance. This dose-response pattern is commonly observed with psychostimulant cognitive modulation. In adolescents, however, methylphenidate had no effect on response inhibition at any dose. Latency of response initiation after the stop cue was not affected by methylphenidate in either adult or adolescent rats. These data establish that dose-response of a commonly prescribed psychostimulant medication is different in adolescents and adults. They further demonstrate that healthy adolescent response inhibition is not as sensitive to psychostimulants as in adults, supporting the idea that the dopamine system is hypoactive in adolescence. PMID:27431940

No adaptive response is induced by chronic low-dose radiation from Ra-226 in the CHSE/F fish embryonic cell line and the HaCaT human epithelial cell line

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

Shi, Xiaopei, E-mail: shix22@mcmaster.ca; Mothersi

Purpose: To determine whether chronic low-dose α-particle radiation from Ra-226 over multiple cell generations can lead to an adaptive response in CHSE/F fish embryonic cells or HaCaT human epithelial cells receiving subsequent acute high-dose γ-ray radiation. Methods: CHSE/F and HaCaT cells were exposed to very low doses of Ra-226 in medium for multiple generations prior to being challenged by a higher dose γ-ray radiation. The clonogenic assay was used to test the clonogenic survival of cells with or without being pretreated by radiation from Ra-226. Results: In general, pretreatment with chronic radiation has no significant influence on the reaction ofmore » cells to the subsequent challenge radiation. Compared to unprimed cells, the change in clonogenic survival of primed cells after receiving challenge radiation is mainly due to the influence of the chronic exposure, and there's little adaptive response induced. However at several dose points, pretreatment of CHSE/F fish cells with chronic radiation resulted in a radiosensitive response to a challenge dose of γ-ray radiation, and pretreatment of HaCaT cells resulted in no effect except for a slightly radioresistant response to the challenge radiation which was not significant. Conclusion: The results suggest that chronic low-dose radiation is not effective enough to induce adaptive response. There was a difference between human and fish cells and it may be important to consider results from multiple species before making conclusions about effects of chronic or low doses of radiation in the environment. The term “radiosensitive” or “adaptive” make no judgment about whether such responses are ultimately beneficial or harmful. - Highlights: • No obvious adaptive response is induced by chronic low-dose radiation from Ra-226. • Priming radiation from Ra-226 sensitized CHSE/F cells to the challenge radiation. • Linear model is inconsistent with current work using chronic low-dose radiation.« less

The alanine detector in BNCT dosimetry: Dose response in thermal and epithermal neutron fields

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

Schmitz, T., E-mail: schmito@uni-mainz.de; Bassler, N.; Blaickner, M.

Purpose: The response of alanine solid state dosimeters to ionizing radiation strongly depends on particle type and energy. Due to nuclear interactions, neutron fields usually also consist of secondary particles such as photons and protons of diverse energies. Various experiments have been carried out in three different neutron beams to explore the alanine dose response behavior and to validate model predictions. Additionally, application in medical neutron fields for boron neutron capture therapy is discussed. Methods: Alanine detectors have been irradiated in the thermal neutron field of the research reactor TRIGA Mainz, Germany, in five experimental conditions, generating different secondary particlemore » spectra. Further irradiations have been made in the epithermal neutron beams at the research reactors FiR 1 in Helsinki, Finland, and Tsing Hua open pool reactor in HsinChu, Taiwan ROC. Readout has been performed with electron spin resonance spectrometry with reference to an absorbed dose standard in a {sup 60}Co gamma ray beam. Absorbed doses and dose components have been calculated using the Monte Carlo codes FLUKA and MCNP. The relative effectiveness (RE), linking absorbed dose and detector response, has been calculated using the Hansen and Olsen alanine response model. Results: The measured dose response of the alanine detector in the different experiments has been evaluated and compared to model predictions. Therefore, a relative effectiveness has been calculated for each dose component, accounting for its dependence on particle type and energy. Agreement within 5% between model and measurement has been achieved for most irradiated detectors. Significant differences have been observed in response behavior between thermal and epithermal neutron fields, especially regarding dose composition and depth dose curves. The calculated dose components could be verified with the experimental results in the different primary and secondary particle fields. Conclusions: The alanine detector can be used without difficulty in neutron fields. The response has been understood with the model used which includes the relative effectiveness. Results and the corresponding discussion lead to the conclusion that application in neutron fields for medical purpose is limited by its sensitivity but that it is a useful tool as supplement to other detectors and verification of neutron source descriptions.« less

The role of land use/land cover dependent preferential flow paths in hydrologic response of steep and seasonal tropical catchments

NASA Astrophysics Data System (ADS)

Cheng, Y.; Ogden, F. L.; Zhu, J.

2017-12-01

The hydrologic behavior of steep catchments with saprolitic soils in the humid seasonal tropics varies with land use and cover, even when they have identical topographic index and slope distributions, underlying geology and soils textures. Forested catchments can produce more baseflow during the dry season compared to catchments containing substantial amount of pasture, the so-called "sponge effect". During rainfall events, forested catchments can also exhibit lower peak runoff rates and runoff efficiencies compared to pasture catchments. We hypothesize that hydrologic effects of land use arise from differences in preferential flow paths (PFPs) formed by biotic and abiotic factors in the upper one to two meters of soil and that land use effects on hydrological response are described by the relative amounts of forest and pasture within a catchment. Furthermore, we hypothesize that infiltration measurements at different scales allow estimation of PFP-related parameters. These hypotheses are tested by a model that explicitly simulates PFPs using distinct input parameter sets for forest and pasture. Runoff observations from three catchments with pasture, forest, and a mosaic of subsistence agricultural land covers allow model evaluation. Multiple objective criteria indicate that field measurements of infiltration enable PFP-relevant parameter identification and that pasture and forest end member parameter sets describe much of the observed difference. Analysis of water balance components and comparison between average transient water table depth and vertical PFP flow capacity demonstrate that the interplay of lateral and vertical PFPs contribute to the sponge-effect and can explain differences in peak runoff and runoff efficiency.

Movements of nonnative brook trout in relation to stream channel slope

Treesearch

Susan B. Adams; Christopher A. Frissell; Bruce E. Rieman

2000-01-01

Abstract.We provide new insights on the ability of naturalized brook trout Salvelinus fontinalis to ascend steep, headwater streams in the western USA. We tested hypotheses that upstream movements by brook trout are limited or absent in reaches of steep streams and are more prevalent and longer in gradually sloping streams. We compared brook trout...

Using Technology in Teacher Preparation: Two Mature Teacher Educators Negotiate the Steep Learning Curve

ERIC Educational Resources Information Center

Monroe, Eula; Tolman, Marvin

2004-01-01

This paper chronicles the ventures of two mature faculty members who continue to negotiate their own steep learning curves in helping teacher education students use current technology. It describes the scaffolding provided within the university setting for the faculty members' growth. Included are elements supported by a PT3 grant that have…

Hardwood silviculture and skyline yarding on steep slopes: economic and environmental impacts

Treesearch

John E. Baumgras; Chris B. LeDoux

1995-01-01

Ameliorating the visual and environmental impact associated with harvesting hardwoods on steep slopes will require the efficient use of skyline yarding along with silvicultural alternatives to clearcutting. In evaluating the effects of these alternatives on harvesting revenue, results of field studies and computer simulations were used to estimate costs and revenue for...

Ride-on lawnmowers warnings: slope measurements and safety-by-separation.

PubMed

Karnes, Edward W; Leonard, S David; Lenorovitz, David R

2012-01-01

Various single-rider open vehicles, such as lawnmowers, are susceptible to overturning on slopes that are too steep for them. Warnings have included separation from the vehicles and avoiding slopes that are too steep. A recommended maximum slope is commonly 15 degrees. However, many individuals cannot evaluate slopes just by sight. Some mower manufacturers have warned about too steep slopes and have provided slope gauges for users to determine the slopes in natural settings. This article evaluated the usefulness of such gauges for users who might be expected to need to evaluate slopes and the efficacy of a separation procedure for avoiding injuries. It was concluded that neither of these were likely to be successful and suggestions are made for alternative approaches.

Effects of low frequency ultrasonic treatment on the maturation of steeped greengage wine.

PubMed

Zheng, Xinhua; Zhang, Min; Fang, Zhongxiang; Liu, Yaping

2014-11-01

To accelerate wine maturation, low frequency ultrasonic waves of 28 kHz and 45 kHz were used to treat the steeped greengage wine. The contents of total acid, total ester, fusel oils and the wine chromaticity were determined before and after the ultrasonic treatment. The volatile compounds were analysed by GC-MS method, and the sensory quality was evaluated by panelist. The results indicated that ultrasonic treatment of the steeped greengage wine at 45 kHz 360 W for 30 min was effective to accelerate the aging process, where the fusel oils and alcohol compounds were significantly reduced and acid and ester compounds were significantly increased. Copyright © 2014 Elsevier Ltd. All rights reserved.

Antibody persistence of two pentavalent DTwP-HB-Hib vaccines to the age of 15-18 months, and response to the booster dose of quadrivalent DTwP-Hib vaccine.

PubMed

Sharma, Hitt; Yadav, Sangeeta; Lalwani, Sanjay; Kapre, Subhash; Jadhav, Suresh; Parekh, Sameer; Palkar, Sonali; Ravetkar, Satish; Bahl, Sunil; Kumar, Rakesh; Shewale, Sunil

2013-01-07

Antibody persistence in children following three doses of primary vaccination with diphtheria, tetanus, whole-cell-pertussis (DTwP), hepatitis B, and Haemophilus influenzae type b (Hib) vaccines (SIIL Pentavac vaccine vs. Easyfive(®) of Panacea Biotec), and response to the booster dose of DTwP-Hib (Quadrovax(®)) vaccine. Children who completed their primary immunization were assessed for antibodies at 15-18 months of age, and then given a booster dose of DTwP-Hib vaccine. Reactogenicity and safety of the booster dose was evaluated. Both pentavalent vaccines demonstrated a good immune response at 15-18 months. Following the booster dose, all vaccinated subjects achieved protective titers against diphtheria, tetanus and Hib, whereas the response to pertussis antigen was ~78%. Fever and irritability was noted in 24%, local pain in 51%, and swelling in 36% of the children following booster dose. Primary immunization with either pentavalent vaccine induced an excellent immunity lasting till the second year of life. A booster dose with DTwP-Hib (Quadrovax(®)) vaccine effectuated a good anamnestic response to all vaccine components, being specially strong for Hib in children previously vaccinated with SIIL liquid pentavalent vaccine (Pentavac(®)). Also, the safety profile of SIIL quadrivalent vaccine (Quadrovax(®)) administered as booster dose was acceptable. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2018-03-01

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

A Comparison of Dose-Response Models for the Parotid Gland in a Large Group of Head-and-Neck Cancer Patients

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

Houweling, Antonetta C., E-mail: A.Houweling@umcutrecht.n; Philippens, Marielle E.P.; Dijkema, Tim

2010-03-15

Purpose: The dose-response relationship of the parotid gland has been described most frequently using the Lyman-Kutcher-Burman model. However, various other normal tissue complication probability (NTCP) models exist. We evaluated in a large group of patients the value of six NTCP models that describe the parotid gland dose response 1 year after radiotherapy. Methods and Materials: A total of 347 patients with head-and-neck tumors were included in this prospective parotid gland dose-response study. The patients were treated with either conventional radiotherapy or intensity-modulated radiotherapy. Dose-volume histograms for the parotid glands were derived from three-dimensional dose calculations using computed tomography scans. Stimulatedmore » salivary flow rates were measured before and 1 year after radiotherapy. A threshold of 25% of the pretreatment flow rate was used to define a complication. The evaluated models included the Lyman-Kutcher-Burman model, the mean dose model, the relative seriality model, the critical volume model, the parallel functional subunit model, and the dose-threshold model. The goodness of fit (GOF) was determined by the deviance and a Monte Carlo hypothesis test. Ranking of the models was based on Akaike's information criterion (AIC). Results: None of the models was rejected based on the evaluation of the GOF. The mean dose model was ranked as the best model based on the AIC. The TD{sub 50} in these models was approximately 39 Gy. Conclusions: The mean dose model was preferred for describing the dose-response relationship of the parotid gland.« less

Microdosimetry measurements characterizing the radiation fields of 300 MeV/u 12C and 185 MeV/u 7Li pencil beams stopping in water

NASA Astrophysics Data System (ADS)

Martino, G.; Durante, M.; Schardt, D.

2010-06-01

In order to characterize the complex radiation field produced by heavy-ion beams in water, in particular the lateral dose fall-off and the radiation quality, microdosimetry measurements were performed at GSI Darmstadt using pencil-like beams of 300 MeV/u 12C and 185 MeV/u 7Li ions delivered by the heavy-ion synchrotron SIS-18. The ion beams (range in water about 17 cm) were stopped in the center of a 30 × 30 × 30 cm3 water phantom and their radiation field was investigated by in-phantom measurements using a tissue-equivalent proportional chamber (TEPC). The chamber was placed at 35 different positions in the central plane at various depths along the beam axis and at radial distances of 0, 1, 2, 5 and 10 cm. The off-axis measurements for both 12C and 7Li ions show very similar distributions of the lineal energy, all peaking between 1 and 10 \\rm keV\\,\\mu m^{-1} which is a typical range covered by secondary hydrogen fragments and neutrons. The radiation quality given by the dose-mean lineal energy \\overline{y}_D was found to be at a constant level of 1-2 \\rm keV\\,\\mu m^{-1} at radial distances larger than 2 cm. The relative absorbed dose at each position was obtained by integration of the measured spectra normalized to the number of incident primary beam particles. The results confirm that the lateral dose profile of heavy ions shows an extremely steep fall-off, with relative values of about 10-3, 10-4 and 10-5 at the 2, 5 and 10 cm distance from the beam axis, respectively. The depth-dose curves at a fixed distance from the beam axis slowly rise until they reach the depth of the Bragg peak, reflecting the build-up of secondary fragments with increasing penetration depth. The measured 12C dose profiles were found to be in good agreement with a similar experimental study at HIMAC (Japan).

Low doses of a neonicotinoid insecticide modify pheromone response thresholds of central but not peripheral olfactory neurons in a pest insect

PubMed Central

Rabhi, Kaouther K.; Deisig, Nina; Demondion, Elodie; Le Corre, Julie; Robert, Guillaume; Tricoire-Leignel, Hélène; Lucas, Philippe; Gadenne, Christophe; Anton, Sylvia

2016-01-01

Insect pest management relies mainly on neurotoxic insecticides, including neonicotinoids, leaving residues in the environment. There is now evidence that low doses of insecticides can have positive effects on pest insects by enhancing various life traits. Because pest insects often rely on sex pheromones for reproduction, and olfactory synaptic transmission is cholinergic, neonicotinoid residues could modify chemical communication. We recently showed that treatments with different sublethal doses of clothianidin could either enhance or decrease behavioural sex pheromone responses in the male moth, Agrotis ipsilon. We investigated now effects of the behaviourally active clothianidin doses on the sensitivity of the peripheral and central olfactory system. We show with extracellular recordings that both tested clothianidin doses do not influence pheromone responses in olfactory receptor neurons. Similarly, in vivo optical imaging does not reveal any changes in glomerular response intensities to the sex pheromone after clothianidin treatments. The sensitivity of intracellularly recorded antennal lobe output neurons, however, is upregulated by a lethal dose 20 times and downregulated by a dose 10 times lower than the lethal dose 0. This correlates with the changes of behavioural responses after clothianidin treatment and suggests the antennal lobe as neural substrate involved in clothianidin-induced behavioural changes. PMID:26842577

Chernobyl Doses. Volume 1. Analysis of Forest Canopy Radiation Response from Multispectral Imagery and the Relationship to Doses

DTIC Science & Technology

1994-09-01

AD-A284 746 Defense Nuclear Agency Alexandria, VA 22310-3398 DNA-TR-92-37-V1 Chernobyl Doses Volume 1-Analysis of Forest Canopy Radiation Response...REPORT DATE 3. REPORT TYPE AND DATES COVERED 940901 Technical 870929- 930930 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Chernobyl Doses Volume 1-Analysis of...volume of the report Chernobyl Doses presents details of a new, quantitative method for remotely sensing ionizing radiation dose to vegetation

EFFECTS OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN ...

EPA Pesticide Factsheets

While the effect that TCDD has on humoral immunity in the mouse has been well documented, it has not been for the rat. n this study, the effect that TCDD has on the antibody plaque-forming cell (PFC) response to sheep red blood cells (SRBC) in adult female B6C3F1 mice and F344 rats was compared. ice or rats were given a single intraperitoneal injection of TCDD at doses ranging from 0.1 to 30 ug/kg, 7 days prior to intravenous immunization with SRBC. our days later the PFC response to SRBC was determined. ice showed a dose related suppression of the PFC response, with an ED50 of 0.71 ug/kg TCDD. n contrast, TCDD failed to suppress and in fact enhanced the PFC response to SRBC in rats at doses as high as 30 ug/kg. he inability of TCDD to suppress the PFC response in rats was unrelated to hepatic CYP1A1 and CYP1A2 induction which was detectable at doses of 1 and 0.3 ug/kg TCDD, respectively. here was no shift in the time to peak PFC response in rats dosed with TCDD, nor was the failure of TCDD to suppress the PFC response in rats related to gender or strain. henotypic analysis of thymocytes and splenic lymphocytes from TCDD-dosed (i.e., 3, 10 or 30 ug/kg) and SREC-immunized mice and rats revealed that CD4-CD8+ splenocytes were reduced in a dose related manner in rats only and that this reduction in CD4-CD8+ was accompanied by a dose related increase in IgM+ splenocytes. hese results demonstrate species differences in the effect of TCDD on the PFC response to SRBC w

Linear response theory for annealing of radiation damage in semiconductor devices

NASA Technical Reports Server (NTRS)

Litovchenko, Vitaly

1988-01-01

A theoretical study of the radiation/annealing response of MOS ICs is described. Although many experiments have been performed in this field, no comprehensive theory dealing with radiation/annealing response has been proposed. Many attempts have been made to apply linear response theory, but no theoretical foundation has been presented. The linear response theory outlined here is capable of describing a broad area of radiation/annealing response phenomena in MOS ICs, in particular, both simultaneous irradiation and annealing, as well as short- and long-term annealing, including the case when annealing is nearing completion. For the first time, a simple procedure is devised to determine the response function from experimental radiation/annealing data. In addition, this procedure enables us to study the effect of variable temperature and dose rate, effects which are of interest in spaceflight. In the past, the shift in threshold potential due to radiation/annealing has usually been assumed to depend on one variable: the time lapse between an impulse dose and the time of observation. While such a suggestion of uniformity in time is certainly true for a broad range of radiation annealing phenomena, it may not hold for some ranges of the variables of interest (temperature, dose rate, etc.). A response function is projected which is dependent on two variables: the time of observation and the time of the impulse dose. This dependence on two variables allows us to extend the theory to the treatment of a variable dose rate. Finally, the linear theory is generalized to the case in which the response is nonlinear with impulse dose, but is proportional to some impulse function of dose. A method to determine both the impulse and response functions is presented.

Toward a unified approach to dose-response modeling in ecotoxicology.

PubMed

Ritz, Christian

2010-01-01

This study reviews dose-response models that are used in ecotoxicology. The focus lies on clarification of differences and similarities between models, and as a side effect, their different guises in ecotoxicology are unravelled. A look at frequently used dose-response models reveals major discrepancies, among other things in naming conventions. Therefore, there is a need for a unified view on dose-response modeling in order to improve the understanding of it and to facilitate communication and comparison of findings across studies, thus realizing its full potential. This study attempts to establish a general framework that encompasses most dose-response models that are of interest to ecotoxicologists in practice. The framework includes commonly used models such as the log-logistic and Weibull models, but also features entire suites of models as found in various guidance documents. An outline on how the proposed framework can be implemented in statistical software systems is also provided.

Occupational Exposure to Diesel Motor Exhaust and Lung Cancer: A Dose-Response Relationship Hidden by Asbestos Exposure Adjustment? The ICARE Study

PubMed Central

Matrat, Mireille; Guida, Florence; Cénée, Sylvie; Févotte, Joelle; Carton, Matthieu; Cyr, Diane; Menvielle, Gwenn; Paget-Bailly, Sophie; Radoï, Loredana; Schmaus, Annie; Bara, Simona; Velten, Michel; Luce, Danièle; Stücker, Isabelle; The Icare Study Group

2015-01-01

Background. In a French large population-based case-control study we investigated the dose-response relationship between lung cancer and occupational exposure to diesel motor exhaust (DME), taking into account asbestos exposure. Methods. Exposure to DME was assessed by questionnaire. Asbestos was taken into account through a global indicator of exposure to occupational carcinogens or by a specific JEM. Results. We found a crude dose response relationship with most of the indicators of DME exposure, including with the cumulative exposure index. All results were affected by adjustment for asbestos exposure. The dose response relationships between DME and lung cancer were observed among subjects never exposed to asbestos. Conclusions. Exposure to DME and to asbestos is frequently found among the same subjects, which may explain why dose-response relationships in previous studies that adjusted for asbestos exposure were inconsistent. PMID:26425123

Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

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

Feinendegen, L.E.; Bond, V.P.; Sondhaus, C.A.

This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced metabolic changes that induce mechanisms of DNA damage mitigation, which do not operate at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in themore » low-dose region. This suggests that the LNT hypothesis should be reexamined. This paper aims at demonstrating tissue effects as an expression of cellular responses, both damaging and defensive, in relation to the energy deposited in cell mass, by use of microdosimetric concepts.« less

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.

Evaluation of ifosfamide salvage therapy for metastatic canine osteosarcoma.

PubMed

Batschinski, K; Dervisis, N G; Kitchell, B E

2014-12-01

A retrospective study was performed to assess toxicity and response rate of ifosfamide salvage treatment for dogs diagnosed with metastatic osteosarcoma (OSA). Dogs diagnosed with OSA and previously treated with standard chemotherapy were included in the study. Nineteen dogs met the inclusion criteria, and 17 dogs were evaluable for response. Ifosfamide doses ranged from 375 to 425 mg m(-2) (median dose 375 mg m(-2)), with a median of two doses administered per dog (range 1-7 doses). The overall response to ifosfamide was 11.8% [complete response (CR) = 1/17, partial response (PR) = 1/17, stable disease (SD) = 2/17, progressive disease (PD) = 13/17]. Two dogs were hospitalized due to ifosfamide toxicosis. The median survival duration from the first dose of ifosfamide to death was 95 days. Ifosfamide was well tolerated, but minor anti-tumour activity was observed. © 2012 Blackwell Publishing Ltd.

The dose-response ratio in electroconvulsive therapy a preliminary study.

PubMed

Price, T R; Mackenzie, T B; Tucker, G J; Culver, C

1978-09-01

To investigate pretreatment patient variables that might correlate with dose-response characteristics of electroconvulsive therapy (ECT) and treatment outcomes, 14 patients were assessed on a daily basis, before and during treatment, using self-report affective scales, three simple paper-and-pencil tests of cognitive function,and finger-tapping speed. From these data, dose-response ratios and treatment outcome measures were derived. The dose-response ratio of ECT was found to correlate with age--the younger the patient, the more favorable the ratio. This finding is discussed in terms of the known relationships between brain monoamine oxidase levels and age, and the established relationship between seizure duration and treatment efficacy. The dose-response ratio over the first two electroconvulsive treatments as well as lesser degrees of initial congnitive and greater degrees of initial affective impairment correlated strongly with greater overall affective improvement. Some clinical and research implications of these findings are discussed.

Pervasive phosphorus limitation of tree species but not communities in tropical forests

NASA Astrophysics Data System (ADS)

Turner, Benjamin L.; Brenes-Arguedas, Tania; Condit, Richard

2018-03-01

Phosphorus availability is widely assumed to limit primary productivity in tropical forests, but support for this paradigm is equivocal. Although biogeochemical theory predicts that phosphorus limitation should be prevalent on old, strongly weathered soils, experimental manipulations have failed to detect a consistent response to phosphorus addition in species-rich lowland tropical forests. Here we show, by quantifying the growth of 541 tropical tree species across a steep natural phosphorus gradient in Panama, that phosphorus limitation is widespread at the level of individual species and strengthens markedly below a threshold of two parts per million exchangeable soil phosphate. However, this pervasive species-specific phosphorus limitation does not translate into a community-wide response, because some species grow rapidly on infertile soils despite extremely low phosphorus availability. These results redefine our understanding of nutrient limitation in diverse plant communities and have important implications for attempts to predict the response of tropical forests to environmental change.

Accepting responsibility for long-term care--a paradox in times of a global nursing shortage?

PubMed

Hirschfeld, Miriam J

2009-03-01

Need for long-term care (LTC) is increasing globally, and nurses have a professional imperative to address the growing need for long-term care (LTC). The author reviews the effect of globalization and the epidemiologic transition upon the growing need for LTC. I also summarize the lessons learned in the developing world, as well as in the industrialized world, based on the existing research evidence. The purpose of this paper is to explain the need for nursing as a profession to accept responsibility for LTC as part of nursing's raison d'etre, despite the global nursing shortage. This includes responsibility for innovative policy, health service, practice, research, nursing education development, and health promotion, because prevention is key to slowing the steep increase in LTC needs. Nurses must develop strategies for clinical practice, management, education, and research in order to increase our ability to meet future needs for LTC.

Architecture of a minimal signaling pathway explains the T-cell response to a 1 million-fold variation in antigen affinity and dose.

PubMed

Lever, Melissa; Lim, Hong-Sheng; Kruger, Philipp; Nguyen, John; Trendel, Nicola; Abu-Shah, Enas; Maini, Philip Kumar; van der Merwe, Philip Anton; Dushek, Omer

2016-10-25

T cells must respond differently to antigens of varying affinity presented at different doses. Previous attempts to map peptide MHC (pMHC) affinity onto T-cell responses have produced inconsistent patterns of responses, preventing formulations of canonical models of T-cell signaling. Here, a systematic analysis of T-cell responses to 1 million-fold variations in both pMHC affinity and dose produced bell-shaped dose-response curves and different optimal pMHC affinities at different pMHC doses. Using sequential model rejection/identification algorithms, we identified a unique, minimal model of cellular signaling incorporating kinetic proofreading with limited signaling coupled to an incoherent feed-forward loop (KPL-IFF) that reproduces these observations. We show that the KPL-IFF model correctly predicts the T-cell response to antigen copresentation. Our work offers a general approach for studying cellular signaling that does not require full details of biochemical pathways.

Radiation Dose-Response Relationships and Risk Assessment

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

Strom, Daniel J.

The notion of a dose-response relationship was probably invented shortly after the discovery of poisons, the invention of alcoholic beverages, and the bringing of fire into a confined space in the forgotten depths of ancient prehistory. The amount of poison or medicine ingested can easily be observed to affect the behavior, health, or sickness outcome. Threshold effects, such as death, could be easily understood for intoxicants, medicine, and poisons. As Paracelsus (1493-1541), the 'father' of modern toxicology said, 'It is the dose that makes the poison.' Perhaps less obvious is the fact that implicit in such dose-response relationships is alsomore » the notion of dose rate. Usually, the dose is administered fairly acutely, in a single injection, pill, or swallow; a few puffs on a pipe; or a meal of eating or drinking. The same amount of intoxicants, medicine, or poisons administered over a week or month might have little or no observable effect. Thus, before the discovery of ionizing radiation in the late 19th century, toxicology ('the science of poisons') and pharmacology had deeply ingrained notions of dose-response relationships. This chapter demonstrates that the notion of a dose-response relationship for ionizing radiation is hopelessly simplistic from a scientific standpoint. While useful from a policy or regulatory standpoint, dose-response relationships cannot possibly convey enough information to describe the problem from a quantitative view of radiation biology, nor can they address societal values. Three sections of this chapter address the concepts, observations, and theories that contribute to the scientific input to the practice of managing risks from exposure to ionizing radiation. The presentation begins with irradiation regimes, followed by responses to high and low doses of ionizing radiation, and a discussion of how all of this can inform radiation risk management. The knowledge that is really needed for prediction of individual risk is presented. The chapter ends with conclusions and recommendations.« less

Harnessing the theoretical foundations of the exponential and beta-Poisson dose-response models to quantify parameter uncertainty using Markov Chain Monte Carlo.

PubMed

Schmidt, Philip J; Pintar, Katarina D M; Fazil, Aamir M; Topp, Edward

2013-09-01

Dose-response models are the essential link between exposure assessment and computed risk values in quantitative microbial risk assessment, yet the uncertainty that is inherent to computed risks because the dose-response model parameters are estimated using limited epidemiological data is rarely quantified. Second-order risk characterization approaches incorporating uncertainty in dose-response model parameters can provide more complete information to decisionmakers by separating variability and uncertainty to quantify the uncertainty in computed risks. Therefore, the objective of this work is to develop procedures to sample from posterior distributions describing uncertainty in the parameters of exponential and beta-Poisson dose-response models using Bayes's theorem and Markov Chain Monte Carlo (in OpenBUGS). The theoretical origins of the beta-Poisson dose-response model are used to identify a decomposed version of the model that enables Bayesian analysis without the need to evaluate Kummer confluent hypergeometric functions. Herein, it is also established that the beta distribution in the beta-Poisson dose-response model cannot address variation among individual pathogens, criteria to validate use of the conventional approximation to the beta-Poisson model are proposed, and simple algorithms to evaluate actual beta-Poisson probabilities of infection are investigated. The developed MCMC procedures are applied to analysis of a case study data set, and it is demonstrated that an important region of the posterior distribution of the beta-Poisson dose-response model parameters is attributable to the absence of low-dose data. This region includes beta-Poisson models for which the conventional approximation is especially invalid and in which many beta distributions have an extreme shape with questionable plausibility. © Her Majesty the Queen in Right of Canada 2013. Reproduced with the permission of the Minister of the Public Health Agency of Canada.

Laser-based irradiation apparatus and method to measure the functional dose-rate response of semiconductor devices

DOEpatents

Horn, Kevin M [Albuquerque, NM

2008-05-20

A broad-beam laser irradiation apparatus can measure the parametric or functional response of a semiconductor device to exposure to dose-rate equivalent infrared laser light. Comparisons of dose-rate response from before, during, and after accelerated aging of a device, or from periodic sampling of devices from fielded operational systems can determine if aging has affected the device's overall functionality. The dependence of these changes on equivalent dose-rate pulse intensity and/or duration can be measured with the apparatus. The synchronized introduction of external electrical transients into the device under test can be used to simulate the electrical effects of the surrounding circuitry's response to a radiation exposure while exposing the device to dose-rate equivalent infrared laser light.

Linearity and reproducibility response of Fricke dosimetry for low energy X-Ray beam

NASA Astrophysics Data System (ADS)

Mantuano, A.; de Amorim, G. J.; David, M. G.; Rosado, P. H. G.; Salata, C.; Magalhães, L. A. G.; deAlmeida, C. E.

2018-03-01

The Fricke dosimeter is the most used, liquid chemical dosimeter. It has been shown to be a feasible option for the absorbed dose standard. The present work aims to determinate a dose-response curve of Fricke solution using different doses and reproducibility test comparing the calculated dose to Fricke solution and Ionizing Chamber. Tests were performed using an X-ray irradiator for biological research at Radiological Science Laboratory (LCR/UERJ). The results showed a linear response to different doses of type A uncertainties from 0.08 to 1.2%. Reproducibility test showed type A uncertainties of 0.16% to the dosimeter.

SU-E-T-264: Preliminary Results On New Optically Stimulated Luminescent Materials for Proton Therapy Dosimetry

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

Doull, B; Zheng, Y; Procure Proton Therapy Center, Oklahoma City, OK

2014-06-01

Purpose: The objective of this work is to test the premise that luminescence materials with less under-response to proton beams can be identified by testing their dose response to low-LET radiation. The goal is to develop new Optically Stimulated Luminescence (OSL) materials with improved response for proton therapy dosimetry. Methods: We first measured the dose response of new OSL materials, synthesized in our laboratory, to low-LET radiation (beta rays from a {sup 90}Sr/{sup 90}Y source) and selected two materials having different OSL saturation characteristics and good dosimetric properties, namely MgB4O7:Ce,Li and MgO:Li. Commercial Al2O3:C was also used for comparison. Thesemore » materials were then irradiated at several depths along a pristine proton beam. The luminescence responses of the materials, relative to the entrance response, were compared with the depth dose profile measured by a multiple-layer ion chamber. Results: The OSL signals of MgB4O7:Ce,Li and MgO:Li were characterized for signal stability, dose response, and response to a clinical proton beam. The materials were also compared with the commercial Al2O3:C. The signals from both MgB4O7:Ce,Li and MgO:Li were relatively stable after a one day delay following irradiation. The low-LET dose response of the materials showed that, over the dose range investigated (up to ∼800 Gy), MgB4O7:Ce,Li did not saturate, whereas MgO:Li and Al2O3:C saturated at doses of ∼100 Gy. MgB4O7:Ce,Li showed less underresponse to proton beams than MgO:Li and Al2O3:C. Conclusion: In general the material with the highest saturation doses for low-LET radiation (MgB4O7:Ce,Li) showed the least under-response to proton beams, which suggests that it may be possible to develop better OSL materials for proton dosimetry if the dose response can be controlled during synthesis. Nevertheless, the degree in which the response to proton beams can be controlled remains to be determined. The research is funded by the Oklahoma Center for the Advancement of Science and Technology (OCAST), project number HR12-055.« less

Dose-Dependent Pheromone Responses of Ips pini, Orthotomicus latiden (Coleoptera: Scolytidae), and associates in stands of lodgepole pine

Treesearch

Daniel R. Miller; John H. Borden; B. Staffan Lidgren

2005-01-01

We conducted four behavioral choice tests in stands of mature lodgepole pine in British Columbia, from 1988 to 1991, to determine the dose-dependent responses of Orthotomicus latidens (LeConte) and Ips pini (Say) to their respective pheromones. Dose-dependent responses were exhibited by I. pini to (±)-ipsdienol and lanierone, with...

Enhanced Medial Collateral Ligament Healing using Mesenchymal Stem Cells: Dosage Effects on Cellular Response and Cytokine Profile

PubMed Central

Saether, Erin E.; Chamberlain, Connie S.; Leiferman, Ellen M.; Kondratko-Mittnacht, Jaclyn R.; Li, Wan Ju; Brickson, Stacey L.; Vanderby, Ray

2013-01-01

Mesenchymal stem cells (MSCs) have potential therapeutic applications for musculoskeletal injuries due to their ability to differentiate into several tissue cell types and modulate immune and inflammatory responses. These immune-modulatory properties were examined in vivo during early stage rat medial collateral ligament healing. Two different cell doses (low dose 1×106 or high dose 4×106 MSCs) were administered at the time of injury and compared with normal ligament healing at days 5 and 14 post-injury. At both times, the high dose MSC group demonstrated a significant decrease in M2 macrophages compared to controls. At day 14, fewer M1 macrophages were detected in the low dose group compared to the high dose group. These results, along with significant changes in procollagen I, proliferating cells, and endothelialization suggest that MSCs can alter the cellular response during healing in a dose-dependent manner. The higher dose ligaments also had increased expression of several pro-inflammatory cytokines at day 5 (IL-1β, IFNγ, IL-2) and increased expression of IL-12 at day 14. Mechanical testing at day 14 revealed increased failure strength and stiffness in low dose ligaments compared to controls. Based on these improved mechanical properties, MSCs enhanced functional healing when applied at a lower dose. Different doses of MSCs uniquely affected the cellular response and cytokine expression in healing ligaments. Interestingly, the lower dose of cells proved to be most effective in improving functional properties. PMID:24174129

The question of nonlinearity in the dose-response relation between particulate matter air pollution and mortality: can Akaike's Information Criterion be trusted to take the right turn?

PubMed

Roberts, Steven; Martin, Michael A

2006-12-15

The shape of the dose-response relation between particulate matter air pollution and mortality is crucial for public health assessment, and departures of this relation from linearity could have important regulatory consequences. A number of investigators have studied the shape of the particulate matter-mortality dose-response relation and concluded that the relation could be adequately described by a linear model. Some of these researchers examined the hypothesis of linearity by comparing Akaike's Information Criterion (AIC) values obtained under linear, piecewise linear, and spline alternative models. However, at the current time, the efficacy of the AIC in this context has not been assessed. The authors investigated AIC as a means of comparing competing dose-response models, using data from Cook County, Illinois, for the period 1987-2000. They found that if nonlinearities exist, the AIC is not always successful in detecting them. In a number of the scenarios considered, AIC was equivocal, picking the correct simulated dose-response model about half of the time. These findings suggest that further research into the shape of the dose-response relation using alternative model selection criteria may be warranted.

A randomized, double-blind, placebo-controlled, dose-ranging study of lisdexamfetamine dimesylate augmentation for major depressive disorder in adults with inadequate response to antidepressant therapy

PubMed Central

Richards, Cynthia; Iosifescu, Dan V; Mago, Rajnish; Sarkis, Elias; Reynolds, James; Geibel, Brooke; Dauphin, Matthew

2017-01-01

Background: This randomized, double-blind, placebo-controlled study evaluated dose-response relationships of lisdexamfetamine dimesylate when used as augmentation for major depressive disorder in individuals exhibiting inadequate responses to antidepressant monotherapy. Methods: Eligible adults (18–65 years) were assigned to antidepressant monotherapy (escitalopram or venlafaxine extended-release) plus lisdexamfetamine dimesylate-matching placebo during an eight-week single-blind lead-in phase. Participants meeting randomization criteria were randomized (1:1:1:1:1) to eight weeks of lisdexamfetamine dimesylate (10, 30, 50, or 70 mg) or placebo while maintaining antidepressant therapy. Dose-responses for changes from augmentation baseline to week 16/early termination for Montgomery-Åsberg Depression Rating Scale total score (primary efficacy endpoint) and vital signs (systolic and diastolic blood pressure and pulse) were assessed using multiple comparisons procedures with modeling. Results: For Montgomery-Åsberg Depression Rating Scale total score change, no significant dose-responses were observed for any candidate dose-response curve (all p>0.10). In the dose-response evaluable population, least squares mean (90% confidence interval) treatment differences versus placebo for Montgomery-Åsberg Depression Rating Scale total score change at week 16 were −1.4 (−3.9, 1.2), 0.1 (−2.5, 2.7), −0.7 (−3.4, 2.0), and −0.9 (−3.5, 1.6) with 10, 30, 50, and 70 mg lisdexamfetamine dimesylate, respectively. For all vital sign parameters, lisdexamfetamine dimesylate exhibited significant dose-responses for all candidate dose-response curves (all p<0.10), with increases observed as lisdexamfetamine dimesylate dose increased; a linear relationship provided the best fit. Mean±standard deviation changes from augmentation baseline for systolic and diastolic blood pressure and pulse at week 16/early termination were −0.7±9.90 and −0.3±7.24 mm Hg and 0.2±10.57 bpm with placebo and were 1.9±9.47 and 0.8±7.40 mm Hg and 3.6±9.74 bpm with lisdexamfetamine dimesylate (all doses combined). The safety and tolerability profile of lisdexamfetamine dimesylate was consistent with previous studies. Conclusions: Lisdexamfetamine dimesylate augmentation did not provide benefit over placebo in adults with inadequate responses to antidepressant monotherapy based on the assessed efficacy measures. PMID:28857719

Evaluation of the efficacy and safety of rivaroxaban using a computer model for blood coagulation.

PubMed

Burghaus, Rolf; Coboeken, Katrin; Gaub, Thomas; Kuepfer, Lars; Sensse, Anke; Siegmund, Hans-Ulrich; Weiss, Wolfgang; Mueck, Wolfgang; Lippert, Joerg

2011-04-22

Rivaroxaban is an oral, direct Factor Xa inhibitor approved in the European Union and several other countries for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery and is in advanced clinical development for the treatment of thromboembolic disorders. Its mechanism of action is antithrombin independent and differs from that of other anticoagulants, such as warfarin (a vitamin K antagonist), enoxaparin (an indirect thrombin/Factor Xa inhibitor) and dabigatran (a direct thrombin inhibitor). A blood coagulation computer model has been developed, based on several published models and preclinical and clinical data. Unlike previous models, the current model takes into account both the intrinsic and extrinsic pathways of the coagulation cascade, and possesses some unique features, including a blood flow component and a portfolio of drug action mechanisms. This study aimed to use the model to compare the mechanism of action of rivaroxaban with that of warfarin, and to evaluate the efficacy and safety of different rivaroxaban doses with other anticoagulants included in the model. Rather than reproducing known standard clinical measurements, such as the prothrombin time and activated partial thromboplastin time clotting tests, the anticoagulant benchmarking was based on a simulation of physiologically plausible clotting scenarios. Compared with warfarin, rivaroxaban showed a favourable sensitivity for tissue factor concentration inducing clotting, and a steep concentration-effect relationship, rapidly flattening towards higher inhibitor concentrations, both suggesting a broad therapeutic window. The predicted dosing window is highly accordant with the final dose recommendation based upon extensive clinical studies.

Evaluation of the Efficacy and Safety of Rivaroxaban Using a Computer Model for Blood Coagulation

PubMed Central

Burghaus, Rolf; Coboeken, Katrin; Gaub, Thomas; Kuepfer, Lars; Sensse, Anke; Siegmund, Hans-Ulrich; Weiss, Wolfgang; Mueck, Wolfgang; Lippert, Joerg

2011-01-01

Rivaroxaban is an oral, direct Factor Xa inhibitor approved in the European Union and several other countries for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery and is in advanced clinical development for the treatment of thromboembolic disorders. Its mechanism of action is antithrombin independent and differs from that of other anticoagulants, such as warfarin (a vitamin K antagonist), enoxaparin (an indirect thrombin/Factor Xa inhibitor) and dabigatran (a direct thrombin inhibitor). A blood coagulation computer model has been developed, based on several published models and preclinical and clinical data. Unlike previous models, the current model takes into account both the intrinsic and extrinsic pathways of the coagulation cascade, and possesses some unique features, including a blood flow component and a portfolio of drug action mechanisms. This study aimed to use the model to compare the mechanism of action of rivaroxaban with that of warfarin, and to evaluate the efficacy and safety of different rivaroxaban doses with other anticoagulants included in the model. Rather than reproducing known standard clinical measurements, such as the prothrombin time and activated partial thromboplastin time clotting tests, the anticoagulant benchmarking was based on a simulation of physiologically plausible clotting scenarios. Compared with warfarin, rivaroxaban showed a favourable sensitivity for tissue factor concentration inducing clotting, and a steep concentration–effect relationship, rapidly flattening towards higher inhibitor concentrations, both suggesting a broad therapeutic window. The predicted dosing window is highly accordant with the final dose recommendation based upon extensive clinical studies. PMID:21526168

Technical Note: PRESAGE three-dimensional dosimetry accurately measures Gamma Knife output factors

PubMed Central

Klawikowski, Slade J.; Yang, James N.; Adamovics, John; Ibbott, Geoffrey S.

2014-01-01

Small-field output factor measurements are traditionally very difficult because of steep dose gradients, loss of lateral electronic equilibrium, and dose volume averaging in finitely sized detectors. Three-dimensional (3D) dosimetry is ideal for measuring small output factors and avoids many of these potential challenges of point and two-dimensional detectors. PRESAGE 3D polymer dosimeters were used to measure the output factors for the 4 mm and 8 mm collimators of the Leksell Perfexion Gamma Knife radiosurgery treatment system. Discrepancies between the planned and measured distance between shot centers were also investigated. A Gamma Knife head frame was mounted onto an anthropomorphic head phantom. Special inserts were machined to hold 60 mm diameter, 70 mm tall cylindrical PRESAGE dosimeters. The phantom was irradiated with one 16 mm shot and either one 4 mm or one 8 mm shot, to a prescribed dose of either 3 Gy or 4 Gy to the 50% isodose line. The two shots were spaced between 30 mm and 60 mm apart and aligned along the central axis of the cylinder. The Presage dosimeters were measured using the DMOS-RPC optical CT scanning system. Five independent 4 mm output factor measurements fell within 2% of the manufacturer’s Monte Carlo simulation-derived nominal value, as did two independent 8 mm output factor measurements. The measured distances between shot centers varied by ± 0.8 mm with respect to the planned shot displacements. On the basis of these results, we conclude that PRESAGE dosimetry is excellently suited to quantify the difficult-to-measure Gamma Knife output factors. PMID:25368961

Rill and gully formation following the 2010 Schultz Fire

Treesearch

Daniel G. Neary; Karen A. Koestner; Ann Youberg; Peter E. Koestner

2011-01-01

The Schultz Fire burned 6,100 ha on the eastern slopes of the San Francisco Peaks across moderate to very steep ponderosa pine and mixed conifer watersheds. There was widespread occurrence of high severity fire, with several watersheds classified as over 50% high severity. This resulted in moderate to severe water repellency in most soils, especially those on steep...

A sediment transport model for incision of gullies on steep topography

Treesearch

Erkan Istanbulluoglu; David G. Tarboton; Robert T. Pack; Charles H. Luce

2003-01-01

We have conducted surveys of gullies that developed in a small, steep watershed in the Idaho Batholith after a severe wildfire followed by intense precipitation. We measured gully length and cross sections to estimate the volumes of sediment loss due to gully formation. These volume estimates are assumed to provide an estimate of sediment transport capacity at each...

Productivity and cost estimators for conventional ground-based skidding on steep terrain using preplanned skid roads

Treesearch

Michael D. Erickson; Curt C. Hassler; Chris B. LeDoux

1991-01-01

Continuous time and motion study techniques were used to develop productivity and cost estimators for the skidding component of ground-based logging systems, operating on steep terrain using preplanned skid roads. Comparisons of productivity and costs were analyzed for an overland random access skidding method, verses a skidding method utilizing a network of preplanned...

Water resources of the River Rouge basin southeastern Michigan

USGS Publications Warehouse

Knutilla, R.L.

1971-01-01

The River Rouge basin is characterized by moderately hilly topography to the northwest graduating to a relatively level land surface to the south east.Stream gradients near the northwestern basin divide are relatively steep; but many become more steep in reaches where they cross beach lines of former glacial lakes. In the lower reaches of the River Rouge gradients lessen.

Fast Back-Propagation Learning Using Steep Activation Functions and Automatic Weight

Treesearch

Tai-Hoon Cho; Richard W. Conners; Philip A. Araman

1992-01-01

In this paper, several back-propagation (BP) learning speed-up algorithms that employ the ãgainä parameter, i.e., steepness of the activation function, are examined. Simulations will show that increasing the gain seemingly increases the speed of convergence and that these algorithms can converge faster than the standard BP learning algorithm on some problems. However,...

F-16 MMC Strafe in Mountainous Terrain

DTIC Science & Technology

2016-04-01

19 Figure 10. Steep fast (480 KIAS ) high-angle strafe...a fast (480 KIAS in this example) approach varies from the recovery radius (4000 feet in this case) and down track range prior to recovery initiation...Steep fast (480 KIAS ) high-angle strafe Alternate Analysis The F-16 community, to some extent, has adopted high-angle strafe as the de facto strafe

Green infrastructure in high-rise residential development on steep slopes in city of Vladivostok

NASA Astrophysics Data System (ADS)

Kopeva, Alla; Ivanova, Olga; Khrapko, Olga

2018-03-01

The purpose of this study is to identify the facilities of green infrastructure that are able to improve living conditions in an urban environment in high-rise residential apartments buildings on steep slopes in the city of Vladivostok. Based on the analysis of theoretical sources and practices that can be observed in the world, green infrastructure facilities have been identified. These facilities meet the criteria of the sustainable development concept, and can be used in the city of Vladivostok. They include green roofs, green walls, and greening of disturbed slopes. All the existing high-rise apartments buildings situated on steep slopes in the city of Vladivostok, have been studied. It is concluded that green infrastructure is necessary to be used in new projects connected with designing and constructing of residential apartments buildings on steep slopes, as well as when upgrading the projects that have already been implemented. That will help to regulate the ecological characteristics of the sites. The results of the research can become a basis for increasing the sustainability of the habitat, and will facilitate the adoption of decisions in the field of urban design and planning.

The impact of steeping, germination and hydrothermal processing of wheat (Triticum aestivum L.) grains on phytate hydrolysis and the distribution, speciation and bio-accessibility of iron and zinc elements.

PubMed

Lemmens, Elien; De Brier, Niels; Spiers, Kathryn M; Ryan, Chris; Garrevoet, Jan; Falkenberg, Gerald; Goos, Peter; Smolders, Erik; Delcour, Jan A

2018-10-30

Chelation of iron and zinc in wheat as phytates lowers their bio-accessibility. Steeping and germination (15 °C, 120 h) lowered phytate content from 0.96% to only 0.81% of initial dry matter. A multifactorial experiment in which (steeped/germinated) wheat was subjected to different time (2-24 h), temperature (20-80 °C) and pH (2.0-8.0) conditions showed that hydrothermal processing of germinated (15 °C, 120 h) wheat at 50 °C and pH 3.8 for 24 h reduced phytate content by 95%. X-ray absorption near-edge structure imaging showed that it indeed abolished chelation of iron to phytate. It also proved that iron was oxidized during steeping, germination and hydrothermal processing. It was further shown that zinc and iron bio-accessibility were respectively 3 and 5% in wheat and 27 and 37% in hydrothermally processed wheat. Thus, hydrothermal processing of (germinated) wheat paves the way for increasing elemental bio-accessibility in whole grain-based products. Copyright © 2018 Elsevier Ltd. All rights reserved.

Geometrical effects of conventional and digital prosthodontic planning wax-ups on lateral occlusal contact number, contact area, and steepness.

PubMed

Abduo, Jaafar

2017-01-01

This study evaluated and compared the effect of conventional and digital wax-ups on three lateral occlusion variables: contact number, contact area, and steepness. Dental casts of 10 patients with Angle Class I relationship were included in the study. All patients required fixed prosthodontic treatment that would affect lateral occlusion. The casts of all patients received conventional and digital wax-ups. For pretreatment, conventional wax-up, and digital wax-up casts, contact number, contact area, and occlusion steepness were measured at four lateral positions, that is, at excursions of 0.5, 1.0, 2.0, and 3.0 mm from maximal intercuspation. Lateral occlusion scheme variables were affected by use of diagnostic wax-ups. For all types of casts, contact number decreased as excursion increased. The two types of wax-ups had similar contact number patterns, and contact number was significantly greater for these casts than for pretreatment casts in the earlier stages of excursion. Similarly, contact area gradually decreased with increasing excursion in the pretreatment and conventional and digital wax-up casts. There was only a minimal decrease in occlusion steepness as excursion increased. However, lateral occlusion was generally steeper for digital wax-up casts.

Methylphenidate has nonlinear dose effects on cued response inhibition in adults but not adolescents.

PubMed

Simon, Nicholas W; Moghaddam, Bita

2017-01-01

Ongoing development of the dopamine system during adolescence may provide a partial mechanism for behavioral and psychiatric vulnerabilities. Despite early evidence for a hyperactive adolescent dopaminergic system, recent data suggest that adolescent dopamine may be functionally hypoactive compared to in adults. While this distinction has been established in response to dopaminergic drugs and natural rewards, little is known about age-related differences in cognitive efficacy of dopaminergic drugs. Using a recently established Cued Response Inhibition Task, we tested the effects of acute systemic methylphenidate, commonly known as Ritalin, on response inhibition and response initiation in adolescent and adults rats. First, we replicated previous data that adolescents are able to inhibit a response to a cue on par with adults, but are slower to produce a rewarded response after a stop cue. Next, we observed that methylphenidate modulated response inhibition in adult rats, with low dose (0.3mg/kg) improving inhibition, and high dose (3mg/kg) impairing performance. This dose-response pattern is commonly observed with psychostimulant cognitive modulation. In adolescents, however, methylphenidate had no effect on response inhibition at any dose. Latency of response initiation after the stop cue was not affected by methylphenidate in either adult or adolescent rats. These data establish that dose-response of a commonly prescribed psychostimulant medication is different in adolescents and adults. They further demonstrate that healthy adolescent response inhibition is not as sensitive to psychostimulants as in adults, supporting the idea that the dopamine system is hypoactive in adolescence. This article is part of a Special Issue entitled SI: Adolescent plasticity. Copyright © 2016 Elsevier B.V. All rights reserved.

Bradykinin B1 and B2 receptors, tumour necrosis factor α and inflammatory hyperalgesia

PubMed Central

Poole, S; Lorenzetti, B B; Cunha, J M; Cunha, F Q; Ferreira, S H

1999-01-01

The effects of BK agonists and antagonists, and other hyperalgesic/antihyperalgesic drugs were measured (3 h after injection of hyperalgesic drugs) in a model of mechanical hyperalgesia (the end-point of which was indicated by a brief apnoea, the retraction of the head and forepaws, and muscular tremor). DALBK inhibited responses to carrageenin, bradykinin, DABK, and kallidin. Responses to kallidin and DABK were inhibited by indomethacin or atenolol and abolished by the combination of indomethacin+atenolol. DALBK or HOE 140, given 30 min before, but not 2 h after, carrageenin, BK, DABK and kallidin reduced hyperalgesic responses to these agents. A small dose of DABK+a small dose of BK evoked a response similar to the response to a much larger dose of DABK or BK, given alone. Responses to BK were antagonized by HOE 140 whereas DALBK antagonized only responses to larger doses of BK. The combination of a small dose of DALBK with a small dose of HOE 140 abolished the response to BK. The hyperalgesic response to LPS (1 μg) was inhibited by DALBK or HOE 140 and abolished by DALBK+HOE 140. The hyperalgesic response to LPS (5 μg) was not antagonized by DALBK+HOE 140. These data suggest: (a) a predominant role for B2 receptors in mediating hyperalgesic responses to BK and to drugs that stimulate BK release, and (b) activation of the hyperalgesic cytokine cascade independently of both B1 and B2 receptors if the hyperalgesic stimulus is of sufficient magnitude. PMID:10188975

The Key Events Dose-Response Framework: a cross-disciplinary mode-of-action based approach to examining dose-response and thresholds.

PubMed

Julien, Elizabeth; Boobis, Alan R; Olin, Stephen S

2009-09-01

The ILSI Research Foundation convened a cross-disciplinary working group to examine current approaches for assessing dose-response and identifying safe levels of intake or exposure for four categories of bioactive agents-food allergens, nutrients, pathogenic microorganisms, and environmental chemicals. This effort generated a common analytical framework-the Key Events Dose-Response Framework (KEDRF)-for systematically examining key events that occur between the initial dose of a bioactive agent and the effect of concern. Individual key events are considered with regard to factors that influence the dose-response relationship and factors that underlie variability in that relationship. This approach illuminates the connection between the processes occurring at the level of fundamental biology and the outcomes observed at the individual and population levels. Thus, it promotes an evidence-based approach for using mechanistic data to reduce reliance on default assumptions, to quantify variability, and to better characterize biological thresholds. This paper provides an overview of the KEDRF and introduces a series of four companion papers that illustrate initial application of the approach to a range of bioactive agents.

A phase I study of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors potentially responsive to mitoxantrone

PubMed Central

Resta, Lee P.; Pili, Roberto; Eisenberger, Mario A.; Spitz, Avery; King, Serina; Porter, Jennifer; Franke, Amy; Boinpally, Ramesh; Sweeney, Christopher J.

2010-01-01

Purpose To find the maximum tolerated dose (MTD) of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors. Methods This was a Phase I study using cohort dose escalation of OSI-461 dosed orally twice daily in combination with mitoxantrone 12 mg/m2 given on Day 1 of each 21-day cycle. Results OSI-461 dose was escalated to 1,000 mg po bid. One patient experienced a dose-limiting toxicity (DLT). Three patients discontinued the study due to adverse events (AE). Two patients (10%) had a partial response, and ten patients (50%) had stable disease as best response. Conclusion The combination of OSI-461 and mitoxantrone was well tolerated. Dose escalation was stopped because of toxicities in a concurrent Phase I trial. The response rate seen in patients with prostate cancer was comparable to response rates seen in trials of mitoxantrone and prednisone alone, and further studies of the combination of OSI-461 and mitoxantrone were not pursued. PMID:20445979

Radiotherapy dose–response analysis for diffuse large B-cell lymphoma with a complete response to chemotherapy

PubMed Central

2012-01-01

Objective To examine the efficacy of different radiation doses after achievement of a complete response to chemotherapy in diffuse large B-cell lymphoma (DLBCL). Methods Patients with stage I-IV DLBCL treated from 1995–2009 at Duke Cancer Institute who achieved a complete response to chemotherapy were reviewed. In-field control, event-free survival, and overall survival were calculated using the Kaplan-Meier method. Dose response was evaluated by grouping treated sites by delivered radiation dose. Results 105 patients were treated with RT to 214 disease sites. Chemotherapy (median 6 cycles) was R-CHOP (65%), CHOP (26%), R-CNOP (2%), or other (7%). Post-chemotherapy imaging was PET/CT (88%), gallium with CT (1%), or CT only (11%). The median RT dose was 30 Gy (range, 12–40 Gy). The median radiation dose was higher for patients with stage I-II disease compared with patients with stage III-IV disease (30 versus 24.5 Gy, p < 0.001). Five-year in-field control, event-free survival, and overall survival for all patients was 94% (95% CI: 89-99%), 84% (95% CI: 77-92%), and 91% (95% CI: 85-97%), respectively. Six patients developed an in-field recurrence at 10 sites, without a clear dose response. In-field failure was higher at sites ≥ 10 cm (14% versus 4%, p = 0.06). Conclusion In-field control was excellent with a combined modality approach when a complete response was achieved after chemotherapy without a clear radiation dose response. PMID:22720801

Cellular response to low dose radiation: Role of phosphatidylinositol-3 kinase like kinases

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

Balajee, A.S.; Meador, J.A.; Su, Y.

It is increasingly realized that human exposure either to an acute low dose or multiple chronic low doses of low LET radiation has the potential to cause different types of cancer. Therefore, the central theme of research for DOE and NASA is focused on understanding the molecular mechanisms and pathways responsible for the cellular response to low dose radiation which would not only improve the accuracy of estimating health risks but also help in the development of predictive assays for low dose radiation risks associated with tissue degeneration and cancer. The working hypothesis for this proposal is that the cellularmore » mechanisms in terms of DNA damage signaling, repair and cell cycle checkpoint regulation are different for low and high doses of low LET radiation and that the mode of action of phosphatidylinositol-3 kinase like kinases (PIKK: ATM, ATR and DNA-PK) determines the dose dependent cellular responses. The hypothesis will be tested at two levels: (I) Evaluation of the role of ATM, ATR and DNA-PK in cellular response to low and high doses of low LET radiation in simple in vitro human cell systems and (II) Determination of radiation responses in complex cell microenvironments such as human EpiDerm tissue constructs. Cellular responses to low and high doses of low LET radiation will be assessed from the view points of DNA damage signaling, DNA double strand break repair and cell cycle checkpoint regulation by analyzing the activities (i.e. post-translational modifications and kinetics of protein-protein interactions) of the key target proteins for PI-3 kinase like kinases both at the intra-cellular and molecular levels. The proteins chosen for this proposal are placed under three categories: (I) sensors/initiators include ATM ser1981, ATR, 53BP1, gamma-H2AX, MDC1, MRE11, Rad50 and Nbs1; (II) signal transducers include Chk1, Chk2, FANCD2 and SMC1; and (III) effectors include p53, CDC25A and CDC25C. The primary goal of this proposal is to elucidate the differences in cellular defense mechanisms between low and high doses of low LET radiation and to define the radiation doses where the cellular DNA damage signaling and repair mechanisms tend to shift. This information is critically important to address and advance some of the low dose research program objectives of DOE. The results of this proposed study will lead to a better understanding of the mechanisms for the cellular responses to low and high doses of low LET radiation. Further, systematic analysis of the role of PIKK signaling pathways as a function of radiation dose in tissue microenvironment will provide useful mechanistic information for improving the accuracy of radiation risk assessment for low doses. Knowledge of radiation responses in tissue microenvironment is important for the accurate prediction of ionizing radiation risks associated with cancer and tissue degeneration in humans.« less

Repeated restraint stress lowers the threshold for response to third ventricle CRF administration.

PubMed

Harris, Ruth B S

2017-03-01

Rats and mice exposed to repeated stress or a single severe stress exhibit a sustained increase in energetic, endocrine, and behavioral response to subsequent novel mild stress. This study tested whether the hyper-responsiveness was due to a lowered threshold of response to corticotropin releasing factor (CRF) or an exaggerated response to a standard dose of CRF. Male Sprague-Dawley rats were subjected to 3h of restraint on each of 3 consecutive days (RRS) or were non-restrained controls. RRS caused a temporary hypophagia but a sustained reduction in body weight. Eight days after the end of restraint, rats received increasing third ventricle doses of CRF (0-3.0μg). The lowest dose of CRF (0.25μg) increased corticosterone release in RRS, but not control rats. Higher doses caused the same stimulation of corticosterone in the two groups of rats. Fifteen days after the end of restraint, rats were food deprived during the light period and received increasing third ventricle doses of CRF at the start of the dark period. The lowest dose of CRF inhibited food intake during the first hour following infusion in RRS, but not control rats. All other doses of CRF inhibited food intake to the same degree in both RRS and control rats. The lowered threshold of response to central CRF is consistent with the chronic hyper-responsiveness to CRF and mild stress in RRS rats during the post-restraint period. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

2017-04-01

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

BYSTANDERS, ADAPTIVE RESPONSES AND GENOMIC INSTABILITY - POTENTIAL MODIFIERS OF LOW-DOSE CANCER RESPONSES.

EPA Science Inventory

Bystanders, Adaptive Responses and Genomic Instability -Potential Modifiers ofLow-Dose
Cancer Responses
.
There has been a concerted effort in the field of radiation biology to better understand cellular
responses that could have an impact on the estin1ation of cancer...

Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts After Exposure to Very Low Dose of High Let Radiation

NASA Technical Reports Server (NTRS)

Hada, M.; George, K.; Chappell, L.; Cucinotta, F. A.

2011-01-01

The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (0.01 - 0.20 Gy) of 170 MeV/u Si-28 ions or 600 MeV/u Fe-56 ions, including doses where on average less than one direct ion traversal per cell nucleus occurs. Chromosomes were analyzed using the whole-chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The responses for doses above 0.1 Gy (more than one ion traverses a cell) showed linear dose responses. However, for doses less than 0.1 Gy, both Si-28 ions and Fe-56 ions showed a dose independent response above background chromosome aberrations frequencies. Possible explanations for our results are non-targeted effects due to aberrant cell signaling [1], or delta-ray dose fluctuations [2] where a fraction of cells receive significant delta-ray doses due to the contributions of multiple ion tracks that do not directly traverse cell nuclei where chromosome aberrations are scored.

Long-term Pulmonary Responses to Quadweekly Intermittent Intratracheal Spray Instillations of Magnetite (Fe3O4) Nanoparticles for 52 Weeks in Fischer 344 Rats.

PubMed

Tada, Yukie; Yano, Norio; Takahashi, Hiroshi; Yuzawa, Katsuhiro; Ando, Hiroshi; Kubo, Yoshikazu; Nagasawa, Akemichi; Inomata, Akiko; Ogata, Akio; Nakae, Dai

2013-12-01

Information about potential risks of iron nanomaterials is still limited, while a wide variety of applications are expected. We recently reported acute phase responses of male and female Fischer 344 rats after a single intratracheal spray instillation of Fe3O4 nanoparticles (magnetite), clearly showing dose-dependent pulmonary inflammatory changes (Tada et al., J Toxicol Pathol 25, 233-239, 2012). The present study assessed long-term responses of male and female Fischer 344 rats to multiple administrations of magnetite. Ten-week-old male and female Fischer 344 rats (n=20/group) were exposed to a total of 13 quadweekly intermittent intratracheal spray instillations of magnetite during the experimental period of 52 weeks, at doses of 0, 0.2 (low), 1.0 (medium) and 5.0 (high-dose) mg/kg body weight per administration. Absolute and relative lung weights of the high-dose group were significantly higher than those of the control group. Macroscopically, slight enlargement and scattered black patches were recognized in the lungs and the lung-associated lymph nodes of the high-dose group. Histopathologically, infiltration of macrophages phagocytosing magnetite (all dose groups) and of chronic inflammatory cells (medium- and high-dose males and high-dose females), alveolar bronchiolization and granuloma (high-dose group) were observed. In addition, alveolar hyperplasias were observed in some rats of the high-dose group, and cytoplasmic overexpression of β-catenin protein was immunohistochemically found in such lesions. The present results clearly show that instilled magnetite causes chronic inflammatory responses in the lung. These responses occur in a dose-dependent manner without apparent differences among sexes.

Straightening Beta: Overdispersion of Lethal Chromosome Aberrations following Radiotherapeutic Doses Leads to Terminal Linearity in the Alpha–Beta Model

PubMed Central

Shuryak, Igor; Loucas, Bradford D.; Cornforth, Michael N.

2017-01-01

Recent technological advances allow precise radiation delivery to tumor targets. As opposed to more conventional radiotherapy—where multiple small fractions are given—in some cases, the preferred course of treatment may involve only a few (or even one) large dose(s) per fraction. Under these conditions, the choice of appropriate radiobiological model complicates the tasks of predicting radiotherapy outcomes and designing new treatment regimens. The most commonly used model for this purpose is the venerable linear-quadratic (LQ) formalism as it applies to cell survival. However, predictions based on the LQ model are frequently at odds with data following very high acute doses. In particular, although the LQ predicts a continuously bending dose–response relationship for the logarithm of cell survival, empirical evidence over the high-dose region suggests that the survival response is instead log-linear with dose. Here, we show that the distribution of lethal chromosomal lesions among individual human cells (lymphocytes and fibroblasts) exposed to gamma rays and X rays is somewhat overdispersed, compared with the Poisson distribution. Further, we show that such overdispersion affects the predicted dose response for cell survival (the fraction of cells with zero lethal lesions). This causes the dose response to approximate log-linear behavior at high doses, even when the mean number of lethal lesions per cell is well fitted by the continuously curving LQ model. Accounting for overdispersion of lethal lesions provides a novel, mechanistically based explanation for the observed shapes of cell survival dose responses that, in principle, may offer a tractable and clinically useful approach for modeling the effects of high doses per fraction. PMID:29312888

Phosphoproteomics profiling of human skin fibroblast cells reveals pathways and proteins affected by low doses of ionizing radiation.

PubMed

Yang, Feng; Waters, Katrina M; Miller, John H; Gritsenko, Marina A; Zhao, Rui; Du, Xiuxia; Livesay, Eric A; Purvine, Samuel O; Monroe, Matthew E; Wang, Yingchun; Camp, David G; Smith, Richard D; Stenoien, David L

2010-11-30

High doses of ionizing radiation result in biological damage; however, the precise relationships between long-term health effects, including cancer, and low-dose exposures remain poorly understood and are currently extrapolated using high-dose exposure data. Identifying the signaling pathways and individual proteins affected at the post-translational level by radiation should shed valuable insight into the molecular mechanisms that regulate dose-dependent responses to radiation. We have identified 7117 unique phosphopeptides (2566 phosphoproteins) from control and irradiated (2 and 50 cGy) primary human skin fibroblasts 1 h post-exposure. Semi-quantitative label-free analyses were performed to identify phosphopeptides that are apparently altered by radiation exposure. This screen identified phosphorylation sites on proteins with known roles in radiation responses including TP53BP1 as well as previously unidentified radiation-responsive proteins such as the candidate tumor suppressor SASH1. Bioinformatic analyses suggest that low and high doses of radiation affect both overlapping and unique biological processes and suggest a role for MAP kinase and protein kinase A (PKA) signaling in the radiation response as well as differential regulation of p53 networks at low and high doses of radiation. Our results represent the most comprehensive analysis of the phosphoproteomes of human primary fibroblasts exposed to multiple doses of ionizing radiation published to date and provide a basis for the systems-level identification of biological processes, molecular pathways and individual proteins regulated in a dose dependent manner by ionizing radiation. Further study of these modified proteins and affected networks should help to define the molecular mechanisms that regulate biological responses to radiation at different radiation doses and elucidate the impact of low-dose radiation exposure on human health.

Phosphoproteomics Profiling of Human Skin Fibroblast Cells Reveals Pathways and Proteins Affected by Low Doses of Ionizing Radiation

PubMed Central

Yang, Feng; Waters, Katrina M.; Miller, John H.; Gritsenko, Marina A.; Zhao, Rui; Du, Xiuxia; Livesay, Eric A.; Purvine, Samuel O.; Monroe, Matthew E.; Wang, Yingchun; Camp, David G.; Smith, Richard D.; Stenoien, David L.

2010-01-01

Background High doses of ionizing radiation result in biological damage; however, the precise relationships between long-term health effects, including cancer, and low-dose exposures remain poorly understood and are currently extrapolated using high-dose exposure data. Identifying the signaling pathways and individual proteins affected at the post-translational level by radiation should shed valuable insight into the molecular mechanisms that regulate dose-dependent responses to radiation. Principal Findings We have identified 7117 unique phosphopeptides (2566 phosphoproteins) from control and irradiated (2 and 50 cGy) primary human skin fibroblasts 1 h post-exposure. Semi-quantitative label-free analyses were performed to identify phosphopeptides that are apparently altered by radiation exposure. This screen identified phosphorylation sites on proteins with known roles in radiation responses including TP53BP1 as well as previously unidentified radiation-responsive proteins such as the candidate tumor suppressor SASH1. Bioinformatic analyses suggest that low and high doses of radiation affect both overlapping and unique biological processes and suggest a role for MAP kinase and protein kinase A (PKA) signaling in the radiation response as well as differential regulation of p53 networks at low and high doses of radiation. Conclusions Our results represent the most comprehensive analysis of the phosphoproteomes of human primary fibroblasts exposed to multiple doses of ionizing radiation published to date and provide a basis for the systems-level identification of biological processes, molecular pathways and individual proteins regulated in a dose dependent manner by ionizing radiation. Further study of these modified proteins and affected networks should help to define the molecular mechanisms that regulate biological responses to radiation at different radiation doses and elucidate the impact of low-dose radiation exposure on human health. PMID:21152398

Synergistic interaction between fentanyl and bupivacaine given intrathecally for labor analgesia.

PubMed

Ngan Kee, Warwick D; Khaw, Kim S; Ng, Floria F; Ng, Karman K L; So, Rita; Lee, Anna

2014-05-01

Lipophilic opioids and local anesthetics are often given intrathecally in combination for labor analgesia. However, the nature of the pharmacologic interaction between these drugs has not been clearly elucidated in humans. Three hundred nulliparous women randomly received 1 of 30 different combinations of fentanyl and bupivacaine intrathecally using a combined spinal-epidural technique for analgesia in the first stage of labor. Visual analogue scale pain scores were recorded for 30 min. Response was defined by percentage decrease in pain score from baseline at 15 and 30 min. Dose-response curves for individual drugs were fitted to a hyperbolic dose-response model using nonlinear regression. The nature of the drug interaction was determined using dose equivalence methodology to compare observed effects of drug combinations with effects predicted by additivity. The derived dose-response models for individual drugs (doses in micrograms) at 15 min were: Effect = 100 × dose / (13.82 + dose) for fentanyl, and Effect = 100 × dose / (1,590 + dose) for bupivacaine. Combinations of fentanyl and bupivacaine produced greater effects than those predicted by additivity at 15 min (P < 0.001) and 30 min (P = 0.015) (mean differences, 9.1 [95% CI, 4.1-14.1] and 6.4 [95% CI, 1.2-11.5] units of the normalized response, respectively), indicating a synergistic interaction. The pharmacologic interaction between intrathecal fentanyl and bupivacaine is synergistic. Characterization and quantification of this interaction provide a theoretical basis and support for the clinical practice of combining intrathecal opioids and local anesthetics.

Properties of model-averaged BMDLs: a study of model averaging in dichotomous response risk estimation.

PubMed

Wheeler, Matthew W; Bailer, A John

2007-06-01

Model averaging (MA) has been proposed as a method of accounting for model uncertainty in benchmark dose (BMD) estimation. The technique has been used to average BMD dose estimates derived from dichotomous dose-response experiments, microbial dose-response experiments, as well as observational epidemiological studies. While MA is a promising tool for the risk assessor, a previous study suggested that the simple strategy of averaging individual models' BMD lower limits did not yield interval estimators that met nominal coverage levels in certain situations, and this performance was very sensitive to the underlying model space chosen. We present a different, more computationally intensive, approach in which the BMD is estimated using the average dose-response model and the corresponding benchmark dose lower bound (BMDL) is computed by bootstrapping. This method is illustrated with TiO(2) dose-response rat lung cancer data, and then systematically studied through an extensive Monte Carlo simulation. The results of this study suggest that the MA-BMD, estimated using this technique, performs better, in terms of bias and coverage, than the previous MA methodology. Further, the MA-BMDL achieves nominal coverage in most cases, and is superior to picking the "best fitting model" when estimating the benchmark dose. Although these results show utility of MA for benchmark dose risk estimation, they continue to highlight the importance of choosing an adequate model space as well as proper model fit diagnostics.

Effects of supplementation with higher levels of manganese and magnesium on immune function.

PubMed

Son, Eun-Wha; Lee, Sung-Ryul; Choi, Hye-Sook; Koo, Hyun-Jung; Huh, Jung-Eun; Kim, Mi-Hyun; Pyo, Suhkneung

2007-06-01

The magnesium (Mg) and manganese (Mn) were evaluated for its effectiveness as an immunomodulator in rats. The treatments were as follows: Group 1, AIN-93M diet (0.05% Mg, 0.001% Mn); Group 2, high-dose Mg (0.1% Mg, 0.001% Mn); and Group 3, high dose Mn (0.05% Mg, 0.01% Mn) (n-12/group). After 12 weeks of supplementation, rats were sacrificed to assess the effect on a range of innate responses (tumoricidal activity, oxidative burst and nitric oxide) and the mitogen-stimulated lymphoproliferative response. Immune function was significantly affected in both the high dose Mg and the Mn group. Lymphocyte proliferative responses and NK cell activity were measured in pooled spleen from each group. The mitogen response of lymphocytes to LPS in the spleen was significantly reduced in high dose Mg-treated groups, whereas the response to ConA was not affected in both high dose minerals-treated groups. The reactive oxygen species level of macrophages was decreased in both groups. These effects were more pronounced in high dose Mg-treated group. Nitric oxide production was also decreased in high dose minerals-treated group. In addition, tumoricidal activities of splenic NK cell and peritoneal macrophage in mineral exposed rats were significantly increased. Moreover, percent death of macrophage was reduced in two groups receiving high dose mineral supplements. Taken together, the present data suggest that high dose trace min erals exert a differential effect on the function of immune cells.

Lidar-Based Rock-Fall Hazard Characterization of Cliffs

USGS Publications Warehouse

Collins, Brian D.; Greg M.Stock,

2017-01-01

Rock falls from cliffs and other steep slopes present numerous challenges for detailed geological characterization. In steep terrain, rock-fall source areas are both dangerous and difficult to access, severely limiting the ability to make detailed structural and volumetric measurements necessary for hazard assessment. Airborne and terrestrial lidar survey methods can provide high-resolution data needed for volumetric, structural, and deformation analyses of rock falls, potentially making these analyses straightforward and routine. However, specific methods to collect, process, and analyze lidar data of steep cliffs are needed to maximize analytical accuracy and efficiency. This paper presents observations showing how lidar data sets should be collected, filtered, registered, and georeferenced to tailor their use in rock fall characterization. Additional observations concerning surface model construction, volumetric calculations, and deformation analysis are also provided.

Sensitivity Challenge of Steep Transistors

NASA Astrophysics Data System (ADS)

Ilatikhameneh, Hesameddin; Ameen, Tarek A.; Chen, ChinYi; Klimeck, Gerhard; Rahman, Rajib

2018-04-01

Steep transistors are crucial in lowering power consumption of the integrated circuits. However, the difficulties in achieving steepness beyond the Boltzmann limit experimentally have hindered the fundamental challenges in application of these devices in integrated circuits. From a sensitivity perspective, an ideal switch should have a high sensitivity to the gate voltage and lower sensitivity to the device design parameters like oxide and body thicknesses. In this work, conventional tunnel-FET (TFET) and negative capacitance FET are shown to suffer from high sensitivity to device design parameters using full-band atomistic quantum transport simulations and analytical analysis. Although Dielectric Engineered (DE-) TFETs based on 2D materials show smaller sensitivity compared with the conventional TFETs, they have leakage issue. To mitigate this challenge, a novel DE-TFET design has been proposed and studied.

Low dose intranasal oxytocin delivered with Breath Powered device dampens amygdala response to emotional stimuli: A peripheral effect-controlled within-subjects randomized dose-response fMRI trial.

PubMed

Quintana, Daniel S; Westlye, Lars T; Alnæs, Dag; Rustan, Øyvind G; Kaufmann, Tobias; Smerud, Knut T; Mahmoud, Ramy A; Djupesland, Per G; Andreassen, Ole A

2016-07-01

It is unclear if and how exogenous oxytocin (OT) reaches the brain to improve social behavior and cognition and what is the optimal dose for OT response. To better understand the delivery routes of intranasal OT administration to the brain and the dose-response, we compared amygdala response to facial stimuli by means of functional magnetic resonance imaging (fMRI) in four treatment conditions, including two different doses of intranasal OT using a novel Breath Powered device, intravenous (IV) OT, which provided similar concentrations of blood plasma OT, and placebo. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults administering a single-dose of these four treatments. We observed a treatment effect on right amygdala activation during the processing of angry and happy face stimuli, with pairwise comparisons revealing reduced activation after the 8IU low dose intranasal treatment compared to placebo. These data suggest the dampening of amygdala activity in response to emotional stimuli occurs via direct intranasal delivery pathways rather than across the blood-brain barrier via systemically circulating OT. This trial is registered at the U.S. National Institutes of Health clinical trial registry (www.clinicaltrials.gov; NCT01983514) and as EudraCT no. 2013-001608-12. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hormetic Response by Silver Nanoparticles on In Vitro Multiplication of Sugarcane (Saccharum spp. Cv. Mex 69-290) Using a Temporary Immersion System.

PubMed

Bello-Bello, Jericó J; Chavez-Santoscoy, Rocío A; Lecona-Guzmán, Carlos A; Bogdanchikova, Nina; Salinas-Ruíz, Josafhat; Gómez-Merino, Fernando Carlos; Pestryakov, Alexey

2017-01-01

Hormesis is considered a dose-response phenomenon characterized by growth stimulation at low doses and inhibition at high doses. The hormetic response by silver nanoparticles (AgNPs) on in vitro multiplication of sugarcane was evaluated using a temporary immersion system. Sugarcane shoots were used as explants cultured in Murashige and Skoog medium with AgNPs at concentrations of 0, 25, 50, 100, and 200 mg/L. Shoot multiplication rate and length were used to determine hormetic response. Total content of phenolic compounds of sugarcane, mineral nutrition, and reactive oxygen species (ROS) was determined. Results were presented as a dose-response curve. Stimulation phase growth was observed at 50 mg/L AgNPs, whereas inhibition phase was detected at 200 mg/L AgNPs. Mineral nutrient analysis showed changes in macronutrient and micronutrient contents due to the effect of AgNPs. Moreover, AgNPs induced ROS production and increased total phenolic content, with a dose-dependent effect. Results suggested that the production of ROS and mineral nutrition are key mechanisms of AgNP-induced hormesis and that phenolic accumulation was obtained as a response of the plant to stress produced by high doses of AgNPs. Therefore, small doses of AgNPs in the culture medium could be an efficient strategy for commercial micropropagation.

Investigations of putative reproductive toxicity of low-dose exposures to vinclozolin in Wistar rats.

PubMed

Flick, Burkhard; Schneider, Steffen; Melching-Kollmuss, Stephanie; Fussell, Karma C; Gröters, Sibylle; Buesen, Roland; Strauss, Volker; van Ravenzwaay, Bennard

2017-04-01

The current investigation examines whether the fungicide vinclozolin, which has an anti-androgenic mode of action, is capable of disrupting endocrine homeostasis at very low doses. The data generated clarify whether a non-monotonic dose-response relationship exists to enhance the current debate about the regulation of endocrine disruptors. Moreover, it is part of a series of investigations assessing the dose-response relationship of single and combined administration of anti-androgenic substances. A pre-postnatal in vivo study design was chosen which was compliant with regulatory testing protocols. The test design was improved by additional endpoints addressing hormone levels, morphology and histopathological examinations. Doses were chosen to represent an effect level (20 mg/kg bw/d), the current NOAEL (4 mg/kg bw/d), and a dose close to the "ADI" (0.005 mg/kg bw/d) for the detection of a possible non-monotonic dose-response curve. Anti-androgenic changes were observable at the effect level but not at lower exposures. Nipple/areola counts appeared to be the most sensitive measure of effect, followed by male sex organ weights at sexual maturation, and finally gross and histopathological findings. The results indicate the absence of evidence for effects at low or very low dose levels. A non-monotonic dose-response relationship was not evident.

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.

Photoelectric-enhanced radiation therapy with quasi-monochromatic computed tomography

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

Jost, Gregor; Mensing, Tristan; Golfier, Sven

2009-06-15

Photoelectric-enhanced radiation therapy is a bimodal therapy, consisting of the administration of highly radiation-absorbing substances into the tumor area and localized regional irradiation with orthovoltage x-rays. Irradiation can be performed by a modified computed tomography (CT) unit equipped with an additional x-ray optical module which converts the polychromatic, fan-shaped CT beam into a monochromatized and focused beam for energy-tuned photoelectric-enhanced radiotherapy. A dedicated x-ray optical module designed for spatial collimation, focusing, and monochromatization was mounted at the exit of the x-ray tube of a clinical CT unit. Spectrally resolved measurements of the resulting beam were performed using an energy-dispersive detectionmore » system calibrated by synchrotron radiation. The spatial photon fluence was determined by film dosimetry. Depth-dose measurements were performed and compared to the polychromatic CT and a therapeutic 6 MV beam. The spatial dose distribution in phantoms using a rotating radiation source (quasi-monochromatic CT and 6 MV, respectively) was investigated by gel dosimetry. The photoelectric dose enhancement for an iodine fraction of 1% in tissue was calculated and verified experimentally. The x-ray optical module selectively filters the energy of the tungsten K{alpha} emission line with an FWHM of 5 keV. The relative photon fluence distribution demonstrates the focusing characteristic of the x-ray optical module. A beam width of about 3 mm was determined at the isocenter of the CT gantry. The depth-dose measurements resulted in a half-depth value of approximately 36 mm for the CT beams (quasi-monochromatic, polychromatic) compared to 154 mm for the 6 MV beam. The rotation of the radiation source leads to a steep dose gradient at the center of rotation; the gel dosimetry yields an entrance-to-peak dose ratio of 1:10.8 for the quasi-monochromatic CT and 1:37.3 for a 6 MV beam of the same size. The photoelectric dose enhancement factor increases from 2.2 to 2.4 by using quasi-monochromatic instead of polychromatic radiation. An additional increase in the radiation dose by a factor of 1.4 due to the focusing characteristic of the x-ray optical module was calculated. Photoelectric-enhanced radiation therapy based on a clinical CT unit combined with an x-ray optical module is a novel therapy option in radiation oncology. The optimized quasi-monochromatic radiation is strongly focused and ensures high photoelectric dose enhancement for iodine.« less

Dosimetric quality, accuracy, and deliverability of modulated radiotherapy treatments for spinal metastases

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

Kairn, Tanya, E-mail: t.kairn@gmail.com; School of Chemistry, Physics, and Mechanical Engineering, Queensland University of Technology, Brisbane; Papworth, Daniel

2016-10-01

Cancer often metastasizes to the vertebra, and such metastases can be treated successfully using simple, static posterior or opposed-pair radiation fields. However, in some cases, including when re-irradiation is required, spinal cord avoidance becomes necessary and more complex treatment plans must be used. This study evaluated 16 sample intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) treatment plans designed to treat 6 typical vertebral and paraspinal volumes using a standard prescription, with the aim of investigating the advantages and limitations of these treatment techniques and providing recommendations for their optimal use in vertebral treatments. Treatment plan quality and beammore » complexity metrics were evaluated using the Treatment And Dose Assessor (TADA) code. A portal-imaging–based quality assurance (QA) system was used to evaluate treatment delivery accuracy, and radiochromic film measurements were used to provide high-resolution verification of treatment plan dose accuracy, especially in the steep dose gradient regions between each vertebral target and spinal cord. All treatment modalities delivered approximately the same doses and the same levels of dose heterogeneity to each planning target volume (PTV), although the minimum PTV doses in the vertebral plans were substantially lower than the prescription, because of the requirement that the plans meet a strict constraint on the dose to the spinal cord and cord planning risk volume (PRV). All plans met required dose constraints on all organs at risk, and all measured PTV-cord dose gradients were steeper than planned. Beam complexity analysis suggested that the IMRT treatment plans were more deliverable (less complex, leading to greater QA success) than the VMAT treatment plans, although the IMRT plans also took more time to deliver. The accuracy and deliverability of VMAT treatment plans were found to be substantially increased by limiting the number of monitor units (MU) per beam at the optimization stage, and thereby limiting beam modulation complexity. The VMAT arcs that were optimized with MU limitation had higher QA pass rates as well as higher modulation complexity scores (less complexity), lower modulation indices (less modulation), lower MU per beam, larger beam segments, and fewer small apertures than the VMAT arcs that were optimized without MU limitation. It is recommended that VMAT treatments for vertebral volumes, where the PTV abuts or surrounds the spinal cord, should be optimized with MU limitation. IMRT treatments may be preferable to the VMAT treatments, for dosimetry and deliverability reasons, but may be inappropriate for some patients because of their increased treatment delivery time.« less

Can reduction of uncertainties in cervix cancer brachytherapy potentially improve clinical outcome?

PubMed

Nesvacil, Nicole; Tanderup, Kari; Lindegaard, Jacob C; Pötter, Richard; Kirisits, Christian

2016-09-01

The aim of this study was to quantify the impact of different types and magnitudes of dosimetric uncertainties in cervix cancer brachytherapy (BT) on tumour control probability (TCP) and normal tissue complication probability (NTCP) curves. A dose-response simulation study was based on systematic and random dose uncertainties and TCP/NTCP models for CTV and rectum. Large patient cohorts were simulated assuming different levels of dosimetric uncertainties. TCP and NTCP were computed, based on the planned doses, the simulated dose uncertainty, and an underlying TCP/NTCP model. Systematic uncertainties of 3-20% and random uncertainties with a 5-30% standard deviation per BT fraction were analysed. Systematic dose uncertainties of 5% lead to a 1% decrease/increase of TCP/NTCP, while random uncertainties of 10% had negligible impact on the dose-response curve at clinically relevant dose levels for target and OAR. Random OAR dose uncertainties of 30% resulted in an NTCP increase of 3-4% for planned doses of 70-80Gy EQD2. TCP is robust to dosimetric uncertainties when dose prescription is in the more flat region of the dose-response curve at doses >75Gy. For OARs, improved clinical outcome is expected by reduction of uncertainties via sophisticated dose delivery and treatment verification. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

PubMed Central

Vaiserman, Alexander M.

2010-01-01

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

Response to low-dose herbicide selection in self-pollinated Avena fatua.

PubMed

Busi, Roberto; Girotto, Marcelo; Powles, Stephen B

2016-03-01

When applied at the correct plant stage and dose, herbicides are highly toxic to plants. At reduced, low herbicide doses (below the recommended dose) plants can survive and display continuous and quantitative variation in dose-survival responses. Recurrent (directional) selection studies can reveal whether such a phenotypic variation in plant survival response to low herbicide dose is heritable and leads to herbicide resistance. In a common experimental garden study, we have subjected a susceptible population of self-pollinated hexaploid Avena fatua to low-dose recurrent selection with the ACCase-inhibiting herbicide diclofop-methyl for three consecutive generations. Significant differences in response to low-dose diclofop-methyl selection were observed between the selected progenies and parent plants, with a twofold diclofop-methyl resistance and cross-resistance to ALS-inhibiting herbicides. Thus, the capacity of self-pollinated A. fatua to respond to low-dose herbicide selection is marginal, and it is much lower than in cross-pollinated L. rigidum. Lolium rigidum in the same experiment evolved 40-fold diclofop-methyl resistance by progressive enrichment of quantitative resistance-endowing traits. Cross-pollination rate, genetic variation and ploidy levels are identified as possible drivers affecting the contrasting capacity of Avena versus Lolium plants to respond to herbicide selection and the subsequent likelihood of resistance evolution at low herbicide dose usage. © 2015 Society of Chemical Industry.

Pharmacokinetics, pharmacodynamics, and dose-response relationship of repaglinide in type 2 diabetes.

PubMed

Strange, P; Schwartz, S L; Graf, R J; Polvino, W; Weston, I; Marbury, T C; Huang, W C; Goldberg, R B

1999-01-01

The pharmacodynamics and dose-response relationship of repaglinide, a novel oral hypoglycemic agent, were evaluated in steady-state treatment of patients with type 2 diabetes. Efficacy of repaglinide (0.25 mg, 0.5 mg, 1 mg, 2 mg, and 4 mg) was compared to that of placebo in a double-blind, randomized, parallel-group, 4-week dose-response clinical trial in 143 patients. Repaglinide was administered 15 minutes before meals (breakfast, lunch, and dinner). Efficacy of repaglinide therapy was assessed by measuring changes from baseline in mean levels of blood glucose (BGmean), fasting serum glucose (FSG), and mean levels of serum insulin (INSmean). Blood concentrations of repaglinide were proportional to the dose administered. INSmean values increased in all repaglinide treatment groups (by 6.7 to 12.9 microU/mL). All doses of repaglinide significantly decreased values of BGmean and FSG as compared with the placebo group. BGmean values stabilized between the second and third week of repaglinide treatment. A well-defined dose-response relationship was observed for BGmean and FSG values. All doses of repaglinide were well tolerated, and there were no serious adverse events. These findings show that the therapeutic reduction of serum glucose levels produced by repaglinide is dose-dependent for the 0.25- to 4-mg dose range. All doses of repaglinide tested were effective and well tolerated in patients with type 2 diabetes.

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.

The Use of Mode of Action Information in Risk Assessment: Quantitative Key Events/Dose-Response Framework for Modeling the Dose-Response for Key Events

EPA Science Inventory

The HESI RISK21 project formed the Dose-Response/Mode-of-Action Subteam to develop strategies for using all available data (in vitro, in vivo, and in silico) to advance the next-generation of chemical risk assessments. A goal of the Subteam is to enhance the existing Mode of Act...

The evaluation of the novel pressor activity of gamma-piperidinobutyramide (WY 20051, DF480).

PubMed Central

Alps, B J; Devoy, P W; Waterfall, J F

1976-01-01

1 gamma-Piperidinobutyramide (Wy 20051, DF480) injected intravenously evoked pressor responses in the anaesthetized ganglion blocked rat preparation over the dose range 2.4 x 10(-6)-3.0 x 10(-4) mol/kg. 2 High doses (greater than 3.8 x 10(-5) mol/kg) or even repeated submaximal doses (1.9 x 10(-5) mol/kg) of Wy 20051 caused tachyphylaxis of this pressor response. 3 The noradrenaline pressor-response curve was shifted significantly to the right of the control curve following a dose of Wy 20051 (1.5 x 10(-4) mol/kg cumulative). 4 The dose-response curve for the pressor action of Wy 20051 was potentiated in reserpine-treated anaesthetized rats. In contrast, tyramine-induced pressor responses were abolished. 5 Wy 20051 contracted the guinea-pig isolated aortic spiral preparation (3.8 x 10(-5)-6.0 x 10(-4) mol) and evoked constrictor responses in the perfused mesenteric vasculature preparation of the rat (5.9 x 10(-7)-1.2 x 10(-5) mol). At higher doses the responses were reduced. 6 Wy 20051-induced constrictor responses of the perfused mesentery were unaffected by blockade of alpha-adrenoceptors or by tachyphylaxis of 5-hydroxytryptamine receptors. 7 The time for abolition of Wy 20051-induced constrictor responses of the mesentery in a calcium-free medium was not significantly different from that required for noradrenaline, but was significantly greater than that for KCl (P less than 0.001). 8 Wy 20051 and noradrenaline, but not KCl, evoked constrictor responses in the depolarized rat mesenteric vasculature. 9 The results indicate that Wy 20051 evokes pressor responses which have some of the characteristics of those of noradrenaline. However, the responses are not elicited by an alpha-adrenoceptor mechanism. PMID:3247

A Generalized QMRA Beta-Poisson Dose-Response Model.

PubMed

Xie, Gang; Roiko, Anne; Stratton, Helen; Lemckert, Charles; Dunn, Peter K; Mengersen, Kerrie

2016-10-01

Quantitative microbial risk assessment (QMRA) is widely accepted for characterizing the microbial risks associated with food, water, and wastewater. Single-hit dose-response models are the most commonly used dose-response models in QMRA. Denoting PI(d) as the probability of infection at a given mean dose d, a three-parameter generalized QMRA beta-Poisson dose-response model, PI(d|α,β,r*), is proposed in which the minimum number of organisms required for causing infection, K min , is not fixed, but a random variable following a geometric distribution with parameter 0

Characterization of Changes in Gene Expression and Biochemical Pathways at Low Levels of Benzene Exposure

PubMed Central

Thomas, Reuben; Hubbard, Alan E.; McHale, Cliona M.; Zhang, Luoping; Rappaport, Stephen M.; Lan, Qing; Rothman, Nathaniel; Vermeulen, Roel; Guyton, Kathryn Z.; Jinot, Jennifer; Sonawane, Babasaheb R.; Smith, Martyn T.

2014-01-01

Benzene, a ubiquitous environmental pollutant, causes acute myeloid leukemia (AML). Recently, through transcriptome profiling of peripheral blood mononuclear cells (PBMC), we reported dose-dependent effects of benzene exposure on gene expression and biochemical pathways in 83 workers exposed across four airborne concentration ranges (from <1 ppm to >10 ppm) compared with 42 subjects with non-workplace ambient exposure levels. Here, we further characterize these dose-dependent effects with continuous benzene exposure in all 125 study subjects. We estimated air benzene exposure levels in the 42 environmentally-exposed subjects from their unmetabolized urinary benzene levels. We used a novel non-parametric, data-adaptive model selection method to estimate the change with dose in the expression of each gene. We describe non-parametric approaches to model pathway responses and used these to estimate the dose responses of the AML pathway and 4 other pathways of interest. The response patterns of majority of genes as captured by mean estimates of the first and second principal components of the dose-response for the five pathways and the profiles of 6 AML pathway response-representative genes (identified by clustering) exhibited similar apparent supra-linear responses. Responses at or below 0.1 ppm benzene were observed for altered expression of AML pathway genes and CYP2E1. Together, these data show that benzene alters disease-relevant pathways and genes in a dose-dependent manner, with effects apparent at doses as low as 100 ppb in air. Studies with extensive exposure assessment of subjects exposed in the low-dose range between 10 ppb and 1 ppm are needed to confirm these findings. PMID:24786086

Toxicogenomics and cancer risk assessment: a framework for key event analysis and dose-response assessment for nongenotoxic carcinogens.

PubMed

Bercu, Joel P; Jolly, Robert A; Flagella, Kelly M; Baker, Thomas K; Romero, Pedro; Stevens, James L

2010-12-01

In order to determine a threshold for nongenotoxic carcinogens, the traditional risk assessment approach has been to identify a mode of action (MOA) with a nonlinear dose-response. The dose-response for one or more key event(s) linked to the MOA for carcinogenicity allows a point of departure (POD) to be selected from the most sensitive effect dose or no-effect dose. However, this can be challenging because multiple MOAs and key events may exist for carcinogenicity and oftentimes extensive research is required to elucidate the MOA. In the present study, a microarray analysis was conducted to determine if a POD could be identified following short-term oral rat exposure with two nongenotoxic rodent carcinogens, fenofibrate and methapyrilene, using a benchmark dose analysis of genes aggregated in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) biological processes, which likely encompass key event(s) for carcinogenicity. The gene expression response for fenofibrate given to rats for 2days was consistent with its MOA and known key events linked to PPARα activation. The temporal response from daily dosing with methapyrilene demonstrated biological complexity with waves of pathways/biological processes occurring over 1, 3, and 7days; nonetheless, the benchmark dose values were consistent over time. When comparing the dose-response of toxicogenomic data to tumorigenesis or precursor events, the toxicogenomics POD was slightly below any effect level. Our results suggest that toxicogenomic analysis using short-term studies can be used to identify a threshold for nongenotoxic carcinogens based on evaluation of potential key event(s) which then can be used within a risk assessment framework. Copyright © 2010 Elsevier Inc. All rights reserved.

Differences in hydrological responses for different vegetation types on a steep slope on the Loess Plateau, China

NASA Astrophysics Data System (ADS)

Duan, Liangxia; Huang, Mingbin; Zhang, Luodan

2016-06-01

Extensive vegetation restoration practices have been implemented to control soil erosion on the Loess Plateau, China. However, no strict guidelines are available to determine the most suitable plant species for vegetation restoration within a given area. The objective of this study was to quantify the changes of each component (soil water storage, surface runoff, and actual evapotranspiration) of a water balance model and soil loss over time under eight different vegetation types, and to further determine the optimal vegetation type for soil and water conservation and sustainable ecological restoration on the steep slopes (>25°) on the Loess Plateau. The results indicated that vegetation type substantially affected soil water storage and that the greatest soil water storage in both the shallow (0-2 m) and the deep soil layers (2-5 m) occurred under Bothriochloa ischaemum L. (BOI). Vegetation type also affected surface runoff and soil losses. The most effective vegetation types for reducing soil erosion were BOI and Sea-buckthorn (Hippophae rhamnoides L.), while Chinese pine (Pinus tabulaeformis Carr.) and Chinese pine + Black locust (Robinia pseudoacacia L.) were the most ineffective types. Soil water dynamics and evapotranspiration varied considerably among the different vegetation types. A soil water surplus was only found under BOI, while insufficient water replenishment existed under the other seven vegetation types. The higher water consumption rates of the seven vegetation types could result in soil desiccation, which could lead to severe water stresses that would adversely affect plant growth. This study suggested that both vegetation type and its effect on controlling soil erosion should be considered when implementing vegetation restoration and that BOI should be highly recommended for vegetation restoration on the steep slopes of the Loess Plateau. A similar approach to the one used in this study could be applied to other regions of the world confronted by the same problems of water scarcity along with the need for vegetation restoration.

Dose-response plasma appearance of coffee chlorogenic and phenolic acids in adults.

PubMed

Renouf, Mathieu; Marmet, Cynthia; Giuffrida, Francesca; Lepage, Mélissa; Barron, Denis; Beaumont, Maurice; Williamson, Gary; Dionisi, Fabiola

2014-02-01

Coffee contains phenolic compounds, mainly chlorogenic acids (CGAs). Even though coffee intake has been associated with some health benefits in epidemiological studies, the bioavailability of coffee phenolics is not fully understood. We performed a dose-response study measuring plasma bioavailability of phenolics after drinking three increasing, but still nutritionally relevant doses of instant pure soluble coffee. The study design was a one treatment (coffee) three-dose randomized cross-over design, with a washout period of 2 wks between visits. CGAs, phenolic acids, and late-appearing metabolites all increased with increasing ingested dose. Hence, the sum of area under the curve was significantly higher for the medium to low dose, and high to medium dose, by 2.23- and 2.38-fold, respectively. CGAs were not well absorbed in their intact form, regardless of the dose. CGA and phenolic acids appeared rapidly in plasma, indicating an early absorption in the gastrointestinal tract. Late-appearing metabolites were the most abundant, regardless of the dose. This study confirmed previous findings about coffee bioavailability but also showed that coffee phenolics appear in a positive dose-response manner in plasma when drank at nutritionally relevant doses. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dose-response relationships in a microneutralization test for foot-and-mouth disease viruses.

PubMed Central

Booth, J. C.; Rweyemamu, M. M.; Pay, T. W.

1978-01-01

Two-dimensional quantal microneutralization tests on foot-and-mouth disease viruses, in which neutralizing antibody activity was titrated against a serial range of virus doses, demonstrated a variety of dose-response curves some of which were rectilinear, others clearly curvilinear. Moreover, in the case of the non-linear responses obtained with some antisera, the shape of the curve was such that antibody titres recorded with doses of virus ranging from 10(3)-10(5) TCD50 were closely similar. Studies were carried out on the effect of varying the conditions of the test on the shape of the dose-response curve: significant differences were obtained after treatment of the antiserum-virus mixtures with anti-species globulin, and when the test was assayed in cells of differing susceptibility to infection. PMID:202650

Plasma Radiation and Acceleration Effectiveness of CME-driven Shocks

NASA Astrophysics Data System (ADS)

Gopalswamy, N.; Schmidt, J. M.

2008-05-01

CME-driven shocks are effective radio radiation generators and accelerators for Solar Energetic Particles (SEPs). We present simulated 3 D time-dependent radio maps of second order plasma radiation generated by CME- driven shocks. The CME with its shock is simulated with the 3 D BATS-R-US CME model developed at the University of Michigan. The radiation is simulated using a kinetic plasma model that includes shock drift acceleration of electrons and stochastic growth theory of Langmuir waves. We find that in a realistic 3 D environment of magnetic field and solar wind outflow of the Sun the CME-driven shock shows a detailed spatial structure of the density, which is responsible for the fine structure of type II radio bursts. We also show realistic 3 D reconstructions of the magnetic cloud field of the CME, which is accelerated outward by magnetic buoyancy forces in the diverging magnetic field of the Sun. The CME-driven shock is reconstructed by tomography using the maximum jump in the gradient of the entropy. In the vicinity of the shock we determine the Alfven speed of the plasma. This speed profile controls how steep the shock can grow and how stable the shock remains while propagating away from the Sun. Only a steep shock can provide for an effective particle acceleration.

Plasma radiation and acceleration effectiveness of CME-driven shocks

NASA Astrophysics Data System (ADS)

Schmidt, Joachim

CME-driven shocks are effective radio radiation generators and accelerators for Solar Energetic Particles (SEPs). We present simulated 3 D time-dependent radio maps of second order plasma radiation generated by CME-driven shocks. The CME with its shock is simulated with the 3 D BATS-R-US CME model developed at the University of Michigan. The radiation is simulated using a kinetic plasma model that includes shock drift acceleration of electrons and stochastic growth theory of Langmuir waves. We find that in a realistic 3 D environment of magnetic field and solar wind outflow of the Sun the CME-driven shock shows a detailed spatial structure of the density, which is responsible for the fine structure of type II radio bursts. We also show realistic 3 D reconstructions of the magnetic cloud field of the CME, which is accelerated outward by magnetic buoyancy forces in the diverging magnetic field of the Sun. The CME-driven shock is reconstructed by tomography using the maximum jump in the gradient of the entropy. In the vicinity of the shock we determine the Alfven speed of the plasma. This speed profile controls how steep the shock can grow and how stable the shock remains while propagating away from the Sun. Only a steep shock can provide for an effective particle acceleration.

Late Holocene geomorphic record of fire in ponderosa pine and mixed-conifer forests, Kendrick Mountain, northern Arizona, USA

USGS Publications Warehouse

Jenkins, S.E.; Hull, Sieg C.; Anderson, D.E.; Kaufman, D.S.; Pearthree, P.A.

2011-01-01

Long-term fire history reconstructions enhance our understanding of fire behaviour and associated geomorphic hazards in forested ecosystems. We used 14C ages on charcoal from fire-induced debris-flow deposits to date prehistoric fires on Kendrick Mountain, northern Arizona, USA. Fire-related debris-flow sedimentation dominates Holocene fan deposition in the study area. Radiocarbon ages indicate that stand-replacing fire has been an important phenomenon in late Holocene ponderosa pine (Pinus ponderosa) and ponderosa pine-mixed conifer forests on steep slopes. Fires have occurred on centennial scales during this period, although temporal hiatuses between recorded fires vary widely and appear to have decreased during the past 2000 years. Steep slopes and complex terrain may be responsible for localised crown fire behaviour through preheating by vertical fuel arrangement and accumulation of excessive fuels. Holocene wildfire-induced debris flow events occurred without a clear relationship to regional climatic shifts (decadal to millennial), suggesting that interannual moisture variability may determine fire year. Fire-debris flow sequences are recorded when (1) sufficient time has passed (centuries) to accumulate fuels; and (2) stored sediment is available to support debris flows. The frequency of reconstructed debris flows should be considered a minimum for severe events in the study area, as fuel production may outpace sediment storage. ?? IAWF 2011.

Characterization and optimization of schizophyllan production from date syrup.

PubMed

Jamshidian, Hajar; Shojaosadati, Seyed Abbas; Vilaplana, Francisco; Mousavi, Seyed Mohammad; Soudi, Mohammad Reza

2016-11-01

This study demonstrates the efficient utilization of low-cost agricultural substrates, particularly date syrup, by Schizophyllum commune ATCC 38548 for schizophyllan production. Initially, one factor-at-a-time method was used to find the best carbon and nitrogen sources for schizophyllan production. Subsequently, response surface methodology was employed to optimize the level of culture medium components to maximize substrate conversion yield and schizophyllan production in submerged culture. Maximum product yield (0.12g schizophyllan/g date syrup) and schizophyllan production (8.5g/l) were obtained at concentrations of date syrup and corn steep liquor, inoculum size and agitation rate at 7.02%w/v, 0.10%w/v, 7.68%v/v and 181rpm, respectively. Sugar composition analysis, FTIR, NMR and molar mass determination revealed the purity and molecular properties of recovered schizophyllan produced from date syrup as glycosidic linkage analysis showed three main schizophyllan characteristic peaks arising from the 3-linked, 3,6-linked and terminal glucose residues. Finally, process economic analysis suggested that use of date syrup and corn steep liquor as nutrients would result in approximately 6-fold reduction in cost of raw materials for schizophyllan production as compared to conventional carbon and nitrogen sources such as sucrose and malt extract. Copyright © 2016 Elsevier B.V. All rights reserved.

Influence of solar flare X-rays on the habitability on the Mars

NASA Astrophysics Data System (ADS)

Jain, Rajmal; Awasthi, Arun K.; Tripathi, Sharad C.; Bhatt, Nipa J.; Khan, Parvaiz A.

2012-08-01

We probe the lethality of X-rays from solar flares to organisms on Mars based on the observations of 10 solar flares. We, firstly, estimate the doses produced by the strong flares observed by the RHESSI and GOES missions during the descending phase of sunspot cycle 23. Next, in order to realize the dependence of dose on flux and steepness of spectra, we model the incident spectra over a wide range of spectral index to estimate dose values and compare them with the observed doses. We calculate the distribution of surficial spectra visible to organisms on the martian surface by employing attenuation of X-rays due to CO2 column densities distribution over the South Pole. The surficial flux distribution after folding with the opacity of water enables us to estimate the dose distribution over the South Pole. The dose measured from the surficial spectrum produced by the observed 10 flares corresponding to the latitudes 50-60°, 60-70°, 70-80° and 80-90°S varies in the range of 6.39 × 10-9-1.80 × 10-6; 4.89 × 10-10-5.21 × 10-8; 5.10 × 10-11-5.20 × 10-9 and 4.42 × 10-10-4.89 × 10-12 gray (1 gray = 104 erg/g) respectively. Comparing the measured as well as the modeled doses with those proposed to be lethal for various organisms by Smith and Scalo (Smith, D.S., Scalo, J. [2007]. Planet. Space Sci. 55, 517-527); we report that the habitability of life on the South Pole remains unaffected even by the strongest solar flare occurred during descending phase of solar cycle 23. Further, the monthly integrated energy released by the solar flares in the most productive month viz. October 2003 and January 2005 from the GOES soft X-ray observations is estimated to be 8.43 and 3.32 × 1032 ergs respectively, which is almost equal in order to the typical energy released by a single strong X-class flare. Therefore, we propose the life near the South Pole region on the Mars remain uninfluenced by X-ray emission even during monster phenomena of energy release on the Sun and/or Star.

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.

Technical Note: On GAFChromic EBT-XD film and the lateral response artifact.

PubMed

Lewis, David F; Chan, Maria F

2016-02-01

The new radiochromic film, GAFChromic EBT-XD, contains the same active material, lithium-10,12-pentacosadiynoate, as GAFChromic EBT3, but the crystalline form is different. This work investigates the effect of this change on the well-known lateral response artifact when EBT-XD film is digitized on a flatbed scanner. The dose response of a single production lot of EBT-XD was characterized by scanning an unexposed film plus a set of films exposed to doses between 2.5 and 50 Gy using 6 MV photons. To characterize the lateral response artifact, the authors used the unexposed film plus a subset of samples exposed to doses between 20 and 50 Gy. Digital images of these films were acquired at seven discrete lateral locations perpendicular to the scan direction on three Epson 10000XL scanners. Using measurements at the discrete lateral positions, the scanner responses were determined as a function of the lateral position of the film. From the data for each scanner, a set of coefficients were derived whereby measured response values could be corrected to remove the effects of the lateral response artifact. The EBT-XD data were analyzed as in their previous work and compared to results reported for EBT3 in that paper. For films scanned in the same orientation and having equal responses, the authors found that the lateral response artifact for EBT-XD and EBT3 films was remarkably similar. For both films, the artifact increases with increased net response. However, as EBT-XD is less sensitive than EBT3, a greater exposure dose is required to reach the same net response. On this basis, the lower sensitivity of EBT-XD relative to EBT3 results in less net response change for equal exposure and a reduction in the impact of the lateral response artifact. The shape of the crystalline active component in EBT-XD and EBT3 does not affect the fundamental existence of the lateral response artifact when the films are digitized on flatbed scanners. Owing its lower sensitivity, EBT-XD film requires higher dose to reach the same response as EBT3, resulting in lesser impact of the lateral response artifact. For doses >10 Gy, the slopes of the EBT-XD red and green channel dose response curves are greater than the corresponding ones for EBT3. For these two reasons, the authors prefer EBT-XD for doses exceeding about 10 Gy.

Technical Note: On GAFChromic EBT-XD film and the lateral response artifact

PubMed Central

Lewis, David F.

2016-01-01

Purpose: The new radiochromic film, GAFChromic EBT-XD, contains the same active material, lithium-10,12-pentacosadiynoate, as GAFChromic EBT3, but the crystalline form is different. This work investigates the effect of this change on the well-known lateral response artifact when EBT-XD film is digitized on a flatbed scanner. Methods: The dose response of a single production lot of EBT-XD was characterized by scanning an unexposed film plus a set of films exposed to doses between 2.5 and 50 Gy using 6 MV photons. To characterize the lateral response artifact, the authors used the unexposed film plus a subset of samples exposed to doses between 20 and 50 Gy. Digital images of these films were acquired at seven discrete lateral locations perpendicular to the scan direction on three Epson 10000XL scanners. Using measurements at the discrete lateral positions, the scanner responses were determined as a function of the lateral position of the film. From the data for each scanner, a set of coefficients were derived whereby measured response values could be corrected to remove the effects of the lateral response artifact. The EBT-XD data were analyzed as in their previous work and compared to results reported for EBT3 in that paper. Results: For films scanned in the same orientation and having equal responses, the authors found that the lateral response artifact for EBT-XD and EBT3 films was remarkably similar. For both films, the artifact increases with increased net response. However, as EBT-XD is less sensitive than EBT3, a greater exposure dose is required to reach the same net response. On this basis, the lower sensitivity of EBT-XD relative to EBT3 results in less net response change for equal exposure and a reduction in the impact of the lateral response artifact. Conclusions: The shape of the crystalline active component in EBT-XD and EBT3 does not affect the fundamental existence of the lateral response artifact when the films are digitized on flatbed scanners. Owing its lower sensitivity, EBT-XD film requires higher dose to reach the same response as EBT3, resulting in lesser impact of the lateral response artifact. For doses >10 Gy, the slopes of the EBT-XD red and green channel dose response curves are greater than the corresponding ones for EBT3. For these two reasons, the authors prefer EBT-XD for doses exceeding about 10 Gy. PMID:26843228

Immunogenicity and safety of a live attenuated shingles (herpes zoster) vaccine (Zostavax®) in individuals aged ≥ 70 years: a randomized study of a single dose vs. two different two-dose schedules.

PubMed

Vesikari, Timo; Hardt, Roland; Rümke, Hans C; Icardi, Giancarlo; Montero, Jordi; Thomas, Stéphane; Sadorge, Christine; Fiquet, Anne

2013-04-01

Disease protection provided by herpes zoster (HZ) vaccination tends to reduce as age increases. This study was designed to ascertain whether a second dose of the HZ vaccine, Zostavax(®), would increase varicella zoster virus (VZV)-specific immune response among individuals aged ≥ 70 y. Individuals aged ≥ 70 y were randomized to receive HZ vaccine in one of three schedules: a single dose (0.65 mL), two doses at 0 and 1 mo, or two doses at 0 and 3 mo. VZV antibody titers were measured at baseline, 4 weeks after each vaccine dose, and 12 mo after the last dose. In total, 759 participants (mean age 76.1 y) were randomized to receive vaccination. Antibody responses were similar after a single dose or two doses of HZ vaccine [post-dose 2/post-dose 1 geometric mean titer (GMT) ratios for the 1-mo or 3-mo schedules were 1.11, 95% confidence interval (CI) 1.02-1.22 and 0.78, 95% CI 0.73-0.85], respectively). The 12-mo post-dose 2/12-mo post-dose 1 GMT ratio was similar for the 1-mo schedule and for the 3-mo schedule (1.06, 95% CI 0.96-1.17 and 1.08, 95% CI 0.98-1.19, respectively). Similar immune responses were observed in participants aged 70-79 y and those aged ≥ 80 y. HZ vaccine was generally well tolerated, with no evidence of increased adverse event incidence after the second dose with either schedule. Compared with a single-dose regimen, two-dose vaccination did not increase VZV antibody responses among individuals aged ≥ 70 y. Antibody persistence after 12 mo was similar with all three schedules.

DOSE-DEPENDENT TRANSITIONS IN MECHANISMS OF TOXICITY: CASE STUDIES

EPA Science Inventory

Experience with dose response and mechanisms of toxicity has shown that multiple mechanisms may exist for a single agent along the continuum of the full dose-response curve. It is highly likely that critical, limiting steps in any given mechanistic pathway may become overwhelmed ...

A dose-responsive model of smoke inhalation injury. Severity-related alteration in cardiopulmonary function.

PubMed Central

Shimazu, T; Yukioka, T; Hubbard, G B; Langlinais, P C; Mason, A D; Pruitt, B A

1987-01-01

The dose responsiveness of selected physiologic indices was studied in a sheep model of smoke inhalation injury. In this model, graded severity of injury was achieved by changing the contact time with smoke (defined by "unit"), whereas other variables were kept constant. Blood gas and cardiopulmonary indices were measured in 70 sheep, including 12 controls, either 24 or 72 hours after exposure to 3, 6, 9, 12, 15, or 18 units of smoke. A 12-unit dose of smoke was fatal within 72 hours and an 18-unit dose was fatal within 24 hours. The best correlation between smoke dose and response was observed in arterial oxygen tension 24 hours after exposure. At 24 hours, most of the cardiopulmonary indices showed significant change only after a 12-unit exposure. Although the exact shape of the dose-response curve could not be defined, sigmoid or curved linear shape was suggested, reflecting the progressive deterioration. Images Fig. 3. Fig. 4A. Fig. 4B. PMID:3606236

No-threshold dose-response curves for nongenotoxic chemicals: Findings and applications for risk assessment

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

Sheehan, Daniel M.

2006-01-15

We tested the hypothesis that no threshold exists when estradiol acts through the same mechanism as an active endogenous estrogen. A Michaelis-Menten (MM) equation accounting for response saturation, background effects, and endogenous estrogen level fit a turtle sex-reversal data set with no threshold and estimated the endogenous dose. Additionally, 31 diverse literature dose-response data sets were analyzed by adding a term for nonhormonal background; good fits were obtained but endogenous dose estimations were not significant due to low resolving power. No thresholds were observed. Data sets were plotted using a normalized MM equation; all 178 data points were accommodated onmore » a single graph. Response rates from {approx}1% to >95% were well fit. The findings contradict the threshold assumption and low-dose safety. Calculating risk and assuming additivity of effects from multiple chemicals acting through the same mechanism rather than assuming a safe dose for nonthresholded curves is appropriate.« less

Hillslope versus riparian zone runoff contributions in headwater catchments: A multi-watershed comparison

NASA Astrophysics Data System (ADS)

McGlynn, B. L.; McGlynn, B. L.; McDonnell, J. J.; Hooper, R. P.; Shanley, J. B.; Hjerdt, K. N.; Hjerdt, K. N.

2001-12-01

It is often assumed that hillslope and riparian areas constitute the two most important and identifiable landscape units contributing to catchment runoff in upland humid catchments. Nevertheless, the relative amount and timing of hillslope versus riparian contributions to stormflow are poorly understood across different watersheds. We quantified the contributions of hillslopes and riparian zones to stormflow using physical, chemical, and isotopic techniques across 3 diverse ({ ~}15 ha) headwater catchments: a highly responsive steep wet watershed (Maimai, New Zealand), a moderately steep snowmelt dominated watershed (Sleepers, River, VT), and at a highly seasonal relatively low relief watershed (Panola Mt., Georgia). We monitored catchment runoff, internal hydrological response, and isotopic and solute dynamics for discrete riparian and hillslope zones within each catchment. Monitored catchment positions, including hillslope trenches at Maimai and Panola, were used to characterize directly, the hydrologic response and source water signatures for hillslope zones and riparian zones. We also examined the spatial and temporal source components of catchment stormflow using 3-component mass balance hydrograph separation techniques. At Maimai, NZ we found that hillslope runoff comprised 47-55% of total runoff during a 70 mm event. Despite the large amount of subsurface hillslope runoff in total catchment stormflow, riparian and channel zones accounted for 28% out of 29% of the total new water measured catchment runoff. Riparian water dominated the storm hydrograph composition early in the event, although hillslope water reached the catchment outlet soon after hillslope water tables were developed. Preliminary results for Sleepers River, VT and Panola Mountain, GA indicate that the timing and relative proportion of hillslope water in catchment runoff is later and smaller than at Maimai. Our multi-catchment comparison suggests that the ratio of the riparian reservoir to the hillslope reservoir/stormflow flux partially controls the relative contributions of hillslope and riparian zones to catchment runoff and solute dynamics.

An adaptive two-stage dose-response design method for establishing proof of concept.

PubMed

Franchetti, Yoko; Anderson, Stewart J; Sampson, Allan R

2013-01-01

We propose an adaptive two-stage dose-response design where a prespecified adaptation rule is used to add and/or drop treatment arms between the stages. We extend the multiple comparison procedures-modeling (MCP-Mod) approach into a two-stage design. In each stage, we use the same set of candidate dose-response models and test for a dose-response relationship or proof of concept (PoC) via model-associated statistics. The stage-wise test results are then combined to establish "global" PoC using a conditional error function. Our simulation studies showed good and more robust power in our design method compared to conventional and fixed designs.

Dose-response approaches for nuclear receptor-mediated ...

EPA Pesticide Factsheets

A public workshop, organized by a Steering Committee of scientists from government, industry, universities, and research organizations, was held at the National Institute of Environmental Health Sciences (NIEHS) in September, 2010. The workshop explored the dose-response implications of toxicant modes of action (MOA) mediated by nuclear receptors. The dominant paradigm in human health risk assessment has been linear extrapolation without a threshold for cancer, and estimation of sub-threshold doses for non-cancer and (in appropriate cases) cancer endpoints. However, recent publications question the application of dose-response modeling approaches with a threshold. The growing body of molecular toxicology information and computational toxicology tools has allowed for exploration of the presence or absence of subthreshold doses for a number of receptor-mediated MOPs. The workshop explored the development of dose-response approaches for nuclear receptor-mediated liver cancer, within a MOA Human Relevance framework (HRF). Case studies addressed activation of the AHR; the CAR/PXR, and the PPARa. This paper describes the workshop process, key issues discussed, and conclusions. The value of an interactive workshop approach to apply current MOA/HRF frameworks was demonstrated. The results may help direct research on the MOA and dose-response of receptor-based toxicity, since there are commonalities for many receptors in the basic pathways involved for late steps in the

Denitrification-Efficiencies of Alternate Carbon Sources

DTIC Science & Technology

1984-07-01

carbon source evaluated, while sweet whey, corn steep liquor , acid whey and soluble potato solids followed in order of decreasing efficiency. Three of...denitrification and total organic carbon removal with ’I. sweet whey 11 3. Percent denitrification and total organic carbon removal with corn steep liquor ...and total organic carbon removal with hydrolyzed sludge 18 10. Percent denitrification and total organic carbon removal with fish stick 19 11

Application of Remotely Piloted Vehicle (RPV) in monitoring and detecting watershed land use change and problem areas

Treesearch

Long-Ming Huang

2000-01-01

Improper cultivation of steep mountainous areas in Taiwan contributes to serious erosion and landslides. Regular patrol, detection, and administration of these problem areas has been an extremely difficult due to the steep and dangerous terrain of many of the forested watersheds in Taiwan. A remotely piloted vehicle (RPV) has been developed for various civil and...

Evaluation of LiF:Mg,Ti (TLD-100) for Intraoperative Electron Radiation Therapy Quality Assurance

PubMed Central

Liuzzi, Raffaele; Savino, Federica; D’Avino, Vittoria; Pugliese, Mariagabriella; Cella, Laura

2015-01-01

Background Purpose of the present work was to investigate thermoluminescent dosimeters (TLDs) response to intraoperative electron radiation therapy (IOERT) beams. In an IOERT treatment, a large single radiation dose is delivered with a high dose-per-pulse electron beam (2–12 cGy/pulse) during surgery. To verify and to record the delivered dose, in vivo dosimetry is a mandatory procedure for quality assurance. The TLDs feature many advantages such as a small detector size and close tissue equivalence that make them attractive for IOERT as in vivo dosimeters. Methods LiF:Mg,Ti dosimeters (TLD-100) were irradiated with different IOERT electron beam energies (5, 7 and 9 MeV) and with a 6 MV conventional photon beam. For each energy, the TLDs were irradiated in the dose range of 0–10 Gy in step of 2Gy. Regression analysis was performed to establish the response variation of thermoluminescent signals with dose and energy. Results The TLD-100 dose-response curves were obtained. In the dose range of 0–10 Gy, the calibration curve was confirmed to be linear for the conventional photon beam. In the same dose region, the quadratic model performs better than the linear model when high dose-per-pulse electron beams were used (F test; p<0.05). Conclusions This study demonstrates that the TLD dose response, for doses ≤10Gy, has a parabolic behavior in high dose-per-pulse electron beams. TLD-100 can be useful detectors for IOERT patient dosimetry if a proper calibration is provided. PMID:26427065

Evaluation of LiF:Mg,Ti (TLD-100) for Intraoperative Electron Radiation Therapy Quality Assurance.

PubMed

Liuzzi, Raffaele; Savino, Federica; D'Avino, Vittoria; Pugliese, Mariagabriella; Cella, Laura

2015-01-01

Purpose of the present work was to investigate thermoluminescent dosimeters (TLDs) response to intraoperative electron radiation therapy (IOERT) beams. In an IOERT treatment, a large single radiation dose is delivered with a high dose-per-pulse electron beam (2-12 cGy/pulse) during surgery. To verify and to record the delivered dose, in vivo dosimetry is a mandatory procedure for quality assurance. The TLDs feature many advantages such as a small detector size and close tissue equivalence that make them attractive for IOERT as in vivo dosimeters. LiF:Mg,Ti dosimeters (TLD-100) were irradiated with different IOERT electron beam energies (5, 7 and 9 MeV) and with a 6 MV conventional photon beam. For each energy, the TLDs were irradiated in the dose range of 0-10 Gy in step of 2 Gy. Regression analysis was performed to establish the response variation of thermoluminescent signals with dose and energy. The TLD-100 dose-response curves were obtained. In the dose range of 0-10 Gy, the calibration curve was confirmed to be linear for the conventional photon beam. In the same dose region, the quadratic model performs better than the linear model when high dose-per-pulse electron beams were used (F test; p<0.05). This study demonstrates that the TLD dose response, for doses ≤10 Gy, has a parabolic behavior in high dose-per-pulse electron beams. TLD-100 can be useful detectors for IOERT patient dosimetry if a proper calibration is provided.

AS03-Adjuvanted, Very-Low-Dose Influenza Vaccines Induce Distinctive Immune Responses Compared to Unadjuvanted High-Dose Vaccines in BALB/c Mice

PubMed Central

Yam, Karen K.; Gupta, Jyotsana; Winter, Kaitlin; Allen, Elizabeth; Brewer, Angela; Beaulieu, Édith; Mallett, Corey P.; Burt, David S.; Ward, Brian J.

2015-01-01

During the 2009–2010 influenza pandemic, an adjuvanted, dose-sparing vaccine was recommended for most Canadians. We hypothesize that differences exist in the responses to AS03-adjuvanted, low antigen (Ag) dose versus unadjuvanted, full-dose vaccines. We investigated the relationship between Ag dose and the oil-in-water emulsion Adjuvant System AS03. BALB/c mice received two IM doses of AS03A or AS03B with exaggerated dilutions of A/Uruguay/716/2007 H3N2 split virion vaccine Ag. Immune responses were assessed 3 weeks after the booster. Unadjuvanted “high” (3 μg) and low-dose (0.03–0.003 μg) vaccines generated similar serum antibody titers and cytokine secretion patterns in restimulated splenocytes. Compared to unadjuvanted “high-dose” vaccination, both AS03A and AS03B-adjuvanted low-dose vaccines tended to elicit higher serum antibody titers, broader induction of cytokine secretion and generated more influenza-specific antibody secreting cells and cytokine-secreting CD4 and CD8 T cells in splenocytes. We show that varying Ag and/or AS03 dose in this influenza vaccination mouse model can strongly influence both the magnitude and pattern of the immune response elicited. These findings are highly relevant given the likelihood of expanded use of adjuvanted, dose-sparing vaccines and raise questions about the use of “standard” doses of vaccines in pre-clinical vaccine studies. PMID:25972874

Evaluating the evidence for non-monotonic dose-response relationships: A systematic literature review and (re-)analysis of in vivo toxicity data in the area of food safety.

PubMed

Varret, C; Beronius, A; Bodin, L; Bokkers, B G H; Boon, P E; Burger, M; De Wit-Bos, L; Fischer, A; Hanberg, A; Litens-Karlsson, S; Slob, W; Wolterink, G; Zilliacus, J; Beausoleil, C; Rousselle, C

2018-01-15

This study aims to evaluate the evidence for the existence of non-monotonic dose-responses (NMDRs) of substances in the area of food safety. This review was performed following the systematic review methodology with the aim to identify in vivo studies published between January 2002 and February 2015 containing evidence for potential NMDRs. Inclusion and reliability criteria were defined and used to select relevant and reliable studies. A set of six checkpoints was developed to establish the likelihood that the data retrieved contained evidence for NMDR. In this review, 49 in vivo studies were identified as relevant and reliable, of which 42 were used for dose-response analysis. These studies contained 179 in vivo dose-response datasets with at least five dose groups (and a control group) as fewer doses cannot provide evidence for NMDR. These datasets were extracted and analyzed using the PROAST software package. The resulting dose-response relationships were evaluated for possible evidence of NMDRs by applying the six checkpoints. In total, 10 out of the 179 in vivo datasets fulfilled all six checkpoints. While these datasets could be considered as providing evidence for NMDR, replicated studies would still be needed to check if the results can be reproduced to rule out that the non-monotonicity was caused by incidental anomalies in that specific study. This approach, combining a systematic review with a set of checkpoints, is new and appears useful for future evaluations of the dose response datasets regarding evidence of non-monotonicity. Published by Elsevier Inc.

TIME COURSE AND DOSE RESPONSE ASSESSMENT OF CHOLINESTERASE (CHE) INHIBITION IN ADULT RATS TREATED ACUTELY WITH CARBARYL, METHOMYL, METHIOCARB, OXAMYL, OR PROPOXUR.

EPA Science Inventory

To compare the toxicity of 5 N-methyl carbamates, the time course and dose response profiles for ChE inhibition were established for each. For the time course comparison, adult male Long Evans rats (n=5 dose group) were dosed orally with either carbaryl (CB; 30 mg/kg in corn oi...

Salmonella Fecal Shedding and Immune Responses are Dose- and Serotype- Dependent in Pigs

PubMed Central

Ivanek, Renata; Österberg, Julia; Gautam, Raju; Sternberg Lewerin, Susanna

2012-01-01

Despite the public health importance of Salmonella infection in pigs, little is known about the associated dynamics of fecal shedding and immunity. In this study, we investigated the transitions of pigs through the states of Salmonella fecal shedding and immune response post-Salmonella inoculation as affected by the challenge dose and serotype. Continuous-time multistate Markov models were developed using published experimental data. The model for shedding had four transient states, of which two were shedding (continuous and intermittent shedding) and two non-shedding (latency and intermittent non-shedding), and one absorbing state representing permanent cessation of shedding. The immune response model had two transient states representing responses below and above the seroconversion level. The effects of two doses [low (0.65×106 CFU/pig) and high (0.65×109 CFU/pig)] and four serotypes (Salmonella Yoruba, Salmonella Cubana, Salmonella Typhimurium, and Salmonella Derby) on the models' transition intensities were evaluated using a proportional intensities model. Results indicated statistically significant effects of the challenge dose and serotype on the dynamics of shedding and immune response. The time spent in the specific states was also estimated. Continuous shedding was on average 10–26 days longer, while intermittent non-shedding was 2–4 days shorter, in pigs challenged with the high compared to low dose. Interestingly, among pigs challenged with the high dose, the continuous and intermittent shedding states were on average up to 10–17 and 3–4 days longer, respectively, in pigs infected with S. Cubana compared to the other three serotypes. Pigs challenged with the high dose of S. Typhimurium or S. Derby seroconverted on average up to 8–11 days faster compared to the low dose. These findings highlight that Salmonella fecal shedding and immune response following Salmonella challenge are dose- and serotype-dependent and that the detection of specific Salmonella strains and immune responses in pigs are time-sensitive. PMID:22523553