Sparsely Ionizing Diagnostic and Natural Background Radiations are Likely Preventing Cancer and Other Genomic-Instability-Associated Diseases

PubMed Central

Scott, Bobby R.; Di Palma, Jennifer

2007-01-01

Routine diagnostic X-rays (e.g., chest X-rays, mammograms, computed tomography scans) and routine diagnostic nuclear medicine procedures using sparsely ionizing radiation forms (e.g., beta and gamma radiations) stimulate the removal of precancerous neo-plastically transformed and other genomically unstable cells from the body (medical radiation hormesis). The indicated radiation hormesis arises because radiation doses above an individual-specific stochastic threshold activate a system of cooperative protective processes that include high-fidelity DNA repair/apoptosis (presumed p53 related), an auxiliary apoptosis process (PAM process) that is presumed p53-independent, and stimulated immunity. These forms of induced protection are called adapted protection because they are associated with the radiation adaptive response. Diagnostic X-ray sources, other sources of sparsely ionizing radiation used in nuclear medicine diagnostic procedures, as well as radioisotope-labeled immunoglobulins could be used in conjunction with apopto-sis-sensitizing agents (e.g., the natural phenolic compound resveratrol) in curing existing cancer via low-dose fractionated or low-dose, low-dose-rate therapy (therapeutic radiation hormesis). Evidence is provided to support the existence of both therapeutic (curing existing cancer) and medical (cancer prevention) radiation hormesis. Evidence is also provided demonstrating that exposure to environmental sparsely ionizing radiations, such as gamma rays, protect from cancer occurrence and the occurrence of other diseases via inducing adapted protection (environmental radiation hormesis). PMID:18648608

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

Yan, H; Chen, Z; Nath, R

Purpose: kV fluoroscopic imaging combined with MV treatment beam imaging has been investigated for intrafractional motion monitoring and correction. It is, however, subject to additional kV imaging dose to normal tissue. To balance tracking accuracy and imaging dose, we previously proposed an adaptive imaging strategy to dynamically decide future imaging type and moments based on motion tracking uncertainty. kV imaging may be used continuously for maximal accuracy or only when the position uncertainty (probability of out of threshold) is high if a preset imaging dose limit is considered. In this work, we propose more accurate methods to estimate tracking uncertaintymore » through analyzing acquired data in real-time. Methods: We simulated motion tracking process based on a previously developed imaging framework (MV + initial seconds of kV imaging) using real-time breathing data from 42 patients. Motion tracking errors for each time point were collected together with the time point’s corresponding features, such as tumor motion speed and 2D tracking error of previous time points, etc. We tested three methods for error uncertainty estimation based on the features: conditional probability distribution, logistic regression modeling, and support vector machine (SVM) classification to detect errors exceeding a threshold. Results: For conditional probability distribution, polynomial regressions on three features (previous tracking error, prediction quality, and cosine of the angle between the trajectory and the treatment beam) showed strong correlation with the variation (uncertainty) of the mean 3D tracking error and its standard deviation: R-square = 0.94 and 0.90, respectively. The logistic regression and SVM classification successfully identified about 95% of tracking errors exceeding 2.5mm threshold. Conclusion: The proposed methods can reliably estimate the motion tracking uncertainty in real-time, which can be used to guide adaptive additional imaging to confirm the tumor is within the margin or initialize motion compensation if it is out of the margin.« less

Bayesian estimation of dose thresholds

NASA Technical Reports Server (NTRS)

Groer, P. G.; Carnes, B. A.

2003-01-01

An example is described of Bayesian estimation of radiation absorbed dose thresholds (subsequently simply referred to as dose thresholds) using a specific parametric model applied to a data set on mice exposed to 60Co gamma rays and fission neutrons. A Weibull based relative risk model with a dose threshold parameter was used to analyse, as an example, lung cancer mortality and determine the posterior density for the threshold dose after single exposures to 60Co gamma rays or fission neutrons from the JANUS reactor at Argonne National Laboratory. The data consisted of survival, censoring times and cause of death information for male B6CF1 unexposed and exposed mice. The 60Co gamma whole-body doses for the two exposed groups were 0.86 and 1.37 Gy. The neutron whole-body doses were 0.19 and 0.38 Gy. Marginal posterior densities for the dose thresholds for neutron and gamma radiation were calculated with numerical integration and found to have quite different shapes. The density of the threshold for 60Co is unimodal with a mode at about 0.50 Gy. The threshold density for fission neutrons declines monotonically from a maximum value at zero with increasing doses. The posterior densities for all other parameters were similar for the two radiation types.

Dosimetrically Triggered Adaptive Intensity Modulated Radiation Therapy for Cervical Cancer

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

Lim, Karen; Stewart, James; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario

2014-09-01

Purpose: The widespread use of intensity modulated radiation therapy (IMRT) for cervical cancer has been limited by internal target and normal tissue motion. Such motion increases the risk of underdosing the target, especially as planning margins are reduced in an effort to reduce toxicity. This study explored 2 adaptive strategies to mitigate this risk and proposes a new, automated method that minimizes replanning workload. Methods and Materials: Thirty patients with cervical cancer participated in a prospective clinical study and underwent pretreatment and weekly magnetic resonance (MR) scans over a 5-week course of daily external beam radiation therapy. Target volumes andmore » organs at risk (OARs) were contoured on each of the scans. Deformable image registration was used to model the accumulated dose (the real dose delivered to the target and OARs) for 2 adaptive replanning scenarios that assumed a very small PTV margin of only 3 mm to account for setup and internal interfractional motion: (1) a preprogrammed, anatomy-driven midtreatment replan (A-IMRT); and (2) a dosimetry-triggered replan driven by target dose accumulation over time (D-IMRT). Results: Across all 30 patients, clinically relevant target dose thresholds failed for 8 patients (27%) if 3-mm margins were used without replanning. A-IMRT failed in only 3 patients and also yielded an additional small reduction in OAR doses at the cost of 30 replans. D-IMRT assured adequate target coverage in all patients, with only 23 replans in 16 patients. Conclusions: A novel, dosimetry-triggered adaptive IMRT strategy for patients with cervical cancer can minimize the risk of target underdosing in the setting of very small margins and substantial interfractional motion while minimizing programmatic workload and cost.« less

ADAPTIVE THRESHOLD LOGIC.

DTIC Science & Technology

The design and construction of a 16 variable threshold logic gate with adaptable weights is described. The operating characteristics of tape wound...and sizes as well as for the 16 input adaptive threshold logic gate. (Author)

Feasibility of MR-only proton dose calculations for prostate cancer radiotherapy using a commercial pseudo-CT generation method

NASA Astrophysics Data System (ADS)

Maspero, Matteo; van den Berg, Cornelis A. T.; Landry, Guillaume; Belka, Claus; Parodi, Katia; Seevinck, Peter R.; Raaymakers, Bas W.; Kurz, Christopher

2017-12-01

A magnetic resonance (MR)-only radiotherapy workflow can reduce cost, radiation exposure and uncertainties introduced by CT-MRI registration. A crucial prerequisite is generating the so called pseudo-CT (pCT) images for accurate dose calculation and planning. Many pCT generation methods have been proposed in the scope of photon radiotherapy. This work aims at verifying for the first time whether a commercially available photon-oriented pCT generation method can be employed for accurate intensity-modulated proton therapy (IMPT) dose calculation. A retrospective study was conducted on ten prostate cancer patients. For pCT generation from MR images, a commercial solution for creating bulk-assigned pCTs, called MR for Attenuation Correction (MRCAT), was employed. The assigned pseudo-Hounsfield Unit (HU) values were adapted to yield an increased agreement to the reference CT in terms of proton range. Internal air cavities were copied from the CT to minimise inter-scan differences. CT- and MRCAT-based dose calculations for opposing beam IMPT plans were compared by gamma analysis and evaluation of clinically relevant target and organ at risk dose volume histogram (DVH) parameters. The proton range in beam’s eye view (BEV) was compared using single field uniform dose (SFUD) plans. On average, a (2%, 2 mm) gamma pass rate of 98.4% was obtained using a 10% dose threshold after adaptation of the pseudo-HU values. Mean differences between CT- and MRCAT-based dose in the DVH parameters were below 1 Gy (<1.5% ). The median proton range difference was 0.1 mm, with on average 96% of all BEV dose profiles showing a range agreement better than 3 mm. Results suggest that accurate MR-based proton dose calculation using an automatic commercial bulk-assignment pCT generation method, originally designed for photon radiotherapy, is feasible following adaptation of the assigned pseudo-HU values.

Adaptive Spike Threshold Enables Robust and Temporally Precise Neuronal Encoding

PubMed Central

Resnik, Andrey; Celikel, Tansu; Englitz, Bernhard

2016-01-01

Neural processing rests on the intracellular transformation of information as synaptic inputs are translated into action potentials. This transformation is governed by the spike threshold, which depends on the history of the membrane potential on many temporal scales. While the adaptation of the threshold after spiking activity has been addressed before both theoretically and experimentally, it has only recently been demonstrated that the subthreshold membrane state also influences the effective spike threshold. The consequences for neural computation are not well understood yet. We address this question here using neural simulations and whole cell intracellular recordings in combination with information theoretic analysis. We show that an adaptive spike threshold leads to better stimulus discrimination for tight input correlations than would be achieved otherwise, independent from whether the stimulus is encoded in the rate or pattern of action potentials. The time scales of input selectivity are jointly governed by membrane and threshold dynamics. Encoding information using adaptive thresholds further ensures robust information transmission across cortical states i.e. decoding from different states is less state dependent in the adaptive threshold case, if the decoding is performed in reference to the timing of the population response. Results from in vitro neural recordings were consistent with simulations from adaptive threshold neurons. In summary, the adaptive spike threshold reduces information loss during intracellular information transfer, improves stimulus discriminability and ensures robust decoding across membrane states in a regime of highly correlated inputs, similar to those seen in sensory nuclei during the encoding of sensory information. PMID:27304526

Adaptive Spike Threshold Enables Robust and Temporally Precise Neuronal Encoding.

PubMed

Huang, Chao; Resnik, Andrey; Celikel, Tansu; Englitz, Bernhard

2016-06-01

Neural processing rests on the intracellular transformation of information as synaptic inputs are translated into action potentials. This transformation is governed by the spike threshold, which depends on the history of the membrane potential on many temporal scales. While the adaptation of the threshold after spiking activity has been addressed before both theoretically and experimentally, it has only recently been demonstrated that the subthreshold membrane state also influences the effective spike threshold. The consequences for neural computation are not well understood yet. We address this question here using neural simulations and whole cell intracellular recordings in combination with information theoretic analysis. We show that an adaptive spike threshold leads to better stimulus discrimination for tight input correlations than would be achieved otherwise, independent from whether the stimulus is encoded in the rate or pattern of action potentials. The time scales of input selectivity are jointly governed by membrane and threshold dynamics. Encoding information using adaptive thresholds further ensures robust information transmission across cortical states i.e. decoding from different states is less state dependent in the adaptive threshold case, if the decoding is performed in reference to the timing of the population response. Results from in vitro neural recordings were consistent with simulations from adaptive threshold neurons. In summary, the adaptive spike threshold reduces information loss during intracellular information transfer, improves stimulus discriminability and ensures robust decoding across membrane states in a regime of highly correlated inputs, similar to those seen in sensory nuclei during the encoding of sensory information.

Contributions of adaptation currents to dynamic spike threshold on slow timescales: Biophysical insights from conductance-based models

NASA Astrophysics Data System (ADS)

Yi, Guosheng; Wang, Jiang; Wei, Xile; Deng, Bin; Li, Huiyan; Che, Yanqiu

2017-06-01

Spike-frequency adaptation (SFA) mediated by various adaptation currents, such as voltage-gated K+ current (IM), Ca2+-gated K+ current (IAHP), or Na+-activated K+ current (IKNa), exists in many types of neurons, which has been shown to effectively shape their information transmission properties on slow timescales. Here we use conductance-based models to investigate how the activation of three adaptation currents regulates the threshold voltage for action potential (AP) initiation during the course of SFA. It is observed that the spike threshold gets depolarized and the rate of membrane depolarization (dV/dt) preceding AP is reduced as adaptation currents reduce firing rate. It is indicated that the presence of inhibitory adaptation currents enables the neuron to generate a dynamic threshold inversely correlated with preceding dV/dt on slower timescales than fast dynamics of AP generation. By analyzing the interactions of ionic currents at subthreshold potentials, we find that the activation of adaptation currents increase the outward level of net membrane current prior to AP initiation, which antagonizes inward Na+ to result in a depolarized threshold and lower dV/dt from one AP to the next. Our simulations demonstrate that the threshold dynamics on slow timescales is a secondary effect caused by the activation of adaptation currents. These findings have provided a biophysical interpretation of the relationship between adaptation currents and spike threshold.

Explicit optimization of plan quality measures in intensity-modulated radiation therapy treatment planning.

PubMed

Engberg, Lovisa; Forsgren, Anders; Eriksson, Kjell; Hårdemark, Björn

2017-06-01

To formulate convex planning objectives of treatment plan multicriteria optimization with explicit relationships to the dose-volume histogram (DVH) statistics used in plan quality evaluation. Conventional planning objectives are designed to minimize the violation of DVH statistics thresholds using penalty functions. Although successful in guiding the DVH curve towards these thresholds, conventional planning objectives offer limited control of the individual points on the DVH curve (doses-at-volume) used to evaluate plan quality. In this study, we abandon the usual penalty-function framework and propose planning objectives that more closely relate to DVH statistics. The proposed planning objectives are based on mean-tail-dose, resulting in convex optimization. We also demonstrate how to adapt a standard optimization method to the proposed formulation in order to obtain a substantial reduction in computational cost. We investigated the potential of the proposed planning objectives as tools for optimizing DVH statistics through juxtaposition with the conventional planning objectives on two patient cases. Sets of treatment plans with differently balanced planning objectives were generated using either the proposed or the conventional approach. Dominance in the sense of better distributed doses-at-volume was observed in plans optimized within the proposed framework. The initial computational study indicates that the DVH statistics are better optimized and more efficiently balanced using the proposed planning objectives than using the conventional approach. © 2017 American Association of Physicists in Medicine.

Ionizing radiation sensitivity of the ocular lens and its dose rate dependence.

PubMed

Hamada, Nobuyuki

2017-10-01

In 2011, the International Commission on Radiological Protection reduced the threshold for the lens effects of low linear energy transfer (LET) radiation. On one hand, the revised threshold of 0.5 Gy is much lower than previously recommended thresholds, but mechanisms behind high radiosensitivity remain incompletely understood. On the other hand, such a threshold is independent of dose rate, in contrast to previously recommended separate thresholds each for single and fractionated/protracted exposures. Such a change was made predicated on epidemiological evidence suggesting that a threshold for fractionated/protracted exposures is not higher than an acute threshold, and that a chronic threshold is uncertain. Thus, the dose rate dependence is still unclear. This paper therefore reviews the current knowledge on the radiosensitivity of the lens and the dose rate dependence of radiation cataractogenesis, and discusses its mechanisms. Mounting biological evidence indicates that the lens cells are not necessarily radiosensitive to cell killing, and the high radiosensitivity of the lens thus appears to be attributable to other mechanisms (e.g., excessive proliferation, abnormal differentiation, a slow repair of DNA double-strand breaks, telomere, senescence, crystallin changes, non-targeted effects and inflammation). Both biological and epidemiological evidence generally supports the lack of dose rate effects. However, there is also biological evidence for the tissue sparing dose rate (or fractionation) effect of low-LET radiation and an enhancing inverse dose fractionation effect of high-LET radiation at a limited range of LET. Emerging epidemiological evidence in chronically exposed individuals implies the inverse dose rate effect. Further biological and epidemiological studies are warranted to gain deeper knowledge on the radiosensitivity of the lens and dose rate dependence of radiation cataractogenesis.

A Critical, Nonlinear Threshold Dictates Bacterial Invasion and Initial Kinetics During Influenza

NASA Astrophysics Data System (ADS)

Smith, Amber M.; Smith, Amanda P.

2016-12-01

Secondary bacterial infections increase morbidity and mortality of influenza A virus (IAV) infections. Bacteria are able to invade due to virus-induced depletion of alveolar macrophages (AMs), but this is not the only contributing factor. By analyzing a kinetic model, we uncovered a nonlinear initial dose threshold that is dependent on the amount of virus-induced AM depletion. The threshold separates the growth and clearance phenotypes such that bacteria decline for dose-AM depletion combinations below the threshold, stay constant near the threshold, and increase above the threshold. In addition, the distance from the threshold correlates to the growth rate. Because AM depletion changes throughout an IAV infection, the dose requirement for bacterial invasion also changes accordingly. Using the threshold, we found that the dose requirement drops dramatically during the first 7d of IAV infection. We then validated these analytical predictions by infecting mice with doses below or above the predicted threshold over the course of IAV infection. These results identify the nonlinear way in which two independent factors work together to support successful post-influenza bacterial invasion. They provide insight into coinfection timing, the heterogeneity in outcome, the probability of acquiring a coinfection, and the use of new therapeutic strategies to combat viral-bacterial coinfections.

Electroconvulsive therapy stimulus titration: Not all it seems.

PubMed

Rosenman, Stephen J

2018-05-01

To examine the provenance and implications of seizure threshold titration in electroconvulsive therapy. Titration of seizure threshold has become a virtual standard for electroconvulsive therapy. It is justified as individualisation and optimisation of the balance between efficacy and unwanted effects. Present day threshold estimation is significantly different from the 1960 studies of Cronholm and Ottosson that are its usual justification. The present form of threshold estimation is unstable and too uncertain for valid optimisation or individualisation of dose. Threshold stimulation (lowest dose that produces a seizure) has proven therapeutically ineffective, and the multiples applied to threshold to attain efficacy have never been properly investigated or standardised. The therapeutic outcomes of threshold estimation (or its multiples) have not been separated from simple dose effects. Threshold estimation does not optimise dose due to its own uncertainties and the different short-term and long-term cognitive and memory effects. Potential harms of titration have not been examined. Seizure threshold titration in electroconvulsive therapy is not a proven technique of dose optimisation. It is widely held and practiced; its benefit and harmlessness assumed but unproven. It is a prematurely settled answer to an unsettled question that discourages further enquiry. It is an example of how practices, assumed scientific, enter medicine by obscure paths.

A Critical, Nonlinear Threshold Dictates Bacterial Invasion and Initial Kinetics During Influenza.

PubMed

Smith, Amber M; Smith, Amanda P

2016-12-15

Secondary bacterial infections increase morbidity and mortality of influenza A virus (IAV) infections. Bacteria are able to invade due to virus-induced depletion of alveolar macrophages (AMs), but this is not the only contributing factor. By analyzing a kinetic model, we uncovered a nonlinear initial dose threshold that is dependent on the amount of virus-induced AM depletion. The threshold separates the growth and clearance phenotypes such that bacteria decline for dose-AM depletion combinations below the threshold, stay constant near the threshold, and increase above the threshold. In addition, the distance from the threshold correlates to the growth rate. Because AM depletion changes throughout an IAV infection, the dose requirement for bacterial invasion also changes accordingly. Using the threshold, we found that the dose requirement drops dramatically during the first 7d of IAV infection. We then validated these analytical predictions by infecting mice with doses below or above the predicted threshold over the course of IAV infection. These results identify the nonlinear way in which two independent factors work together to support successful post-influenza bacterial invasion. They provide insight into coinfection timing, the heterogeneity in outcome, the probability of acquiring a coinfection, and the use of new therapeutic strategies to combat viral-bacterial coinfections.

Estimation of Second Primary Cancer Risk After Treatment with Radioactive Iodine for Differentiated Thyroid Carcinoma.

PubMed

Corrêa, Nilton Lavatori; de Sá, Lidia Vasconcellos; de Mello, Rossana Corbo Ramalho

2017-02-01

An increase in the incidence of second primary cancers is the late effect of greatest concern that could occur in differentiated thyroid carcinoma (DTC) patients treated with radioactive iodine (RAI). The decision to treat a patient with RAI should therefore incorporate a careful risk-benefit analysis. The objective of this work was to adapt the risk-estimation models developed by the Biological Effects of Ionizing Radiation Committee to local epidemiological characteristics in order to assess the carcinogenesis risk from radiation in a population of Brazilian DTC patients treated with RAI. Absorbed radiation doses in critical organs were also estimated to determine whether they exceeded the thresholds for deterministic effects. A total of 416 DTC patients treated with RAI were retrospectively studied. Four organs were selected for absorbed dose estimation and subsequent calculation of carcinogenic risk: the kidney, stomach, salivary glands, and bone marrow. Absorbed doses were calculated by dose factors (absorbed dose per unit activity administered) previously established and based on standard human models. The lifetime attributable risk (LAR) of incidence of cancer as a function of age, sex, and organ-specific dose was estimated, relating it to the activity of RAI administered in the initial treatment. The salivary glands received the greatest absorbed doses of radiation, followed by the stomach, kidney, and bone marrow. None of these, however, surpassed the threshold for deterministic effects for a single administration of RAI. Younger patients received the same level of absorbed dose in the critical organs as older patients did. The lifetime attributable risk for stomach cancer incidence was by far the highest, followed in descending order by salivary-gland cancer, leukemia, and kidney cancer. RAI in a single administration is safe in terms of deterministic effects because even high-administered activities do not result in absorbed doses that exceed the thresholds for significant tissue reactions. The Biological Effects of Ionizing Radiation Committee mathematical models are a practical method of quantifying the risks of a second primary cancer, demonstrating a marked decrease in risk for younger patients with the administration of lower RAI activities and suggesting that only the smallest activities necessary to promote an effective ablation should be administered in low-risk DTC patients.

The Limits to Adaptation; A Systems Approach

EPA Science Inventory

The Limits to Adaptation: A Systems Approach. The ability to adapt to climate change is delineated by capacity thresholds, after which climate damages begin to overwhelm the adaptation response. Such thresholds depend upon physical properties (natural processes and engineering...

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

Homeopathy: clarifying its relationship to hormesis.

PubMed

Calabrese, Edward J; Jonas, Wayne B

2010-07-01

This paper presents the case that certain types of homeopathic medicine may represent a form of hormesis, that is, either pre- or post-conditioning hormesis. An example of a post-conditioning model by van Wijk and colleagues demonstrated successful enhancement of adaptive responses using below-toxic threshold doses (i.e. hormetic doses) of inducing agents when administered subsequent to a highly toxic chemical exposure, thus satisfying a basic experimental biomedical standard. Of note is that this model uses exposures within a measurable predicted hormetic range, unlike most forms of homeopathy. This experimental framework (along with a pre-conditioning model developed by Bellavite) provides a possible vehicle by which certain aspect(s) of homeopathy may be integrated into mainstream biomedical assessment and clinical practice.

Optimizing drug-dose alerts using commercial software throughout an integrated health care system.

PubMed

Saiyed, Salim M; Greco, Peter J; Fernandes, Glenn; Kaelber, David C

2017-11-01

All default electronic health record and drug reference database vendor drug-dose alerting recommendations (single dose, daily dose, dose frequency, and dose duration) were silently turned on in inpatient, outpatient, and emergency department areas for pediatric-only and nonpediatric-only populations. Drug-dose alerts were evaluated during a 3-month period. Drug-dose alerts fired on 12% of orders (104 098/834 911). System-level and drug-specific strategies to decrease drug-dose alerts were analyzed. System-level strategies included: (1) turning off all minimum drug-dosing alerts, (2) turning off all incomplete information drug-dosing alerts, (3) increasing the maximum single-dose drug-dose alert threshold to 125%, (4) increasing the daily dose maximum drug-dose alert threshold to 125%, and (5) increasing the dose frequency drug-dose alert threshold to more than 2 doses per day above initial threshold. Drug-specific strategies included changing drug-specific maximum single and maximum daily drug-dose alerting parameters for the top 22 drug categories by alert frequency. System-level approaches decreased alerting to 5% (46 988/834 911) and drug-specific approaches decreased alerts to 3% (25 455/834 911). Drug-dose alerts varied between care settings and patient populations. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Adaptive threshold shearlet transform for surface microseismic data denoising

NASA Astrophysics Data System (ADS)

Tang, Na; Zhao, Xian; Li, Yue; Zhu, Dan

2018-06-01

Random noise suppression plays an important role in microseismic data processing. The microseismic data is often corrupted by strong random noise, which would directly influence identification and location of microseismic events. Shearlet transform is a new multiscale transform, which can effectively process the low magnitude of microseismic data. In shearlet domain, due to different distributions of valid signals and random noise, shearlet coefficients can be shrunk by threshold. Therefore, threshold is vital in suppressing random noise. The conventional threshold denoising algorithms usually use the same threshold to process all coefficients, which causes noise suppression inefficiency or valid signals loss. In order to solve above problems, we propose the adaptive threshold shearlet transform (ATST) for surface microseismic data denoising. In the new algorithm, we calculate the fundamental threshold for each direction subband firstly. In each direction subband, the adjustment factor is obtained according to each subband coefficient and its neighboring coefficients, in order to adaptively regulate the fundamental threshold for different shearlet coefficients. Finally we apply the adaptive threshold to deal with different shearlet coefficients. The experimental denoising results of synthetic records and field data illustrate that the proposed method exhibits better performance in suppressing random noise and preserving valid signal than the conventional shearlet denoising method.

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...

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...

The Limits to Adaptation: A Systems Approach

EPA Science Inventory

The ability to adapt to climate change is delineated by capacity thresholds, after which climate damages begin to overwhelm the adaptation response. Such thresholds depend upon physical properties (natural processes and engineering parameters), resource constraints (expressed th...

Characterizing Decision-Analysis Performances of Risk Prediction Models Using ADAPT Curves.

PubMed

Lee, Wen-Chung; Wu, Yun-Chun

2016-01-01

The area under the receiver operating characteristic curve is a widely used index to characterize the performance of diagnostic tests and prediction models. However, the index does not explicitly acknowledge the utilities of risk predictions. Moreover, for most clinical settings, what counts is whether a prediction model can guide therapeutic decisions in a way that improves patient outcomes, rather than to simply update probabilities.Based on decision theory, the authors propose an alternative index, the "average deviation about the probability threshold" (ADAPT).An ADAPT curve (a plot of ADAPT value against the probability threshold) neatly characterizes the decision-analysis performances of a risk prediction model.Several prediction models can be compared for their ADAPT values at a chosen probability threshold, for a range of plausible threshold values, or for the whole ADAPT curves. This should greatly facilitate the selection of diagnostic tests and prediction models.

Wavelet-based adaptive thresholding method for image segmentation

NASA Astrophysics Data System (ADS)

Chen, Zikuan; Tao, Yang; Chen, Xin; Griffis, Carl

2001-05-01

A nonuniform background distribution may cause a global thresholding method to fail to segment objects. One solution is using a local thresholding method that adapts to local surroundings. In this paper, we propose a novel local thresholding method for image segmentation, using multiscale threshold functions obtained by wavelet synthesis with weighted detail coefficients. In particular, the coarse-to- fine synthesis with attenuated detail coefficients produces a threshold function corresponding to a high-frequency- reduced signal. This wavelet-based local thresholding method adapts to both local size and local surroundings, and its implementation can take advantage of the fast wavelet algorithm. We applied this technique to physical contaminant detection for poultry meat inspection using x-ray imaging. Experiments showed that inclusion objects in deboned poultry could be extracted at multiple resolutions despite their irregular sizes and uneven backgrounds.

Hydroxyisohexyl 3-cyclohexene carboxaldehyde allergy: relationship between patch test and repeated open application test thresholds.

PubMed

Fischer, L A; Menné, T; Avnstorp, C; Kasting, G B; Johansen, J D

2009-09-01

Hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) is a synthetic fragrance ingredient. Case reports of allergy to HICC appeared in the 1980s, and HICC has recently been included in the European baseline series. Human elicitation dose-response studies performed with different allergens have shown a significant relationship between the patch-test threshold and the repeated open application test (ROAT) threshold, which mimics some real-life exposure situations. Fragrance ingredients are special as significant amounts of allergen may evaporate from the skin. The study aimed to investigate the relationship between elicitation threshold doses at the patch test and the ROAT, using HICC as the allergen. The expected evaporation rate was calculated. Seventeen HICC-allergic persons were tested with a dilution series of HICC in a patch test and a ROAT (duration up to 21 days). Seventeen persons with no HICC allergy were included as control group for the ROAT. Results The response frequency to the ROAT (in microg HICC cm(-2) per application) was significantly higher than the response frequency to the patch test at one of the tested doses. Furthermore the response rate to the accumulated ROAT dose was significantly lower at half of the doses compared with the patch test. The evaporation rate of HICC was calculated to be 72% over a 24-h period. The ROAT threshold in dose per area per application is lower than the patch test threshold; furthermore the accumulated ROAT threshold is higher than the patch test threshold, which can probably be explained by the evaporation of HICC from the skin in the open test.

Role of extrinsic noise in the sensitivity of the rod pathway: rapid dark adaptation of nocturnal vision in humans.

PubMed

Reeves, Adam; Grayhem, Rebecca

2016-03-01

Rod-mediated 500 nm test spots were flashed in Maxwellian view at 5 deg eccentricity, both on steady 10.4 deg fields of intensities (I) from 0.00001 to 1.0 scotopic troland (sc td) and from 0.2 s to 1 s after extinguishing the field. On dim fields, thresholds of tiny (5') tests were proportional to √I (Rose-DeVries law), while thresholds after extinction fell within 0.6 s to the fully dark-adapted absolute threshold. Thresholds of large (1.3 deg) tests were proportional to I (Weber law) and extinction thresholds, to √I. rod thresholds are elevated by photon-driven noise from dim fields that disappears at field extinction; large spot thresholds are additionally elevated by neural light adaptation proportional to √I. At night, recovery from dimly lit fields is fast, not slow.

Robust Adaptive Thresholder For Document Scanning Applications

NASA Astrophysics Data System (ADS)

Hsing, To R.

1982-12-01

In document scanning applications, thresholding is used to obtain binary data from a scanner. However, due to: (1) a wide range of different color backgrounds; (2) density variations of printed text information; and (3) the shading effect caused by the optical systems, the use of adaptive thresholding to enhance the useful information is highly desired. This paper describes a new robust adaptive thresholder for obtaining valid binary images. It is basically a memory type algorithm which can dynamically update the black and white reference level to optimize a local adaptive threshold function. The results of high image quality from different types of simulate test patterns can be obtained by this algorithm. The software algorithm is described and experiment results are present to describe the procedures. Results also show that the techniques described here can be used for real-time signal processing in the varied applications.

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...

Synergy of adaptive thresholds and multiple transmitters in free-space optical communication.

PubMed

Louthain, James A; Schmidt, Jason D

2010-04-26

Laser propagation through extended turbulence causes severe beam spread and scintillation. Airborne laser communication systems require special considerations in size, complexity, power, and weight. Rather than using bulky, costly, adaptive optics systems, we reduce the variability of the received signal by integrating a two-transmitter system with an adaptive threshold receiver to average out the deleterious effects of turbulence. In contrast to adaptive optics approaches, systems employing multiple transmitters and adaptive thresholds exhibit performance improvements that are unaffected by turbulence strength. Simulations of this system with on-off-keying (OOK) showed that reducing the scintillation variations with multiple transmitters improves the performance of low-frequency adaptive threshold estimators by 1-3 dB. The combination of multiple transmitters and adaptive thresholding provided at least a 10 dB gain over implementing only transmitter pointing and receiver tilt correction for all three high-Rytov number scenarios. The scenario with a spherical-wave Rytov number R=0.20 enjoyed a 13 dB reduction in the required SNR for BER's between 10(-5) to 10(-3), consistent with the code gain metric. All five scenarios between 0.06 and 0.20 Rytov number improved to within 3 dB of the SNR of the lowest Rytov number scenario.

Vibratory Adaptation of Cutaneous Mechanoreceptive Afferents

PubMed Central

Bensmaïa, S. J.; Leung, Y. Y.; Hsiao, S. S.; Johnson, K. O.

2007-01-01

The objective of this study was to investigate the effects of extended suprathreshold vibratory stimulation on the sensitivity of slowly adapting type 1 (SA1), rapidly adapting (RA), and Pacinian (PC) afferents. To that end, an algorithm was developed to track afferent absolute (I0) and entrainment (I1) thresholds as they change over time. We recorded afferent responses to periliminal vibratory test stimuli, which were interleaved with intense vibratory conditioning stimuli during the adaptation period of each experimental run. From these measurements, the algorithm allowed us to infer changes in the afferents’ sensitivity. We investigated the stimulus parameters that affect adaptation by assessing the degree to which adaptation depends on the amplitude and frequency of the adapting stimulus. For all three afferent types, I0 and I1 increased with increasing adaptation frequency and amplitude. The degree of adaptation seems to be independent of the firing rate evoked in the afferent by the conditioning stimulus. In the analysis, we distinguished between additive adaptation (in which I0 and I1 shift equally) and multiplicative effects (in which the ratio I1/I0 remains constant). RA threshold shifts are almost perfectly additive. SA1 threshold shifts are close to additive and far from multiplicative (I1 threshold shifts are twice the shifts). PC shifts are more difficult to classify. We used an I0 integrate-and-fire model to study the possible neural mechanisms. A change in transducer gain predicts a multiplicative change in I0 and I1 and is thus ruled out as a mechanism underlying SA1 and RA adaptation. A change in the resting action potential threshold predicts equal, additive change in I0 and I1 and thus accounts well for RA adaptation. A change in the degree of refractoriness during the relative refractory period predicts an additional change in I1 such as that observed for SA1 fibers. We infer that adaptation is caused by an increase in spiking thresholds produced by ion flow through transducer channels in the receptor membrane. In a companion paper, we describe the time-course of vibratory adaptation and recovery for SA1, RA, and PC fibers. PMID:16014802

Damage threshold of platinum coating used for optics for self-seeding of soft x-ray free electron laser

DOE PAGES

Krzywinski, Jacek; Cocco, Daniele; Moeller, Stefan; ...

2015-02-23

We investigated the experimental damage threshold of platinum coating on a silicon substrate illuminated by soft x-ray radiation at grazing incidence angle of 2.1 deg. The coating was the same as the blazed grating used for the soft X-ray self-seeding optics of the Linac Coherent Light Source free electron laser. The irradiation condition was chosen such that the absorbed dose was similar to the maximum dose expected for the grating. The expected dose was simulated by solving the Helmholtz equation in non-homogenous media. The experiment was performed at 900 eV photon energy for both single pulse and multi-shot conditions. Wemore » have not observed single shot damage. This corresponds to a single shot damage threshold being higher than 3 J/cm 2. The multiple shot damage threshold measured for 10 shots and about 600 shots was determined to be 0.95 J/cm 2 and 0.75 J/cm 2 respectively. The damage threshold occurred at an instantaneous dose which is higher that the melt dose of platinum.« less

Defect Detection of Steel Surfaces with Global Adaptive Percentile Thresholding of Gradient Image

NASA Astrophysics Data System (ADS)

Neogi, Nirbhar; Mohanta, Dusmanta K.; Dutta, Pranab K.

2017-12-01

Steel strips are used extensively for white goods, auto bodies and other purposes where surface defects are not acceptable. On-line surface inspection systems can effectively detect and classify defects and help in taking corrective actions. For detection of defects use of gradients is very popular in highlighting and subsequently segmenting areas of interest in a surface inspection system. Most of the time, segmentation by a fixed value threshold leads to unsatisfactory results. As defects can be both very small and large in size, segmentation of a gradient image based on percentile thresholding can lead to inadequate or excessive segmentation of defective regions. A global adaptive percentile thresholding of gradient image has been formulated for blister defect and water-deposit (a pseudo defect) in steel strips. The developed method adaptively changes the percentile value used for thresholding depending on the number of pixels above some specific values of gray level of the gradient image. The method is able to segment defective regions selectively preserving the characteristics of defects irrespective of the size of the defects. The developed method performs better than Otsu method of thresholding and an adaptive thresholding method based on local properties.

Classification of radiation effects for dose limitation purposes: history, current situation and future prospects

PubMed Central

Hamada, Nobuyuki; Fujimichi, Yuki

2014-01-01

Radiation exposure causes cancer and non-cancer health effects, each of which differs greatly in the shape of the dose–response curve, latency, persistency, recurrence, curability, fatality and impact on quality of life. In recent decades, for dose limitation purposes, the International Commission on Radiological Protection has divided such diverse effects into tissue reactions (formerly termed non-stochastic and deterministic effects) and stochastic effects. On the one hand, effective dose limits aim to reduce the risks of stochastic effects (cancer/heritable effects) and are based on the detriment-adjusted nominal risk coefficients, assuming a linear-non-threshold dose response and a dose and dose rate effectiveness factor of 2. On the other hand, equivalent dose limits aim to avoid tissue reactions (vision-impairing cataracts and cosmetically unacceptable non-cancer skin changes) and are based on a threshold dose. However, the boundary between these two categories is becoming vague. Thus, we review the changes in radiation effect classification, dose limitation concepts, and the definition of detriment and threshold. Then, the current situation is overviewed focusing on (i) stochastic effects with a threshold, (ii) tissue reactions without a threshold, (iii) target organs/tissues for circulatory disease, (iv) dose levels for limitation of cancer risks vs prevention of non-life-threatening tissue reactions vs prevention of life-threatening tissue reactions, (v) mortality or incidence of thyroid cancer, and (vi) the detriment for tissue reactions. For future discussion, one approach is suggested that classifies radiation effects according to whether effects are life threatening, and radiobiological research needs are also briefly discussed. PMID:24794798

Adaptive threshold control for auto-rate fallback algorithm in IEEE 802.11 multi-rate WLANs

NASA Astrophysics Data System (ADS)

Wu, Qilin; Lu, Yang; Zhu, Xiaolin; Ge, Fangzhen

2012-03-01

The IEEE 802.11 standard supports multiple rates for data transmission in the physical layer. Nowadays, to improve network performance, a rate adaptation scheme called auto-rate fallback (ARF) is widely adopted in practice. However, ARF scheme suffers performance degradation in multiple contending nodes environments. In this article, we propose a novel rate adaptation scheme called ARF with adaptive threshold control. In multiple contending nodes environment, the proposed scheme can effectively mitigate the frame collision effect on rate adaptation decision by adaptively adjusting rate-up and rate-down threshold according to the current collision level. Simulation results show that the proposed scheme can achieve significantly higher throughput than the other existing rate adaptation schemes. Furthermore, the simulation results also demonstrate that the proposed scheme can effectively respond to the varying channel condition.

Mode of Action (MOA) and Dose-Response Approaches for Nuclear Receptors

EPA Science Inventory

Abstract: The presence of sub-threshold doses for non-cancer and (in appropriate cases) cancer has been the dominant paradigm for the practice of risk assessment, but the application of dose-response modeling approaches that include a threshold have been questioned in a 2009 NRC ...

Closed-loop adaptation of neurofeedback based on mental effort facilitates reinforcement learning of brain self-regulation.

PubMed

Bauer, Robert; Fels, Meike; Royter, Vladislav; Raco, Valerio; Gharabaghi, Alireza

2016-09-01

Considering self-rated mental effort during neurofeedback may improve training of brain self-regulation. Twenty-one healthy, right-handed subjects performed kinesthetic motor imagery of opening their left hand, while threshold-based classification of beta-band desynchronization resulted in proprioceptive robotic feedback. The experiment consisted of two blocks in a cross-over design. The participants rated their perceived mental effort nine times per block. In the adaptive block, the threshold was adjusted on the basis of these ratings whereas adjustments were carried out at random in the other block. Electroencephalography was used to examine the cortical activation patterns during the training sessions. The perceived mental effort was correlated with the difficulty threshold of neurofeedback training. Adaptive threshold-setting reduced mental effort and increased the classification accuracy and positive predictive value. This was paralleled by an inter-hemispheric cortical activation pattern in low frequency bands connecting the right frontal and left parietal areas. Optimal balance of mental effort was achieved at thresholds significantly higher than maximum classification accuracy. Rating of mental effort is a feasible approach for effective threshold-adaptation during neurofeedback training. Closed-loop adaptation of the neurofeedback difficulty level facilitates reinforcement learning of brain self-regulation. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

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

A composite microdose Adaptive Response (AR) and Bystander Effect (BE) model-application to low LET and high LET AR and BE data.

PubMed

Leonard, Bobby E

2008-08-01

It has been suggested that Adaptive Response (AR) may reduce risk of adverse health effects due to ionizing radiation. But very low dose Bystander Effects (BE) may impose dominant deleterious human risks. These conflicting behaviors have stimulated controversy regarding the Linear No-Threshold human risk model. A dose and dose rate-dependent microdose model, to examine AR behavior, was developed in prior work. In the prior work a number of in vitro and in vivo dose response data were examined with the model. Recent new data show AR behavior with some evidence of very low dose BE. The purpose of this work is to supplement the microdose model to encompass the Brenner and colleagues BaD (Bystander and Direct Damage) model and apply this composite model to obtain new knowledge regarding AR and BE and illustrate the use of the model to plan radio-biology experiments. The biophysical composite AR and BE Microdose Model quantifies the accumulation of hits (Poisson distributed, microdose specific energy depositions) to cell nucleus volumes. This new composite AR and BE model provides predictions of dose response at very low dose BE levels, higher dose AR levels and even higher dose Direct (linear-quadratic) Damage radiation levels. We find good fits of the model to both BE data from the Columbia University microbeam facility and combined AR and BE data for low Linear Energy Transfer (LET) and high LET data. A Bystander Factor of about 27,000 and an AR protection factor of 0.61 are obtained for the low LET in vivo mouse spleen exposures. A Bystander Factor of 317 and an AR protection factor of 0.53 are obtained for high LET radon alpha particles in human lymphocytes. In both cases the AR is activated at most by one or two radiation induced charged particle traversals through the cell nucleus. The results of the model analysis is consistent with a premise that both Bystander damage and Adaptive Response radioprotection can occur in the same cell type, derived from the same cell species. The model provides an analytical tool to biophysically study the combined effects of BE and AR.

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

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

Bruner, A.

1976-09-01

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

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...

The risk equivalent of an exposure to-, versus a dose of radiation

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

Bond, V.P.

The long-term potential carcinogenic effects of low-level exposure (LLE) are addressed. The principal point discussed is linear, no-threshold dose-response curve. That the linear no-threshold, or proportional relationship is widely used is seen in the way in which the values for cancer risk coefficients are expressed - in terms of new cases, per million persons exposed, per year, per unit exposure or dose. This implies that the underlying relationship is proportional, i.e., ''linear, without threshold''. 12 refs., 9 figs., 1 tab.

DARK ADAPTATION IN DINEUTES

PubMed Central

Clark, Leonard B.

1938-01-01

The level of dark adaptation of the whirligig beetle can be measured in terms of the threshold intensity calling forth a response. The course of dark adaptation was determined at levels of light adaptation of 6.5, 91.6, and 6100 foot-candles. All data can be fitted by the same curve. This indicates that dark adaptation follows parts of the same course irrespective of the level of light adaptation. The intensity of the adapting light determines the level at which dark adaptation will begin. The relation between log aI 0 (instantaneous threshold) and log of adapting light intensity is linear over the range studied. PMID:19873056

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

PubMed

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

2013-12-01

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

An adaptive threshold detector and channel parameter estimator for deep space optical communications

NASA Technical Reports Server (NTRS)

Arabshahi, P.; Mukai, R.; Yan, T. -Y.

2001-01-01

This paper presents a method for optimal adaptive setting of ulse-position-modulation pulse detection thresholds, which minimizes the total probability of error for the dynamically fading optical fee space channel.

Unipolar Terminal-Attractor Based Neural Associative Memory with Adaptive Threshold

NASA Technical Reports Server (NTRS)

Liu, Hua-Kuang (Inventor); Barhen, Jacob (Inventor); Farhat, Nabil H. (Inventor); Wu, Chwan-Hwa (Inventor)

1996-01-01

A unipolar terminal-attractor based neural associative memory (TABAM) system with adaptive threshold for perfect convergence is presented. By adaptively setting the threshold values for the dynamic iteration for the unipolar binary neuron states with terminal-attractors for the purpose of reducing the spurious states in a Hopfield neural network for associative memory and using the inner-product approach, perfect convergence and correct retrieval is achieved. Simulation is completed with a small number of stored states (M) and a small number of neurons (N) but a large M/N ratio. An experiment with optical exclusive-OR logic operation using LCTV SLMs shows the feasibility of optoelectronic implementation of the models. A complete inner-product TABAM is implemented using a PC for calculation of adaptive threshold values to achieve a unipolar TABAM (UIT) in the case where there is no crosstalk, and a crosstalk model (CRIT) in the case where crosstalk corrupts the desired state.

Unipolar terminal-attractor based neural associative memory with adaptive threshold

NASA Technical Reports Server (NTRS)

Liu, Hua-Kuang (Inventor); Barhen, Jacob (Inventor); Farhat, Nabil H. (Inventor); Wu, Chwan-Hwa (Inventor)

1993-01-01

A unipolar terminal-attractor based neural associative memory (TABAM) system with adaptive threshold for perfect convergence is presented. By adaptively setting the threshold values for the dynamic iteration for the unipolar binary neuron states with terminal-attractors for the purpose of reducing the spurious states in a Hopfield neural network for associative memory and using the inner product approach, perfect convergence and correct retrieval is achieved. Simulation is completed with a small number of stored states (M) and a small number of neurons (N) but a large M/N ratio. An experiment with optical exclusive-OR logic operation using LCTV SLMs shows the feasibility of optoelectronic implementation of the models. A complete inner-product TABAM is implemented using a PC for calculation of adaptive threshold values to achieve a unipolar TABAM (UIT) in the case where there is no crosstalk, and a crosstalk model (CRIT) in the case where crosstalk corrupts the desired state.

Adaptive spline autoregression threshold method in forecasting Mitsubishi car sales volume at PT Srikandi Diamond Motors

NASA Astrophysics Data System (ADS)

Susanti, D.; Hartini, E.; Permana, A.

2017-01-01

Sale and purchase of the growing competition between companies in Indonesian, make every company should have a proper planning in order to win the competition with other companies. One of the things that can be done to design the plan is to make car sales forecast for the next few periods, it’s required that the amount of inventory of cars that will be sold in proportion to the number of cars needed. While to get the correct forecasting, on of the methods that can be used is the method of Adaptive Spline Threshold Autoregression (ASTAR). Therefore, this time the discussion will focus on the use of Adaptive Spline Threshold Autoregression (ASTAR) method in forecasting the volume of car sales in PT.Srikandi Diamond Motors using time series data.In the discussion of this research, forecasting using the method of forecasting value Adaptive Spline Threshold Autoregression (ASTAR) produce approximately correct.

Optimizing phytoremediation of heavy metal-contaminated soil by exploiting plants' stress adaptation.

PubMed

Barocsi, Attila; Csintalan, Zsolt; Kocsanyi, Laszlo; Dushenkov, Slavik; Kuperberg, J Michael; Kucharski, Rafal; Richter, Peter I

2003-01-01

Soil phytoextraction is based on the ability of plants to extract contaminants from the soil. For less bioavailable metals, such as Pb, a chelator is added to the soil to mobilize the metal. The effect can be significant and in certain species, heavy metal accumulation can rapidly increase 10-fold. Accumulation of high levels of toxic metals may result in irreversible damage to the plant. Monitoring and controlling the phytotoxicity caused by EDTA-induced metal accumulation is crucial to optimize the remedial process, i.e. to achieve maximum uptake. We describe an EDTA-application procedure that minimizes phytotoxicity by increasing plant tolerance and allows phytoextraction of elevated levels of Pb and Cd. Brassica juncea is tested in soil with typical Pb and Cd concentrations of 500 mg kg-1 and 15 mg kg-1, respectively. Instead of a single dose treatment, the chelator is applied in multiple doses, that is, in several small increments, thus providing time for plants to initiate their adaptation mechanisms and raise their damage threshold. In situ monitoring of plant stress conditions by chlorophyll fluorescence recording allows for the identification of the saturating heavy metal accumulation process and of simultaneous plant deterioration.

A Critique of Recent Epidemiologic Studies of Cancer Mortality Among Nuclear Workers.

PubMed

Scott, Bobby R

2018-01-01

Current justification by linear no-threshold (LNT) cancer risk model advocates for its use in low-dose radiation risk assessment is now mainly based on results from flawed and unreliable epidemiologic studies that manufacture small risk increases (ie, phantom risks). Four such studies of nuclear workers, essentially carried out by the same group of epidemiologists, are critiqued in this article. Three of the studies that forcibly applied the LNT model (inappropriate null hypothesis) to cancer mortality data and implicated increased mortality risk from any radiation exposure, no matter how small the dose, are demonstrated to manufacture risk increases for doses up to 100 mSv (or 100 mGy). In a study where risk reduction (hormetic effect/adaptive response) was implicated for nuclear workers, it was assumed by the researchers to relate to a "strong healthy worker effect" with no consideration of the possibility that low radiation doses may help prevent cancer mortality (which is consistent with findings from basic radiobiological research). It was found with basic research that while large radiation doses suppress our multiple natural defenses (barriers) against cancer, these barriers are enhanced by low radiation doses, thereby decreasing cancer risk, essentially rendering the LNT model to be inconsistent with the data.

Antinociceptive effects of nalbuphine hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Sanchez-Migallon Guzman, David; KuKanich, Butch; Keuler, Nicholas S; Klauer, Julia M; Paul-Murphy, Joanne R

2011-06-01

To evaluate the antinociceptive effects and duration of action of nalbuphine HCl administered IM on thermal thresholds in Hispaniolan Amazon parrots (Amazona ventralis). 14 healthy adult Hispaniolan Amazon parrots of unknown sex. 3 doses of nalbuphine (12.5, 25, and 50 mg/kg, IM) and saline (0.9% NaCl) solution (control treatment) were evaluated in a blinded complete crossover experimental design by use of foot withdrawal threshold to a noxious thermal stimulus. Baseline data on thermal threshold were generated 1 hour before administration of nalbuphine or saline solution; thermal threshold measurements were obtained 0.5, 1.5, 3, and 6 hours after administration. Nalbuphine administered IM at 12.5 mg/kg significantly increased the thermal threshold (mean change, 2.4°C), compared with results for the control treatment, and significantly changed thermal threshold for up to 3 hours, compared with baseline results (mean change, 2.6° to 3.8°C). Higher doses of nalbuphine did not significantly change thermal thresholds, compared with results for the control treatment, but had a significant effect, compared with baseline results, for up to 3 and 1.5 hours after administration, respectively. Nalbuphine administered IM at 12.5 mg/kg significantly increased the foot withdrawal threshold to a thermal noxious stimulus in Hispaniolan Amazon parrots. Higher doses of nalbuphine did not result in significantly increased thermal thresholds or a longer duration of action and would be expected to result in less analgesic effect than lower doses. Further studies are needed to fully evaluate the analgesic effects of nalbuphine in psittacine species.

Lower-upper-threshold correlation for underwater range-gated imaging self-adaptive enhancement.

PubMed

Sun, Liang; Wang, Xinwei; Liu, Xiaoquan; Ren, Pengdao; Lei, Pingshun; He, Jun; Fan, Songtao; Zhou, Yan; Liu, Yuliang

2016-10-10

In underwater range-gated imaging (URGI), enhancement of low-brightness and low-contrast images is critical for human observation. Traditional histogram equalizations over-enhance images, with the result of details being lost. To compress over-enhancement, a lower-upper-threshold correlation method is proposed for underwater range-gated imaging self-adaptive enhancement based on double-plateau histogram equalization. The lower threshold determines image details and compresses over-enhancement. It is correlated with the upper threshold. First, the upper threshold is updated by searching for the local maximum in real time, and then the lower threshold is calculated by the upper threshold and the number of nonzero units selected from a filtered histogram. With this method, the backgrounds of underwater images are constrained with enhanced details. Finally, the proof experiments are performed. Peak signal-to-noise-ratio, variance, contrast, and human visual properties are used to evaluate the objective quality of the global and regions of interest images. The evaluation results demonstrate that the proposed method adaptively selects the proper upper and lower thresholds under different conditions. The proposed method contributes to URGI with effective image enhancement for human eyes.

Subsurface characterization with localized ensemble Kalman filter employing adaptive thresholding

NASA Astrophysics Data System (ADS)

Delijani, Ebrahim Biniaz; Pishvaie, Mahmoud Reza; Boozarjomehry, Ramin Bozorgmehry

2014-07-01

Ensemble Kalman filter, EnKF, as a Monte Carlo sequential data assimilation method has emerged promisingly for subsurface media characterization during past decade. Due to high computational cost of large ensemble size, EnKF is limited to small ensemble set in practice. This results in appearance of spurious correlation in covariance structure leading to incorrect or probable divergence of updated realizations. In this paper, a universal/adaptive thresholding method is presented to remove and/or mitigate spurious correlation problem in the forecast covariance matrix. This method is, then, extended to regularize Kalman gain directly. Four different thresholding functions have been considered to threshold forecast covariance and gain matrices. These include hard, soft, lasso and Smoothly Clipped Absolute Deviation (SCAD) functions. Three benchmarks are used to evaluate the performances of these methods. These benchmarks include a small 1D linear model and two 2D water flooding (in petroleum reservoirs) cases whose levels of heterogeneity/nonlinearity are different. It should be noted that beside the adaptive thresholding, the standard distance dependant localization and bootstrap Kalman gain are also implemented for comparison purposes. We assessed each setup with different ensemble sets to investigate the sensitivity of each method on ensemble size. The results indicate that thresholding of forecast covariance yields more reliable performance than Kalman gain. Among thresholding function, SCAD is more robust for both covariance and gain estimation. Our analyses emphasize that not all assimilation cycles do require thresholding and it should be performed wisely during the early assimilation cycles. The proposed scheme of adaptive thresholding outperforms other methods for subsurface characterization of underlying benchmarks.

Lowering threshold energy for femtosecond laser pulse photodisruption through turbid media using adaptive optics

NASA Astrophysics Data System (ADS)

Hansen, A.; Ripken, Tammo; Krueger, Ronald R.; Lubatschowski, Holger

2011-03-01

Focussed femtosecond laser pulses are applied in ophthalmic tissues to create an optical breakdown and therefore a tissue dissection through photodisruption. The threshold irradiance for the optical breakdown depends on the photon density in the focal volume which can be influenced by the pulse energy, the size of the irradiated area (focus), and the irradiation time. For an application in the posterior eye segment the aberrations of the anterior eye elements cause a distortion of the wavefront and therefore an increased focal volume which reduces the photon density and thus raises the required energy for surpassing the threshold irradiance. The influence of adaptive optics on lowering the pulse energy required for photodisruption by refining a distorted focus was investigated. A reduction of the threshold energy can be shown when using adaptive optics. The spatial confinement with adaptive optics furthermore raises the irradiance at constant pulse energy. The lowered threshold energy allows for tissue dissection with reduced peripheral damage. This offers the possibility for moving femtosecond laser surgery from corneal or lental applications in the anterior eye to vitreal or retinal applications in the posterior eye.

Self-Tuning Threshold Method for Real-Time Gait Phase Detection Based on Ground Contact Forces Using FSRs.

PubMed

Tang, Jing; Zheng, Jianbin; Wang, Yang; Yu, Lie; Zhan, Enqi; Song, Qiuzhi

2018-02-06

This paper presents a novel methodology for detecting the gait phase of human walking on level ground. The previous threshold method (TM) sets a threshold to divide the ground contact forces (GCFs) into on-ground and off-ground states. However, the previous methods for gait phase detection demonstrate no adaptability to different people and different walking speeds. Therefore, this paper presents a self-tuning triple threshold algorithm (STTTA) that calculates adjustable thresholds to adapt to human walking. Two force sensitive resistors (FSRs) were placed on the ball and heel to measure GCFs. Three thresholds (i.e., high-threshold, middle-threshold andlow-threshold) were used to search out the maximum and minimum GCFs for the self-adjustments of thresholds. The high-threshold was the main threshold used to divide the GCFs into on-ground and off-ground statuses. Then, the gait phases were obtained through the gait phase detection algorithm (GPDA), which provides the rules that determine calculations for STTTA. Finally, the STTTA reliability is determined by comparing the results between STTTA and Mariani method referenced as the timing analysis module (TAM) and Lopez-Meyer methods. Experimental results show that the proposed method can be used to detect gait phases in real time and obtain high reliability when compared with the previous methods in the literature. In addition, the proposed method exhibits strong adaptability to different wearers walking at different walking speeds.

Design and assessment of a robust voltage amplifier with 2.5 GHz GBW and >100 kGy total dose tolerance

NASA Astrophysics Data System (ADS)

Verbeeck, J.; Leroux, P.; Steyaert, M.

2011-01-01

A differential voltage amplifier with a gain-bandwidth product of 2.5Ghz and using adaptive biasing has been designed in a standard CMOS technology and assessed under radiation and temperature variations. The principle used in this ASIC will be employed in the design of a Gbps TIA with improved tolerance for γ-irradiation and temperature for an optical instrumentation (LIDAR) receiver aiming at operation in harsh environments. The voltage amplifier was tested under gamma radiation and features a gain degradation of merely 4.5% up to a total dose of 100kGy. In order to verify the radiation effects on the IC, the threshold voltage shift of the separate transistors has been investigated. Temperature characterization has shown that the amplifier features a reduction of the voltage gain by only 5.6% for a temperature range of -40 till 130 °C.

Response-adapted treatment with upfront high-dose chemotherapy followed by autologous stem-cell transplantation rescue or consolidation phase high-dose methotrexate for primary central nervous system lymphoma: a long-term mono-center study.

PubMed

Nakasu, Yoko; Mitsuya, Koichi; Hayashi, Nakamasa; Okamura, Ikue; Mori, Keita; Enami, Terukazu; Tatara, Raine; Nakasu, Satoshi; Ikeda, Takashi

2016-01-01

Treatment regimens for primary central nervous system lymphoma (PCNSL) include high-dose methotrexate (HD-MTX)-based chemotherapy, with or without radiotherapy and are based on studies of selected patient groups. This retrospective study assessed a consistent strategy of response-adapted protocol applied for patients including age >65 years in a cancer center for 10 years longitudinally. Case notes were studied of 61 consecutively treated patients with PCNSL histologically diagnosed between 2003 and 2013. Clinical follow-up during and after treatment included neurologic examination and magnetic resonance imaging. Of the patients studied, 14.8 % (9/61) were clinically unfit for chemotherapy; the remaining 85.2 % (52/61) of patients were treated with HD-MTX. Of these patients, 58 % (30/52) achieved an initial complete response, with a median survival of 100.1 months. Of these response-adapted patients, 33 % (10/30) were <65 years and were treated with upfront high-dose chemotherapy and autologous stem-cell transplantation (HDC-ASCT). The remaining response-adapted patients included 53 % (16/30) who were ≥65 years underwent consolidation with HD-MTX, and 14 % (4/30) who chose radiotherapy. The median survival of patients with HDC-ASCT had not yet been reached compared with 67.6 months for patients with HD-MTX consolidation treatment (p = 0.26). At the end of the study, 75 % (39/52) of patients had died mainly owing to progression or relapse of PCNSL. Multivariate analysis showed that age younger than 65 years (p = 0.02) and complete response for up-front HD-MTX (p = 0.001) were independent prognostic indicators of overall survival. In conclusion, this single-center retrospective clinical study has shown that treatment of PCNSL with upfront HDC-ASCT and consolidation phase HD-MTX monotherapy may be feasible, even for elderly patients in a routine clinical setting, using the three-step selection by eligibility and response to initial HD-MTX, and age threshold of 65 years for ASCT.

Pharmacological Studies of NOP Receptor Agonists as Novel Analgesics

DTIC Science & Technology

2008-05-01

in non-human primates. a. Study behavioral effects of ultra- low doses of intrathecal N/OFQ over a wide dose range using a warm water tail...threshold of monkeys. Figure 1 compares the effects of ultra- low doses of intrathecal N/OFQ (i.e., 1 fmol and 1 pmol) with those of a mu opioid...findings indicate that ultra- low doses of intrathecal N/OFQ did not change the monkey’s thermal nociceptive threshold (Figure 1, middle panels

A Purkinje shift in the spectral sensitivity of grey squirrels

PubMed Central

Silver, Priscilla H.

1966-01-01

1. The light-adapted spectral sensitivity of the grey squirrel has been determined by an automated training method at a level about 6 log units above the squirrel's absolute threshold. 2. The maximum sensitivity is near 555 nm, under light-adapted conditions, compared with the dark-adapted maximum near 500 nm found by a similar method. 3. Neither the light-adapted nor the dark-adapted behavioural threshold agrees with electrophysiological findings using single flash techniques, but there is agreement with e.r.g. results obtained with sinusoidal stimuli. PMID:5972118

EXACT DOSE X-IRRADIATION OF VARIOUS REGIONS OF THE HEAD AND VISUAL SENSATIONS--X-RAY LOCATION METHOD OF STUDY OF THE REACTIVITY OF THE CENTRAL NERVOUS SYSTEM

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

Gurtovoi, G.K.; Burdianskaya, E.O.

1960-01-01

The primary substrate excited by threshold doses of x radiation of the normal human eye causes perception of a light flash in the retinal region. The threshold dose for the retina is about 1 mr; the threshold absorbed dose is about 1 mrad. Persons with a removed eyeball, on irradiation of the operated region with a frontal x-ray beam, perceive a flash of light at definite doses of radiation. Six persons taking part in an experiment saw a flash at doses of 17 to 150 mr (different observers saw flash at different doses) and did not see flash at dosesmore » of 5 to 90 mr. The cause of x-ray phosphene on frontal irradiation of the region of the removed eye with threshold doses is neither the reactivity of the optic nerve stump, the reactivity of the parts of the brain irradiated, nor the sensitivity of the skin receptors. In the cases considered, the cause of x-ray phosphene was irradiation of the retina of the nomnal eye by scattered x rays. The averaged coefficient of scatter was about 2%. On irradiation of the occiptal regions of the brain in subjects with normal eyes at a dose of about 150 mr, one subject perceived a flash of light. In this case, the absorbed dose for the occipital regions of the brain was about 40 mrad. The reason for this phenomenon must be explored. Stimulation of the cerebral formations (after atrophic changes in the visual tract and cortex) by x radia tion with a dose of up to 3 r, did not cause visual sensations. With the disposition of the beam, the absorbed dose for the chiasma was about 1 rad and for the occipital regions about 0.2 rad. In the study of threshold visual sensation and their causes on x irradiation of various regions of the head, it is important to apply defined doses of radiation. Scatter of the x rays in the head must be taken into consideration. (auth)« less

Threshold dose for discrimination of nicotine via cigarette smoking.

PubMed

Perkins, Kenneth A; Kunkle, Nicole; Karelitz, Joshua L; Michael, Valerie C; Donny, Eric C

2016-06-01

The lowest nicotine threshold "dose" in cigarettes discriminated from a cigarette containing virtually no nicotine may help inform the minimum dose maintaining dependence. Spectrum research cigarettes (from NIDA) differing in nicotine content were used to evaluate a procedure to determine discrimination thresholds. Dependent smokers (n = 18; 13 M, 5 F) were tested on ability to discriminate cigarettes with nicotine contents of 11, 5, 2.4, and 1.3 mg/g, one per session, from the "ultralow" cigarette with 0.4 mg/g, after having discriminated 16 mg/g from 0.4 mg/g (all had 9-10 mg "tar"). Exposure to each was limited to 4 puffs/trial. All subjects were abstinent from smoking overnight prior to each session, and the number of sessions was determined by the participant's success in discrimination behavior on >80 % of trials. Subjective perceptions and behavioral choice between cigarettes were also assessed and related to discrimination behavior. The median threshold was 11 mg/g, but the range was 2.4 to 16 mg/g, suggesting wide variability in discrimination threshold. Compared to the ultralow, puff choice was greater for the subject's threshold dose but only marginal for the subthreshold (next lowest nicotine) cigarette. Threshold and subthreshold also differed on subjective perceptions but not withdrawal relief. Under these testing conditions, threshold content for discriminating nicotine via cigarettes may be 11 mg/g or greater for most smokers, but some can discriminate nicotine contents one-half or one-quarter this amount. Further study with other procedures and cigarette exposure amounts may identify systematic differences in nicotine discrimination thresholds.

Absorbed dose thresholds and absorbed dose rate limitations for studies of electron radiation effects on polyetherimides

NASA Technical Reports Server (NTRS)

Long, Edward R., Jr.; Long, Sheila Ann T.; Gray, Stephanie L.; Collins, William D.

1989-01-01

The threshold values of total absorbed dose for causing changes in tensile properties of a polyetherimide film and the limitations of the absorbed dose rate for accelerated-exposure evaluation of the effects of electron radiation in geosynchronous orbit were studied. Total absorbed doses from 1 kGy to 100 MGy and absorbed dose rates from 0.01 MGy/hr to 100 MGy/hr were investigated, where 1 Gy equals 100 rads. Total doses less than 2.5 MGy did not significantly change the tensile properties of the film whereas doses higher than 2.5 MGy significantly reduced elongation-to-failure. There was no measurable effect of the dose rate on the tensile properties for accelerated electron exposures.

Threshold-driven optimization for reference-based auto-planning

NASA Astrophysics Data System (ADS)

Long, Troy; Chen, Mingli; Jiang, Steve; Lu, Weiguo

2018-02-01

We study threshold-driven optimization methodology for automatically generating a treatment plan that is motivated by a reference DVH for IMRT treatment planning. We present a framework for threshold-driven optimization for reference-based auto-planning (TORA). Commonly used voxel-based quadratic penalties have two components for penalizing under- and over-dosing of voxels: a reference dose threshold and associated penalty weight. Conventional manual- and auto-planning using such a function involves iteratively updating the preference weights while keeping the thresholds constant, an unintuitive and often inconsistent method for planning toward some reference DVH. However, driving a dose distribution by threshold values instead of preference weights can achieve similar plans with less computational effort. The proposed methodology spatially assigns reference DVH information to threshold values, and iteratively improves the quality of that assignment. The methodology effectively handles both sub-optimal and infeasible DVHs. TORA was applied to a prostate case and a liver case as a proof-of-concept. Reference DVHs were generated using a conventional voxel-based objective, then altered to be either infeasible or easy-to-achieve. TORA was able to closely recreate reference DVHs in 5-15 iterations of solving a simple convex sub-problem. TORA has the potential to be effective for auto-planning based on reference DVHs. As dose prediction and knowledge-based planning becomes more prevalent in the clinical setting, incorporating such data into the treatment planning model in a clear, efficient way will be crucial for automated planning. A threshold-focused objective tuning should be explored over conventional methods of updating preference weights for DVH-guided treatment planning.

Review of Chinese Environmental Risk Assessment Regulations and Case Studies

PubMed Central

Meng, Xiaojie; Zhang, Yan; Zhao, Yuchao; Lou, In Chio; Gao, Jixi

2012-01-01

Environmental risk assessment is an essential step in the development of solutions for pollution problems and new environmental regulations. An assessment system for environmental risks has been developed in China in recent decades. However, many of the Chinese technical guidelines, standards, and regulations were directly adapted from those of developed countries, and were not based on the Chinese environmental and socioeconomic context. Although existing environmental regulations for pollutants are usually obtained by extrapolations from high-dose toxicological data to low-dose scenarios using linear-non-threshold (LNT) models, toxicologists have argued that J-shaped or inverse J-shaped curves may dominate the dose–response relationships for environmental pollutants at low doses because low exposures stimulate biological protective mechanisms that are ineffective at higher doses. The costs of regulations based on LNT and J-shaped models could therefore be dramatically different. Since economic factors strongly affect the decision-making process, particularly for developing countries, it is time to strengthen basic research to provide more scientific support for Chinese environmental regulations. In this paper, we summarize current Chinese environmental policies and standards and the application of environmental risk assessment in China, and recommend a more scientific approach to the development of Chinese regulations. PMID:22740787

A Phase II, Randomized, Double-Blind, Placebo Controlled, Dose-Response Trial of the Melatonin Effect on the Pain Threshold of Healthy Subjects

PubMed Central

Stefani, Luciana Cadore; Muller, Suzana; Torres, Iraci L. S.; Razzolini, Bruna; Rozisky, Joanna R.; Fregni, Felipe; Markus, Regina; Caumo, Wolnei

2013-01-01

Background Previous studies have suggested that melatonin may produce antinociception through peripheral and central mechanisms. Based on the preliminary encouraging results of studies of the effects of melatonin on pain modulation, the important question has been raised of whether there is a dose relationship in humans of melatonin on pain modulation. Objective The objective was to evaluate the analgesic dose response of the effects of melatonin on pressure and heat pain threshold and tolerance and the sedative effects. Methods Sixty-one healthy subjects aged 19 to 47 y were randomized into one of four groups: placebo, 0.05 mg/kg sublingual melatonin, 0.15 mg/kg sublingual melatonin or 0.25 mg/kg sublingual melatonin. We determine the pressure pain threshold (PPT) and the pressure pain tolerance (PPTo). Quantitative sensory testing (QST) was used to measure the heat pain threshold (HPT) and the heat pain tolerance (HPTo). Sedation was assessed with a visual analogue scale and bispectral analysis. Results Serum plasma melatonin levels were directly proportional to the melatonin doses given to each subject. We observed a significant effect associated with dose group. Post hoc analysis indicated significant differences between the placebo vs. the intermediate (0.15 mg/kg) and the highest (0.25 mg/kg) melatonin doses for all pain threshold and sedation level tests. A linear regression model indicated a significant association between the serum melatonin concentrations and changes in pain threshold and pain tolerance (R2 = 0.492 for HPT, R2 = 0.538 for PPT, R2 = 0.558 for HPTo and R2 = 0.584 for PPTo). Conclusions The present data indicate that sublingual melatonin exerts well-defined dose-dependent antinociceptive activity. There is a correlation between the plasma melatonin drug concentration and acute changes in the pain threshold. These results provide additional support for the investigation of melatonin as an analgesic agent. Brazilian Clinical Trials Registry (ReBec): (U1111-1123-5109). IRB: Research Ethics Committee at the Hospital de Clínicas de Porto Alegre. PMID:25947930

A comparison of the fragmentation thresholds and inertial cavitation doses of different ultrasound contrast agents

NASA Astrophysics Data System (ADS)

Chen, Wen-Shiang; Matula, Thomas J.; Brayman, Andrew A.; Crum, Lawrence A.

2003-01-01

Contrast bubble destruction is important in several new diagnostic and therapeutic applications. The pressure threshold of destruction is determined by the shell material, while the propensity for of the bubbles to undergo inertial cavitation (IC) depends both on the gas and shell properties of the ultrasound contrast agent (UCA). The ultrasonic fragmentation thresholds of three specific UCAs (Optison, Sonazoid, and biSpheres), each with different shell and gas properties, were determined under various acoustic conditions. The acoustic emissions generated by the agents, or their derivatives, characteristic of IC after fragmentation, was also compared, using cumulated broadband-noise emissions (IC ``dose''). Albumin-shelled Optison and surfactant-shelled Sonazoid had low fragmentation thresholds (mean=0.13 and 0.15 MPa at 1.1 MHz, 0.48 and 0.58 MPa at 3.5 MHz, respectively), while polymer-shelled biSpheres had a significant higher threshold (mean=0.19 and 0.23 MPa at 1.1 MHz, 0.73 and 0.96 MPa for thin- and thick-shell biSpheres at 3.5 MHz, respectively, p<0.01). At comparable initial concentrations, surfactant-shelled Sonazoid produced a much larger IC dose after shell destruction than did either biSpheres or Optison (p<0.01). Thick-shelled biSpheres had the highest fragmentation threshold and produced the lowest IC dose. More than two and five acoustic cycles, respectively, were necessary for the thin- and thick-shell biSpheres to reach a steady-state fragmentation threshold.

Predicting coral bleaching hotspots: the role of regional variability in thermal stress and potential adaptation rates

NASA Astrophysics Data System (ADS)

Teneva, Lida; Karnauskas, Mandy; Logan, Cheryl A.; Bianucci, Laura; Currie, Jock C.; Kleypas, Joan A.

2012-03-01

Sea surface temperature fields (1870-2100) forced by CO2-induced climate change under the IPCC SRES A1B CO2 scenario, from three World Climate Research Programme Coupled Model Intercomparison Project Phase 3 (WCRP CMIP3) models (CCSM3, CSIRO MK 3.5, and GFDL CM 2.1), were used to examine how coral sensitivity to thermal stress and rates of adaption affect global projections of coral-reef bleaching. The focus of this study was two-fold, to: (1) assess how the impact of Degree-Heating-Month (DHM) thermal stress threshold choice affects potential bleaching predictions and (2) examine the effect of hypothetical adaptation rates of corals to rising temperature. DHM values were estimated using a conventional threshold of 1°C and a variability-based threshold of 2σ above the climatological maximum Coral adaptation rates were simulated as a function of historical 100-year exposure to maximum annual SSTs with a dynamic rather than static climatological maximum based on the previous 100 years, for a given reef cell. Within CCSM3 simulations, the 1°C threshold predicted later onset of mild bleaching every 5 years for the fraction of reef grid cells where 1°C > 2σ of the climatology time series of annual SST maxima (1961-1990). Alternatively, DHM values using both thresholds, with CSIRO MK 3.5 and GFDL CM 2.1 SSTs, did not produce drastically different onset timing for bleaching every 5 years. Across models, DHMs based on 1°C thermal stress threshold show the most threatened reefs by 2100 could be in the Central and Western Equatorial Pacific, whereas use of the variability-based threshold for DHMs yields the Coral Triangle and parts of Micronesia and Melanesia as bleaching hotspots. Simulations that allow corals to adapt to increases in maximum SST drastically reduce the rates of bleaching. These findings highlight the importance of considering the thermal stress threshold in DHM estimates as well as potential adaptation models in future coral bleaching projections.

Radiation and cataract.

PubMed

Rehani, Madan M; Vano, Eliseo; Ciraj-Bjelac, Olivera; Kleiman, Norman J

2011-09-01

When this paper was about to go to press, the International Commission on Radiological Protection released a statement recommending a change in the threshold dose for the eye lens and dose limits for eye for occupationally exposed persons. It is clear that the earlier published threshold for radiation cataract is no longer valid. Epidemiological studies among Chernobyl clean-up workers, A bomb survivors, astronauts, residents of contaminated buildings, radiological technicians and recent surveys of staff in interventional rooms indicate that there is an increased incidence of lens opacities at doses below 1 Gy. Nevertheless, eye lens dosimetry is at a primitive stage and needs to be developed further. Despite uncertainties concerning dose threshold and dosimetry, it is possible to significantly reduce the risk of radiation cataract through the use of appropriate eye protection. By increasing awareness among those at risk and better adoption and increased usage of protective measures, radiation cataract can become preventable despite lowering of dose limits.

Developing Bayesian adaptive methods for estimating sensitivity thresholds (d′) in Yes-No and forced-choice tasks

PubMed Central

Lesmes, Luis A.; Lu, Zhong-Lin; Baek, Jongsoo; Tran, Nina; Dosher, Barbara A.; Albright, Thomas D.

2015-01-01

Motivated by Signal Detection Theory (SDT), we developed a family of novel adaptive methods that estimate the sensitivity threshold—the signal intensity corresponding to a pre-defined sensitivity level (d′ = 1)—in Yes-No (YN) and Forced-Choice (FC) detection tasks. Rather than focus stimulus sampling to estimate a single level of %Yes or %Correct, the current methods sample psychometric functions more broadly, to concurrently estimate sensitivity and decision factors, and thereby estimate thresholds that are independent of decision confounds. Developed for four tasks—(1) simple YN detection, (2) cued YN detection, which cues the observer's response state before each trial, (3) rated YN detection, which incorporates a Not Sure response, and (4) FC detection—the qYN and qFC methods yield sensitivity thresholds that are independent of the task's decision structure (YN or FC) and/or the observer's subjective response state. Results from simulation and psychophysics suggest that 25 trials (and sometimes less) are sufficient to estimate YN thresholds with reasonable precision (s.d. = 0.10–0.15 decimal log units), but more trials are needed for FC thresholds. When the same subjects were tested across tasks of simple, cued, rated, and FC detection, adaptive threshold estimates exhibited excellent agreement with the method of constant stimuli (MCS), and with each other. These YN adaptive methods deliver criterion-free thresholds that have previously been exclusive to FC methods. PMID:26300798

The Comparison Study of Quadratic Infinite Beam Program on Optimization Instensity Modulated Radiation Therapy Treatment Planning (IMRTP) between Threshold and Exponential Scatter Method with CERR® In The Case of Lung Cancer

NASA Astrophysics Data System (ADS)

Hardiyanti, Y.; Haekal, M.; Waris, A.; Haryanto, F.

2016-08-01

This research compares the quadratic optimization program on Intensity Modulated Radiation Therapy Treatment Planning (IMRTP) with the Computational Environment for Radiotherapy Research (CERR) software. We assumed that the number of beams used for the treatment planner was about 9 and 13 beams. The case used the energy of 6 MV with Source Skin Distance (SSD) of 100 cm from target volume. Dose calculation used Quadratic Infinite beam (QIB) from CERR. CERR was used in the comparison study between Gauss Primary threshold method and Gauss Primary exponential method. In the case of lung cancer, the threshold variation of 0.01, and 0.004 was used. The output of the dose was distributed using an analysis in the form of DVH from CERR. The maximum dose distributions obtained were on the target volume (PTV) Planning Target Volume, (CTV) Clinical Target Volume, (GTV) Gross Tumor Volume, liver, and skin. It was obtained that if the dose calculation method used exponential and the number of beam 9. When the dose calculation method used the threshold and the number of beam 13, the maximum dose distributions obtained were on the target volume PTV, GTV, heart, and skin.

3D-segmentation of the 18F-choline PET signal for target volume definition in radiation therapy of the prostate.

PubMed

Ciernik, I Frank; Brown, Derek W; Schmid, Daniel; Hany, Thomas; Egli, Peter; Davis, J Bernard

2007-02-01

Volumetric assessment of PET signals becomes increasingly relevant for radiotherapy (RT) planning. Here, we investigate the utility of 18F-choline PET signals to serve as a structure for semi-automatic segmentation for forward treatment planning of prostate cancer. 18F-choline PET and CT scans of ten patients with histologically proven prostate cancer without extracapsular growth were acquired using a combined PET/CT scanner. Target volumes were manually delineated on CT images using standard software. Volumes were also obtained from 18F-choline PET images using an asymmetrical segmentation algorithm. PTVs were derived from CT 18F-choline PET based clinical target volumes (CTVs) by automatic expansion and comparative planning was performed. As a read-out for dose given to non-target structures, dose to the rectal wall was assessed. Planning target volumes (PTVs) derived from CT and 18F-choline PET yielded comparable results. Optimal matching of CT and 18F-choline PET derived volumes in the lateral and cranial-caudal directions was obtained using a background-subtracted signal thresholds of 23.0+/-2.6%. In antero-posterior direction, where adaptation compensating for rectal signal overflow was required, optimal matching was achieved with a threshold of 49.5+/-4.6%. 3D-conformal planning with CT or 18F-choline PET resulted in comparable doses to the rectal wall. Choline PET signals of the prostate provide adequate spatial information amendable to standardized asymmetrical region growing algorithms for PET-based target volume definition for external beam RT.

Technological challenges of addressing new and more complex migrating products from novel food packaging materials.

PubMed

Munro, Ian C; Haighton, Lois A; Lynch, Barry S; Tafazoli, Shahrzad

2009-12-01

The risk assessment of migration products resulting from packaging material has and continues to pose a difficult challenge. In most jurisdictions, there are regulatory requirements for the approval or notification of food contact substances that will be used in packaging. These processes generally require risk assessment to ensure safety concerns are addressed. The science of assessing food contact materials was instrumental in the development of the concept of Threshold of Regulation and the Threshold of Toxicological Concern procedures. While the risk assessment process is in place, the technology of food packaging continues to evolve to include new initiatives, such as the inclusion of antimicrobial substances or enzyme systems to prevent spoilage, use of plastic packaging intended to remain on foods as they are being cooked, to the introduction of more rigid, stable and reusable materials, and active packaging to extend the shelf-life of food. Each new technology brings with it the potential for exposure to new and possibly novel substances as a result of migration, interaction with other chemical packaging components, or, in the case of plastics now used in direct cooking of products, degradation products formed during heating. Furthermore, the presence of trace levels of certain chemicals from packaging that were once accepted as being of low risk based on traditional toxicology studies are being challenged on the basis of reports of adverse effects, particularly with respect to endocrine disruption, alleged to occur at very low doses. A recent example is the case of bisphenol A. The way forward to assess new packaging technologies and reports of very low dose effects in non-standard studies of food contact substances is likely to remain controversial. However, the risk assessment paradigm is sufficiently robust and flexible to be adapted to meet these challenges. The use of the Threshold of Regulation and the Threshold of Toxicological Concern concepts may play a critical role in the risk assessment of new food packaging technologies in the future.

Stochastic analysis of epidemics on adaptive time varying networks

NASA Astrophysics Data System (ADS)

Kotnis, Bhushan; Kuri, Joy

2013-06-01

Many studies investigating the effect of human social connectivity structures (networks) and human behavioral adaptations on the spread of infectious diseases have assumed either a static connectivity structure or a network which adapts itself in response to the epidemic (adaptive networks). However, human social connections are inherently dynamic or time varying. Furthermore, the spread of many infectious diseases occur on a time scale comparable to the time scale of the evolving network structure. Here we aim to quantify the effect of human behavioral adaptations on the spread of asymptomatic infectious diseases on time varying networks. We perform a full stochastic analysis using a continuous time Markov chain approach for calculating the outbreak probability, mean epidemic duration, epidemic reemergence probability, etc. Additionally, we use mean-field theory for calculating epidemic thresholds. Theoretical predictions are verified using extensive simulations. Our studies have uncovered the existence of an “adaptive threshold,” i.e., when the ratio of susceptibility (or infectivity) rate to recovery rate is below the threshold value, adaptive behavior can prevent the epidemic. However, if it is above the threshold, no amount of behavioral adaptations can prevent the epidemic. Our analyses suggest that the interaction patterns of the infected population play a major role in sustaining the epidemic. Our results have implications on epidemic containment policies, as awareness campaigns and human behavioral responses can be effective only if the interaction levels of the infected populace are kept in check.

Linear-No-Threshold Default Assumptions for Noncancer and Nongenotoxic Cancer Risks: A Mathematical and Biological Critique.

PubMed

Bogen, Kenneth T

2016-03-01

To improve U.S. Environmental Protection Agency (EPA) dose-response (DR) assessments for noncarcinogens and for nonlinear mode of action (MOA) carcinogens, the 2009 NRC Science and Decisions Panel recommended that the adjustment-factor approach traditionally applied to these endpoints should be replaced by a new default assumption that both endpoints have linear-no-threshold (LNT) population-wide DR relationships. The panel claimed this new approach is warranted because population DR is LNT when any new dose adds to a background dose that explains background levels of risk, and/or when there is substantial interindividual heterogeneity in susceptibility in the exposed human population. Mathematically, however, the first claim is either false or effectively meaningless and the second claim is false. Any dose-and population-response relationship that is statistically consistent with an LNT relationship may instead be an additive mixture of just two quasi-threshold DR relationships, which jointly exhibit low-dose S-shaped, quasi-threshold nonlinearity just below the lower end of the observed "linear" dose range. In this case, LNT extrapolation would necessarily overestimate increased risk by increasingly large relative magnitudes at diminishing values of above-background dose. The fact that chemically-induced apoptotic cell death occurs by unambiguously nonlinear, quasi-threshold DR mechanisms is apparent from recent data concerning this quintessential toxicity endpoint. The 2009 NRC Science and Decisions Panel claims and recommendations that default LNT assumptions be applied to DR assessment for noncarcinogens and nonlinear MOA carcinogens are therefore not justified either mathematically or biologically. © 2015 The Author. Risk Analysis published by Wiley Periodicals, Inc. on behalf of Society for Risk Analysis.

MO-DE-207A-12: Toward Patient-Specific 4DCT Reconstruction Using Adaptive Velocity Binning

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

Morris, E.D.; Glide-Hurst, C.; Wayne State University, Detroit, MI

2016-06-15

Purpose: While 4DCT provides organ/tumor motion information, it often samples data over 10–20 breathing cycles. For patients presenting with compromised pulmonary function, breathing patterns can change over the acquisition time, potentially leading to tumor delineation discrepancies. This work introduces a novel adaptive velocity-modulated binning (AVB) 4DCT algorithm that modulates the reconstruction based on the respiratory waveform, yielding a patient-specific 4DCT solution. Methods: AVB was implemented in a research reconstruction configuration. After filtering the respiratory waveform, the algorithm examines neighboring data to a phase reconstruction point and the temporal gate is widened until the difference between the reconstruction point and waveformmore » exceeds a threshold value—defined as percent difference between maximum/minimum waveform amplitude. The algorithm only impacts reconstruction if the gate width exceeds a set minimum temporal width required for accurate reconstruction. A sensitivity experiment of threshold values (0.5, 1, 5, 10, and 12%) was conducted to examine the interplay between threshold, signal to noise ratio (SNR), and image sharpness for phantom and several patient 4DCT cases using ten-phase reconstructions. Individual phase reconstructions were examined. Subtraction images and regions of interest were compared to quantify changes in SNR. Results: AVB increased signal in reconstructed 4DCT slices for respiratory waveforms that met the prescribed criteria. For the end-exhale phases, where the respiratory velocity is low, patient data revealed a threshold of 0.5% demonstrated increased SNR in the AVB reconstructions. For intermediate breathing phases, threshold values were required to be >10% to notice appreciable changes in CT intensity with AVB. AVB reconstructions exhibited appreciably higher SNR and reduced noise in regions of interest that were photon deprived such as the liver. Conclusion: We demonstrated that patient-specific velocity-based 4DCT reconstruction is feasible. Image noise was reduced with AVB, suggesting potential applications for low-dose acquisitions and to improve 4DCT reconstruction for irregular breathing patients. The submitting institution holds research agreements with Philips Healthcare.« less

Characterization of Rod Function Phenotypes Across a Range of Age-Related Macular Degeneration Severities and Subretinal Drusenoid Deposits

PubMed Central

Flynn, Oliver J.; Cukras, Catherine A.; Jeffrey, Brett G.

2018-01-01

Purpose To examine spatial changes in rod-mediated function in relationship to local structural changes across the central retina in eyes with a spectrum of age-related macular degeneration (AMD) disease severity. Methods Participants were categorized into five AMD severity groups based on fundus features. Scotopic thresholds were measured at 14 loci spanning ±18° along the vertical meridian from one eye of each of 42 participants (mean = 71.7 ± 9.9 years). Following a 30% bleach, dark adaptation was measured at eight loci (±12°). Rod intercept time (RIT) was defined from the time to detect a −3.1 log cd/m2 stimulus. RITslope was defined from the linear fit of RIT with decreasing retinal eccentricity. The presence of subretinal drusenoid deposits (SDD), ellipsoid (EZ) band disruption, and drusen at the test loci was evaluated using optical coherence tomography. Results Scotopic thresholds indicated greater rod function loss in the macula, which correlated with increasing AMD group severity. RITslope, which captures the spatial change in the rate of dark adaptation, increased with AMD severity (P < 0.0001). Three rod function phenotypes emerged: RF1, normal rod function; RF2, normal scotopic thresholds but slowed dark adaptation; and RF3, elevated scotopic thresholds with slowed dark adaptation. Dark adaptation was slowed at all loci with SDD or EZ band disruption, and at 32% of loci with no local structural changes. Conclusions Three rod function phenotypes were defined from combined measurement of scotopic threshold and dark adaptation. Spatial changes in dark adaptation across the macula were captured with RITslope, which may be a useful outcome measure for functional studies of AMD. PMID:29847647

Characterization of Rod Function Phenotypes Across a Range of Age-Related Macular Degeneration Severities and Subretinal Drusenoid Deposits.

PubMed

Flynn, Oliver J; Cukras, Catherine A; Jeffrey, Brett G

2018-05-01

To examine spatial changes in rod-mediated function in relationship to local structural changes across the central retina in eyes with a spectrum of age-related macular degeneration (AMD) disease severity. Participants were categorized into five AMD severity groups based on fundus features. Scotopic thresholds were measured at 14 loci spanning ±18° along the vertical meridian from one eye of each of 42 participants (mean = 71.7 ± 9.9 years). Following a 30% bleach, dark adaptation was measured at eight loci (±12°). Rod intercept time (RIT) was defined from the time to detect a -3.1 log cd/m2 stimulus. RITslope was defined from the linear fit of RIT with decreasing retinal eccentricity. The presence of subretinal drusenoid deposits (SDD), ellipsoid (EZ) band disruption, and drusen at the test loci was evaluated using optical coherence tomography. Scotopic thresholds indicated greater rod function loss in the macula, which correlated with increasing AMD group severity. RITslope, which captures the spatial change in the rate of dark adaptation, increased with AMD severity (P < 0.0001). Three rod function phenotypes emerged: RF1, normal rod function; RF2, normal scotopic thresholds but slowed dark adaptation; and RF3, elevated scotopic thresholds with slowed dark adaptation. Dark adaptation was slowed at all loci with SDD or EZ band disruption, and at 32% of loci with no local structural changes. Three rod function phenotypes were defined from combined measurement of scotopic threshold and dark adaptation. Spatial changes in dark adaptation across the macula were captured with RITslope, which may be a useful outcome measure for functional studies of AMD.

In-vitro singlet oxygen threshold dose at PDT with Radachlorin photosensitizer

NASA Astrophysics Data System (ADS)

Klimenko, V. V.; Shmakov, S. V.; Kaydanov, N. E.; Knyazev, N. A.; Kazakov, N. V.; Rusanov, A. A.; Bogdanov, A. A.; Dubina, M. V.

2017-07-01

In this present study we investigate the Radachlorin photosensitizer accumulation in K562 cells and Hela cells and determined the cell viability after PDT. Using the macroscopic singlet oxygen modeling and cellular photosensitizer concentration the singlet oxygen threshold doses for K562 cells and Hela cells were calculated.

EXPOSURE DOMAINS: ROLE OF TIMING, PATTERN AND MAGNITUDE OF EXPOSURE ON HEALTH RISKS

EPA Science Inventory

Environmental health risk assessment may be broadly separated into assessment of risks from exposures to agents affecting health endpoints for which it may be presumed there is no dose threshold, and to agents affecting endpoints that more likely have a dose threshold. For hea...

Commentary: Ethical Issues of Current Health-Protection Policies on Low-Dose Ionizing Radiation

PubMed Central

Socol, Yehoshua; Dobrzyński, Ludwik; Doss, Mohan; Feinendegen, Ludwig E.; Janiak, Marek K.; Miller, Mark L.; Sanders, Charles L.; Scott, Bobby R.; Ulsh, Brant; Vaiserman, Alexander

2014-01-01

The linear no-threshold (LNT) model of ionizing-radiation-induced cancer is based on the assumption that every radiation dose increment constitutes increased cancer risk for humans. The risk is hypothesized to increase linearly as the total dose increases. While this model is the basis for radiation safety regulations, its scientific validity has been questioned and debated for many decades. The recent memorandum of the International Commission on Radiological Protection admits that the LNT-model predictions at low doses are “speculative, unproven, undetectable and ‘phantom’.” Moreover, numerous experimental, ecological, and epidemiological studies show that low doses of sparsely-ionizing or sparsely-ionizing plus highly-ionizing radiation may be beneficial to human health (hormesis/adaptive response). The present LNT-model-based regulations impose excessive costs on the society. For example, the median-cost medical program is 5000 times more cost-efficient in saving lives than controlling radiation emissions. There are also lives lost: e.g., following Fukushima accident, more than 1000 disaster-related yet non-radiogenic premature deaths were officially registered among the population evacuated due to radiation concerns. Additional negative impacts of LNT-model-inspired radiophobia include: refusal of some patients to undergo potentially life-saving medical imaging; discouragement of the study of low-dose radiation therapies; motivation for radiological terrorism and promotion of nuclear proliferation. PMID:24910586

A comparison of the ability of a 4:1 ketogenic diet and a 6.3:1 ketogenic diet to elevate seizure thresholds in adult and young rats.

PubMed

Nylen, Kirk; Likhodii, Sergei; Abdelmalik, Peter A; Clarke, Jasper; Burnham, W McIntyre

2005-08-01

The pentylenetetrazol (PTZ) infusion test was used to compare seizure thresholds in adult and young rats fed either a 4:1 ketogenic diet (KD) or a 6.3:1 KD. We hypothesized that both KDs would significantly elevate seizure thresholds and that the 4:1 KD would serve as a better model of the KD used clinically. Ninety adult rats and 75 young rats were placed on one of five experimental diets: (a) a 4:1 KD, (b) a control diet balanced to the 4:1 KD, (c) a 6.3:1 KD, (d) a standard control diet, or (e) an ad libitum standard control diet. All subjects were seizure tested by using the PTZ infusion test. Blood glucose and beta-hydroxybutyrate (beta-OHB) levels were measured. Neither KD elevated absolute "latencies to seizure" in young or adult rats. Similarly, neither KD elevated "threshold doses" in adult rats. In young rats, the 6.3:1 KD, but not the 4:1 KD, significantly elevated threshold doses. The 6.3:1 KD group showed poorer weight gain than the 4:1 KD group when compared with respective controls. The most dramatic discrepancies were seen in young rats. "Threshold doses" and "latency to seizure" data provided conflicting measures of seizure threshold. This was likely due to the inflation of threshold doses calculated by using the much smaller body weights found in the 6.3:1 KD group. Ultimately, the PTZ infusion test in rats may not be a good preparation to model the anticonvulsant effects of the KD seen clinically, especially when dietary treatments lead to significantly mismatched body weights between the groups.

Maintained cocaine self-administration is determined by quantal responses: implications for the measurement of antagonist potency.

PubMed

Norman, Andrew B; Tabet, Michael R; Norman, Mantana K; Tsibulsky, Vladimir L

2014-02-01

The change in frequency of cocaine self-administration as a function of the unit dose is widely assumed to represent a graded pharmacodynamic response. Alternatively, a pharmacological theory states that during maintained self-administration, a quantal response occurs at a minimum maintained cocaine concentration (satiety threshold). Rats self-administered cocaine at unit doses spanning an 8-fold range from 0.75 to 6 µmol/kg. Despite an approximately 7-fold difference in the interinjection intervals, there were no differences in the plasma cocaine concentration at the time of lever press across this range of unit doses, consistent with the satiety threshold representing an equiactive cocaine concentration. Because self-administration always occurs when cocaine concentrations decline back to the satiety threshold, this behavior represents a process of automatic back titration of equiactive agonist concentrations. Therefore, the lower frequency of self-administration at higher unit doses is caused by an increase in the duration of the cocaine-induced satiety response, and the graded dose-frequency relationship is due to cocaine pharmacokinetics. After the interinjection intervals at a particular unit dose were stable, rats were injected with the competitive D₁-like dopamine receptor antagonist R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH23390; 15 nmol/kg intravenously) and the session continued. At all cocaine unit doses, SCH23390 accelerated self-administration with a concomitant increase in the calculated satiety threshold, and these equiactive cocaine concentration ratios were independent of the cocaine unit dose. Therefore, the measurement of antagonist potency requires only a single unit dose of cocaine, selected on the basis of convenience, and using multiple cocaine unit doses is redundant.

Quantitative comparison of the results obtained by the multiple-dose guinea pig maximization test and the non-radioactive murine local lymph-node assay for various biocides.

PubMed

Yamano, Tetsuo; Shimizu, Mitsuru; Noda, Tsutomu

2005-07-01

We compared the results of the multiple-dose guinea pig maximization test (GPMT) and the non-radioactive murine local lymph-node assay (LLNA) for various biocides. Thirteen out of 17 positive biocides in the GPMT gave positive results in the LLNA. In the GPMT, the minimum first induction doses ranged over four orders (0.00005-0.5%), while elicitation-threshold doses, which were evaluated using an optimally sensitized group of animals in the multiple-dose studies, ranged over five orders (0.00006-2.8%). In the LLNA, minimum induction doses ranged over more than three orders (0.01-30%). With respect to 13 biocides that were positive in both the GPMT and the LLNA, results were quantitatively compared. When compared after conversion to corresponding area doses (microg/cm), the minimum doses required to elicit skin reaction in guinea pigs were always lower than that for induction in mice with all biocides. Correlation between minimum induction doses from the GPMT and the LLNA seemed poor (r=0.57), while that between minimum induction doses in the LLNA and elicitation-threshold doses in the GPMT was relatively good (r=0.73). The results suggest the possibility to estimate human elicitation-threshold doses, which are definitely lacking in the process of risk assessment for skin-sensitizers, from the data of the LLNA.

The threshold vs LNT showdown: Dose rate findings exposed flaws in the LNT model part 1. The Russell-Muller debate

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

Calabrese, Edward J., E-mail: edwardc@schoolph.uma

This paper assesses the discovery of the dose-rate effect in radiation genetics and how it challenged fundamental tenets of the linear non-threshold (LNT) dose response model, including the assumptions that all mutational damage is cumulative and irreversible and that the dose-response is linear at low doses. Newly uncovered historical information also describes how a key 1964 report by the International Commission for Radiological Protection (ICRP) addressed the effects of dose rate in the assessment of genetic risk. This unique story involves assessments by two leading radiation geneticists, Hermann J. Muller and William L. Russell, who independently argued that the report'smore » Genetic Summary Section on dose rate was incorrect while simultaneously offering vastly different views as to what the report's summary should have contained. This paper reveals occurrences of scientific disagreements, how conflicts were resolved, which view(s) prevailed and why. During this process the Nobel Laureate, Muller, provided incorrect information to the ICRP in what appears to have been an attempt to manipulate the decision-making process and to prevent the dose-rate concept from being adopted into risk assessment practices. - Highlights: • The discovery of radiation dose rate challenged the scientific basis of LNT. • Radiation dose rate occurred in males and females. • The dose rate concept supported a threshold dose-response for radiation.« less

Dose responses for adaption to low doses of (60)Co gamma rays and (3)H beta particles in normal human fibroblasts.

PubMed

Broome, E J; Brown, D L; Mitchel, R E J

2002-08-01

The dose response for adaption to radiation at low doses was compared in normal human fibroblasts (AG1522) exposed to either (60)Co gamma rays or (3)H beta particles. Cells were grown in culture to confluence and exposed at either 37 degrees C or 0 degrees C to (3)H beta-particle or (60)Co gamma-ray adapting doses ranging from 0.1 mGy to 500 mGy. These cells, and unexposed control cells, were allowed to adapt during a fixed 3-h, 37 degrees C incubation prior to a 4-Gy challenge dose of (60)Co gamma rays. Adaption was assessed by measuring micronucleus frequency in cytokinesis-blocked, binucleate cells. No adaption was detected in cells exposed to (60)Co gamma radiation at 37 degrees C after a dose of 0.1 mGy given at a low dose rate or to 500 mGy given at a high dose rate. However, low-dose-rate exposure (1-3 mGy/min) to any dose between 1 and 500 mGy from either radiation, delivered at either temperature, caused cells to adapt and reduced the micronucleus frequency that resulted from the subsequent 4-Gy exposure. Within this dose range, the magnitude of the reduction was the same, regardless of the dose or radiation type. These results demonstrate that doses as low as (on average) about one track per cell (1 mGy) produce the same maximum adaptive response as do doses that deposit many tracks per cell, and that the two radiations were not different in this regard. Exposure at a temperature where metabolic processes, including DNA repair, were inactive (0 degrees C) did not alter the result, indicating that the adaptive response is not sensitive to changes in the accumulation of DNA damage within this range. The results also show that the RBE for low doses of tritium beta-particle radiation is 1, using adaption as the end point.

Expected treatment dose construction and adaptive inverse planning optimization: Implementation for offline head and neck cancer adaptive radiotherapy

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

Yan Di; Liang Jian

Purpose: To construct expected treatment dose for adaptive inverse planning optimization, and evaluate it on head and neck (h and n) cancer adaptive treatment modification. Methods: Adaptive inverse planning engine was developed and integrated in our in-house adaptive treatment control system. The adaptive inverse planning engine includes an expected treatment dose constructed using the daily cone beam (CB) CT images in its objective and constrains. Feasibility of the adaptive inverse planning optimization was evaluated retrospectively using daily CBCT images obtained from the image guided IMRT treatment of 19 h and n cancer patients. Adaptive treatment modification strategies with respect tomore » the time and the number of adaptive inverse planning optimization during the treatment course were evaluated using the cumulative treatment dose in organs of interest constructed using all daily CBCT images. Results: Expected treatment dose was constructed to include both the delivered dose, to date, and the estimated dose for the remaining treatment during the adaptive treatment course. It was used in treatment evaluation, as well as in constructing the objective and constraints for adaptive inverse planning optimization. The optimization engine is feasible to perform planning optimization based on preassigned treatment modification schedule. Compared to the conventional IMRT, the adaptive treatment for h and n cancer illustrated clear dose-volume improvement for all critical normal organs. The dose-volume reductions of right and left parotid glands, spine cord, brain stem and mandible were (17 {+-} 6)%, (14 {+-} 6)%, (11 {+-} 6)%, (12 {+-} 8)%, and (5 {+-} 3)% respectively with the single adaptive modification performed after the second treatment week; (24 {+-} 6)%, (22 {+-} 8)%, (21 {+-} 5)%, (19 {+-} 8)%, and (10 {+-} 6)% with three weekly modifications; and (28 {+-} 5)%, (25 {+-} 9)%, (26 {+-} 5)%, (24 {+-} 8)%, and (15 {+-} 9)% with five weekly modifications. Conclusions: Adaptive treatment modification can be implemented including the expected treatment dose in the adaptive inverse planning optimization. The retrospective evaluation results demonstrate that utilizing the weekly adaptive inverse planning optimization, the dose distribution of h and n cancer treatment can be largely improved.« less

Noise adaptive wavelet thresholding for speckle noise removal in optical coherence tomography.

PubMed

Zaki, Farzana; Wang, Yahui; Su, Hao; Yuan, Xin; Liu, Xuan

2017-05-01

Optical coherence tomography (OCT) is based on coherence detection of interferometric signals and hence inevitably suffers from speckle noise. To remove speckle noise in OCT images, wavelet domain thresholding has demonstrated significant advantages in suppressing noise magnitude while preserving image sharpness. However, speckle noise in OCT images has different characteristics in different spatial scales, which has not been considered in previous applications of wavelet domain thresholding. In this study, we demonstrate a noise adaptive wavelet thresholding (NAWT) algorithm that exploits the difference of noise characteristics in different wavelet sub-bands. The algorithm is simple, fast, effective and is closely related to the physical origin of speckle noise in OCT image. Our results demonstrate that NAWT outperforms conventional wavelet thresholding.

Molecular Signaling Network Motifs Provide a Mechanistic Basis for Cellular Threshold Responses

PubMed Central

Bhattacharya, Sudin; Conolly, Rory B.; Clewell, Harvey J.; Kaminski, Norbert E.; Andersen, Melvin E.

2014-01-01

Background: Increasingly, there is a move toward using in vitro toxicity testing to assess human health risk due to chemical exposure. As with in vivo toxicity testing, an important question for in vitro results is whether there are thresholds for adverse cellular responses. Empirical evaluations may show consistency with thresholds, but the main evidence has to come from mechanistic considerations. Objectives: Cellular response behaviors depend on the molecular pathway and circuitry in the cell and the manner in which chemicals perturb these circuits. Understanding circuit structures that are inherently capable of resisting small perturbations and producing threshold responses is an important step towards mechanistically interpreting in vitro testing data. Methods: Here we have examined dose–response characteristics for several biochemical network motifs. These network motifs are basic building blocks of molecular circuits underpinning a variety of cellular functions, including adaptation, homeostasis, proliferation, differentiation, and apoptosis. For each motif, we present biological examples and models to illustrate how thresholds arise from specific network structures. Discussion and Conclusion: Integral feedback, feedforward, and transcritical bifurcation motifs can generate thresholds. Other motifs (e.g., proportional feedback and ultrasensitivity)produce responses where the slope in the low-dose region is small and stays close to the baseline. Feedforward control may lead to nonmonotonic or hormetic responses. We conclude that network motifs provide a basis for understanding thresholds for cellular responses. Computational pathway modeling of these motifs and their combinations occurring in molecular signaling networks will be a key element in new risk assessment approaches based on in vitro cellular assays. Citation: Zhang Q, Bhattacharya S, Conolly RB, Clewell HJ III, Kaminski NE, Andersen ME. 2014. Molecular signaling network motifs provide a mechanistic basis for cellular threshold responses. Environ Health Perspect 122:1261–1270; http://dx.doi.org/10.1289/ehp.1408244 PMID:25117432

Atomic bomb health benefits.

PubMed

Luckey, T D

2008-01-01

Media reports of deaths and devastation produced by atomic bombs convinced people around the world that all ionizing radiation is harmful. This concentrated attention on fear of miniscule doses of radiation. Soon the linear no threshold (LNT) paradigm was converted into laws. Scientifically valid information about the health benefits from low dose irradiation was ignored. Here are studies which show increased health in Japanese survivors of atomic bombs. Parameters include decreased mutation, leukemia and solid tissue cancer mortality rates, and increased average lifespan. Each study exhibits a threshold that repudiates the LNT dogma. The average threshold for acute exposures to atomic bombs is about 100 cSv. Conclusions from these studies of atomic bomb survivors are: One burst of low dose irradiation elicits a lifetime of improved health.Improved health from low dose irradiation negates the LNT paradigm.Effective triage should include radiation hormesis for survivor treatment.

Dose-response effects of corneal anesthetics.

PubMed

Polse, K A; Keener, R J; Jauregui, M J

1978-01-01

With double-masking procedures, the dose-response curves for 0.1, 0.2, and 0.4% benoxinate and 0.125, 0.25, and 0.50% proparacaine hydrochloride were determined by monitoring changes in corneal touch threshold after applying each anesthetic. The level of corneal anesthesia necessary for applanation tonometry was also determined. The maximum increase in threshold that could be measured following instillation of 50 microliter of the drug was 200 mg/mm2 All 6 anesthetic solutions produced this amount of decreased corneal sensitivity. Recovery from the anesthetic was exponential for all concentrations; however, the lower doses had the shortest duration. For applanation tonometry, the corneal threshold for touch must be 75 mg/mm2 or higher. We conclude that a quarter to a half of the commonly used anesthetic dose is sufficient for routine tonometric evaluation.

Determination of the threshold dose distribution in photodynamic action from in vitro experiments.

PubMed

de Faria, Clara Maria Gonçalves; Inada, Natalia Mayumi; Kurachi, Cristina; Bagnato, Vanderlei Salvador

2016-09-01

The concept of threshold in photodynamic action on cells or microorganisms is well observed in experiments but not fully explored on in vitro experiments. The intercomparison between light and used photosensitizer among many experiments is also poorly evaluated. In this report, we present an analytical model that allows extracting from the survival rate experiments the data of the threshold dose distribution, ie, the distribution of energies and photosensitizer concentration necessary to produce death of cells. Then, we use this model to investigate photodynamic therapy (PDT) data previously published in literature. The concept of threshold dose distribution instead of "single value of threshold" is a rich concept for the comparison of photodynamic action in different situations, allowing analyses of its efficiency as well as determination of optimized conditions for PDT. We observed that, in general, as it becomes more difficult to kill a population, the distribution tends to broaden, which means it presents a large spectrum of threshold values within the same cell type population. From the distribution parameters (center peak and full width), we also observed a clear distinction among cell types regarding their response to PDT that can be quantified. Comparing data obtained from the same cell line and used photosensitizer (PS), where the only distinct condition was the light source's wavelength, we found that the differences on the distribution parameters were comparable to the differences on the PS absorption. At last, we observed evidence that the threshold dose distribution matches the curve of apoptotic activity for some PSs. Copyright © 2016 Elsevier B.V. All rights reserved.

Optical communication system performance with tracking error induced signal fading.

NASA Technical Reports Server (NTRS)

Tycz, M.; Fitzmaurice, M. W.; Premo, D. A.

1973-01-01

System performance is determined for an optical communication system using noncoherent detection in the presence of tracking error induced signal fading assuming (1) binary on-off modulation (OOK) with both fixed and adaptive threshold receivers, and (2) binary polarization modulation (BPM). BPM is shown to maintain its inherent 2- to 3-dB advantage over OOK when adaptive thresholding is used, and to have a substantially greater advantage when the OOK system is restricted to a fixed decision threshold.

A case study for online plan adaptation using helical tomotherapy

PubMed Central

Neilson, Christopher E.; Yartsev, Slav

2012-01-01

Helical tomotherapy's ability to provide daily megavoltage (MV) computed tomography (CT) images for patient set-up verification allows for the creation of adapted plans. As plans become more complex by introducing sharper dose gradients in an effort to spare healthy tissue, inter-fraction changes of organ position with respect to plan become a limiting factor in the correct dose delivery to the target. Tomotherapy's planned adaptive option provides the possibility to evaluate the dose distribution for each fraction and subsequently adapt the original plan to the current anatomy. In this study, 30 adapted plans were created using new contours based on the daily MVCT studies of a bladder cancer patient with considerable anatomical variations. Dose to the rectum and two planning target volumes (PTVs) were compared between the original plan, the dose that was actually delivered to the patient, and the theoretical dose from the 30 adapted plans. The adaptation simulation displayed a lower dose to 35% and 50% of the rectum compared to no adaptation at all, while maintaining an equivalent dose to the PTVs. Although online adaptation is currently too time-consuming, it has the potential to improve the effectiveness of radiotherapy. PMID:22557799

Reactive oxygen species spermine metabolites generated from amine oxidases and radiation represent a therapeutic gain in cancer treatments.

PubMed

Amendola, Roberto; Cervelli, Manuela; Fratini, Emiliano; Sallustio, Davide E; Tempera, Giampiero; Ueshima, Taichi; Mariottini, Paolo; Agostinelli, Enzo

2013-09-01

The most frequent interventions in cancer therapy are currently the destruction of cells by irradiation or administration of drugs both able to induce radical formation and toxic metabolites by enzyme-catalyzed reactions. The aim of this study was to determine the cell viability of cells undergoing a DNA damage threshold accomplished by ROS overproduction via both ectopic expression of murine spermine oxidase (mSMOX) and bovine serum amine oxidase (BSAO) enzymes. Low dose of X-irradiation delivers a challenging dose of damage as evaluated in proficient Chinese hamster AA8 cell line and both deficient transcription-coupled nucleotide excision repair (NER) UV61 cells and deficient base excision repair (BER) EM9 cells, at 6 and 24 h after exposure. The priming dose of ROS overexposure by mSMOX provokes an adaptive response in N18TG2, AA8 and EM9 cell lines at 24 h. Interestingly, in the UV61 cells, ROS overexposure by mSMOX delivers an earlier adaptive response to radiation. The enzymatic formation of toxic metabolites has mainly been investigated on wild-type (WT) and multidrug-resistant (MDR) cancer cell lines, using and spermine as substrate of the BSAO enzyme. MDR cells are more sensitive to the toxic polyamine metabolites than WT cells, thus indicating a new therapeutic strategy to overcome MDR tumors. Since SMOX in mammals is differentially activated in a tissue-specific manner and cancer cells can differ in terms of DNA repair and MDR capabilities, it could be of interest to simultaneously treat with very low dose of X-rays and/or to alter SMOX metabolism to generate a differential response in healthy and cancer tissues.

Pharmacokinetics and toxicity of intrathecal liposomal cytarabine in children and adolescents following age-adapted dosing.

PubMed

Peyrl, Andreas; Sauermann, Robert; Chocholous, Monika; Azizi, Amedeo A; Jäger, Walter; Höferl, Martina; Slavc, Irene

2014-02-01

Assessment of the optimal drug dose for intrathecal therapy in children is challenging because of the non-linear increase in cerebrospinal fluid (CSF) volume throughout childhood and potential differences in the elimination rate in children versus adults. The present study was designed to prospectively collect pharmacokinetic and safety data on age-adapted intrathecal liposomal cytarabine in children aged >3 years. Sixteen patients with malignant brain tumours were included in the study. Children aged 3-10 years received liposomal cytarabine 35 mg with concomitant dexamethasone, and those aged >10 years received 50 mg. Serial CSF and plasma samples were collected before administration and 1 h, 12 h, 24 h, 1 week and 2 weeks post-dosing. CSF was analysed for free and encapsulated cytarabine, and plasma was analysed for free cytarabine. The average elimination half-life values in children aged 3-10 years and in those aged >10 years, treated with liposomal cytarabine 35 mg and 50 mg, respectively, were 40.9 and 43.7 h for free cytarabine and 31.5 and 36.4 h for encapsulated cytarabine in CSF. Although these values were lower than those previously reported, cytarabine concentrations exceeded the cytotoxic threshold of 0.1 mg/L in all patients until 1 week post-intraventricular administration. Cytarabine concentrations in plasma were negligible. In general, liposomal cytarabine was well tolerated, with relevant but manageable toxicities. Liposomal cytarabine in doses of 35 mg for children aged 3-10 years and 50 mg for older patients shows sufficient drug exposure for at least 1 week and appears to be well tolerated.

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

PubMed

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

2017-12-01

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

Involvement of ATP-sensitive potassium channels and the opioid system in the anticonvulsive effect of zolpidem in mice.

PubMed

Sheikhi, Mehdi; Shirzadian, Armin; Dehdashtian, Amir; Amiri, Shayan; Ostadhadi, Sattar; Ghasemi, Mehdi; Dehpour, Ahmad Reza

2016-09-01

Zolpidem is a hypnotic medication that mainly exerts its function through activating γ-aminobutyric acid (GABA)A receptors. There is some evidence that zolpidem may have anticonvulsive effects. However, the mechanisms underlying this effect have not been elucidated yet. In the present study, we used the pentylentetrazole (PTZ)-induced generalized seizure model in mice to investigate whether zolpidem can affect seizure threshold. We also further evaluated the roles of ATP-sensitive potassium (KATP) channels as well as μ-opioid receptors in the effects of zolpidem on seizure threshold. Our data showed that zolpidem in a dose-dependent manner increased the PTZ-induced seizure threshold. The noneffective (i.e., did not significantly alter the PTZ-induced seizure threshold by itself) doses of KATP channel blocker (glibenclamide) and nonselective opioid receptor antagonist (naloxone) were able to inhibit the anticonvulsive effect of zolpidem. Additionally, noneffective doses of either KATP channel opener (cromakalim) or nonselective μ-opioid receptor agonist (morphine) in combination with a noneffective dose of zolpidem exerted a significant anticonvulsive effect on PTZ-induced seizures in mice. A combination of noneffective doses of naloxone and glibenclamide, which separately did not affect zolpidem effect on seizure threshold, inhibited the anticonvulsive effects of zolpidem. These results suggest a role for KATP channels and the opioid system, alone or in combination, in the anticonvulsive effects of zolpidem. Copyright © 2016 Elsevier Inc. All rights reserved.

Thresholds for Coral Bleaching: Are Synergistic Factors and Shifting Thresholds Changing the Landscape for Management? (Invited)

NASA Astrophysics Data System (ADS)

Eakin, C.; Donner, S. D.; Logan, C. A.; Gledhill, D. K.; Liu, G.; Heron, S. F.; Christensen, T.; Rauenzahn, J.; Morgan, J.; Parker, B. A.; Hoegh-Guldberg, O.; Skirving, W. J.; Strong, A. E.

2010-12-01

As carbon dioxide rises in the atmosphere, climate change and ocean acidification are modifying important physical and chemical parameters in the oceans with resulting impacts on coral reef ecosystems. Rising CO2 is warming the world’s oceans and causing corals to bleach, with both alarming frequency and severity. The frequent return of stressful temperatures has already resulted in major damage to many of the world’s coral reefs and is expected to continue in the foreseeable future. Warmer oceans also have contributed to a rise in coral infectious diseases. Both bleaching and infectious disease can result in coral mortality and threaten one of the most diverse ecosystems on Earth and the important ecosystem services they provide. Additionally, ocean acidification from rising CO2 is reducing the availability of carbonate ions needed by corals to build their skeletons and perhaps depressing the threshold for bleaching. While thresholds vary among species and locations, it is clear that corals around the world are already experiencing anomalous temperatures that are too high, too often, and that warming is exceeding the rate at which corals can adapt. This is despite a complex adaptive capacity that involves both the coral host and the zooxanthellae, including changes in the relative abundance of the latter in their coral hosts. The safe upper limit for atmospheric CO2 is probably somewhere below 350ppm, a level we passed decades ago, and for temperature is a sustained global temperature increase of less than 1.5°C above pre-industrial levels. How much can corals acclimate and/or adapt to the unprecedented fast changing environmental conditions? Any change in the threshold for coral bleaching as the result of acclimation and/or adaption may help corals to survive in the future but adaptation to one stress may be maladaptive to another. There also is evidence that ocean acidification and nutrient enrichment modify this threshold. What do shifting thresholds mean for identifying limits and taking management actions to adapt to climate change?

The threshold vs LNT showdown: Dose rate findings exposed flaws in the LNT model part 2. How a mistake led BEIR I to adopt LNT

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

Calabrese, Edward J., E-mail: edwardc@schoolph.uma

This paper reveals that nearly 25 years after the used Russell's dose-rate data to support the adoption of the linear-no-threshold (LNT) dose response model for genetic and cancer risk assessment, Russell acknowledged a significant under-reporting of the mutation rate of the historical control group. This error, which was unknown to BEIR I, had profound implications, leading it to incorrectly adopt the LNT model, which was a decision that profoundly changed the course of risk assessment for radiation and chemicals to the present. -- Highlights: • The BEAR I Genetics Panel made an error in denying dose rate for mutation. •more » The BEIR I Genetics Subcommittee attempted to correct this dose rate error. • The control group used for risk assessment by BEIR I is now known to be in error. • Correcting this error contradicts the LNT, supporting a threshold model.« less

Combined exposure to X-irradiation followed by N-ethyl-N-nitrosourea treatment alters the frequency and spectrum of Ikaros point mutations in murine T-cell lymphoma.

PubMed

Kakinuma, Shizuko; Nishimura, Mayumi; Amasaki, Yoshiko; Takada, Mayumi; Yamauchi, Kazumi; Sudo, Satomi; Shang, Yi; Doi, Kazutaka; Yoshinaga, Shinji; Shimada, Yoshiya

2012-09-01

Ionizing radiation is a well-known carcinogen, but its potency may be influenced by other environmental carcinogens, which is of practical importance in the assessment of risk. Data are scarce, however, on the combined effect of radiation with other environmental carcinogens and the underlying mechanisms involved. We studied the mode and mechanism of the carcinogenic effect of radiation in combination with N-ethyl-N-nitrosourea (ENU) using doses approximately equal to the corresponding thresholds. B6C3F1 mice exposed to fractionated X-irradiation (Kaplan's method) followed by ENU developed T-cell lymphomas in a dose-dependent manner. Radiation doses above an apparent threshold acted synergistically with ENU to promote lymphoma development, whereas radiation doses below that threshold antagonized lymphoma development. Ikaros, which regulates the commitment and differentiation of lymphoid lineage cells, is a critical tumor suppressor gene frequently altered in both human and mouse lymphomas and shows distinct mutation spectra between X-ray- and ENU-induced lymphomas. In the synergistically induced lymphomas, we observed a low frequency of LOH and an inordinate increase of Ikaros base substitutions characteristic of ENU-induced point mutations, G:C to A:T at non-CpG, A:T to G:C, G:C to T:A and A:T to T:A. This suggests that radiation doses above an apparent threshold activate the ENU mutagenic pathway. This is the first report on the carcinogenic mechanism elicited by combined exposure to carcinogens below and above threshold doses based on the mutation spectrum of the causative gene. These findings constitute a basis for assessing human cancer risk following exposure to multiple carcinogens. Copyright © 2012 Elsevier B.V. All rights reserved.

Thermal antinociception after dexmedetomidine administration in cats: a dose-finding study.

PubMed

Slingsby, L S; Taylor, P M

2008-04-01

The optimum dose of dexmedetomidine for antinociception to a thermal stimulus was determined in a crossover study of 12 cats. In five treatment groups (n = 10 per group), dexmedetomidine was administered intramuscularly (i.m.) at 2, 5, 10, 20 and 40 microg/kg; positive and negative controls were administered buprenorphine (20 microg/kg, i.m.) and 0.9% saline (0.006 mL/kg, i.m.) respectively. Baseline thermal thresholds and visual analogue scale (VAS) sedation scores were obtained prior to drug treatment and then at regular intervals until 24 h after administration. The summary measures of overall mean thresholds and overall mean VAS scores were investigated using a univariate general linear model for multiple factors with post hoc Tukey's tests (P < 0.05). Only dexmedetomidine at 40 microg/kg displayed an analgesic effect (less than that of buprenorphine). The VAS for sedation did not significantly affect the thresholds obtained and treatment was the only significant factor to influence VAS. Dexmedetomidine resulted in higher VAS for sedation than saline and buprenorphine. Dexmedetomidine at 40 microg/kg significantly increased nociceptive thresholds compared with saline control, but less than buprenorphine. Dexmedetomidine produced dose-dependent sedation, but only the highest dose produced analgesia, suggesting that induction of analgesia requires the highest dose (or an additional analgesic) in the clinical setting.

The anticonvulsant action of nafimidone on kindled amygdaloid seizures in rats.

PubMed

Albertson, T E; Walby, W F

1988-01-01

The anticonvulsant effectiveness of nafimidone (1-[2-naphthoylmethyl]imidazole hydrochloride) was evaluated in the kindled amygdaloid seizure model in rats. Nafimidone (3.1-120 mg/kg i.p.) was evaluated at 30 min in previously kindled rats using both threshold (20 microA increments) and supranthreshold (400 microA) paradigms. Nafimidone (25-50 mg/kg) significantly reduced supranthreshold elicited afterdischarge length and seizure severity only at doses with some prestimulation toxicity. The maximum anticonvulsant effectiveness for the 25 mg/kg i.p. dose of nafimidone was seen between 15 and 30 min utilizing a suprathreshold kindling paradigm. Nafimidone did not significantly elevate seizure thresholds at the doses tested; however, nafimidone (3.1-50 mg/kg) reduced the severity and afterdischarge duration of threshold elicited seizures in a non-dose response manner. Drug-induced electroencephalographic spikes were seen in both cortex and amygdala in most kindled rats receiving 100-120 mg/kg i.p. within 30 min of dosing before electrical stimulation. The frequency of spike and wave complexes increased in most of these animals leading to drug-induced spontaneous seizures and death in approximately 25% before electrical stimulation. This study has demonstrated that although nafimidone can modify both threshold and suprathreshold elicited kindled amygdaloid seizures, it lacks significant specificity in this model of epilepsy.

Radiation Dose-Volume Effects in the Stomach and Small Bowel

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

Kavanagh, Brian D., E-mail: Brian.Kavanagh@ucdenver.ed; Pan, Charlie C.; Dawson, Laura A.

2010-03-01

Published data suggest that the risk of moderately severe (>=Grade 3) radiation-induced acute small-bowel toxicity can be predicted with a threshold model whereby for a given dose level, D, if the volume receiving that dose or greater (VD) exceeds a threshold quantity, the risk of toxicity escalates. Estimates of VD depend on the means of structure segmenting (e.g., V15 = 120 cc if individual bowel loops are outlined or V45 = 195 cc if entire peritoneal potential space of bowel is outlined). A similar predictive model of acute toxicity is not available for stomach. Late small-bowel/stomach toxicity is likely relatedmore » to maximum dose and/or volume threshold parameters qualitatively similar to those related to acute toxicity risk. Concurrent chemotherapy has been associated with a higher risk of acute toxicity, and a history of abdominal surgery has been associated with a higher risk of late toxicity.« less

Atomic Bomb Health Benefits

PubMed Central

Luckey, T. D.

2008-01-01

Media reports of deaths and devastation produced by atomic bombs convinced people around the world that all ionizing radiation is harmful. This concentrated attention on fear of miniscule doses of radiation. Soon the linear no threshold (LNT) paradigm was converted into laws. Scientifically valid information about the health benefits from low dose irradiation was ignored. Here are studies which show increased health in Japanese survivors of atomic bombs. Parameters include decreased mutation, leukemia and solid tissue cancer mortality rates, and increased average lifespan. Each study exhibits a threshold that repudiates the LNT dogma. The average threshold for acute exposures to atomic bombs is about 100 cSv. Conclusions from these studies of atomic bomb survivors are: One burst of low dose irradiation elicits a lifetime of improved health.Improved health from low dose irradiation negates the LNT paradigm.Effective triage should include radiation hormesis for survivor treatment. PMID:19088902

An adaptive embedded mesh procedure for leading-edge vortex flows

NASA Technical Reports Server (NTRS)

Powell, Kenneth G.; Beer, Michael A.; Law, Glenn W.

1989-01-01

A procedure for solving the conical Euler equations on an adaptively refined mesh is presented, along with a method for determining which cells to refine. The solution procedure is a central-difference cell-vertex scheme. The adaptation procedure is made up of a parameter on which the refinement decision is based, and a method for choosing a threshold value of the parameter. The refinement parameter is a measure of mesh-convergence, constructed by comparison of locally coarse- and fine-grid solutions. The threshold for the refinement parameter is based on the curvature of the curve relating the number of cells flagged for refinement to the value of the refinement threshold. Results for three test cases are presented. The test problem is that of a delta wing at angle of attack in a supersonic free-stream. The resulting vortices and shocks are captured efficiently by the adaptive code.

Olfactory Detection Thresholds and Adaptation in Adults with Autism Spectrum Condition

ERIC Educational Resources Information Center

Tavassoli, T.; Baron-Cohen, S.

2012-01-01

Sensory issues have been widely reported in Autism Spectrum Conditions (ASC). Since olfaction is one of the least investigated senses in ASC, the current studies explore olfactory detection thresholds and adaptation to olfactory stimuli in adults with ASC. 80 participants took part, 38 (18 females, 20 males) with ASC and 42 control participants…

Microscopy mineral image enhancement based on improved adaptive threshold in nonsubsampled shearlet transform domain

NASA Astrophysics Data System (ADS)

Li, Liangliang; Si, Yujuan; Jia, Zhenhong

2018-03-01

In this paper, a novel microscopy mineral image enhancement method based on adaptive threshold in non-subsampled shearlet transform (NSST) domain is proposed. First, the image is decomposed into one low-frequency sub-band and several high-frequency sub-bands. Second, the gamma correction is applied to process the low-frequency sub-band coefficients, and the improved adaptive threshold is adopted to suppress the noise of the high-frequency sub-bands coefficients. Third, the processed coefficients are reconstructed with the inverse NSST. Finally, the unsharp filter is used to enhance the details of the reconstructed image. Experimental results on various microscopy mineral images demonstrated that the proposed approach has a better enhancement effect in terms of objective metric and subjective metric.

Regulatory implications of a linear non-threshold (LNT) dose-based risks.

PubMed

Aleta, C R

2009-01-01

Current radiation protection regulatory limits are based on the linear non-threshold (LNT) theory using health data from atomic bombing survivors. Studies in recent years sparked debate on the validity of the theory, especially at low doses. The present LNT overestimates radiation risks since the dosimetry included only acute gammas and neutrons; the role of other bomb-caused factors, e.g. fallout, induced radioactivity, thermal radiation (UVR), electromagnetic pulse (EMP), and blast, were excluded. Studies are proposed to improve the dose-response relationship.

SU-F-R-11: Designing Quality and Safety Informatics Through Implementation of a CT Radiation Dose Monitoring Program

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

Wilson, JM; Samei, E; Departments of Physics, Electrical and Computer Engineering, and Biomedical Engineering, and Medical Physics Graduate Program, Duke University, Durham, NC

2016-06-15

Purpose: Recent legislative and accreditation requirements have driven rapid development and implementation of CT radiation dose monitoring solutions. Institutions must determine how to improve quality, safety, and consistency of their clinical performance. The purpose of this work was to design a strategy and meaningful characterization of results from an in-house, clinically-deployed dose monitoring solution. Methods: A dose monitoring platform was designed by our imaging physics group that focused on extracting protocol parameters, dose metrics, and patient demographics and size. Compared to most commercial solutions, which focus on individual exam alerts and global thresholds, the program sought to characterize overall consistencymore » and targeted thresholds based on eight analytic interrogations. Those were based on explicit questions related to protocol application, national benchmarks, protocol and size-specific dose targets, operational consistency, outliers, temporal trends, intra-system variability, and consistent use of electronic protocols. Using historical data since the start of 2013, 95% and 99% intervals were used to establish yellow and amber parameterized dose alert thresholds, respectively, as a function of protocol, scanner, and size. Results: Quarterly reports have been generated for three hospitals for 3 quarters of 2015 totaling 27880, 28502, 30631 exams, respectively. Four adult and two pediatric protocols were higher than external institutional benchmarks. Four protocol dose levels were being inconsistently applied as a function of patient size. For the three hospitals, the minimum and maximum amber outlier percentages were [1.53%,2.28%], [0.76%,1.8%], [0.94%,1.17%], respectively. Compared with the electronic protocols, 10 protocols were found to be used with some inconsistency. Conclusion: Dose monitoring can satisfy requirements with global alert thresholds and patient dose records, but the real value is in optimizing patient-specific protocols, balancing image quality trade-offs that dose-reduction strategies promise, and improving the performance and consistency of a clinical operation. Data plots that capture patient demographics and scanner performance demonstrate that value.« less

Thermosensitivity is reduced during fever induced by Staphylococcus aureus cells walls in rabbits.

PubMed

Tøien, Ø; Mercer, J B

1996-05-01

Thermosensitivity (TS) and threshold core temperature for metabolic cold defence were determined in six conscious rabbits before, and at seven different times after i.v. injection of killed Staphylococcus aureus (8 x 10(7) or 2 x 10(7) cell walls x kg(-1)) by exposure to short periods (5-10 min) of body cooling. Heat was extracted with a chronically implanted intravascular heat exchanger. TS was calculated by regression of metabolic heat production (M) and core temperature, as indicated by hypothalamic temperature. Threshold for cold defence (shivering threshold) was calculated as the core temperature at which the thermosensitivity line crossed preinjection resting M. The shivering thresholds followed the shape of the fever response. TS was significantly reduced (up to 49%) during the time course of fever induced by the highest dose of pyrogen only. At both high and low doses of pyrogen TS correlated negatively with shivering threshold (r = 0.66 and 0.79 respectively) with similar slopes. The reduction in TS during fever was thus associated with the increase in shivering threshold resulting from the pyrogen injection and not by the dose of pyrogen. Model considerations indicate, however, that changes in sensitivity of the thermosensory input to the hypothalamic controller may affect threshold changes but cause negligible TS changes. It is more likely that the reduction in TS is effected in the specific hypothalamic effector pathways.

Wavelet tree structure based speckle noise removal for optical coherence tomography

NASA Astrophysics Data System (ADS)

Yuan, Xin; Liu, Xuan; Liu, Yang

2018-02-01

We report a new speckle noise removal algorithm in optical coherence tomography (OCT). Though wavelet domain thresholding algorithms have demonstrated superior advantages in suppressing noise magnitude and preserving image sharpness in OCT, the wavelet tree structure has not been investigated in previous applications. In this work, we propose an adaptive wavelet thresholding algorithm via exploiting the tree structure in wavelet coefficients to remove the speckle noise in OCT images. The threshold for each wavelet band is adaptively selected following a special rule to retain the structure of the image across different wavelet layers. Our results demonstrate that the proposed algorithm outperforms conventional wavelet thresholding, with significant advantages in preserving image features.

Hair dosimetry following neutron irradiation.

PubMed

Lebaron-Jacobs, L; Gaillard-Lecanu, E; Briot, F; Distinguin, S; Boisson, P; Exmelin, L; Racine, Y; Berard, P; Flüry-Herard, A; Miele, A; Fottorino, R

2007-05-01

Use of hair as a biological dosimeter of neutron exposure was proposed a few years ago. To date, the (32)S(n,p)(32)P reaction in hair with a threshold of 2.5 MeV is the best choice to determine the fast neutron dose using body activation. This information is essential with regards to the heterogeneity of the neutron transfer to the organism. This is a very important parameter for individual dose reconstruction from the surface to the deeper tissues. This evaluation is essential to the adapted management of irradiated victims by specialized medical staff. Comparison exercises between clinical biochemistry laboratories from French sites (the CEA and COGEMA) and from the IRSN were carried out to validate the measurement of (32)P activity in hair and to improve the techniques used to perform this examination. Hair was placed on a phantom and was irradiated at different doses in the SILENE reactor (Valduc, France). Different parameters were tested: variation of hair type, minimum weight of hair sample, hair wash before measurement, delivery period of results, and different irradiation configurations. The results obtained in these comparison exercises by the different laboratories showed an excellent correlation. This allowed the assessment of a dose-activity relationship and confirmed the feasibility and the interest of (32)P measurement in hair following fast neutron irradiation.

When do Indians feel hot? Internet searches indicate seasonality suppresses adaptation to heat

NASA Astrophysics Data System (ADS)

Singh, Tanya; Siderius, Christian; Van der Velde, Ype

2018-05-01

In a warming world an increasing number of people are being exposed to heat, making a comfortable thermal environment an important need. This study explores the potential of using Regional Internet Search Frequencies (RISF) for air conditioning devices as an indicator for thermal discomfort (i.e. dissatisfaction with the thermal environment) with the aim to quantify the adaptation potential of individuals living across different climate zones and at the high end of the temperature range, in India, where access to health data is limited. We related RISF for the years 2011–2015 to daily daytime outdoor temperature in 17 states and determined at which temperature RISF for air conditioning starts to peak, i.e. crosses a ‘heat threshold’, in each state. Using the spatial variation in heat thresholds, we explored whether people continuously exposed to higher temperatures show a lower response to heat extremes through adaptation (e.g. physiological, behavioural or psychological). State-level heat thresholds ranged from 25.9 °C in Madhya Pradesh to 31.0 °C in Orissa. Local adaptation was found to occur at state level: the higher the average temperature in a state, the higher the heat threshold; and the higher the intra-annual temperature range (warmest minus coldest month) the lower the heat threshold. These results indicate there is potential within India to adapt to warmer temperatures, but that a large intra-annual temperature variability attenuates this potential to adapt to extreme heat. This winter ‘reset’ mechanism should be taken into account when assessing the impact of global warming, with changes in minimum temperatures being an important factor in addition to the change in maximum temperatures itself. Our findings contribute to a better understanding of local heat thresholds and people’s adaptive capacity, which can support the design of local thermal comfort standards and early heat warning systems.

A low, adaptive dose of gamma-rays reduced the number and altered the spectrum of S1- mutants in human-hamster hybrid AL cells

NASA Technical Reports Server (NTRS)

Ueno, A. M.; Vannais, D. B.; Gustafson, D. L.; Wong, J. C.; Waldren, C. A.

1996-01-01

We examined the effects of a low, adaptive dose of 137Cs-gamma-irradiation (0.04 Gy) on the number and kinds of mutants induced in AL human-hamster hybrid cells by a later challenge dose of 4 Gy. The yield of S1- mutants was significantly less (by 53%) after exposure to both the adaptive and challenge doses compared to the challenge dose alone. The yield of hprt- mutants was similarly decreased. Incubation with cycloheximide (CX) or 3-aminobenzamide largely negated the decrease in mutant yield. The adaptive dose did not perturb the cell cycle, was not cytotoxic, and did not of itself increase the mutant yield above background. The adaptive dose did, however, alter the spectrum of S1- mutants from populations exposed only to the adaptive dose, as well as affecting the spectrum of S1- mutants generated by the challenge dose. The major change in both cases was a significant increase in the proportion of complex mutations compared to small mutations and simple deletions.

Psychophysical Measurement of Rod and Cone Thresholds in Stargardt Disease with Full-Field Stimuli

PubMed Central

Collison, Frederick T.; Fishman, Gerald A.; McAnany, J. Jason; Zernant, Jana; Allikmets, Rando

2014-01-01

Purpose To investigate psychophysical thresholds in Stargardt disease with the full-field stimulus test (FST). Methods Visual acuity (VA), spectral-domain optical coherence tomography (SD-OCT), full-field electroretinogram (ERG), and FST measurements were made in one eye of 24 patients with Stargardt disease. Dark-adapted rod FST thresholds were measured with short-wavelength stimuli, and cone FST thresholds were obtained from the cone plateau phase of dark adaptation using long-wavelength stimuli. Correlation coefficients were calculated for FST thresholds versus macular thickness, VA and ERG amplitudes. Results Stargardt patient FST cone thresholds correlated significantly with VA, macular thickness, and ERG cone-response amplitudes (all P<0.01). The patients’ FST rod thresholds correlated with ERG rod-response amplitudes (P<0.01), but not macular thickness (P=0.05). All Stargardt disease patients with flecks confined to the macula and most of the patients with flecks extending outside of the macula had normal FST thresholds. All patients with extramacular atrophic changes had elevated FST cone thresholds and most had elevated FST rod thresholds. Conclusion FST rod and cone threshold elevation in Stargardt disease patients correlated well with measures of structure and function, as well as ophthalmoscopic retinal appearance. FST appears to be a useful tool for assessing rod and cone function in Stargardt disease. PMID:24695063

SU-E-T-571: Prostate IMRT QA: Prediction of the Range of Rectal NTCP Using a 2D Field Approach Based on Variations of the Rectal Wall Motion and Thickness.

PubMed

Grigorov, G; Chow, J; Foster, K

2012-06-01

The aims of this study is to (1) introduce a 2D field of possible rectal normal tissue complication probability (NTCP) in prostate intensity modulated radiotherapy (IMRT) plan, so that based on a given prescribed dose the rectal NTCP is merely a function of the rectal wall thickness and rectal motion; and (2) separate the 2D field of rectal NTCP into area of low risk and area of high risk for rectal toxicity < Grade II, based on the threshold rectal NTCP. The 2D field of NTCP model was developed using ten randomly selected prostate IMRT plans. The clinical rectal geometry was initially represented by the cylindrical contour in the treatment planning system. Different combinations of rectal motions, rectal wall thicknesses, planning target volume margins and prescribed doses were used to determine the NTCP in prostate IMRT plans. It was found that the functions bordering the 2D field for the given AP, LR and SI direction can be described as exponential, quadratic and linear equations, respectively. A ratio of the area of 2D field containing data of the low risk NTCP to the entire area of the field was introduced and calculated. Although our method is based on the Kutcher's dose response model and published tissue parameters, other mathematical models can be used in our approach. The 2D field of rectal NTCP is useful to estimate the rectal NTCP range in the prostate pre-treatment and treatment QA. Our method can determine the patient's threshold immobilization for a given rectal wall thickness so that prescribed dose can be delivered to the prostate to avoid rectal complication. Our method is also applicable to multi-phase prostate IMRT, and can be adapted to any treatment planning systems. © 2012 American Association of Physicists in Medicine.

Lowered threshold energy for femtosecond laser induced optical breakdown in a water based eye model by aberration correction with adaptive optics.

PubMed

Hansen, Anja; Géneaux, Romain; Günther, Axel; Krüger, Alexander; Ripken, Tammo

2013-06-01

In femtosecond laser ophthalmic surgery tissue dissection is achieved by photodisruption based on laser induced optical breakdown. In order to minimize collateral damage to the eye laser surgery systems should be optimized towards the lowest possible energy threshold for photodisruption. However, optical aberrations of the eye and the laser system distort the irradiance distribution from an ideal profile which causes a rise in breakdown threshold energy even if great care is taken to minimize the aberrations of the system during design and alignment. In this study we used a water chamber with an achromatic focusing lens and a scattering sample as eye model and determined breakdown threshold in single pulse plasma transmission loss measurements. Due to aberrations, the precise lower limit for breakdown threshold irradiance in water is still unknown. Here we show that the threshold energy can be substantially reduced when using adaptive optics to improve the irradiance distribution by spatial beam shaping. We found that for initial aberrations with a root-mean-square wave front error of only one third of the wavelength the threshold energy can still be reduced by a factor of three if the aberrations are corrected to the diffraction limit by adaptive optics. The transmitted pulse energy is reduced by 17% at twice the threshold. Furthermore, the gas bubble motions after breakdown for pulse trains at 5 kilohertz repetition rate show a more transverse direction in the corrected case compared to the more spherical distribution without correction. Our results demonstrate how both applied and transmitted pulse energy could be reduced during ophthalmic surgery when correcting for aberrations. As a consequence, the risk of retinal damage by transmitted energy and the extent of collateral damage to the focal volume could be minimized accordingly when using adaptive optics in fs-laser surgery.

Lowered threshold energy for femtosecond laser induced optical breakdown in a water based eye model by aberration correction with adaptive optics

PubMed Central

Hansen, Anja; Géneaux, Romain; Günther, Axel; Krüger, Alexander; Ripken, Tammo

2013-01-01

In femtosecond laser ophthalmic surgery tissue dissection is achieved by photodisruption based on laser induced optical breakdown. In order to minimize collateral damage to the eye laser surgery systems should be optimized towards the lowest possible energy threshold for photodisruption. However, optical aberrations of the eye and the laser system distort the irradiance distribution from an ideal profile which causes a rise in breakdown threshold energy even if great care is taken to minimize the aberrations of the system during design and alignment. In this study we used a water chamber with an achromatic focusing lens and a scattering sample as eye model and determined breakdown threshold in single pulse plasma transmission loss measurements. Due to aberrations, the precise lower limit for breakdown threshold irradiance in water is still unknown. Here we show that the threshold energy can be substantially reduced when using adaptive optics to improve the irradiance distribution by spatial beam shaping. We found that for initial aberrations with a root-mean-square wave front error of only one third of the wavelength the threshold energy can still be reduced by a factor of three if the aberrations are corrected to the diffraction limit by adaptive optics. The transmitted pulse energy is reduced by 17% at twice the threshold. Furthermore, the gas bubble motions after breakdown for pulse trains at 5 kilohertz repetition rate show a more transverse direction in the corrected case compared to the more spherical distribution without correction. Our results demonstrate how both applied and transmitted pulse energy could be reduced during ophthalmic surgery when correcting for aberrations. As a consequence, the risk of retinal damage by transmitted energy and the extent of collateral damage to the focal volume could be minimized accordingly when using adaptive optics in fs-laser surgery. PMID:23761849

Thresholds of Toxicological Concern - Setting a threshold for testing below which there is little concern.

PubMed

Hartung, Thomas

2017-01-01

Low dose, low risk; very low dose, no real risk. Setting a pragmatic threshold below which concerns become negligible is the purpose of thresholds of toxicological concern (TTC). The idea is that such threshold values do not need to be established for each and every chemical based on experimental data, but that by analyzing the distribution of lowest or no-effect doses of many chemicals, a TTC can be defined - typically using the 5th percentile of this distribution and lowering it by an uncertainty factor of, e.g., 100. In doing so, TTC aims to compare exposure information (dose) with a threshold below which any hazard manifestation is very unlikely to occur. The history and current developments of this concept are reviewed and the application of TTC for different regulated products and their hazards is discussed. TTC lends itself as a pragmatic filter to deprioritize testing needs whenever real-life exposures are much lower than levels where hazard manifestation would be expected, a situation that is called "negligible exposure" in the REACH legislation, though the TTC concept has not been fully incorporated in its implementation (yet). Other areas and regulations - especially in the food sector and for pharmaceutical impurities - are more proactive. Large, curated databases on toxic effects of chemicals provide us with the opportunity to set TTC for many hazards and substance classes and thus offer a precautionary second tier for risk assessments if hazard cannot be excluded. This allows focusing testing efforts better on relevant exposures to chemicals.

Comparison of singlet oxygen threshold dose for PDT.

PubMed

Zhu, Timothy C; Liu, Baochang; Kim, Michele M; McMillan, Dayton; Liang, Xing; Finlay, Jarod C; Busch, Theresa M

2014-02-01

Macroscopic modeling of singlet oxygen ( 1 O 2 ) is of particular interest because it is the major cytotoxic agent causing biological effects for type II photosensitizers during PDT. We have developed a macroscopic model to calculate reacted singlet oxygen concentration ([1O2] rx for PDT. An in-vivo RIF tumor mouse model is used to correlate the necrosis depth to the calculation based on explicit PDT dosimetry of light fluence distribution, tissue optical properties, and photosensitizer concentrations. Inputs to the model include 4 photosensitizer specific photochemical parameters along with the apparent singlet oxygen threshold concentration. Photosensitizer specific model parameters are determined for several type II photosensitizers (Photofrin, BPD, and HPPH). The singlet oxygen threshold concentration is approximately 0.41 - 0.56 mM for all three photosensitizers studied, assuming that the fraction of singlet oxygen generated that interacts with the cell is ( f = 1). In comparison, value derived from other in-vivo mice studies is 0.4 mM for mTHPC. However, the singlet oxygen threshold doses were reported to be 7.9 and 12.1 mM for a multicell in-vitro EMT6/Ro spheroid model for mTHPC and Photofrin PDT, respectively. The sensitivity of threshold singlet oxygen dose for our experiment is examined. The possible influence of vascular vs. apoptotic cell killing mechanism on the singlet oxygen threshold dose is discussed using the BPD with different drug-light intervals 3 hrs vs. 15 min. The observed discrepancies between different experiments warrant further investigation to explain the cause of the difference.

Comparison of singlet oxygen threshold dose for PDT

PubMed Central

Zhu, Timothy C; Liu, Baochang; Kim, Michele M.; McMillan, Dayton; Liang, Xing; Finlay, Jarod C.; Busch, Theresa M.

2015-01-01

Macroscopic modeling of singlet oxygen (1O2) is of particular interest because it is the major cytotoxic agent causing biological effects for type II photosensitizers during PDT. We have developed a macroscopic model to calculate reacted singlet oxygen concentration ([1O2]rx for PDT. An in-vivo RIF tumor mouse model is used to correlate the necrosis depth to the calculation based on explicit PDT dosimetry of light fluence distribution, tissue optical properties, and photosensitizer concentrations. Inputs to the model include 4 photosensitizer specific photochemical parameters along with the apparent singlet oxygen threshold concentration. Photosensitizer specific model parameters are determined for several type II photosensitizers (Photofrin, BPD, and HPPH). The singlet oxygen threshold concentration is approximately 0.41 – 0.56 mM for all three photosensitizers studied, assuming that the fraction of singlet oxygen generated that interacts with the cell is (f = 1). In comparison, value derived from other in-vivo mice studies is 0.4 mM for mTHPC. However, the singlet oxygen threshold doses were reported to be 7.9 and 12.1 mM for a multicell in-vitro EMT6/Ro spheroid model for mTHPC and Photofrin PDT, respectively. The sensitivity of threshold singlet oxygen dose for our experiment is examined. The possible influence of vascular vs. apoptotic cell killing mechanism on the singlet oxygen threshold dose is discussed using the BPD with different drug-light intervals 3 hrs vs. 15 min. The observed discrepancies between different experiments warrant further investigation to explain the cause of the difference. PMID:25999651

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

Otake, M.; Schull, W.J.

The occurrence of lenticular opacities among atomic bomb survivors in Hiroshima and Nagasaki detected in 1963-1964 has been examined in reference to their ..gamma.. and neutron doses. A lenticular opacity in this context implies an ophthalmoscopic and slit lamp biomicroscopic defect in the axial posterior aspect of the lens which may or may not interfere measureably with visual acuity. Several different dose-response models were fitted to the data after the effects of age at time of bombing (ATB) were examined. Some postulate the existence of a threshold(s), others do not. All models assume a ''background'' exists, that is, that somemore » number of posterior lenticular opacities are ascribable to events other than radiation exposure. Among these alternatives we can show that a simple linear ..gamma..-neutron relationship which assumes no threshold does not fit the data adequately under the T65 dosimetry, but does fit the recent Oak Ridge and Lawrence Livermore estimates. Other models which envisage quadratic terms in gamma and which may or may not assume a threshold are compatible with the data. The ''best'' fit, that is, the one with the smallest X/sup 2/ and largest tail probability, is with a ''linear gamma:linear neutron'' model which postulates a ..gamma.. threshold but no threshold for neutrons. It should be noted that the greatest difference in the dose-response models associated with the three different sets of doses involves the neutron component, as is, of course, to be expected. No effect of neutrons on the occurrence of lenticular opacities is demonstrable with either the Lawrence Livermore or Oak Ridge estimates.« less

Effects of nicotine and minor tobacco alkaloids on intracranial-self-stimulation in rats.

PubMed

Harris, Andrew C; Tally, Laura; Muelken, Peter; Banal, Andrew; Schmidt, Clare E; Cao, Qing; LeSage, Mark G

2015-08-01

While nicotine is the primary addictive compound in tobacco, other tobacco constituents including minor alkaloids (e.g., nornicotine, anabasine) may also contribute to tobacco addiction by mimicking or enhancing the effects of nicotine. Further evaluating the behavioral effects of minor alkaloids is essential for understanding their impact on tobacco addiction and informing development of tobacco product standards by the FDA. This study compared the addiction-related effects of nicotine and the minor alkaloids nornicotine, anabasine, myosmine, anatabine, and cotinine on intracranial self-stimulation (ICSS) thresholds in rats. Acute injection of nicotine produced reinforcement-enhancing (ICSS threshold-decreasing) effects at low to moderate doses, and reinforcement-attenuating/aversive (ICSS threshold-increasing) effects at high doses. Nornicotine and anabasine produced similar biphasic effects on ICSS thresholds, although with lower potency compared to nicotine. Myosmine only elevated ICSS thresholds at relatively high doses, while anatabine and cotinine did not influence ICSS thresholds at any dose. None of the alkaloids significantly influenced ICSS response latencies, indicating a lack of nonspecific motoric effects. These findings indicate that some minor tobacco alkaloids can either fully (nornicotine, anabasine) or partially (myosmine) mimic nicotine's addiction-related effects on ICSS, albeit at reduced potency. These findings emphasize the need for further study of the abuse potential of minor alkaloids, including evaluation of their effects when combined with nicotine and other tobacco constituents to better simulate tobacco exposure in humans. Such work is essential for informing FDA regulation of tobacco products and could also lead to the development of novel pharmacotherapies for tobacco addiction. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Ultra-low-dose computed tomographic angiography with model-based iterative reconstruction compared with standard-dose imaging after endovascular aneurysm repair: a prospective pilot study.

PubMed

Naidu, Sailen G; Kriegshauser, J Scott; Paden, Robert G; He, Miao; Wu, Qing; Hara, Amy K

2014-12-01

An ultra-low-dose radiation protocol reconstructed with model-based iterative reconstruction was compared with our standard-dose protocol. This prospective study evaluated 20 men undergoing surveillance-enhanced computed tomography after endovascular aneurysm repair. All patients underwent standard-dose and ultra-low-dose venous phase imaging; images were compared after reconstruction with filtered back projection, adaptive statistical iterative reconstruction, and model-based iterative reconstruction. Objective measures of aortic contrast attenuation and image noise were averaged. Images were subjectively assessed (1 = worst, 5 = best) for diagnostic confidence, image noise, and vessel sharpness. Aneurysm sac diameter and endoleak detection were compared. Quantitative image noise was 26% less with ultra-low-dose model-based iterative reconstruction than with standard-dose adaptive statistical iterative reconstruction and 58% less than with ultra-low-dose adaptive statistical iterative reconstruction. Average subjective noise scores were not different between ultra-low-dose model-based iterative reconstruction and standard-dose adaptive statistical iterative reconstruction (3.8 vs. 4.0, P = .25). Subjective scores for diagnostic confidence were better with standard-dose adaptive statistical iterative reconstruction than with ultra-low-dose model-based iterative reconstruction (4.4 vs. 4.0, P = .002). Vessel sharpness was decreased with ultra-low-dose model-based iterative reconstruction compared with standard-dose adaptive statistical iterative reconstruction (3.3 vs. 4.1, P < .0001). Ultra-low-dose model-based iterative reconstruction and standard-dose adaptive statistical iterative reconstruction aneurysm sac diameters were not significantly different (4.9 vs. 4.9 cm); concordance for the presence of endoleak was 100% (P < .001). Compared with a standard-dose technique, an ultra-low-dose model-based iterative reconstruction protocol provides comparable image quality and diagnostic assessment at a 73% lower radiation dose.

Quantitative assessment of the dose-response of alkylating agents in DNA repair proficient and deficient ames tester strains.

PubMed

Tang, Leilei; Guérard, Melanie; Zeller, Andreas

2014-01-01

Mutagenic and clastogenic effects of some DNA damaging agents such as methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS) have been demonstrated to exhibit a nonlinear or even "thresholded" dose-response in vitro and in vivo. DNA repair seems to be mainly responsible for these thresholds. To this end, we assessed several mutagenic alkylators in the Ames test with four different strains of Salmonella typhimurium: the alkyl transferases proficient strain TA1535 (Ogt+/Ada+), as well as the alkyl transferases deficient strains YG7100 (Ogt+/Ada-), YG7104 (Ogt-/Ada+) and YG7108 (Ogt-/Ada-). The known genotoxins EMS, MMS, temozolomide (TMZ), ethylnitrosourea (ENU) and methylnitrosourea (MNU) were tested in as many as 22 concentration levels. Dose-response curves were statistically fitted by the PROAST benchmark dose model and the Lutz-Lutz "hockeystick" model. These dose-response curves suggest efficient DNA-repair for lesions inflicted by all agents in strain TA1535. In the absence of Ogt, Ada is predominantly repairing methylations but not ethylations. It is concluded that the capacity of alkyl-transferases to successfully repair DNA lesions up to certain dose levels contributes to genotoxicity thresholds. Copyright © 2013 Wiley Periodicals, Inc.

Automatic video shot boundary detection using k-means clustering and improved adaptive dual threshold comparison

NASA Astrophysics Data System (ADS)

Sa, Qila; Wang, Zhihui

2018-03-01

At present, content-based video retrieval (CBVR) is the most mainstream video retrieval method, using the video features of its own to perform automatic identification and retrieval. This method involves a key technology, i.e. shot segmentation. In this paper, the method of automatic video shot boundary detection with K-means clustering and improved adaptive dual threshold comparison is proposed. First, extract the visual features of every frame and divide them into two categories using K-means clustering algorithm, namely, one with significant change and one with no significant change. Then, as to the classification results, utilize the improved adaptive dual threshold comparison method to determine the abrupt as well as gradual shot boundaries.Finally, achieve automatic video shot boundary detection system.

A Shearlet-based algorithm for quantum noise removal in low-dose CT images

NASA Astrophysics Data System (ADS)

Zhang, Aguan; Jiang, Huiqin; Ma, Ling; Liu, Yumin; Yang, Xiaopeng

2016-03-01

Low-dose CT (LDCT) scanning is a potential way to reduce the radiation exposure of X-ray in the population. It is necessary to improve the quality of low-dose CT images. In this paper, we propose an effective algorithm for quantum noise removal in LDCT images using shearlet transform. Because the quantum noise can be simulated by Poisson process, we first transform the quantum noise by using anscombe variance stabilizing transform (VST), producing an approximately Gaussian noise with unitary variance. Second, the non-noise shearlet coefficients are obtained by adaptive hard-threshold processing in shearlet domain. Third, we reconstruct the de-noised image using the inverse shearlet transform. Finally, an anscombe inverse transform is applied to the de-noised image, which can produce the improved image. The main contribution is to combine the anscombe VST with the shearlet transform. By this way, edge coefficients and noise coefficients can be separated from high frequency sub-bands effectively. A number of experiments are performed over some LDCT images by using the proposed method. Both quantitative and visual results show that the proposed method can effectively reduce the quantum noise while enhancing the subtle details. It has certain value in clinical application.

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

Automatic treatment plan re-optimization for adaptive radiotherapy guided with the initial plan DVHs.

PubMed

Li, Nan; Zarepisheh, Masoud; Uribe-Sanchez, Andres; Moore, Kevin; Tian, Zhen; Zhen, Xin; Graves, Yan Jiang; Gautier, Quentin; Mell, Loren; Zhou, Linghong; Jia, Xun; Jiang, Steve

2013-12-21

Adaptive radiation therapy (ART) can reduce normal tissue toxicity and/or improve tumor control through treatment adaptations based on the current patient anatomy. Developing an efficient and effective re-planning algorithm is an important step toward the clinical realization of ART. For the re-planning process, manual trial-and-error approach to fine-tune planning parameters is time-consuming and is usually considered unpractical, especially for online ART. It is desirable to automate this step to yield a plan of acceptable quality with minimal interventions. In ART, prior information in the original plan is available, such as dose-volume histogram (DVH), which can be employed to facilitate the automatic re-planning process. The goal of this work is to develop an automatic re-planning algorithm to generate a plan with similar, or possibly better, DVH curves compared with the clinically delivered original plan. Specifically, our algorithm iterates the following two loops. An inner loop is the traditional fluence map optimization, in which we optimize a quadratic objective function penalizing the deviation of the dose received by each voxel from its prescribed or threshold dose with a set of fixed voxel weighting factors. In outer loop, the voxel weighting factors in the objective function are adjusted according to the deviation of the current DVH curves from those in the original plan. The process is repeated until the DVH curves are acceptable or maximum iteration step is reached. The whole algorithm is implemented on GPU for high efficiency. The feasibility of our algorithm has been demonstrated with three head-and-neck cancer IMRT cases, each having an initial planning CT scan and another treatment CT scan acquired in the middle of treatment course. Compared with the DVH curves in the original plan, the DVH curves in the resulting plan using our algorithm with 30 iterations are better for almost all structures. The re-optimization process takes about 30 s using our in-house optimization engine.

Enhanced Sensitivity to Rapid Input Fluctuations by Nonlinear Threshold Dynamics in Neocortical Pyramidal Neurons.

PubMed

Mensi, Skander; Hagens, Olivier; Gerstner, Wulfram; Pozzorini, Christian

2016-02-01

The way in which single neurons transform input into output spike trains has fundamental consequences for network coding. Theories and modeling studies based on standard Integrate-and-Fire models implicitly assume that, in response to increasingly strong inputs, neurons modify their coding strategy by progressively reducing their selective sensitivity to rapid input fluctuations. Combining mathematical modeling with in vitro experiments, we demonstrate that, in L5 pyramidal neurons, the firing threshold dynamics adaptively adjust the effective timescale of somatic integration in order to preserve sensitivity to rapid signals over a broad range of input statistics. For that, a new Generalized Integrate-and-Fire model featuring nonlinear firing threshold dynamics and conductance-based adaptation is introduced that outperforms state-of-the-art neuron models in predicting the spiking activity of neurons responding to a variety of in vivo-like fluctuating currents. Our model allows for efficient parameter extraction and can be analytically mapped to a Generalized Linear Model in which both the input filter--describing somatic integration--and the spike-history filter--accounting for spike-frequency adaptation--dynamically adapt to the input statistics, as experimentally observed. Overall, our results provide new insights on the computational role of different biophysical processes known to underlie adaptive coding in single neurons and support previous theoretical findings indicating that the nonlinear dynamics of the firing threshold due to Na+-channel inactivation regulate the sensitivity to rapid input fluctuations.

Temporal resolution in children.

PubMed

Wightman, F; Allen, P; Dolan, T; Kistler, D; Jamieson, D

1989-06-01

The auditory temporal resolving power of young children was measured using an adaptive forced-choice psychophysical paradigm that was disguised as a video game. 20 children between 3 and 7 years of age and 5 adults were asked to detect the presence of a temporal gap in a burst of half-octave-band noise at band center frequencies of 400 and 2,000 Hz. The minimum detectable gap (gap threshold) was estimated adaptively in 20-trial runs. The mean gap thresholds in the 400-Hz condition were higher for the younger children than for the adults, with the 3-year-old children producing the highest thresholds. Gap thresholds in the 2,000-Hz condition were generally lower than in the 400-Hz condition and showed a similar age effect. All the individual adaptive runs were "adult-like," suggesting that the children were generally attentive to the task during each run. However, the variability of threshold estimates from run to run was substantial, especially in the 3-5-year-old children. Computer simulations suggested that this large within-subjects variability could have resulted from frequent, momentary lapses of attention, which would lead to "guessing" on a substantial portion of the trials.

Method for Assessing Contrast Performance under Lighting Conditions such as Entering a Tunnel on Sunny Day.

PubMed

Huang, Y; Menozzi, M

2015-04-01

Clinical assessment of dark adaptation is time consuming and requires a specialised instrumentation such as a nyktometer. It is therefore not surprising that dark adaptation is rarely tested in practice. As for the case of testing fitness of a driver, demands on adaptation in daily driving tasks mostly depart from settings in a nyktometer. In daily driving, adaptation is stressed by high and fast transitions of light levels, and the period of time which is relevant to safe driving starts right after a transition and ends several seconds later. In the nyktometer dark adaptation is tested after completion of the adaptation process. RESULTS of a nyktometer test may therefore deliver little information about adaptation shortly after light transitions. In an attempt to develop a clinical test aiming to fulfill both a short measurement time and offering test conditions comparable to conditions in driving, we conducted a preliminary study in which contrast sensitivity thresholds were recorded for light transitions as found in daily driving tasks and for various times after transition onsets. Contrast sensitivity performance is compared to dark adaptation performance as assessed by a myktometer. Contrast sensitivity thresholds were recorded in 17 participants by means of a twin projection apparatus. The apparatus enabled the projection of an adapting field and of a Landolt ring both with a variable luminance. Five different stepwise transitions in levels of adapting luminance were tested. All transitions occurred from bright to dark. The Landolt ring was flashed 100 or 500 ms after the transition had occurred. Participants were instructed to report the orientation of the Landolt ring. A Rodenstock Nyktometer, Plate 501, was used to record dark adaptation threshold. Experimental data from the proposed test revealed a noticeably increasing contrast detection threshold measured in dark adaptation in the stronger transition from 14 000 to 8 cd/m2 than in the weaker transition from 2000 to 8 cd/m2. By raising the dark adaption luminance level from 8 to 60 cd/m2 in the stronger transition case, the contrast detection threshold was then improved by a factor of four. Another main finding showed that for the adaptation process from strong glare stimuli to the dark adaptation, a peak deterioration in contrast sensitivity occurred at the light adaptation level of 6000 cd/m2. Comparing the contrast performance assessed by the proposed test with that of the nyktometer test, there was no clear correlation between the two methods. Our suggested method to assess dark adaptation performance proved to be practical in use and, since the patient does not have to spend a long time to attain complete dark adaptation, the method required a short time for measurement. Our negative experience in the use of the myktometer was in agreement with reported experience in the literature. Georg Thieme Verlag KG Stuttgart · New York.

Early Biochemical Effects of an Organic Mercury Fungicide on Infants: ``Dose Makes the Poison''

NASA Astrophysics Data System (ADS)

Gotelli, Carlos A.; Astolfi, Emilio; Cox, Christopher; Cernichiari, Elsa; Clarkson, Thomas W.

1985-02-01

Phenylmercury absorbed through the skin from contaminated diapers affected urinary excretion in infants in Buenos Aires. The effects were reversible and quantitatively related to the concentration of urinary mercury. Excretion of γ -glutamyl transpeptidase, an enzyme in the brush borders of renal tubular cells, increased in a dose-dependent manner when mercury excretion exceeded a ``threshold'' value. Urine volume also increased but at a higher threshold with respect to mercury. The results support the threshold concept of the systemic toxicity of metals. γ -Glutamyl transpeptidase is a useful and sensitive marker for preclinical effects of toxic metals.

Network Motif Basis of Threshold Responses

EPA Science Inventory

There has been a long-running debate over the existence of thresholds for adverse effects. The difficulty stems from two fundamental challenges: (i) statistical analysis by itself cannot prove the existence of a threshold, i.e., a dose below which there is no effect; and (ii) the...

Adaptive time-sequential binary sensing for high dynamic range imaging

NASA Astrophysics Data System (ADS)

Hu, Chenhui; Lu, Yue M.

2012-06-01

We present a novel image sensor for high dynamic range imaging. The sensor performs an adaptive one-bit quantization at each pixel, with the pixel output switched from 0 to 1 only if the number of photons reaching that pixel is greater than or equal to a quantization threshold. With an oracle knowledge of the incident light intensity, one can pick an optimal threshold (for that light intensity) and the corresponding Fisher information contained in the output sequence follows closely that of an ideal unquantized sensor over a wide range of intensity values. This observation suggests the potential gains one may achieve by adaptively updating the quantization thresholds. As the main contribution of this work, we propose a time-sequential threshold-updating rule that asymptotically approaches the performance of the oracle scheme. With every threshold mapped to a number of ordered states, the dynamics of the proposed scheme can be modeled as a parametric Markov chain. We show that the frequencies of different thresholds converge to a steady-state distribution that is concentrated around the optimal choice. Moreover, numerical experiments show that the theoretical performance measures (Fisher information and Craḿer-Rao bounds) can be achieved by a maximum likelihood estimator, which is guaranteed to find globally optimal solution due to the concavity of the log-likelihood functions. Compared with conventional image sensors and the strategy that utilizes a constant single-photon threshold considered in previous work, the proposed scheme attains orders of magnitude improvement in terms of sensor dynamic ranges.

Low-energy electron effects on tensile modulus and infrared transmission properties of a polypyromellitimide film

NASA Technical Reports Server (NTRS)

Ferl, J. E.; Long, E. R., Jr.

1981-01-01

Infrared (IR) spectroscopy and tensile modulus testing were used to evaluate the importance of experimental procedure on changes in properties of pyromellitic dianhydride-p,p prime-oxydianiline film exposed to electron radiation. The radiation exposures were accelerated, approximate equivalents to the total dose expected for a 30 year mission in geosynchronous Earth orbit. The change in the tensile modulus depends more on the dose rate and the time interval between exposure and testing than on total dose. The IR data vary with both total dose and dose rate. A threshold dose rate exists below which reversible radiation effects on the IR spectra occur. Above the threshold dose rate, irreversible effects occur with the appearance of a new band. Post-irradiation and in situ IR absorption bands are significantly different. It is suggested that the electron radiation induced metastable, excites molecular states.

Image denoising in mixed Poisson-Gaussian noise.

PubMed

Luisier, Florian; Blu, Thierry; Unser, Michael

2011-03-01

We propose a general methodology (PURE-LET) to design and optimize a wide class of transform-domain thresholding algorithms for denoising images corrupted by mixed Poisson-Gaussian noise. We express the denoising process as a linear expansion of thresholds (LET) that we optimize by relying on a purely data-adaptive unbiased estimate of the mean-squared error (MSE), derived in a non-Bayesian framework (PURE: Poisson-Gaussian unbiased risk estimate). We provide a practical approximation of this theoretical MSE estimate for the tractable optimization of arbitrary transform-domain thresholding. We then propose a pointwise estimator for undecimated filterbank transforms, which consists of subband-adaptive thresholding functions with signal-dependent thresholds that are globally optimized in the image domain. We finally demonstrate the potential of the proposed approach through extensive comparisons with state-of-the-art techniques that are specifically tailored to the estimation of Poisson intensities. We also present denoising results obtained on real images of low-count fluorescence microscopy.

Lower thresholds for lifetime health effects in mammals from high-LET radiation - Comparison with chronic low-LET radiation.

PubMed

Sazykina, Tatiana G; Kryshev, Alexander I

2016-12-01

Lower threshold dose rates and confidence limits are quantified for lifetime radiation effects in mammalian animals from internally deposited alpha-emitting radionuclides. Extensive datasets on effects from internal alpha-emitters are compiled from the International Radiobiological Archives. In total, the compiled database includes 257 records, which are analyzed by means of non-parametric order statistics. The generic lower threshold for alpha-emitters in mammalian animals (combined datasets) is 6.6·10 -5  Gy day -1 . Thresholds for individual alpha-emitting elements differ considerably: plutonium and americium - 2.0·10 -5  Gy day -1 ; radium - 2.1·10 -4  Gy day -1 . Threshold for chronic low-LET radiation is previously estimated at 1·10 -3  Gy day -1 . For low exposures, the following values of alpha radiation weighting factor w R for internally deposited alpha-emitters in mammals are quantified: w R (α) = 15 as a generic value for the whole group of alpha-emitters; w R (Pu) = 50 for plutonium; w R (Am) = 50 for americium; w R (Ra) = 5 for radium. These values are proposed to serve as radiation weighting factors in calculations of equivalent doses to non-human biota. The lower threshold dose rate for long-lived mammals (dogs) is significantly lower than comparing with the threshold for short-lived mammals (mice): 2.7·10 -5  Gy day -1 , and 2.0·10 -4  Gy day -1 , respectively. The difference in thresholds is exactly reflecting the relationship between the natural longevity of these two species. Graded scale of severity in lifetime radiation effects in mammals is developed, based on compiled datasets. Being placed on the severity scale, the effects of internal alpha-emitters are situated in the zones of considerably lower dose rates than effects of the same severity caused by low-LET radiation. RBE values, calculated for effects of equal severity, are found to depend on the intensity of chronic exposure: different RBE values are characteristic for low, moderate, and high lifetime exposures (30, 70, and 13, respectively). The results of the study provide a basis for selecting correct values of radiation weighting factors in dose assessment to non-human biota. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pro-oxidant Induced DNA Damage in Human Lymphoblastoid Cells: Homeostatic Mechanisms of Genotoxic Tolerance

PubMed Central

Seager, Anna L.

2012-01-01

Oxidative stress contributes to many disease etiologies including ageing, neurodegeneration, and cancer, partly through DNA damage induction (genotoxicity). Understanding the i nteractions of free radicals with DNA is fundamental to discern mutation risks. In genetic toxicology, regulatory authorities consider that most genotoxins exhibit a linear relationship between dose and mutagenic response. Yet, homeostatic mechanisms, including DNA repair, that allow cells to tolerate low levels of genotoxic exposure exist. Acceptance of thresholds for genotoxicity has widespread consequences in terms of understanding cancer risk and regulating human exposure to chemicals/drugs. Three pro-oxidant chemicals, hydrogen peroxide (H2O2), potassium bromate (KBrO3), and menadione, were examined for low dose-response curves in human lymphoblastoid cells. DNA repair and antioxidant capacity were assessed as possible threshold mechanisms. H2O2 and KBrO3, but not menadione, exhibited thresholded responses, containing a range of nongenotoxic low doses. Levels of the DNA glycosylase 8-oxoguanine glycosylase were unchanged in response to pro- oxidant stress. DNA repair–focused gene expression arrays reported changes in ATM and BRCA1, involved in double-strand break repair, in response to low-dose pro-oxidant exposure; however, these alterations were not substantiated at the protein level. Determination of oxidatively induced DNA damage in H2O2-treated AHH-1 cells reported accumulation of thymine glycol above the genotoxic threshold. Further, the H2O2 dose-response curve was shifted by modulating the antioxidant glutathione. Hence, observed pro- oxidant thresholds were due to protective capacities of base excision repair enzymes and antioxidants against DNA damage, highlighting the importance of homeostatic mechanisms in “genotoxic tolerance.” PMID:22539617

Evidence Accumulator or Decision Threshold – Which Cortical Mechanism are We Observing?

PubMed Central

Simen, Patrick

2012-01-01

Most psychological models of perceptual decision making are of the accumulation-to-threshold variety. The neural basis of accumulation in parietal and prefrontal cortex is therefore a topic of great interest in neuroscience. In contrast, threshold mechanisms have received less attention, and their neural basis has usually been sought in subcortical structures. Here I analyze a model of a decision threshold that can be implemented in the same cortical areas as evidence accumulators, and whose behavior bears on two open questions in decision neuroscience: (1) When ramping activity is observed in a brain region during decision making, does it reflect evidence accumulation? (2) Are changes in speed-accuracy tradeoffs and response biases more likely to be achieved by changes in thresholds, or in accumulation rates and starting points? The analysis suggests that task-modulated ramping activity, by itself, is weak evidence that a brain area mediates evidence accumulation as opposed to threshold readout; and that signs of modulated accumulation are as likely to indicate threshold adaptation as adaptation of starting points and accumulation rates. These conclusions imply that how thresholds are modeled can dramatically impact accumulator-based interpretations of this data. PMID:22737136

OPTIMIZING THE PRECISION OF TOXICITY THRESHOLD ESTIMATION USING A TWO-STAGE EXPERIMENTAL DESIGN

EPA Science Inventory

An important consideration for risk assessment is the existence of a threshold, i.e., the highest toxicant dose where the response is not distinguishable from background. We have developed methodology for finding an experimental design that optimizes the precision of threshold mo...

A threshold dose distribution approach for the study of PDT resistance development: A threshold distribution approach for the study of PDT resistance.

PubMed

de Faria, Clara Maria Gonçalves; Inada, Natalia Mayumi; Vollet-Filho, José Dirceu; Bagnato, Vanderlei Salvador

2018-05-01

Photodynamic therapy (PDT) is a technique with well-established principles that often demands repeated applications for sequential elimination of tumor cells. An important question concerns the way surviving cells from a treatment behave in the subsequent one. Threshold dose is a core concept in PDT dosimetry, as the minimum amount of energy to be delivered for cell destruction via PDT. Concepts of threshold distribution have shown to be an important tool for PDT results analysis in vitro. In this study, we used some of these concepts for demonstrating subsequent treatments with partial elimination of cells modify the distribution, which represents an increased resistance of the cells to the photodynamic action. HepG2 and HepaRG were used as models of tumor and normal liver cells and a protocol to induce resistance, consisted of repeated PDT sessions using Photogem® as a photosensitizer, was applied to the tumor ones. The response of these cells to PDT was assessed using a standard viability assay and the dose response curves were used for deriving the threshold distributions. The changes in the distribution revealed that the resistance protocol effectively eliminated the most sensitive cells. Nevertheless, HepaRG cell line was the most resistant one among the cells analyzed, which indicates a specificity in clinical applications that enables the use of high doses and drug concentrations with minimal damage to the surrounding normal tissue. Copyright © 2018 Elsevier B.V. All rights reserved.

D-optimal experimental designs to test for departure from additivity in a fixed-ratio mixture ray.

PubMed

Coffey, Todd; Gennings, Chris; Simmons, Jane Ellen; Herr, David W

2005-12-01

Traditional factorial designs for evaluating interactions among chemicals in a mixture may be prohibitive when the number of chemicals is large. Using a mixture of chemicals with a fixed ratio (mixture ray) results in an economical design that allows estimation of additivity or nonadditive interaction for a mixture of interest. This methodology is extended easily to a mixture with a large number of chemicals. Optimal experimental conditions can be chosen that result in increased power to detect departures from additivity. Although these designs are used widely for linear models, optimal designs for nonlinear threshold models are less well known. In the present work, the use of D-optimal designs is demonstrated for nonlinear threshold models applied to a fixed-ratio mixture ray. For a fixed sample size, this design criterion selects the experimental doses and number of subjects per dose level that result in minimum variance of the model parameters and thus increased power to detect departures from additivity. An optimal design is illustrated for a 2:1 ratio (chlorpyrifos:carbaryl) mixture experiment. For this example, and in general, the optimal designs for the nonlinear threshold model depend on prior specification of the slope and dose threshold parameters. Use of a D-optimal criterion produces experimental designs with increased power, whereas standard nonoptimal designs with equally spaced dose groups may result in low power if the active range or threshold is missed.

Dose-response relationships for the onset of avoidance of sonar by free-ranging killer whales.

PubMed

Miller, Patrick J O; Antunes, Ricardo N; Wensveen, Paul J; Samarra, Filipa I P; Alves, Ana Catarina; Tyack, Peter L; Kvadsheim, Petter H; Kleivane, Lars; Lam, Frans-Peter A; Ainslie, Michael A; Thomas, Len

2014-02-01

Eight experimentally controlled exposures to 1-2 kHz or 6-7 kHz sonar signals were conducted with four killer whale groups. The source level and proximity of the source were increased during each exposure in order to reveal response thresholds. Detailed inspection of movements during each exposure session revealed sustained changes in speed and travel direction judged to be avoidance responses during six of eight sessions. Following methods developed for Phase-I clinical trials in human medicine, response thresholds ranging from 94 to 164 dB re 1 μPa received sound pressure level (SPL) were fitted to Bayesian dose-response functions. Thresholds did not consistently differ by sonar frequency or whether a group had previously been exposed, with a mean SPL response threshold of 142 ± 15 dB (mean ± s.d.). High levels of between- and within-individual variability were identified, indicating that thresholds depended upon other undefined contextual variables. The dose-response functions indicate that some killer whales started to avoid sonar at received SPL below thresholds assumed by the U.S. Navy. The predicted extent of habitat over which avoidance reactions occur depends upon whether whales responded to proximity or received SPL of the sonar or both, but was large enough to raise concerns about biological consequences to the whales.

TU-AB-303-11: Predict Parotids Deformation Applying SIS Epidemiological Model in H&N Adaptive RT

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

Maffei, N; Guidi, G; University of Bologna, Bologna, Bologna

2015-06-15

Purpose: The aim is to investigate the use of epidemiological models to predict morphological variations in patients undergoing radiation therapy (RT). The susceptible-infected-susceptible (SIS) deterministic model was applied to simulate warping within a focused region of interest (ROI). Hypothesis is to consider each voxel like a single subject of the whole sample and to treat displacement vector fields like an infection. Methods: Using Raystation hybrid deformation algorithms and automatic re-contouring based on mesh grid, we post-processed 360 MVCT images of 12 H&N patients treated with Tomotherapy. Study focused on parotid glands, identified by literature and previous analysis, as ROI moremore » susceptible to warping in H&N region. Susceptible (S) and infectious (I) cases were identified in voxels with inter-fraction movement respectively under and over a set threshold. IronPython scripting allowed to export positions and displacement data of surface voxels for every fraction. A MATLAB homemade toolbox was developed to model the SIS. Results: SIS model was validated simulating organ motion on QUASAR phantom. Applying model in patients, within a [0–1cm] range, a single voxel movement of 0.4cm was selected as displacement threshold. SIS indexes were evaluated by MATLAB simulations. Dynamic time warping algorithm was used to assess matching between model and parotids behavior days of treatments. The best fit of the model was obtained with contact rate of 7.89±0.94 and recovery rate of 2.36±0.21. Conclusion: SIS model can follow daily structures evolutions, making possible to compare warping conditions and highlighting challenges due to abnormal variation and set-up errors. By epidemiology approach, organ motion could be assessed and predicted not in terms of average of the whole ROI, but in a voxel-by-voxel deterministic trend. Identifying anatomical region subjected to variations, would be possible to focus clinic controls within a cohort of pre-selected patients eligible for adaptive RT. The research is partially co-funded by the Italian Research Grant: Dose warping methods for IGRT and Adaptive RT: dose accumulation based on organ motion and anatomical variations of the patients during radiation therapy treatments,MoH (GR-2010-2318757) and Tecnologie Avanzate S.r.l.(Italy)« less

Adaptive evolution influences the infectious dose of MERS-CoV necessary to achieve severe respiratory disease.

PubMed

Douglas, Madeline G; Kocher, Jacob F; Scobey, Trevor; Baric, Ralph S; Cockrell, Adam S

2018-04-01

We recently established a mouse model (288-330 +/+ ) that developed acute respiratory disease resembling human pathology following infection with a high dose (5 × 10 6 PFU) of mouse-adapted MERS-CoV (icMERSma1). Although this high dose conferred fatal respiratory disease in mice, achieving similar pathology at lower viral doses may more closely reflect naturally acquired infections. Through continued adaptive evolution of icMERSma1 we generated a novel mouse-adapted MERS-CoV (maM35c4) capable of achieving severe respiratory disease at doses between 10 3 and 10 5 PFU. Novel mutations were identified in the maM35c4 genome that may be responsible for eliciting etiologies of acute respiratory distress syndrome at 10-1000 fold lower viral doses. Importantly, comparative genetics of the two mouse-adapted MERS strains allowed us to identify specific mutations that remained fixed through an additional 20 cycles of adaptive evolution. Our data indicate that the extent of MERS-CoV adaptation determines the minimal infectious dose required to achieve severe respiratory disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Shape anomaly detection under strong measurement noise: An analytical approach to adaptive thresholding

NASA Astrophysics Data System (ADS)

Krasichkov, Alexander S.; Grigoriev, Eugene B.; Bogachev, Mikhail I.; Nifontov, Eugene M.

2015-10-01

We suggest an analytical approach to the adaptive thresholding in a shape anomaly detection problem. We find an analytical expression for the distribution of the cosine similarity score between a reference shape and an observational shape hindered by strong measurement noise that depends solely on the noise level and is independent of the particular shape analyzed. The analytical treatment is also confirmed by computer simulations and shows nearly perfect agreement. Using this analytical solution, we suggest an improved shape anomaly detection approach based on adaptive thresholding. We validate the noise robustness of our approach using typical shapes of normal and pathological electrocardiogram cycles hindered by additive white noise. We show explicitly that under high noise levels our approach considerably outperforms the conventional tactic that does not take into account variations in the noise level.

Subtle changes in brain functions produced by single doses of mevinphos (Phosdrin).

DOT National Transportation Integrated Search

1973-02-01

Mevinphos (Phosdrin) was found to inhibit the amplitude of hippocampal evoked potentials in unanesthetized squirrel monkeys with chronically indwelling electrodes. The threshold dose was 0.050 mg/kg and the maximal dose studied was 0.200 mg/kg. Doses...

A Novel Zero Velocity Interval Detection Algorithm for Self-Contained Pedestrian Navigation System with Inertial Sensors

PubMed Central

Tian, Xiaochun; Chen, Jiabin; Han, Yongqiang; Shang, Jianyu; Li, Nan

2016-01-01

Zero velocity update (ZUPT) plays an important role in pedestrian navigation algorithms with the premise that the zero velocity interval (ZVI) should be detected accurately and effectively. A novel adaptive ZVI detection algorithm based on a smoothed pseudo Wigner–Ville distribution to remove multiple frequencies intelligently (SPWVD-RMFI) is proposed in this paper. The novel algorithm adopts the SPWVD-RMFI method to extract the pedestrian gait frequency and to calculate the optimal ZVI detection threshold in real time by establishing the function relationships between the thresholds and the gait frequency; then, the adaptive adjustment of thresholds with gait frequency is realized and improves the ZVI detection precision. To put it into practice, a ZVI detection experiment is carried out; the result shows that compared with the traditional fixed threshold ZVI detection method, the adaptive ZVI detection algorithm can effectively reduce the false and missed detection rate of ZVI; this indicates that the novel algorithm has high detection precision and good robustness. Furthermore, pedestrian trajectory positioning experiments at different walking speeds are carried out to evaluate the influence of the novel algorithm on positioning precision. The results show that the ZVI detected by the adaptive ZVI detection algorithm for pedestrian trajectory calculation can achieve better performance. PMID:27669266

A Unified Nonlinear Adaptive Approach for Detection and Isolation of Engine Faults

NASA Technical Reports Server (NTRS)

Tang, Liang; DeCastro, Jonathan A.; Zhang, Xiaodong; Farfan-Ramos, Luis; Simon, Donald L.

2010-01-01

A challenging problem in aircraft engine health management (EHM) system development is to detect and isolate faults in system components (i.e., compressor, turbine), actuators, and sensors. Existing nonlinear EHM methods often deal with component faults, actuator faults, and sensor faults separately, which may potentially lead to incorrect diagnostic decisions and unnecessary maintenance. Therefore, it would be ideal to address sensor faults, actuator faults, and component faults under one unified framework. This paper presents a systematic and unified nonlinear adaptive framework for detecting and isolating sensor faults, actuator faults, and component faults for aircraft engines. The fault detection and isolation (FDI) architecture consists of a parallel bank of nonlinear adaptive estimators. Adaptive thresholds are appropriately designed such that, in the presence of a particular fault, all components of the residual generated by the adaptive estimator corresponding to the actual fault type remain below their thresholds. If the faults are sufficiently different, then at least one component of the residual generated by each remaining adaptive estimator should exceed its threshold. Therefore, based on the specific response of the residuals, sensor faults, actuator faults, and component faults can be isolated. The effectiveness of the approach was evaluated using the NASA C-MAPSS turbofan engine model, and simulation results are presented.

Threshold irradiation dose for amorphization of silicon carbide

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

Snead, L.L.; Zinkle, S.J.

1997-04-01

The amorphization of silicon carbide due to ion and electron irradiation is reviewed with emphasis on the temperature-dependent critical dose for amorphization. The effect of ion mass and energy on the threshold dose for amorphization is summarized, showing only a weak dependence near room temperature. Results are presented for 0.56 MeV silicon ions implanted into single crystal 6H-SiC as a function of temperature and ion dose. From this, the critical dose for amorphization is found as a function of temperature at depths well separated from the implanted ion region. Results are compared with published data generated using electrons and xenonmore » ions as the irradiating species. High resolution TEM analysis is presented for the Si ion series showing the evolution of elongated amorphous islands oriented such that their major axis is parallel to the free surface. This suggests that surface of strain effects may be influencing the apparent amorphization threshold. Finally, a model for the temperature threshold for amorphization is described using the Si ion irradiation flux and the fitted interstitial migration energy which was found to be {approximately}0.56 eV. This model successfully explains the difference in the temperature-dependent amorphization behavior of SiC irradiated with 0.56 MeV silicon ions at 1 x 10{sup {minus}3} dpa/s and with fission neutrons irradiated at 1 x 10{sup {minus}6} dpa/s irradiated to 15 dpa in the temperature range of {approximately}340 {+-} 10K.« less

A comparative study of xylazine-induced mechanical hypoalgesia in donkeys and horses.

PubMed

Lizarraga, Ignacio; Beths, Thierry

2012-09-01

To compare the effects of xylazine on mechanical nociceptive thresholds in donkeys and horses. Randomized, controlled, crossover, Latin-square, operator-blinded design. Six 3.1 ± 0.89 year old standard donkeys weighing 145.0 ± 30.5 kg and six 9.6 ± 4.4 year old Thoroughbred horses weighing 456.0 ± 69.0 kg. Each animal received one of four doses of xylazine (0.5, 0.7, 0.9, and 1.1 mg kg(-1) ), or acepromazine (0.05 mg kg(-1) ) or saline solution (0.9%) intravenously and mechanical nociceptive thresholds were assessed over 90 minutes. The areas under the threshold change versus time curve values for 60 minutes (AUC(0-60) ) post-drug administration were used to compare the effect of treatment. A 1-week interval was allowed between successive trials on each animal. All doses of xylazine, but not acepromazine or saline, increased mechanical thresholds for up to 60 minutes. Xylazine-induced hypoalgesia was dose-dependent and corresponding AUC(0-60) values for each treatment were not significantly different between donkeys and horses (p ≥ 0.0697). The hypoalgesic effects of xylazine at four different doses were not different between donkeys and horses. Xylazine induced a similar degree of mechanical hypoalgesia in donkeys and horses suggesting that similar doses are needed for both species with regard to analgesia. © 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

Optimization strategies with resource scarcity: From immunization of networks to the traveling salesman problem

NASA Astrophysics Data System (ADS)

Bellingeri, Michele; Agliari, Elena; Cassi, Davide

2015-10-01

The best strategy to immunize a complex network is usually evaluated in terms of the percolation threshold, i.e. the number of vaccine doses which make the largest connected cluster (LCC) vanish. The strategy inducing the minimum percolation threshold represents the optimal way to immunize the network. Here we show that the efficacy of the immunization strategies can change during the immunization process. This means that, if the number of doses is limited, the best strategy is not necessarily the one leading to the smallest percolation threshold. This outcome should warn about the adoption of global measures in order to evaluate the best immunization strategy.

Modern Adaptive Analytics Approach to Lowering Seismic Network Detection Thresholds

NASA Astrophysics Data System (ADS)

Johnson, C. E.

2017-12-01

Modern seismic networks present a number of challenges, but perhaps most notably are those related to 1) extreme variation in station density, 2) temporal variation in station availability, and 3) the need to achieve detectability for much smaller events of strategic importance. The first of these has been reasonably addressed in the development of modern seismic associators, such as GLASS 3.0 by the USGS/NEIC, though some work still remains to be done in this area. However, the latter two challenges demand special attention. Station availability is impacted by weather, equipment failure or the adding or removing of stations, and while thresholds have been pushed to increasingly smaller magnitudes, new algorithms are needed to achieve even lower thresholds. Station availability can be addressed by a modern, adaptive architecture that maintains specified performance envelopes using adaptive analytics coupled with complexity theory. Finally, detection thresholds can be lowered using a novel approach that tightly couples waveform analytics with the event detection and association processes based on a principled repicking algorithm that uses particle realignment for enhanced phase discrimination.

Vehicle tracking using fuzzy-based vehicle detection window with adaptive parameters

NASA Astrophysics Data System (ADS)

Chitsobhuk, Orachat; Kasemsiri, Watjanapong; Glomglome, Sorayut; Lapamonpinyo, Pipatphon

2018-04-01

In this paper, fuzzy-based vehicle tracking system is proposed. The proposed system consists of two main processes: vehicle detection and vehicle tracking. In the first process, the Gradient-based Adaptive Threshold Estimation (GATE) algorithm is adopted to provide the suitable threshold value for the sobel edge detection. The estimated threshold can be adapted to the changes of diverse illumination conditions throughout the day. This leads to greater vehicle detection performance compared to a fixed user's defined threshold. In the second process, this paper proposes the novel vehicle tracking algorithms namely Fuzzy-based Vehicle Analysis (FBA) in order to reduce the false estimation of the vehicle tracking caused by uneven edges of the large vehicles and vehicle changing lanes. The proposed FBA algorithm employs the average edge density and the Horizontal Moving Edge Detection (HMED) algorithm to alleviate those problems by adopting fuzzy rule-based algorithms to rectify the vehicle tracking. The experimental results demonstrate that the proposed system provides the high accuracy of vehicle detection about 98.22%. In addition, it also offers the low false detection rates about 3.92%.

3D SAPIV particle field reconstruction method based on adaptive threshold.

PubMed

Qu, Xiangju; Song, Yang; Jin, Ying; Li, Zhenhua; Wang, Xuezhen; Guo, ZhenYan; Ji, Yunjing; He, Anzhi

2018-03-01

Particle image velocimetry (PIV) is a necessary flow field diagnostic technique that provides instantaneous velocimetry information non-intrusively. Three-dimensional (3D) PIV methods can supply the full understanding of a 3D structure, the complete stress tensor, and the vorticity vector in the complex flows. In synthetic aperture particle image velocimetry (SAPIV), the flow field can be measured with large particle intensities from the same direction by different cameras. During SAPIV particle reconstruction, particles are commonly reconstructed by manually setting a threshold to filter out unfocused particles in the refocused images. In this paper, the particle intensity distribution in refocused images is analyzed, and a SAPIV particle field reconstruction method based on an adaptive threshold is presented. By using the adaptive threshold to filter the 3D measurement volume integrally, the three-dimensional location information of the focused particles can be reconstructed. The cross correlations between images captured from cameras and images projected by the reconstructed particle field are calculated for different threshold values. The optimal threshold is determined by cubic curve fitting and is defined as the threshold value that causes the correlation coefficient to reach its maximum. The numerical simulation of a 16-camera array and a particle field at two adjacent time events quantitatively evaluates the performance of the proposed method. An experimental system consisting of a camera array of 16 cameras was used to reconstruct the four adjacent frames in a vortex flow field. The results show that the proposed reconstruction method can effectively reconstruct the 3D particle fields.

Effect of two doses of carbamylated allergoid extract of dust mite on nasal reactivity.

PubMed

Scalone, G; Compalati, E; Bruno, M E; Mistrello, G

2013-11-01

Background and Objective. Single SLIT studies with native allergen extracts support a dose-response effect for clinical and immunological outcomes. Conversely for carbamylated allergoids this dose-response effects is less evident, likely because the threshold for efficacy is more easily reached through the enhanced bioavailability of the extract consequent to the selective chemical modification. Thus this pilot study investigates the dose-response effect on nasal specific reactivity and safety of two unusual doses of carbamylated allergoid in patients mono-sensitized to house dust mites. Methods. A prospective open randomized study involved 6-65 year-old Italian patients with clinically relevant sensitization to house dust mites and positive response to nasal provocation challenge. Monomeric carbamylated allergoid was delivered once daily at the dose of 1000 AU or 2000 AU from June to September 2009, during the lowest level of mites exposure. Primary outcomes were the change of the threshold of allergen concentration for a positive nasal provocation test (NPT) before and after the treatment and the product safety. Secondary outcome was the change  in the mean percentage fall of peak nasal inspiratory flow (PNIF) following nasal challenge. Results. Thirty-four patients were enrolled. Fifteen in group 1 and 14 in group 2 concluded the study. After 12 weeks all patients treated in group 1 and all but one in group 2 showed an increase in the threshold dose provoking a positive NPT. Those with no symptoms onset with the highest dose delivered were 80% in group 1 and 78.6% in group 2 (p=0.92). From first to second challenge, the mean percentage fall of PNIF  was reduced with no statistical difference between groups (p=0.95), and with no difference between the final mean percentage falls (p=0.65). No serious adverse reactions occurred and the frequency of events, all mild, was similar in the two groups. Conclusions. Twelve weeks of carbamylated sublingual allergoid delivered at 1000AU or 2000AU once daily appear equally safe and show comparable effect in increasing  the threshold of allergen concentration for a positive nasal provocation test, confirming the apparent absence of a dose response effect for the used doses.

Epidemic spreading on preferred degree adaptive networks.

PubMed

Jolad, Shivakumar; Liu, Wenjia; Schmittmann, B; Zia, R K P

2012-01-01

We study the standard SIS model of epidemic spreading on networks where individuals have a fluctuating number of connections around a preferred degree κ. Using very simple rules for forming such preferred degree networks, we find some unusual statistical properties not found in familiar Erdös-Rényi or scale free networks. By letting κ depend on the fraction of infected individuals, we model the behavioral changes in response to how the extent of the epidemic is perceived. In our models, the behavioral adaptations can be either 'blind' or 'selective'--depending on whether a node adapts by cutting or adding links to randomly chosen partners or selectively, based on the state of the partner. For a frozen preferred network, we find that the infection threshold follows the heterogeneous mean field result λ(c)/μ = <κ>/<κ2> and the phase diagram matches the predictions of the annealed adjacency matrix (AAM) approach. With 'blind' adaptations, although the epidemic threshold remains unchanged, the infection level is substantially affected, depending on the details of the adaptation. The 'selective' adaptive SIS models are most interesting. Both the threshold and the level of infection changes, controlled not only by how the adaptations are implemented but also how often the nodes cut/add links (compared to the time scales of the epidemic spreading). A simple mean field theory is presented for the selective adaptations which capture the qualitative and some of the quantitative features of the infection phase diagram.

Evaluating the risk of death via the hematopoietic syndrome mode for prolonged exposure of nuclear workers to radiation delivered at very low rates.

PubMed

Scott, B R; Lyzlov, A F; Osovets, S V

1998-05-01

During a Phase-I effort, studies were planned to evaluate deterministic (nonstochastic) effects of chronic exposure of nuclear workers at the Mayak atomic complex in the former Soviet Union to relatively high levels (> 0.25 Gy) of ionizing radiation. The Mayak complex has been used, since the late 1940's, to produce plutonium for nuclear weapons. Workers at Site A of the complex were involved in plutonium breeding using nuclear reactors, and some were exposed to relatively large doses of gamma rays plus relatively small neutron doses. The Weibull normalized-dose model, which has been set up to evaluate the risk of specific deterministic effects of combined, continuous exposure of humans to alpha, beta, and gamma radiations, is here adapted for chronic exposure to gamma rays and neutrons during repeated 6-h work shifts--as occurred for some nuclear workers at Site A. Using the adapted model, key conclusions were reached that will facilitate a Phase-II study of deterministic effects among Mayak workers. These conclusions include the following: (1) neutron doses may be more important for Mayak workers than for Japanese A-bomb victims in Hiroshima and can be accounted for using an adjusted dose (which accounts for neutron relative biological effectiveness); (2) to account for dose-rate effects, normalized dose X (a dimensionless fraction of an LD50 or ED50) can be evaluated in terms of an adjusted dose; (3) nonlinear dose-response curves for the risk of death via the hematopoietic mode can be converted to linear dose-response curves (for low levels of risk) using a newly proposed dimensionless dose, D = X(V), in units of Oklad (where D is pronounced "deh"), and V is the shape parameter in the Weibull model; (4) for X < or = Xo, where Xo is the threshold normalized dose, D = 0; (5) unlike absorbed dose, the dose D can be averaged over different Mayak workers in order to calculate the average risk of death via the hematopoietic mode for the population exposed at Site A; and (6) the expected cases of death via the hematopoietic syndrome mode for Mayak workers chronically exposed during work shifts at Site A to gamma rays and neutrons can be predicted using ln(2)B M[D]; where B (pronounced "beh") is the number of workers at risk (criticality accident victims excluded); and M[D] is the average (mean) value of D (averaged over the worker population at risk, for Site A, for the time period considered). These results can be used to facilitate a Phase II study of deterministic radiation effects among Mayak workers chronically exposed to gamma rays and neutrons.

Synthetic CT for MRI-based liver stereotactic body radiotherapy treatment planning

NASA Astrophysics Data System (ADS)

Bredfeldt, Jeremy S.; Liu, Lianli; Feng, Mary; Cao, Yue; Balter, James M.

2017-04-01

A technique for generating MRI-derived synthetic CT volumes (MRCTs) is demonstrated in support of adaptive liver stereotactic body radiation therapy (SBRT). Under IRB approval, 16 subjects with hepatocellular carcinoma were scanned using a single MR pulse sequence (T1 Dixon). Air-containing voxels were identified by intensity thresholding on T1-weighted, water and fat images. The envelope of the anterior vertebral bodies was segmented from the fat image and fuzzy-C-means (FCM) was used to classify each non-air voxel as mid-density, lower-density, bone, or marrow in the abdomen, with only bone and marrow classified within the vertebral body envelope. MRCT volumes were created by integrating the product of the FCM class probability with its assigned class density for each voxel. MRCTs were deformably aligned with corresponding planning CTs and 2-ARC-SBRT-VMAT plans were optimized on MRCTs. Fluence was copied onto the CT density grids, dose recalculated, and compared. The liver, vertebral bodies, kidneys, spleen and cord had median Hounsfield unit differences of less than 60. Median target dose metrics were all within 0.1 Gy with maximum differences less than 0.5 Gy. OAR dose differences were similarly small (median: 0.03 Gy, std:0.26 Gy). Results demonstrate that MRCTs derived from a single abdominal imaging sequence are promising for use in SBRT dose calculation.

TU-H-CAMPUS-JeP3-02: Automated Dose Accumulation and Dose Accuracy Assessment for Online Or Offline Adaptive Replanning

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

Chen, G; Ahunbay, E; Li, X

Purpose: With introduction of high-quality treatment imaging during radiation therapy (RT) delivery, e.g., MR-Linac, adaptive replanning of either online or offline becomes appealing. Dose accumulation of delivered fractions, a prerequisite for the adaptive replanning, can be cumbersome and inaccurate. The purpose of this work is to develop an automated process to accumulate daily doses and to assess the dose accumulation accuracy voxel-by-voxel for adaptive replanning. Methods: The process includes the following main steps: 1) reconstructing daily dose for each delivered fraction with a treatment planning system (Monaco, Elekta) based on the daily images using machine delivery log file and consideringmore » patient repositioning if applicable, 2) overlaying the daily dose to the planning image based on deformable image registering (DIR) (ADMIRE, Elekta), 3) assessing voxel dose deformation accuracy based on deformation field using predetermined criteria, and 4) outputting accumulated dose and dose-accuracy volume histograms and parameters. Daily CTs acquired using a CT-on-rails during routine CT-guided RT for sample patients with head and neck and prostate cancers were used to test the process. Results: Daily and accumulated doses (dose-volume histograms, etc) along with their accuracies (dose-accuracy volume histogram) can be robustly generated using the proposed process. The test data for a head and neck cancer case shows that the gross tumor volume decreased by 20% towards the end of treatment course, and the parotid gland mean dose increased by 10%. Such information would trigger adaptive replanning for the subsequent fractions. The voxel-based accuracy in the accumulated dose showed that errors in accumulated dose near rigid structures were small. Conclusion: A procedure as well as necessary tools to automatically accumulate daily dose and assess dose accumulation accuracy is developed and is useful for adaptive replanning. Partially supported by Elekta, Inc.« less

Psychophysical measurements in children: challenges, pitfalls, and considerations.

PubMed

Witton, Caroline; Talcott, Joel B; Henning, G Bruce

2017-01-01

Measuring sensory sensitivity is important in studying development and developmental disorders. However, with children, there is a need to balance reliable but lengthy sensory tasks with the child's ability to maintain motivation and vigilance. We used simulations to explore the problems associated with shortening adaptive psychophysical procedures, and suggest how these problems might be addressed. We quantify how adaptive procedures with too few reversals can over-estimate thresholds, introduce substantial measurement error, and make estimates of individual thresholds less reliable. The associated measurement error also obscures group differences. Adaptive procedures with children should therefore use as many reversals as possible, to reduce the effects of both Type 1 and Type 2 errors. Differences in response consistency, resulting from lapses in attention, further increase the over-estimation of threshold. Comparisons between data from individuals who may differ in lapse rate are therefore problematic, but measures to estimate and account for lapse rates in analyses may mitigate this problem.

Oscillation patterns are enhanced and firing threshold is lowered in medullary respiratory neuron discharges by threshold doses of a μ-opioid receptor agonist

PubMed Central

Mifflin, Steve W.

2017-01-01

μ-Opioid receptors are distributed widely in the brain stem respiratory network, and opioids with selectivity for μ-type receptors slow in vivo respiratory rhythm in lowest effective doses. Several studies have reported μ-opioid receptor effects on the three-phase rhythm of respiratory neurons, but there are until now no reports of opioid effects on oscillatory activity within respiratory discharges. In this study, effects of the μ-opioid receptor agonist fentanyl on spike train discharge properties of several different types of rhythm-modulating medullary respiratory neuron discharges were analyzed. Doses of fentanyl that were just sufficient for prolongation of discharges and slowing of the three-phase respiratory rhythm also produced pronounced enhancement of spike train properties. Oscillation and burst patterns detected by autocorrelation measurements were greatly enhanced, and interspike intervals were prolonged. Spike train properties under control conditions and after fentanyl were uniform within each experiment, but varied considerably between experiments, which might be related to variability in acid-base balance in the brain stem extracellular fluid. Discharge threshold was shifted to more negative levels of membrane potential. The effects on threshold are postulated to result from opioid-mediated disinhibition and postsynaptic enhancement of N-methyl-d- aspartate receptor current. Lowering of firing threshold, enhancement of spike train oscillations and bursts and prolongation of discharges by lowest effective doses of fentanyl could represent compensatory adjustments in the brain stem respiratory network to override opioid blunting of CO2/pH chemosensitivity. PMID:28202437

CEM43°C thermal dose thresholds: a potential guide for magnetic resonance radiofrequency exposure levels?

PubMed

van Rhoon, Gerard C; Samaras, Theodoros; Yarmolenko, Pavel S; Dewhirst, Mark W; Neufeld, Esra; Kuster, Niels

2013-08-01

To define thresholds of safe local temperature increases for MR equipment that exposes patients to radiofrequency fields of high intensities for long duration. These MR systems induce heterogeneous energy absorption patterns inside the body and can create localised hotspots with a risk of overheating. The MRI + EUREKA research consortium organised a "Thermal Workshop on RF Hotspots". The available literature on thresholds for thermal damage and the validity of the thermal dose (TD) model were discussed. The following global TD threshold guidelines for safe use of MR are proposed: 1. All persons: maximum local temperature of any tissue limited to 39 °C 2. Persons with compromised thermoregulation AND (a) Uncontrolled conditions: maximum local temperature limited to 39 °C (b) Controlled conditions: TD < 2 CEM43°C 3. Persons with uncompromised thermoregulation AND (a) Uncontrolled conditions: TD < 2 CEM43°C (b) Controlled conditions: TD < 9 CEM43°C The following definitions are applied: Controlled conditions A medical doctor or a dedicated trained person can respond instantly to heat-induced physiological stress Compromised thermoregulation All persons with impaired systemic or reduced local thermoregulation • Standard MRI can cause local heating by radiofrequency absorption. • Monitoring thermal dose (in units of CEM43°C) can control risk during MRI. • 9 CEM43°C seems an acceptable thermal dose threshold for most patients. • For skin, muscle, fat and bone,16 CEM43°C is likely acceptable.

Oscillation patterns are enhanced and firing threshold is lowered in medullary respiratory neuron discharges by threshold doses of a μ-opioid receptor agonist.

PubMed

Lalley, Peter M; Mifflin, Steve W

2017-05-01

μ-Opioid receptors are distributed widely in the brain stem respiratory network, and opioids with selectivity for μ-type receptors slow in vivo respiratory rhythm in lowest effective doses. Several studies have reported μ-opioid receptor effects on the three-phase rhythm of respiratory neurons, but there are until now no reports of opioid effects on oscillatory activity within respiratory discharges. In this study, effects of the μ-opioid receptor agonist fentanyl on spike train discharge properties of several different types of rhythm-modulating medullary respiratory neuron discharges were analyzed. Doses of fentanyl that were just sufficient for prolongation of discharges and slowing of the three-phase respiratory rhythm also produced pronounced enhancement of spike train properties. Oscillation and burst patterns detected by autocorrelation measurements were greatly enhanced, and interspike intervals were prolonged. Spike train properties under control conditions and after fentanyl were uniform within each experiment, but varied considerably between experiments, which might be related to variability in acid-base balance in the brain stem extracellular fluid. Discharge threshold was shifted to more negative levels of membrane potential. The effects on threshold are postulated to result from opioid-mediated disinhibition and postsynaptic enhancement of N -methyl-d- aspartate receptor current. Lowering of firing threshold, enhancement of spike train oscillations and bursts and prolongation of discharges by lowest effective doses of fentanyl could represent compensatory adjustments in the brain stem respiratory network to override opioid blunting of CO 2 /pH chemosensitivity. Copyright © 2017 the American Physiological Society.

Determining lower threshold concentrations for synergistic effects.

PubMed

Bjergager, Maj-Britt Andersen; Dalhoff, Kristoffer; Kretschmann, Andreas; Nørgaard, Katrine Banke; Mayer, Philipp; Cedergreen, Nina

2017-01-01

Though only occurring rarely, synergistic interactions between chemicals in mixtures have long been a point of focus. Most studies analyzing synergistic interactions used unrealistically high chemical concentrations. The aim of the present study is to determine the threshold concentration below which proven synergists cease to act as synergists towards the aquatic crustacean Daphnia magna. To do this, we compared several approaches and test-setups to evaluate which approach gives the most conservative estimate for the lower threshold for synergy for three known azole synergists. We focus on synergistic interactions between the pyrethroid insecticide, alpha-cypermethrin, and one of the three azole fungicides prochloraz, propiconazole or epoxiconazole measured on Daphnia magna immobilization. Three different experimental setups were applied: A standard 48h acute toxicity test, an adapted 48h test using passive dosing for constant chemical exposure concentrations, and a 14-day test. Synergy was defined as occuring in mixtures where either EC 50 values decreased more than two-fold below what was predicted by concentration addition (horizontal assessment) or as mixtures where the fraction of immobile organisms increased more than two-fold above what was predicted by independent action (vertical assessment). All three tests confirmed the hypothesis of the existence of a lower azole threshold concentration below which no synergistic interaction was observed. The lower threshold concentration, however, decreased with increasing test duration from 0.026±0.013μM (9.794±4.897μgL -1 ), 0.425±0.089μM (145.435±30.46μgL -1 ) and 0.757±0.253μM (249.659±83.44μgL -1 ) for prochloraz, propiconazole and epoxiconazole in standard 48h toxicity tests to 0.015±0.004μM (5.651±1.507μgL -1 ), 0.145±0.025μM (49.619±8.555μgL -1 ) and 0.122±0.0417μM (40.236±13.75μgL -1 ), respectively, in the 14-days tests. Testing synergy in relation to concentration addition provided the most conservative values. The threshold values for the vertical assessments in tests where the two could be compared were in general 1.2 to 4.7 fold higher than the horizontal assessments. Using passive dosing rather than dilution series or spiking did not lower the threshold significantly. Below the threshold for synergy, slight antagony could often be observed. This is most likely due to induction of enzymes active in metabolization of alpha-cypermethrin. The results emphasize the importance of test duration when assessing synergy, but also show that azole concentrations within the typically monitored range of up to 0.5μgL -1 are not likely to cause severe synergy concerning Daphnia magna immobilization. Copyright © 2016 Elsevier B.V. All rights reserved.

Frequently Asked Questions on Potassium Iodide (KI)

MedlinePlus

... recommendation is to treat them at the lowest threshold (with respect to predicted radioactive dose to the ... old should be treated at a slightly higher threshold. Finally, anyone over 40 years old should be ...

Effect of eccentricity and light level on the timing of light adaptation mechanisms.

PubMed

Barrionuevo, Pablo A; Matesanz, Beatriz M; Gloriani, Alejandro H; Arranz, Isabel; Issolio, Luis; Mar, Santiago; Aparicio, Juan A

2018-04-01

We explored the complexity of the light adaptation process, assessing adaptation recovery (Ar) at different eccentricities and light levels. Luminance thresholds were obtained with transient background fields at mesopic and photopic light levels for temporal retinal eccentricities (0°-15°) with test/background stimulus size of 0.5°/1° using a staircase procedure in a two-channel Maxwellian view optical system. Ar was obtained in comparison with steady data [Vis. Res.125, 12 (2016)VISRAM0042-698910.1016/j.visres.2016.04.008]. Light level proportionally affects Ar only at fovea. Photopic extrafoveal thresholds were one log unit higher for transient conditions. Adaptation was equally fast at low light levels for different retinal locations with variations mainly affected by noise. These results evidence different timing in the mechanisms of adaptation involved.

Resilience thinking: integrating resilience, adaptability and transformability

Treesearch

Carl Folke; Stephen R. Carpenter; Brian Walker; Marten Scheffer; Terry Chapin; Johan Rockstrom

2010-01-01

Resilience thinking addresses the dynamics and development of complex social-ecological systems (SES). Three aspects are central: resilience, adaptability and transformability. These aspects interrelate across multiple scales. Resilience in this context is the capacity of a SES to continually change and adapt yet remain within critical thresholds. Adaptability is part...

Reduced suppression of CO2-induced ventilatory stimulation by endomorphins relative to morphine.

PubMed

Czapla, Marc A; Zadina, James E

2005-10-19

Opioids are among the most effective analgesics, but a major limitation for their therapeutic usefulness is their induction of respiratory depression. Endomorphin-1 (EM1), in contrast to several other mu opioids, exhibits a threshold for respiratory depression that is well above its threshold for analgesia. Its effect on sensitivity to CO(2), however, remains unknown. Minute ventilation (V(E)) in 2, 4, and 6% CO(2) was measured before and after systemic administration of EM1, endomorphin-2 (EM2), DAMGO, and morphine in the conscious rat. EM1 and EM2 attenuated the hypercapnic ventilatory response (HCVR) only in high doses, while DAMGO and morphine diminished the HCVR in much lower doses. The ventilatory effects of high doses of all 4 agonists were blocked by the mu-opioid antagonist naloxone (0.4 mg/kg i.v.), but not by the peripherally restricted mu-opioid antagonist, methyl-naloxone (0.4 mg/kg i.v.). It was concluded that the endomorphins attenuated the HCVR only in large doses, well beyond the analgesic threshold, and did so through a centrally mediated mu-opioid mechanism.

Response of pMOS dosemeters on gamma-ray irradiation during its re-use.

PubMed

Pejovic, Milic M; Pejovic, Momcilo M; Jaksic, Aleksandar B

2013-08-01

Response of pMOS dosemeters during two successive irradiations with gamma-ray irradiation to a dose of 35 Gy and annealing at room and elevated temperature has been studied. The response was followed on the basis of threshold voltage shift, determined from transfer characteristics, as a function of absorbed dose or annealing time. It was shown that the threshold voltage shifts during first and second irradiation for the gate bias during irradiation of 5 and 2.5 V insignificantly differ although complete fading was not achieved after the first cycle of annealing. In order to analyse the defects formed in oxide and at the interface during irradiation and annealing, which are responsible for threshold voltage shift, midgap and charge-pumping techniques were used. It was shown that during first irradiation and annealing a dominant influence to threshold voltage shift is made by fixed oxide traps, while at the beginning of the second annealing cycle, threshold voltage shift is a consequence of both fixed oxide traps and slow switching traps.

Impact of PET and MRI threshold-based tumor volume segmentation on patient-specific targeted radionuclide therapy dosimetry using CLR1404.

PubMed

Besemer, Abigail E; Titz, Benjamin; Grudzinski, Joseph J; Weichert, Jamey P; Kuo, John S; Robins, H Ian; Hall, Lance T; Bednarz, Bryan P

2017-07-06

Variations in tumor volume segmentation methods in targeted radionuclide therapy (TRT) may lead to dosimetric uncertainties. This work investigates the impact of PET and MRI threshold-based tumor segmentation on TRT dosimetry in patients with primary and metastatic brain tumors. In this study, PET/CT images of five brain cancer patients were acquired at 6, 24, and 48 h post-injection of 124 I-CLR1404. The tumor volume was segmented using two standardized uptake value (SUV) threshold levels, two tumor-to-background ratio (TBR) threshold levels, and a T1 Gadolinium-enhanced MRI threshold. The dice similarity coefficient (DSC), jaccard similarity coefficient (JSC), and overlap volume (OV) metrics were calculated to compare differences in the MRI and PET contours. The therapeutic 131 I-CLR1404 voxel-level dose distribution was calculated from the 124 I-CLR1404 activity distribution using RAPID, a Geant4 Monte Carlo internal dosimetry platform. The TBR, SUV, and MRI tumor volumes ranged from 2.3-63.9 cc, 0.1-34.7 cc, and 0.4-11.8 cc, respectively. The average  ±  standard deviation (range) was 0.19  ±  0.13 (0.01-0.51), 0.30  ±  0.17 (0.03-0.67), and 0.75  ±  0.29 (0.05-1.00) for the JSC, DSC, and OV, respectively. The DSC and JSC values were small and the OV values were large for both the MRI-SUV and MRI-TBR combinations because the regions of PET uptake were generally larger than the MRI enhancement. Notable differences in the tumor dose volume histograms were observed for each patient. The mean (standard deviation) 131 I-CLR1404 tumor doses ranged from 0.28-1.75 Gy GBq -1 (0.07-0.37 Gy GBq -1 ). The ratio of maximum-to-minimum mean doses for each patient ranged from 1.4-2.0. The tumor volume and the interpretation of the tumor dose is highly sensitive to the imaging modality, PET enhancement metric, and threshold level used for tumor volume segmentation. The large variations in tumor doses clearly demonstrate the need for standard protocols for multimodality tumor segmentation in TRT dosimetry.

Impact of PET and MRI threshold-based tumor volume segmentation on patient-specific targeted radionuclide therapy dosimetry using CLR1404

NASA Astrophysics Data System (ADS)

Besemer, Abigail E.; Titz, Benjamin; Grudzinski, Joseph J.; Weichert, Jamey P.; Kuo, John S.; Robins, H. Ian; Hall, Lance T.; Bednarz, Bryan P.

2017-08-01

Variations in tumor volume segmentation methods in targeted radionuclide therapy (TRT) may lead to dosimetric uncertainties. This work investigates the impact of PET and MRI threshold-based tumor segmentation on TRT dosimetry in patients with primary and metastatic brain tumors. In this study, PET/CT images of five brain cancer patients were acquired at 6, 24, and 48 h post-injection of 124I-CLR1404. The tumor volume was segmented using two standardized uptake value (SUV) threshold levels, two tumor-to-background ratio (TBR) threshold levels, and a T1 Gadolinium-enhanced MRI threshold. The dice similarity coefficient (DSC), jaccard similarity coefficient (JSC), and overlap volume (OV) metrics were calculated to compare differences in the MRI and PET contours. The therapeutic 131I-CLR1404 voxel-level dose distribution was calculated from the 124I-CLR1404 activity distribution using RAPID, a Geant4 Monte Carlo internal dosimetry platform. The TBR, SUV, and MRI tumor volumes ranged from 2.3-63.9 cc, 0.1-34.7 cc, and 0.4-11.8 cc, respectively. The average  ±  standard deviation (range) was 0.19  ±  0.13 (0.01-0.51), 0.30  ±  0.17 (0.03-0.67), and 0.75  ±  0.29 (0.05-1.00) for the JSC, DSC, and OV, respectively. The DSC and JSC values were small and the OV values were large for both the MRI-SUV and MRI-TBR combinations because the regions of PET uptake were generally larger than the MRI enhancement. Notable differences in the tumor dose volume histograms were observed for each patient. The mean (standard deviation) 131I-CLR1404 tumor doses ranged from 0.28-1.75 Gy GBq-1 (0.07-0.37 Gy GBq-1). The ratio of maximum-to-minimum mean doses for each patient ranged from 1.4-2.0. The tumor volume and the interpretation of the tumor dose is highly sensitive to the imaging modality, PET enhancement metric, and threshold level used for tumor volume segmentation. The large variations in tumor doses clearly demonstrate the need for standard protocols for multimodality tumor segmentation in TRT dosimetry.

Different contributions of dopamine D1 and D2 receptor activity to alcohol potentiation of brain stimulation reward in C57BL/6J and DBA/2J mice.

PubMed

Fish, Eric W; DiBerto, Jeffrey F; Krouse, Michael C; Robinson, J Elliott; Malanga, C J

2014-08-01

C57BL/6J (C57) and DBA/2J (DBA) mice respond differently to drugs that affect dopamine systems, including alcohol. The current study compared effects of D1 and D2 receptor agonists and antagonists, and the interaction between D1/D2 antagonists and alcohol, on intracranial self-stimulation in male C57 and DBA mice to determine the role of dopamine receptors in the effects of alcohol on brain stimulation reward (BSR). In the initial strain comparison, dose effects on BSR thresholds and maximum operant response rates were determined for the D1 receptor agonist SKF-82958 (±-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; 0.1-0.56 mg/kg) and antagonist SCH 23390 (+-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepinehydrochloride; 0.003-0.056 mg/kg), and the D2 receptor agonist quinpirole (0.1-3.0 mg/kg) and antagonist raclopride (0.01-0.56 mg/kg). For the alcohol interaction, SCH 23390 (0.003 mg/kg) or raclopride (0.03 mg/kg) was given before alcohol (0.6-2.4 g/kg p.o.). D1 antagonism dose-dependently elevated and SKF-82958 dose-dependently lowered BSR threshold in both strains; DBA mice were more sensitive to SKF-82958 effects. D2 antagonism dose-dependently elevated BSR threshold only in C57 mice. Low doses of quinpirole elevated BSR threshold equally in both strains, whereas higher doses of quinpirole lowered BSR threshold only in C57 mice. SCH 23390, but not raclopride, prevented lowering of BSR threshold by alcohol in DBA mice. Conversely, raclopride, but not SCH 23390, prevented alcohol potentiation of BSR in C57 mice. These results extend C57 and DBA strain differences to D1/D2 sensitivity of BSR, and suggest differential involvement of D1 and D2 receptors in the acute rewarding effects of alcohol in these two mouse strains. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

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

PubMed

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

2002-12-01

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

Reliability of TMS phosphene threshold estimation: Toward a standardized protocol.

PubMed

Mazzi, Chiara; Savazzi, Silvia; Abrahamyan, Arman; Ruzzoli, Manuela

Phosphenes induced by transcranial magnetic stimulation (TMS) are a subjectively described visual phenomenon employed in basic and clinical research as index of the excitability of retinotopically organized areas in the brain. Phosphene threshold estimation is a preliminary step in many TMS experiments in visual cognition for setting the appropriate level of TMS doses; however, the lack of a direct comparison of the available methods for phosphene threshold estimation leaves unsolved the reliability of those methods in setting TMS doses. The present work aims at fulfilling this gap. We compared the most common methods for phosphene threshold calculation, namely the Method of Constant Stimuli (MOCS), the Modified Binary Search (MOBS) and the Rapid Estimation of Phosphene Threshold (REPT). In two experiments we tested the reliability of PT estimation under each of the three methods, considering the day of administration, participants' expertise in phosphene perception and the sensitivity of each method to the initial values used for the threshold calculation. We found that MOCS and REPT have comparable reliability when estimating phosphene thresholds, while MOBS estimations appear less stable. Based on our results, researchers and clinicians can estimate phosphene threshold according to MOCS or REPT equally reliably, depending on their specific investigation goals. We suggest several important factors for consideration when calculating phosphene thresholds and describe strategies to adopt in experimental procedures. Copyright © 2017 Elsevier Inc. All rights reserved.

Application of Adaptive Design Methodology in Development of a Long-Acting Glucagon-Like Peptide-1 Analog (Dulaglutide): Statistical Design and Simulations

PubMed Central

Skrivanek, Zachary; Berry, Scott; Berry, Don; Chien, Jenny; Geiger, Mary Jane; Anderson, James H.; Gaydos, Brenda

2012-01-01

Background Dulaglutide (dula, LY2189265), a long-acting glucagon-like peptide-1 analog, is being developed to treat type 2 diabetes mellitus. Methods To foster the development of dula, we designed a two-stage adaptive, dose-finding, inferentially seamless phase 2/3 study. The Bayesian theoretical framework is used to adaptively randomize patients in stage 1 to 7 dula doses and, at the decision point, to either stop for futility or to select up to 2 dula doses for stage 2. After dose selection, patients continue to be randomized to the selected dula doses or comparator arms. Data from patients assigned the selected doses will be pooled across both stages and analyzed with an analysis of covariance model, using baseline hemoglobin A1c and country as covariates. The operating characteristics of the trial were assessed by extensive simulation studies. Results Simulations demonstrated that the adaptive design would identify the correct doses 88% of the time, compared to as low as 6% for a fixed-dose design (the latter value based on frequentist decision rules analogous to the Bayesian decision rules for adaptive design). Conclusions This article discusses the decision rules used to select the dula dose(s); the mathematical details of the adaptive algorithm—including a description of the clinical utility index used to mathematically quantify the desirability of a dose based on safety and efficacy measurements; and a description of the simulation process and results that quantify the operating characteristics of the design. PMID:23294775

Relationships Between Vestibular Measures as Potential Predictors for Spaceflight Sensorimotor Adaptation

NASA Technical Reports Server (NTRS)

Clark, T. K.; Peters, B.; Gadd, N. E.; De Dios, Y. E.; Wood, S.; Bloomberg, J. J.; Mulavara, A. P.

2016-01-01

Introduction: During space exploration missions astronauts are exposed to a series of novel sensorimotor environments, requiring sensorimotor adaptation. Until adaptation is complete, sensorimotor decrements occur, affecting critical tasks such as piloted landing or docking. Of particularly interest are locomotion tasks such as emergency vehicle egress or extra-vehicular activity. While nearly all astronauts eventually adapt sufficiently, it appears there are substantial individual differences in how quickly and effectively this adaptation occurs. These individual differences in capacity for sensorimotor adaptation are poorly understood. Broadly, we aim to identify measures that may serve as pre-flight predictors of and individual's adaptation capacity to spaceflight-induced sensorimotor changes. As a first step, since spaceflight is thought to involve a reinterpretation of graviceptor cues (e.g. otolith cues from the vestibular system) we investigate the relationships between various measures of vestibular function in humans. Methods: In a set of 15 ground-based control subjects, we quantified individual differences in vestibular function using three measures: 1) ocular vestibular evoked myogenic potential (oVEMP), 2) computerized dynamic posturography and 3) vestibular perceptual thresholds. oVEMP responses are elicited using a mechanical stimuli approach. Computerized dynamic posturography was used to quantify Sensory Organization Tests (SOTs), including SOT5M which involved performing pitching head movements while balancing on a sway-reference support surface with eyes closed. We implemented a vestibular perceptual threshold task using the tilt capabilities of the Tilt-Translation Sled (TTS) at JSC. On each trial, the subject was passively roll-tilted left ear down or right ear down in the dark and verbally provided a forced-choice response regarding which direction they felt tilted. The motion profile was a single-cycle sinusoid of angular acceleration with a duration of 5 seconds (frequency of 0.2 Hz), which was selected as it requires sensory integration of otolith and semicircular canal cues. Stimuli direction was randomized and magnitude was determined using an adaptive sampling procedure. One hundred trials were provided and each subject's responses were fit with a psychometric curve to estimate the subject's threshold. Results: Roll tilt perceptual thresholds at 0.2 Hz ranged from 0.5 degrees to 1.82 degrees across the 15 subjects (geometric mean of 1.04 degrees), consistent with previous studies. The inter-individual variability in thresholds may be able to help explain individual differences observed in sensorimotor adaptation to spaceflight. Analysis is ongoing for the oVEMPS and computerized dynamic posturography to identify relationships between the various vestibular measures. Discussion: Predicting individual differences in sensorimotor adaptation is critical both for the development of personalized countermeasures and mission planning. Here we aim to develop a basis of vestibular tests and parameters which may serve as predictors of individual differences in sensorimotor adaptability through studying the relationship between these measures.

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.

The Random-Threshold Generalized Unfolding Model and Its Application of Computerized Adaptive Testing

ERIC Educational Resources Information Center

Wang, Wen-Chung; Liu, Chen-Wei; Wu, Shiu-Lien

2013-01-01

The random-threshold generalized unfolding model (RTGUM) was developed by treating the thresholds in the generalized unfolding model as random effects rather than fixed effects to account for the subjective nature of the selection of categories in Likert items. The parameters of the new model can be estimated with the JAGS (Just Another Gibbs…

Obtaining the Optimal Dose in Alcohol Dependence Studies

PubMed Central

Wages, Nolan A.; Liu, Lei; O’Quigley, John; Johnson, Bankole A.

2012-01-01

In alcohol dependence studies, the treatment effect at different dose levels remains to be ascertained. Establishing this effect would aid us in identifying the best dose that has satisfactory efficacy while minimizing the rate of adverse events. We advocate the use of dose-finding methodology that has been successfully implemented in the cancer and HIV settings to identify the optimal dose in a cost-effective way. Specifically, we describe the continual reassessment method (CRM), an adaptive design proposed for cancer trials to reconcile the needs of dose-finding experiments with the ethical demands of established medical practice. We are applying adaptive designs for identifying the optimal dose of medications for the first time in the context of pharmacotherapy research in alcoholism. We provide an example of a topiramate trial as an illustration of how adaptive designs can be used to locate the optimal dose in alcohol treatment trials. It is believed that the introduction of adaptive design methods will enable the development of medications for the treatment of alcohol dependence to be accelerated. PMID:23189064

The antiepileptic activity of Vitex agnus castus extract on amygdala kindled seizures in male rats.

PubMed

Saberi, Mehdi; Rezvanizadeh, Alireza; Bakhtiarian, Azam

2008-08-22

The antiepileptic activity of hydrophilic extract of Vitex agnus castus fruit (Vitex) was evaluated by the kindling model of epilepsy. Intact male rats (250-300 g) were stereotaxically implanted with a tripolar and two monopolar electrodes in amygdala and dura, respectively. The afterdischarge (AD) threshold was determined in each animal and stimulated daily until fully kindled. The animals were administered different doses (60, 120 or 180 mg/kg) of Vitex or 0.1 ml of hydro alcoholic solvent intra-peritoneally (i.p.) and kindling parameters including AD threshold, seizure stages (SS), afterdischarge duration (ADD), stage 4 latency (S4L) and stage 5 duration (S5D) were recorded 30 min post-injection. The obtained data showed that even low dose (60 mg/kg) of Vitex could significantly increase the AD threshold and decrease the ADD and S5D (P<0.05). These changes were more significant with higher doses (120 or 180 mg/kg) for ADD (P<0.01) and S5D (P<0.001). Vitex at the dose of 120 mg/kg, induced significant increment in S4L (P<0.05). This effect was more prominent at the dose of 180 mg/kg (P<0.001). The latter dose could significantly reduce seizure stage (P<0.01) and most of the animals did not show S5. These results indicate that Vitex can reduce or prevent epileptic activity as demonstrated by reduction of ADD and S5D (length of convulsion) in a dose dependent manner. In conclusion, Vitex at appropriate dose can probably reduce or control epileptic activities.

Computing mammographic density from a multiple regression model constructed with image-acquisition parameters from a full-field digital mammographic unit

PubMed Central

Lu, Lee-Jane W.; Nishino, Thomas K.; Khamapirad, Tuenchit; Grady, James J; Leonard, Morton H.; Brunder, Donald G.

2009-01-01

Breast density (the percentage of fibroglandular tissue in the breast) has been suggested to be a useful surrogate marker for breast cancer risk. It is conventionally measured using screen-film mammographic images by a labor intensive histogram segmentation method (HSM). We have adapted and modified the HSM for measuring breast density from raw digital mammograms acquired by full-field digital mammography. Multiple regression model analyses showed that many of the instrument parameters for acquiring the screening mammograms (e.g. breast compression thickness, radiological thickness, radiation dose, compression force, etc) and image pixel intensity statistics of the imaged breasts were strong predictors of the observed threshold values (model R2=0.93) and %density (R2=0.84). The intra-class correlation coefficient of the %-density for duplicate images was estimated to be 0.80, using the regression model-derived threshold values, and 0.94 if estimated directly from the parameter estimates of the %-density prediction regression model. Therefore, with additional research, these mathematical models could be used to compute breast density objectively, automatically bypassing the HSM step, and could greatly facilitate breast cancer research studies. PMID:17671343

Molecular Mechanisms That Underlie the Dynamic Adaptation of Innate Monocyte Memory to Varying Stimulant Strength of TLR Ligands.

PubMed

Yuan, Ruoxi; Geng, Shuo; Li, Liwu

2016-01-01

In adaptation to rising stimulant strength, innate monocytes can be dynamically programed to preferentially express either pro- or anti-inflammatory mediators. Such dynamic innate adaptation or programing may bear profound relevance in host health and disease. However, molecular mechanisms that govern innate adaptation to varying strength of stimulants are not well understood. Using lipopolysaccharide (LPS), the model stimulant of toll-like-receptor 4 (TLR4), we reported that the expressions of pro-inflammatory mediators are preferentially sustained in monocytes adapted by lower doses of LPS, and suppressed/tolerized in monocytes adapted by higher doses of LPS. Mechanistically, monocytes adapted by super-low dose LPS exhibited higher levels of transcription factor, interferon regulatory factor 5 (IRF5), and reduced levels of transcriptional modulator B lymphocyte-induced maturation protein-1 (Blimp-1). Intriguingly, the inflammatory monocyte adaptation by super-low dose LPS is dependent upon TRAM/TRIF but not MyD88. Similar to LPS, we also observed biphasic inflammatory adaptation and tolerance in monocytes challenged with varying dosages of TLR7 agonist. In sharp contrast, rising doses of TLR3 agonist preferentially caused inflammatory adaptation without inducing tolerance. At the molecular level, the differential regulation of IRF5 and Blimp-1 coincides with unique monocyte adaptation dynamics by TLR4/7 and TLR3 agonists. Our study provides novel clue toward the understanding of monocyte adaptation and memory toward distinct TLR ligands.

Resistance of Salmonella typhimurium TA 1535 to O6-guanine methylation and mutagenesis induced by low doses of N-methyl-N'-nitro-N-nitrosoguanidine: an apparent constitutive repair activity.

PubMed

Guttenplan, J B; Milstein, S

1982-01-01

Salmonella tester strains which are reverted by base-pair substitution mutagens are relatively insensitive to the mutagenic effects of N-methyl-N-nitroso compounds. One reason for this insensitivity is the ability of these strains to withstand low doses of these compounds before they become sensitive to their mutagenic effects. In this report it is shown that mutagenesis induced by treatment of Salmonella typhimurium TA 1535 with N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) in buffer is biphasic with a low sensitivity range at low doses where little mutagenesis occurs, followed by a high sensitivity range whose onset begins after an apparent threshold dose has been exceeded. levels of O6-methylguanine (O6-MeG) in the DNA extracted from the bacteria follow a similar dose-response curve suggesting a dependency of mutagenesis on O6-MeG. In contrast, levels of 7-methylguanine (7-MeG) in the DNA increase linearly with dose. O6-MeG was undetectable at the lowest dose of MNNG whereas 7-MeG was readily detectable. Although such resistance to O6-alkylation has been demonstrated in MNNG- pretreated (adapted) E. coli, it has not been reported in unpretreated cells. Then isolated DNA was treated with MNNG a linear dose-response in the generation of O6-MeG was observed. The lack of O6-MeG in DNA isolated from MNNG treated cells after low doses is attributed to a saturable, constitutive repair activity in the bacteria. An attempt to observe the removal of O6-MeG from the bacteria after exposure to a short challenge dose of N-nitroso-N-methylurea (NMU) followed by a subsequent incubation in buffer was unsuccessful, probably because all the repair occurred within the time necessary to treat and lyse the cells.

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

Mechanisms of carcinogensis: dose response

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

Gehring, P.J.; Blau, G.E.

There is great controversy whether the carcinogenicity of chemicals is dose-dependent and whether a threshold dose exists below which cancer will not be induced by exposure. Evidence for dose-dependency exists and is believed to be accepted generally if extricated as it should be from the threshold concept. The threshold concept conflict is not likely to be resolved in the foreseeable future; proponents and opponents argue their case in a manner similar to those arguing religion. In this paper the various arguments are reviewed. Subsequently, a chemical process model for carcinogenesis is developed based on the generally accepted evidence that themore » carcinogenic activity of many chemicals can be related to electrophilic alkylation of DNA. Using this model, some incidence of cancer, albeit negligible, will be predicted regardless how low the dose. However, the model revelas that the incidence of cancer induced by real-life exposures is likely to be greatly overestimated by currently used stochastic statistical extrapolations. Even more important, modeling of the chemical processes involved in the fate of a carcinogenic chemical in the body reveals experimental approaches to elucidating the mechanism(s) of carcinogenesis and ultimately a more scientifically sound basis for assessing the hazard of low-level exposure to a chemical carcinogen.« less

Radiation dose to the eyes and parotids during CT of the sinuses.

PubMed

Bassim, Marc K; Ebert, Charles S; Sit, Roger C; Senior, Brent A

2005-10-01

To measure the radiation dose to the lens and parotid during high-resolution computed tomography scan of the sinuses. Nine cadaver heads were scanned in the axial plane by means of a fine-cut (0.75 mm) protocol. Images were then reconstructed in the coronal and sagittal planes for use with the image guidance software. Thermoluminescent dosimeters were taped over the eyes and parotids and used to measure the radiation dose absorbed by these organs. Doses obtained were 29.5 mGy for the lens and around 30 mGy for the parotid. The measured doses are lower than the reported acute thresholds of 500-2000 mGy for lens opacities and well below the threshold of 2500 mGy for damage to the parotid. These results demonstrate minimal risk from radiation through the use of high-resolution computed tomography and support the use of such a protocol for diagnosis and preoperative planning.

Development of a Bayesian response-adaptive trial design for the Dexamethasone for Excessive Menstruation study.

PubMed

Holm Hansen, Christian; Warner, Pamela; Parker, Richard A; Walker, Brian R; Critchley, Hilary Od; Weir, Christopher J

2017-12-01

It is often unclear what specific adaptive trial design features lead to an efficient design which is also feasible to implement. This article describes the preparatory simulation study for a Bayesian response-adaptive dose-finding trial design. Dexamethasone for Excessive Menstruation aims to assess the efficacy of Dexamethasone in reducing excessive menstrual bleeding and to determine the best dose for further study. To maximise learning about the dose response, patients receive placebo or an active dose with randomisation probabilities adapting based on evidence from patients already recruited. The dose-response relationship is estimated using a flexible Bayesian Normal Dynamic Linear Model. Several competing design options were considered including: number of doses, proportion assigned to placebo, adaptation criterion, and number and timing of adaptations. We performed a fractional factorial study using SAS software to simulate virtual trial data for candidate adaptive designs under a variety of scenarios and to invoke WinBUGS for Bayesian model estimation. We analysed the simulated trial results using Normal linear models to estimate the effects of each design feature on empirical type I error and statistical power. Our readily-implemented approach using widely available statistical software identified a final design which performed robustly across a range of potential trial scenarios.

Calibration of an eye lens dosemeter in terms of Hp(3) to be used in interventional radiology

NASA Astrophysics Data System (ADS)

Borges, F. L. S.; Guimarães, M. C.; Da Silva, T. A.; Nogueira Tavares, M. S.

2014-11-01

Recently, the International Commission on Radiological Protection has reviewed epidemiological evidences suggesting that there were tissue reaction effects in the eye lens below the previously considered absorbed dose threshold. A new statement related to the eye lens was issued that changed the absorbed dose threshold and reduced the dose limits for occupationally exposed persons. As consequence, some planned exposures require eye lens dosimetry and a debate was raised on the adequacy of the dosimetric quantity and on its method of measurement. The aim of this work was to study the methodology for calibrating the EYE-DTM holder with a TLD-100H Harshaw chip detector and to determine its angular and energy dependences in terms of personal dose equivalent, Hp(3).

Effect of harmane on the convulsive threshold in epilepsy models in mice.

PubMed

Aricioglu, Feyza; Yillar, Okan; Korcegez, Eylem; Berkman, Kemal

2003-12-01

The study investigated the activity of harmane on maximal electroshock seizures (MES) and seizures induced by pentilentetrazole (PTZ) in mice. Initial studies established convulsive current 50 (CC(50)) values or MES and effective dose 50 (ED(50)) for PTZ to produce seizures. Harmane (2.5, 5.0, or 10 mg/kg intraperitoneally) increased the threshold of seizures in MES dose-dependently. The convulsions produced by PTZ were decreased by the low dose of harmane (2.5 mg/kg), but the high dose of harmane (10 mg/kg) resulted in worse grade V convulsions followed by more lethality compared with PTZ alone. Therefore, harmane seems to be protective against grand mal seizures in the MES model but not against a petit mal seizure model (PTZ) in mice.

Thresholds of allergenic proteins in foods

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

Hourihane, Jonathan O'B.; Knulst, Andre C.

2005-09-01

Threshold doses or Estimated Eliciting Doses (EEDs) represent an important new field of research in food allergy. Clinicians and regulators have embraced some toxicological concepts such as LOAEL and NOAEL and applied them to an area of significant clinical uncertainty and interest. The impact of intrinsic human factors (e.g., asthma and exercise) and extrinsic event factors (e.g., season, location and especially dose of allergen) on a future allergic reaction in the community needs to be considered carefully when interpreting results of clinical and research low-dose food challenges. The ongoing cooperation of food allergy research groups in medicine, food science andmore » government will surely deliver results of the highest importance to the wider communities of allergology, food science and technology and the increasing number of allergic consumers.« less

Impairment of retinal increment thresholds in Huntington's disease.

PubMed

Paulus, W; Schwarz, G; Werner, A; Lange, H; Bayer, A; Hofschuster, M; Müller, N; Zrenner, E

1993-10-01

We have investigated detection thresholds for a foveal blue test light using a Maxwellian view system in 61 normal subjects, 19 patients with Huntington's chorea, 14 patients with Tourette's syndrome, and 20 patients with schizophrenia. Ten measurements were made: The blue test light (1 degree diameter, 500 msec duration) was presented either superimposed on a yellow adaptation field (5 degree diameter) or 500 msec after switching off this field (transient tritanopia effect). In both cases five different background intensities were presented. The only abnormality found was in patients with Huntington's chorea. During adaptation these patients' thresholds are significantly higher than normal (p < 0.005). No change was found in the transient tritanopia effect. Huntington's disease causes degeneration of several different transmitter systems in the brain. Increment threshold testing allows for noninvasive investigation of patients and confirms the involvement of the retina in the degenerative process in Huntington's chorea.

Adaptive gain and filtering circuit for a sound reproduction system

NASA Technical Reports Server (NTRS)

Engebretson, A. Maynard (Inventor); O'Connell, Michael P. (Inventor)

1998-01-01

Adaptive compressive gain and level dependent spectral shaping circuitry for a hearing aid include a microphone to produce an input signal and a plurality of channels connected to a common circuit output. Each channel has a preset frequency response. Each channel includes a filter with a preset frequency response to receive the input signal and to produce a filtered signal, a channel amplifier to amplify the filtered signal to produce a channel output signal, a threshold register to establish a channel threshold level, and a gain circuit. The gain circuit increases the gain of the channel amplifier when the channel output signal falls below the channel threshold level and decreases the gain of the channel amplifier when the channel output signal rises above the channel threshold level. A transducer produces sound in response to the signal passed by the common circuit output.

Development of a Voice Activity Controlled Noise Canceller

PubMed Central

Abid Noor, Ali O.; Samad, Salina Abdul; Hussain, Aini

2012-01-01

In this paper, a variable threshold voice activity detector (VAD) is developed to control the operation of a two-sensor adaptive noise canceller (ANC). The VAD prohibits the reference input of the ANC from containing some strength of actual speech signal during adaptation periods. The novelty of this approach resides in using the residual output from the noise canceller to control the decisions made by the VAD. Thresholds of full-band energy and zero-crossing features are adjusted according to the residual output of the adaptive filter. Performance evaluation of the proposed approach is quoted in terms of signal to noise ratio improvements as well mean square error (MSE) convergence of the ANC. The new approach showed an improved noise cancellation performance when tested under several types of environmental noise. Furthermore, the computational power of the adaptive process is reduced since the output of the adaptive filter is efficiently calculated only during non-speech periods. PMID:22778667

Assessment of olfactory threshold in patients undergoing radiotherapy for head and neck malignancies.

PubMed

Jalali, Mir Mohammad; Gerami, Hooshang; Rahimi, Abbas; Jafari, Manizheh

2014-10-01

Radiotherapy is a common treatment modality for patients with head and neck malignancies. As the nose lies within the field of radiotherapy of the head and neck, the olfactory fibers and olfactory receptors may be affected by radiation. The aim of this study was to evaluate changes in olfactory threshold in patients with head and neck malignancies who have received radiation to the head and neck. The olfactory threshold of patients with head and neck malignancies was assessed prospectively before radiation therapy and serially for up to 6 months after radiotherapy using sniff bottles. In vivo dosimetry was performed using 82 LiF (MCP) chips and a thermoluminescent dosimeter (TLD) system. Sixty-one patients were recruited before radiotherapy was commenced. Seven patients did not return for evaluation after radiation. Fifty-four patients were available for follow-up assessment (28 women, 26 men; age, 22-86 years; median, 49 years). Total radiation dose was 50.1 Gy (range, 30-66 Gy). Mean olfactory threshold scores were found to deteriorate significantly at various timepoints after radiotherapy (11.7 before radiotherapy versus 4.0 at Month 6, general linear model, P<0.0001). With in vivo dosimetry, we found that the median measured dose to the olfactory area was 334 µC. We also identified a cutoff point according to the dose to the olfactory epithelium. Olfactory threshold was significantly decreased 2-6 weeks after initiation of therapy, with cumulative local radiation >135 µC (Mann-Whitney U test, P=0.01). Deterioration in olfactory threshold scores was found at 6 months after initiation of radiation therapy. Provided that these results are reproducible, an evaluation of olfactory functioning in patients with head and neck malignancies using in vivo dosimetry may be useful for determining the optimal dose for patients treated with conformal radiotherapy techniques while avoiding the side effects of radiation.

Disturbances of rod threshold forced by briefly exposed luminous lines, edges, disks and annuli

PubMed Central

Hallett, P. E.

1971-01-01

1. When the dark-adapted eye is exposed to a brief duration (2 msec) luminous line the resulting threshold disturbance is much sharper (decay constant of ca. 10 min arc) than would be expected in a system which is known to integrate the effects of light quanta over a distance of 1 deg or so. 2. When the forcing input is a pair of brief duration parallel luminous lines the threshold disturbance falls off sharply at the outsides of the pattern but on the inside a considerable spread of threshold-raising effects may occur unless the lines are sufficiently far apart. 3. The threshold disturbance due to a briefly exposed edge shows an overshoot reminiscent of `lateral inhibition'. 4. If the threshold is measured at the centre of a black disk presented in a briefly lit surround then (a) the dependence of threshold on time interval between test and surround suggests that the threshold elevation is due to a non-optical effect which is not `metacontrast'; (b) the dependence of threshold on black disk diameter is consistent with the notion that the spatial threshold disturbance is progressively sharpened as the separation of luminous edges increases. 5. If the threshold is measured at the centre of briefly exposed luminous disks of various diameters one obtains the same evidence for an `antagonistic centre-surround' system as that produced by other workers (e.g. Westheimer, 1965) for the steadily light-adapted eye. 6. The previous paper (Hallett, 1971) showed that brief illumination of the otherwise dark-adapted eye can rapidly and substantially change the extent of spatial integration. The present paper shows that brief illumination leads to substantial `inhibitory' effects. 7. Earlier approaches are reviewed: (a) the linear system signal/noise theory of the time course of threshold disturbances (Hallett, 1969b) is illustrated by the case of a small subtense flash superimposed on a large oscillatory background; (b) the spatial weighting functions of some other authors are given. 8. A possible non-linear model is briefly described: the line weighting function for the receptive field centre is taken to be a single Gaussian, as is customary, but the line weighting function for the inhibitory surround is bimodal. PMID:5145728

Threshold detection in an on-off binary communications channel with atmospheric scintillation

NASA Technical Reports Server (NTRS)

Webb, W. E.; Marino, J. T., Jr.

1974-01-01

The optimum detection threshold in an on-off binary optical communications system operating in the presence of atmospheric turbulence was investigated assuming a poisson detection process and log normal scintillation. The dependence of the probability of bit error on log amplitude variance and received signal strength was analyzed and semi-emperical relationships to predict the optimum detection threshold derived. On the basis of this analysis a piecewise linear model for an adaptive threshold detection system is presented. Bit error probabilities for non-optimum threshold detection system were also investigated.

Threshold detection in an on-off binary communications channel with atmospheric scintillation

NASA Technical Reports Server (NTRS)

Webb, W. E.

1975-01-01

The optimum detection threshold in an on-off binary optical communications system operating in the presence of atmospheric turbulence was investigated assuming a poisson detection process and log normal scintillation. The dependence of the probability of bit error on log amplitude variance and received signal strength was analyzed and semi-empirical relationships to predict the optimum detection threshold derived. On the basis of this analysis a piecewise linear model for an adaptive threshold detection system is presented. The bit error probabilities for nonoptimum threshold detection systems were also investigated.

Ultra-high spatial resolution multi-energy CT using photon counting detector technology

NASA Astrophysics Data System (ADS)

Leng, S.; Gutjahr, R.; Ferrero, A.; Kappler, S.; Henning, A.; Halaweish, A.; Zhou, W.; Montoya, J.; McCollough, C.

2017-03-01

Two ultra-high-resolution (UHR) imaging modes, each with two energy thresholds, were implemented on a research, whole-body photon-counting-detector (PCD) CT scanner, referred to as sharp and UHR, respectively. The UHR mode has a pixel size of 0.25 mm at iso-center for both energy thresholds, with a collimation of 32 × 0.25 mm. The sharp mode has a 0.25 mm pixel for the low-energy threshold and 0.5 mm for the high-energy threshold, with a collimation of 48 × 0.25 mm. Kidney stones with mixed mineral composition and lung nodules with different shapes were scanned using both modes, and with the standard imaging mode, referred to as macro mode (0.5 mm pixel and 32 × 0.5 mm collimation). Evaluation and comparison of the three modes focused on the ability to accurately delineate anatomic structures using the high-spatial resolution capability and the ability to quantify stone composition using the multi-energy capability. The low-energy threshold images of the sharp and UHR modes showed better shape and texture information due to the achieved higher spatial resolution, although noise was also higher. No noticeable benefit was shown in multi-energy analysis using UHR compared to standard resolution (macro mode) when standard doses were used. This was due to excessive noise in the higher resolution images. However, UHR scans at higher dose showed improvement in multi-energy analysis over macro mode with regular dose. To fully take advantage of the higher spatial resolution in multi-energy analysis, either increased radiation dose, or application of noise reduction techniques, is needed.

Physiologic variability at the verge of systemic inflammation: multiscale entropy of heart rate variability is affected by very low doses of endotoxin.

PubMed

Herlitz, Georg N; Arlow, Renee L; Cheung, Nora H; Coyle, Susette M; Griffel, Benjamin; Macor, Marie A; Lowry, Stephen F; Calvano, Steve E; Gale, Stephen C

2015-02-01

Human injury or infection induces systemic inflammation with characteristic neuroendocrine responses. Fluctuations in autonomic function during inflammation are reflected by beat-to-beat variation in heart rate, termed heart rate variability (HRV). In the present study, we determine threshold doses of endotoxin needed to induce observable changes in markers of systemic inflammation, investigate whether metrics of HRV exhibit a differing threshold dose from other inflammatory markers, and investigate the size of data sets required for meaningful use of multiscale entropy (MSE) analysis of HRV. Healthy human volunteers (n = 25) were randomized to receive placebo (normal saline) or endotoxin/lipopolysaccharide (LPS): 0.1, 0.25, 0.5, 1.0, or 2.0 ng/kg administered intravenously. Vital signs were recorded every 30 min for 6 h and then at 9, 12, and 24 h after LPS. Blood samples were drawn at specific time points for cytokine measurements. Heart rate variability analysis was performed using electrocardiogram epochs of 5 min. Multiscale entropy for HRV was calculated for all dose groups to scale factor 40. The lowest significant threshold dose was noted in core temperature at 0.25 ng/kg. Endogenous tumor necrosis factor α and interleukin 6 were significantly responsive at the next dosage level (0.5 ng/kg) along with elevations in circulating leukocytes and heart rate. Responses were exaggerated at higher doses (1 and 2 ng/kg). Time domain and frequency domain HRV metrics similarly suggested a threshold dose, differing from placebo at 1.0 and 2.0 ng/kg, below which no clear pattern in response was evident. By applying repeated-measures analysis of variance across scale factors, a significant decrease in MSE was seen at 1.0 and 2.0 ng/kg by 2 h after exposure to LPS. Although not statistically significant below 1.0 ng/kg, MSE unexpectedly decreased across all groups in an orderly dose-response pattern not seen in the other outcomes. By using repeated-measures analysis of variance across scale factors, MSE can detect autonomic change after LPS challenge in a group of 25 subjects using electrocardiogram epochs of only 5 min and entropy analysis to scale factor of only 40, potentially facilitating MSE's wider use as a research tool or bedside monitor. Traditional markers of inflammation generally exhibit threshold dose behavior. In contrast, MSE's apparent continuous dose-response pattern, although not statistically verifiable in this study, suggests a potential subclinical harbinger of infectious or other insult. The possible derangement of autonomic complexity prior to or independent of the cytokine surge cannot be ruled out. Future investigation should focus on confirmation of overt inflammation following observed decreases in MSE in a clinical setting.

Physiologic variability at the verge of systemic inflammation: multi-scale entropy of heart rate variability is affected by very low doses of endotoxin

PubMed Central

Herlitz, Georg N.; Sanders, Renee L.; Cheung, Nora H.; Coyle, Susette M.; Griffel, Benjamin; Macor, Marie A.; Lowry, Stephen F.; Calvano, Steve E.; Gale, Stephen C.

2014-01-01

Introduction Human injury or infection induces systemic inflammation with characteristic neuro-endocrine responses. Fluctuations in autonomic function during inflammation are reflected by beat-to-beat variation in heart rate, termed heart rate variability (HRV). In the present study, we determine threshold doses of endotoxin needed to induce observable changes in markers of systemic inflammation, we investigate whether metrics of HRV exhibit a differing threshold dose from other inflammatory markers, and we investigate the size of data sets required for meaningful use of multi-scale entropy (MSE) analysis of HRV. Methods Healthy human volunteers (n=25) were randomized to receive placebo (normal saline) or endotoxin/lipopolysaccharide (LPS): 0.1, 0.25, 0.5, 1.0, or 2.0 ng/kg administered intravenously. Vital signs were recorded every 30 minutes for 6 hours and then at 9, 12, and 24 hours after LPS. Blood samples were drawn at specific time points for cytokine measurements. HRV analysis was performed using EKG epochs of 5 minutes. MSE for HRV was calculated for all dose groups to scale factor 40. Results The lowest significant threshold dose was noted in core temperature at 0.25ng/kg. Endogenous TNF-α and IL-6 were significantly responsive at the next dosage level (0.5ng/kg) along with elevations in circulating leukocytes and heart rate. Responses were exaggerated at higher doses (1 and 2 ng/kg). Time domain and frequency domain HRV metrics similarly suggested a threshold dose, differing from placebo at 1.0 and 2.0 ng/kg, below which no clear pattern in response was evident. By applying repeated-measures ANOVA across scale factors, a significant decrease in MSE was seen at 1.0 and 2.0 ng/kg by 2 hours post exposure to LPS. While not statistically significant below 1.0 ng/kg, MSE unexpectedly decreased across all groups in an orderly dose-response pattern not seen in the other outcomes. Conclusions By usingrANOVA across scale factors, MSE can detect autonomic change after LPS challenge in a group of 25 subjects using EKG epochs of only 5 minutes and entropy analysis to scale factor of only 40, potentially facilitating MSE’s wider use as a research tool or bedside monitor. Traditional markers of inflammation generally exhibit threshold dose behavior. In contrast, MSE’s apparent continuous dose-response pattern, while not statistically verifiable in this study, suggests a potential subclinical harbinger of infectious or other insult. The possible derangement of autonomic complexity prior to or independent of the cytokine surge cannot be ruled out. Future investigation should focus on confirmation of overt inflammation following observed decreases in MSE in a clinical setting. PMID:25526373

TH-A-BRF-02: BEST IN PHYSICS (JOINT IMAGING-THERAPY) - Modeling Tumor Evolution for Adaptive Radiation Therapy

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

Liu, Y; Lee, CG; Chan, TCY

2014-06-15

Purpose: To develop mathematical models of tumor geometry changes under radiotherapy that may support future adaptive paradigms. Methods: A total of 29 cervical patients were scanned using MRI, once for planning and weekly thereafter for treatment monitoring. Using the tumor volumes contoured by a radiologist, three mathematical models were investigated based on the assumption of a stochastic process of tumor evolution. The “weekly MRI” model predicts tumor geometry for the following week from the last two consecutive MRI scans, based on the voxel transition probability. The other two models use only the first pair of consecutive MRI scans, and themore » transition probabilities were estimated via tumor type classified from the entire data set. The classification is based on either measuring the tumor volume (the “weekly volume” model), or implementing an auxiliary “Markov chain” model. These models were compared to a constant volume approach that represents the current clinical practice, using various model parameters; e.g., the threshold probability β converts the probability map into a tumor shape (larger threshold implies smaller tumor). Model performance was measured using volume conformity index (VCI), i.e., the union of the actual target and modeled target volume squared divided by product of these two volumes. Results: The “weekly MRI” model outperforms the constant volume model by 26% on average, and by 103% for the worst 10% of cases in terms of VCI under a wide range of β. The “weekly volume” and “Markov chain” models outperform the constant volume model by 20% and 16% on average, respectively. They also perform better than the “weekly MRI” model when β is large. Conclusion: It has been demonstrated that mathematical models can be developed to predict tumor geometry changes for cervical cancer undergoing radiotherapy. The models can potentially support adaptive radiotherapy paradigm by reducing normal tissue dose. This research was supported in part by the Ontario Consortium for Adaptive Interventions in Radiation Oncology (OCAIRO) funded by the Ontario Research Fund (ORF) and the MITACS Accelerate Internship Program.« less

Addressing the limits to adaptation across four damage--response systems

EPA Science Inventory

Our ability to adapt to climate change is not boundless, and previous modeling shows that capacity limited adaptation will play a policy-significant role in future decisions about climate change. These limits are delineated by capacity thresholds, after which climate damages beg...

Investigation of Adaptive-threshold Approaches for Determining Area-Time Integrals from Satellite Infrared Data to Estimate Convective Rain Volumes

NASA Technical Reports Server (NTRS)

Smith, Paul L.; VonderHaar, Thomas H.

1996-01-01

The principal goal of this project is to establish relationships that would allow application of area-time integral (ATI) calculations based upon satellite data to estimate rainfall volumes. The research is being carried out as a collaborative effort between the two participating organizations, with the satellite data analysis to determine values for the ATIs being done primarily by the STC-METSAT scientists and the associated radar data analysis to determine the 'ground-truth' rainfall estimates being done primarily at the South Dakota School of Mines and Technology (SDSM&T). Synthesis of the two separate kinds of data and investigation of the resulting rainfall-versus-ATI relationships is then carried out jointly. The research has been pursued using two different approaches, which for convenience can be designated as the 'fixed-threshold approach' and the 'adaptive-threshold approach'. In the former, an attempt is made to determine a single temperature threshold in the satellite infrared data that would yield ATI values for identifiable cloud clusters which are closely related to the corresponding rainfall amounts as determined by radar. Work on the second, or 'adaptive-threshold', approach for determining the satellite ATI values has explored two avenues: (1) attempt involved choosing IR thresholds to match the satellite ATI values with ones separately calculated from the radar data on a case basis; and (2) an attempt involved a striaghtforward screening analysis to determine the (fixed) offset that would lead to the strongest correlation and lowest standard error of estimate in the relationship between the satellite ATI values and the corresponding rainfall volumes.

What Deters Students from Studying Abroad? Evidence from Four European Countries and Its Implications for Higher Education Policy

ERIC Educational Resources Information Center

Netz, Nicolai

2015-01-01

This study examines factors that deter students in Austria, Germany, Switzerland and the Netherlands from studying abroad. Using an adaptation of the Rubicon model of action phases, the path to gaining study abroad experience is conceptualised as a process involving two thresholds: the decision threshold and the realisation threshold. Theoretical…

Avascular Necrosis of the Femoral Head After Palliative Radiotherapy in Metastatic Prostate Cancer: Absence of a Dose Threshold?

PubMed

Daoud, Alia M; Hudson, Mack; Magnus, Kenneth G; Huang, Fleur; Danielson, Brita L; Venner, Peter; Saluja, Ronak; LeGuerrier, Bronwen; Daly, Helene; Emmenegger, Urban; Fairchild, Alysa

2016-03-06

Avascular necrosis (AVN) is the final common pathway resulting from insufficient blood supply to bone, commonly the femoral head. There are many postulated etiologies of non-traumatic AVN, including corticosteroids, bisphosphonates, and radiotherapy (RT). However, it is unclear whether there is a dose threshold for the development of RT-induced AVN. In this case report, we describe a patient with prostate cancer metastatic to bone diagnosed with AVN after receiving single-fraction palliative RT to the left femoral head. Potential contributing factors are discussed, along with a review of other reported cases. At present, the RT dose threshold below which there is no risk for AVN is unknown, and therefore detrimental impact from the RT cannot be excluded. Given the possibility that RT-induced AVN is a stochastic effect, it is important to be aware of the possibility of this diagnosis in any patient with a painful hip who has received RT to the femoral head.

Cross-contamination of foods and implications for food allergic patients.

PubMed

Taylor, Steve L; Baumert, Joseph L

2010-07-01

Cross-contamination presents a risk of unknown magnitude for food allergic consumers. Published cases likely represent the tip of a rather large iceberg. Cross-contamination can occur in homes, restaurants, food manufacturing plants, and on farms. The frequency of cross-contamination as the cause of accidental exposures to allergenic foods is unknown. Food allergic individuals can react to ingestion of trace levels of the offending food, although a highly variable range of threshold doses exist among populations of food allergic individuals. The magnitude of the risk posed to food allergic consumers by cross-contamination is characterized by the frequency of exposure to cross-contaminated foods, the dose of exposure, and the individual's threshold dose. The food and food service industry (and food preparers in homes as well) have the responsibility to provide and prepare foods that are safe for food allergic consumers, but quality of life may be improved with the recognition that safe (though very low) thresholds do exist.

76 FR 53847 - New International Commission on Radiological Protection; Recommendations on the Annual Dose Limit...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-30

... Radiological Protection; Recommendations on the Annual Dose Limit to the Lens of the Eye AGENCY: Nuclear... Protection (ICRP) recommendations for the limitation of annual dose to the lens of the eye. This significant... might be lower than previously considered. For the lens of the eye, the threshold in absorbed dose for...

Step Detection Robust against the Dynamics of Smartphones

PubMed Central

Lee, Hwan-hee; Choi, Suji; Lee, Myeong-jin

2015-01-01

A novel algorithm is proposed for robust step detection irrespective of step mode and device pose in smartphone usage environments. The dynamics of smartphones are decoupled into a peak-valley relationship with adaptive magnitude and temporal thresholds. For extracted peaks and valleys in the magnitude of acceleration, a step is defined as consisting of a peak and its adjacent valley. Adaptive magnitude thresholds consisting of step average and step deviation are applied to suppress pseudo peaks or valleys that mostly occur during the transition among step modes or device poses. Adaptive temporal thresholds are applied to time intervals between peaks or valleys to consider the time-varying pace of human walking or running for the correct selection of peaks or valleys. From the experimental results, it can be seen that the proposed step detection algorithm shows more than 98.6% average accuracy for any combination of step mode and device pose and outperforms state-of-the-art algorithms. PMID:26516857

Positive-negative corresponding normalized ghost imaging based on an adaptive threshold

NASA Astrophysics Data System (ADS)

Li, G. L.; Zhao, Y.; Yang, Z. H.; Liu, X.

2016-11-01

Ghost imaging (GI) technology has attracted increasing attention as a new imaging technique in recent years. However, the signal-to-noise ratio (SNR) of GI with pseudo-thermal light needs to be improved before it meets engineering application demands. We therefore propose a new scheme called positive-negative correspondence normalized GI based on an adaptive threshold (PCNGI-AT) to achieve a good performance with less amount of data. In this work, we use both the advantages of normalized GI (NGI) and positive-negative correspondence GI (P-NCGI). The correctness and feasibility of the scheme were proved in theory before we designed an adaptive threshold selection method, in which the parameter of object signal selection conditions is replaced by the normalizing value. The simulation and experimental results reveal that the SNR of the proposed scheme is better than that of time-correspondence differential GI (TCDGI), avoiding the calculation of the matrix of correlation and reducing the amount of data used. The method proposed will make GI far more practical in engineering applications.

Why do shape aftereffects increase with eccentricity?

PubMed

Gheorghiu, Elena; Kingdom, Frederick A A; Bell, Jason; Gurnsey, Rick

2011-12-20

Studies have shown that spatial aftereffects increase with eccentricity. Here, we demonstrate that the shape-frequency and shape-amplitude aftereffects, which describe the perceived shifts in the shape of a sinusoidal-shaped contour following adaptation to a slightly different sinusoidal-shaped contour, also increase with eccentricity. Why does this happen? We first demonstrate that the perceptual shift increases with eccentricity for stimuli of fixed sizes. These shifts are not attenuated by variations in stimulus size; in fact, at each eccentricity the degree of perceptual shift is scale-independent. This scale independence is specific to the aftereffect because basic discrimination thresholds (in the absence of adaptation) decrease as size increases. Structural aspects of the displays were found to have a modest effect on the degree of perceptual shift; the degree of adaptation depends modestly on distance between stimuli during adaptation and post-adaptation testing. There were similar temporal rates of decline of adaptation across the visual field and higher post-adaptation discrimination thresholds in the periphery than in the center. The observed results are consistent with greater sensitivity reduction in adapted mechanisms following adaptation in the periphery or an eccentricity-dependent increase in the bandwidth of the shape-frequency- and shape-amplitude-selective mechanisms.

Automatic treatment plan re-optimization for adaptive radiotherapy guided with the initial plan DVHs

NASA Astrophysics Data System (ADS)

Li, Nan; Zarepisheh, Masoud; Uribe-Sanchez, Andres; Moore, Kevin; Tian, Zhen; Zhen, Xin; Jiang Graves, Yan; Gautier, Quentin; Mell, Loren; Zhou, Linghong; Jia, Xun; Jiang, Steve

2013-12-01

Adaptive radiation therapy (ART) can reduce normal tissue toxicity and/or improve tumor control through treatment adaptations based on the current patient anatomy. Developing an efficient and effective re-planning algorithm is an important step toward the clinical realization of ART. For the re-planning process, manual trial-and-error approach to fine-tune planning parameters is time-consuming and is usually considered unpractical, especially for online ART. It is desirable to automate this step to yield a plan of acceptable quality with minimal interventions. In ART, prior information in the original plan is available, such as dose-volume histogram (DVH), which can be employed to facilitate the automatic re-planning process. The goal of this work is to develop an automatic re-planning algorithm to generate a plan with similar, or possibly better, DVH curves compared with the clinically delivered original plan. Specifically, our algorithm iterates the following two loops. An inner loop is the traditional fluence map optimization, in which we optimize a quadratic objective function penalizing the deviation of the dose received by each voxel from its prescribed or threshold dose with a set of fixed voxel weighting factors. In outer loop, the voxel weighting factors in the objective function are adjusted according to the deviation of the current DVH curves from those in the original plan. The process is repeated until the DVH curves are acceptable or maximum iteration step is reached. The whole algorithm is implemented on GPU for high efficiency. The feasibility of our algorithm has been demonstrated with three head-and-neck cancer IMRT cases, each having an initial planning CT scan and another treatment CT scan acquired in the middle of treatment course. Compared with the DVH curves in the original plan, the DVH curves in the resulting plan using our algorithm with 30 iterations are better for almost all structures. The re-optimization process takes about 30 s using our in-house optimization engine. This work was originally presented at the 54th AAPM annual meeting in Charlotte, NC, July 29-August 2, 2012.

Impact of Fast Sodium Channel Inactivation on Spike Threshold Dynamics and Synaptic Integration

PubMed Central

Platkiewicz, Jonathan; Brette, Romain

2011-01-01

Neurons spike when their membrane potential exceeds a threshold value. In central neurons, the spike threshold is not constant but depends on the stimulation. Thus, input-output properties of neurons depend both on the effect of presynaptic spikes on the membrane potential and on the dynamics of the spike threshold. Among the possible mechanisms that may modulate the threshold, one strong candidate is Na channel inactivation, because it specifically impacts spike initiation without affecting the membrane potential. We collected voltage-clamp data from the literature and we found, based on a theoretical criterion, that the properties of Na inactivation could indeed cause substantial threshold variability by itself. By analyzing simple neuron models with fast Na inactivation (one channel subtype), we found that the spike threshold is correlated with the mean membrane potential and negatively correlated with the preceding depolarization slope, consistent with experiments. We then analyzed the impact of threshold dynamics on synaptic integration. The difference between the postsynaptic potential (PSP) and the dynamic threshold in response to a presynaptic spike defines an effective PSP. When the neuron is sufficiently depolarized, this effective PSP is briefer than the PSP. This mechanism regulates the temporal window of synaptic integration in an adaptive way. Finally, we discuss the role of other potential mechanisms. Distal spike initiation, channel noise and Na activation dynamics cannot account for the observed negative slope-threshold relationship, while adaptive conductances (e.g. K+) and Na inactivation can. We conclude that Na inactivation is a metabolically efficient mechanism to control the temporal resolution of synaptic integration. PMID:21573200

Adaptive Radiation Therapy for Localized Mesothelioma with Mediastinal Metastasis Using Helical Tomotherapy

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

Renaud, James; Yartsev, Slav; Department of Oncology, University of Western Ontario, London, Ontario

2009-10-01

The purpose of this study was to compare 2 adaptive radiotherapy strategies with helical tomotherapy. A patient having mesothelioma with mediastinal nodes was treated using helical tomotherapy with pretreatment megavoltage CT (MVCT) imaging. Gross tumor volumes (GTVs) were outlined on every MVCT study. Two alternatives for adapting the treatment were investigated: (1) keeping the prescribed dose to the targets while reducing the dose to the OARs and (2) escalating the target dose while maintaining the original level of healthy tissue sparing. Intensity modulated radiotherapy (step-and-shoot IMRT) and 3D conformal radiotherapy (3DCRT) plans for the patient were generated and compared. Themore » primary lesion and nodal mass regressed by 16.2% and 32.5%, respectively. Adapted GTVs and reduced planning target volume (PTV) margins of 4 mm after 22 fractions decrease the planned mean lung dose by 19.4%. For dose escalation, the planned prescribed doses may be increased from 50.0 to 58.7 Gy in PTV{sub 1} and from 60.0 to 70.5 Gy in PTV{sub 2}. The step-and-shoot IMRT plan was better in sparing healthy tissue but did not provide target coverage as well as the helical tomotherapy plan. The 3DCRT plan resulted in a prohibitively high planned dose to the spinal cord. MVCT studies provide information both for setup correction and plan adaptation. Improved healthy tissue sparing and/or dose escalation can be achieved by adaptive planning.« less

Intravenously administered oxotremorine and atropine, in doses known to affect pain threshold, affect the intraspinal release of acetylcholine in rats.

PubMed

Abelson, Klas S P; Höglund, A Urban

2002-04-01

Both systemically and intrathecally administered cholinergic agonists produce antinociception while cholinergic antagonists decrease pain threshold. The mechanism and the site of action of these substances are not known. In the present study it was hypothesized that systemically administered muscarinic agonists and antagonists modify nociceptive threshold by affecting intraspinal release of acetylcholine (ACh). Catheters were inserted into the femoral vein in rats maintained on isoflurane anaesthesia for administration of oxotremorine (10-300 microg/kg) and atropine (0.1, 10, 5000 microg/kg). Spinal microdialysis probes were placed intraspinally at approximately the C2-C5 spinal level for sampling of acetylcholine and dialysis delivery of atropine (0.1, 1, 10 nM). Additionally, the tail-flick behaviour was tested on conscious rats injected intraperitoneally with saline, atropine (10, 100 and 5000 microg/kg), or subcutaneously with oxotremorine (30, 100, 300 microg/kg). Subcutaneous administration of oxotremorine (30, 100, 300 microg/kg) significantly increased the tail-flick latency. These doses of oxotremorine dose-dependently increased the intraspinal release of acetylcholine. Intravenously administered atropine, in a dose that produced hyperalgesia (5000 microg/kg) in the tail-flick test, significantly decreased the intraspinal release of acetylcholine. Our results suggest an association between pain threshold and acetylcholine release in spinal cord. It is also suggested that an approximately 30% increase in basal ACh release produces antinociception and that a 30% decrease in basal release produces hyperalgesia.

A feature alignment score for online cone-beam CT-based image-guided radiotherapy for prostate cancer.

PubMed

Hargrave, Catriona; Deegan, Timothy; Poulsen, Michael; Bednarz, Tomasz; Harden, Fiona; Mengersen, Kerrie

2018-05-17

To develop a method for scoring online cone-beam CT (CBCT)-to-planning CT image feature alignment to inform prostate image-guided radiotherapy (IGRT) decision-making. The feasibility of incorporating volume variation metric thresholds predictive of delivering planned dose into weighted functions, was investigated. Radiation therapists and radiation oncologists participated in workshops where they reviewed prostate CBCT-IGRT case examples and completed a paper-based survey of image feature matching practices. For 36 prostate cancer patients, one daily CBCT was retrospectively contoured then registered with their plan to simulate delivered dose if (a) no online setup corrections and (b) online image alignment and setup corrections, were performed. Survey results were used to select variables for inclusion in classification and regression tree (CART) and boosted regression trees (BRT) modeling of volume variation metric thresholds predictive of delivering planned dose to the prostate, proximal seminal vesicles (PSV), bladder, and rectum. Weighted functions incorporating the CART and BRT results were used to calculate a score of individual tumor and organ at risk image feature alignment (FAS TV _ OAR ). Scaled and weighted FAS TV _ OAR were then used to calculate a score of overall treatment compliance (FAS global ) for a given CBCT-planning CT registration. The FAS TV _ OAR were assessed for sensitivity, specificity, and predictive power. FAS global thresholds indicative of high, medium, or low overall treatment plan compliance were determined using coefficients from multiple linear regression analysis. Thirty-two participants completed the prostate CBCT-IGRT survey. While responses demonstrated consensus of practice for preferential ranking of planning CT and CBCT match features in the presence of deformation and rotation, variation existed in the specified thresholds for observed volume differences requiring patient repositioning or repeat bladder and bowel preparation. The CART and BRT modeling indicated that for a given registration, a Dice similarity coefficient >0.80 and >0.60 for the prostate and PSV, respectively, and a maximum Hausdorff distance <8.0 mm for both structures were predictive of delivered dose ± 5% of planned dose. A normalized volume difference <1.0 and a CBCT anterior rectum wall >1.0 mm anterior to the planning CT anterior rectum wall were predictive of delivered dose >5% of planned rectum dose. A normalized volume difference <0.88, and a CBCT bladder wall >13.5 mm inferior and >5.0 mm posterior to the planning CT bladder were predictive of delivered dose >5% of planned bladder dose. A FAS TV _ OAR >0 is indicative of delivery of planned dose. For calculated FAS TV _ OAR for the prostate, PSV, bladder, and rectum using test data, sensitivity was 0.56, 0.75, 0.89, and 1.00, respectively; specificity 0.90, 0.94, 0.59, and 1.00, respectively; positive predictive power 0.90, 0.86, 0.53, and 1.00, respectively; and negative predictive power 0.56, 0.89, 0.91, and 1.00, respectively. Thresholds for the calculated FAS global of were low <60, medium 60-80, and high >80, with a 27% misclassification rate for the test data. A FAS global incorporating nested FAS TV _ OAR and volume variation metric thresholds predictive of treatment plan compliance was developed, offering an alternative to pretreatment dose calculations to assess treatment delivery accuracy. © 2018 American Association of Physicists in Medicine.

A lack of association between severity of nicotine withdrawal and individual differences in compensatory nicotine self-administration in rats

PubMed Central

Harris, Andrew C.; Pentel, Paul R.; Burroughs, Danielle; Staley, Mylissa D.; LeSage, Mark G.

2013-01-01

Rationale Compensatory smoking may represent an adverse consequence of smoking reduction or the use of reduced nicotine tobacco products. Factors contributing to individual variability in compensation are poorly understood. Objective To examine whether severity of nicotine withdrawal as measured by elevated intracranial self-stimulation (ICSS) thresholds is related to individual differences in compensatory nicotine self-administration (NSA) following unit dose reduction. Methods Rats were trained for ICSS and NSA (0.06 mg/kg/inf). After stabilization, effects of reducing the nicotine unit dose to 0.03 mg/kg/inf were examined. Following reacquisition of NSA (0.06 mg/kg/inf), effects of antagonist-precipitated withdrawal and saline extinction (spontaneous withdrawal) were examined. Results Reducing the NSA unit dose produced partial compensation as indicated by increased infusion rates but a 35% mean decrease in daily nicotine intake. Magnitude of compensation varied considerably among rats. Dose reduction did not elicit withdrawal in rats as a group, although there were substantial increases in ICSS thresholds in some animals. Intracranial self-stimulation thresholds were consistently elevated during precipitated and spontaneous withdrawal, confirming that rats were nicotine-dependent. Individual differences in compensation were not correlated with changes in ICSS thresholds during dose reduction, precipitated withdrawal, or spontaneous withdrawal. In a secondary analysis, greater precipitated withdrawal severity predicted greater initial nicotine-seeking during extinction. Conclusions Severity of nicotine withdrawal was not related to the degree of compensation in this protocol. These data do not support a role for nicotine withdrawal in individual differences in compensation during reduced nicotine exposure, but do suggest that withdrawal may contribute to nicotine-seeking during early abstinence. PMID:21494791

Enhanced Sensitivity to Rapid Input Fluctuations by Nonlinear Threshold Dynamics in Neocortical Pyramidal Neurons

PubMed Central

Mensi, Skander; Hagens, Olivier; Gerstner, Wulfram; Pozzorini, Christian

2016-01-01

The way in which single neurons transform input into output spike trains has fundamental consequences for network coding. Theories and modeling studies based on standard Integrate-and-Fire models implicitly assume that, in response to increasingly strong inputs, neurons modify their coding strategy by progressively reducing their selective sensitivity to rapid input fluctuations. Combining mathematical modeling with in vitro experiments, we demonstrate that, in L5 pyramidal neurons, the firing threshold dynamics adaptively adjust the effective timescale of somatic integration in order to preserve sensitivity to rapid signals over a broad range of input statistics. For that, a new Generalized Integrate-and-Fire model featuring nonlinear firing threshold dynamics and conductance-based adaptation is introduced that outperforms state-of-the-art neuron models in predicting the spiking activity of neurons responding to a variety of in vivo-like fluctuating currents. Our model allows for efficient parameter extraction and can be analytically mapped to a Generalized Linear Model in which both the input filter—describing somatic integration—and the spike-history filter—accounting for spike-frequency adaptation—dynamically adapt to the input statistics, as experimentally observed. Overall, our results provide new insights on the computational role of different biophysical processes known to underlie adaptive coding in single neurons and support previous theoretical findings indicating that the nonlinear dynamics of the firing threshold due to Na+-channel inactivation regulate the sensitivity to rapid input fluctuations. PMID:26907675

Salicylate-Induced Hearing Loss and Gap Detection Deficits in Rats

PubMed Central

Radziwon, Kelly E.; Stolzberg, Daniel J.; Urban, Maxwell E.; Bowler, Rachael A.; Salvi, Richard J.

2015-01-01

To test the “tinnitus gap-filling” hypothesis in an animal psychoacoustic paradigm, rats were tested using a go/no-go operant gap detection task in which silent intervals of various durations were embedded within a continuous noise. Gap detection thresholds were measured before and after treatment with a dose of sodium salicylate (200 mg/kg) that reliably induces tinnitus in rats. Noise-burst detection thresholds were also measured to document the amount of hearing loss and aid in interpreting the gap detection results. As in the previous human psychophysical experiments, salicylate had little or no effect on gap thresholds measured in broadband noise presented at high-stimulus levels (30–60 dB SPL); gap detection thresholds were always 10 ms or less. Salicylate also did not affect gap thresholds presented in narrowband noise at 60 dB SPL. Therefore, rats treated with a dose of salicylate that reliably induces tinnitus have no difficulty detecting silent gaps as long as the noise in which they are embedded is clearly audible. PMID:25750635

Dose conversion coefficients for monoenergetic electrons incident on a realistic human eye model with different lens cell populations

NASA Astrophysics Data System (ADS)

Nogueira, P.; Zankl, M.; Schlattl, H.; Vaz, P.

2011-11-01

The radiation-induced posterior subcapsular cataract has long been generally accepted to be a deterministic effect that does not occur at doses below a threshold of at least 2 Gy. Recent epidemiological studies indicate that the threshold for cataract induction may be much lower or that there may be no threshold at all. A thorough study of this subject requires more accurate dose estimates for the eye lens than those available in ICRP Publication 74. Eye lens absorbed dose per unit fluence conversion coefficients for electron irradiation were calculated using a geometrical model of the eye that takes into account different cell populations of the lens epithelium, together with the MCNPX Monte Carlo radiation transport code package. For the cell population most sensitive to ionizing radiation—the germinative cells—absorbed dose per unit fluence conversion coefficients were determined that are up to a factor of 4.8 higher than the mean eye lens absorbed dose conversion coefficients for electron energies below 2 MeV. Comparison of the results with previously published values for a slightly different eye model showed generally good agreement for all electron energies. Finally, the influence of individual anatomical variability was quantified by positioning the lens at various depths below the cornea. A depth difference of 2 mm between the shallowest and the deepest location of the germinative zone can lead to a difference between the resulting absorbed doses of up to nearly a factor of 5000 for electron energy of 0.7 MeV.

Dose conversion coefficients for monoenergetic electrons incident on a realistic human eye model with different lens cell populations.

PubMed

Nogueira, P; Zankl, M; Schlattl, H; Vaz, P

2011-11-07

The radiation-induced posterior subcapsular cataract has long been generally accepted to be a deterministic effect that does not occur at doses below a threshold of at least 2 Gy. Recent epidemiological studies indicate that the threshold for cataract induction may be much lower or that there may be no threshold at all. A thorough study of this subject requires more accurate dose estimates for the eye lens than those available in ICRP Publication 74. Eye lens absorbed dose per unit fluence conversion coefficients for electron irradiation were calculated using a geometrical model of the eye that takes into account different cell populations of the lens epithelium, together with the MCNPX Monte Carlo radiation transport code package. For the cell population most sensitive to ionizing radiation-the germinative cells-absorbed dose per unit fluence conversion coefficients were determined that are up to a factor of 4.8 higher than the mean eye lens absorbed dose conversion coefficients for electron energies below 2 MeV. Comparison of the results with previously published values for a slightly different eye model showed generally good agreement for all electron energies. Finally, the influence of individual anatomical variability was quantified by positioning the lens at various depths below the cornea. A depth difference of 2 mm between the shallowest and the deepest location of the germinative zone can lead to a difference between the resulting absorbed doses of up to nearly a factor of 5000 for electron energy of 0.7 MeV.

Theoretical and experimental approaches to possible thresholds of response in carcinogenicity

EPA Science Inventory

The determination and utilization of the actual low dose-response relationship for chemical carcinogens has long interested toxicologists, experimental pathologists, modelers and risk assessors. To date, no unequivocal examples of carcinogenic thresholds in humans are known. Ho...

Plasma Membrane Permeabilization by 60- and 600-ns Electric Pulses Is Determined by the Absorbed Dose

PubMed Central

Ibey, Bennett L.; Xiao, Shu; Schoenbach, Karl H.; Murphy, Michael R.; Pakhomov, Andrei G.

2008-01-01

We explored how the effect of plasma membrane permeabilization by nanosecond-duration electric pulses (nsEP) depends on the physical characteristics of exposure. The resting membrane resistance (Rm) and membrane potential (MP) were measured in cultured GH3 and CHO cells by conventional whole-cell patch-clamp technique. Intact cells were exposed to a single nsEP (60 or 600 ns duration, 0-22 kV/cm), followed by patch-clamp measurements after a 2-3 min delay. Consistent with earlier findings, nsEP caused long-lasting Rm decrease, accompanied by the loss of MP. The threshold for these effects was about 6 kV/cm for 60 ns pulses, and about 1 kV/cm for 600 ns pulses. Further analysis established that it was neither pulse duration nor the E-field amplitude per se, but the absorbed dose that determined the magnitude of the biological effect. In other words, exposure to nsEP at either pulse duration caused equal effects if the absorbed doses were equal. The threshold absorbed dose to produce plasma membrane effects in either GH3 or CHO cells at either pulse duration was found to be at or below 10 mJ/g. Despite being determined by the dose, the nsEP effect clearly is not thermal, as the maximum heating at the threshold dose is less than 0.01 °C. The use of the absorbed dose as a universal exposure metric may help to compare and quantify nsEP sensitivity of different cell types and of cells in different physiological conditions. The absorbed dose may also prove to be a more useful metric than the incident E-field in determining safety limits for high peak, lowaverage power EMF emissions. PMID:18839412

Adaptive Treatment Strategies in Youth Mental Health: A Commentary on Advantages, Challenges, and Potential Directions.

PubMed

Sherrill, Joel T

2016-01-01

This commentary underscores the importance and potential of the research approaches and intervention strategies described in the JCCAP special issue on the Science of Adaptive Treatment Strategies in Child and Adolescent Mental Health for addressing the widely observed heterogeneity in response to even our most promising research-informed interventions. First, the commentary briefly summarizes the advantages of these approaches and highlights how these programs of research are responsive to widely agreed-upon calls for more personalized, prescriptive interventions. Next, the commentary briefly discusses key common challenges and gaps in our knowledge that might be addressed to advance the development, testing, and implementation of adaptive intervention strategies. For example, research to identify robust moderators that might serve as potential tailoring variables for initial assignment and sequencing of interventions, efforts to operationalize surrogate endpoints for early identification of individuals who are unlikely to respond to first-line interventions, and research that helps define what constitutes an adequate exposure (i.e., dose) or response threshold (e.g., response that suggests the need to intensify, switch, or augment interventions) would inform decision rules for adaptive algorithms. The commentary concludes with a discussion of potential strategies and current initiatives that might ultimately help facilitate research on more targeted, prescriptive approaches to intervening, including efforts to encourage investigators to use common data elements, to share and integrate data across trials, and to employ a more mechanism-based approach to intervention development and testing.

Dose-response studies and 'no-effect-levels' of N-nitroso compounds: some general aspects.

PubMed

Preussmann, R

1980-01-01

One major problem in the evaluation of potential carcinogenic food additives and contaminants is that of thresholds or, better, of 'no-adverse-effect-levels'. Arguments in favor of the postulated 'irreversibility' of carcinogenic effects are based on dose-response studies, single dose and multigeneration experiments as well as on the concept of somatic mutation as the first step in carcinogenesis with subsequent transmittance of induced defects during cell replication. The problem of extrapolation of results of animal experiments using high doses to low exposure and low incidences in man is not yet solved satisfactorily. Possible practical consequences include zero tolerance, acceptable thresholds at low risk and safety factors. Acceptable intakes should never be considered constants but should be changeable as soon as new facts in regard to the safety evaluation are available.

A prospective study on radiation-induced changes in hearing function

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

Herrmann, Franziska; Doerr, Wolfgang; Experimental Center, Medical Faculty Carl Gustav Carus, University of Technology-Dresden, Dresden

Purpose: To quantitate changes in hearing function after radiotherapy for head-and-neck tumors. Methods and Materials: At the Department of Radiotherapy and Radiation Oncology, 32 patients were irradiated for head-and-neck tumors. Three-dimensional treatment planning was applied. Total tumor doses were 30.0-77.6 Gy, local doses to the inner ear (n = 64) ranged from 1.7 to 64.3 Gy. Audiometry was performed before the onset of radiotherapy (RT), at a tumor dose of 40 Gy or at the end of palliative treatment, at the end of curative RT, and 2-6 months post-RT. Assays applied were frequency-specific threshold measurements for air and bone conduction,more » measurements according to Weber and Rinne, tympanometry and assessment of the stapedius reflex. Results: Age and prior disease significantly decreased, whereas previous or concurrent alcohol consumption significantly increased hearing ability. A significant reduction in hearing ability during RT was found for high frequencies (at 40 Gy) and low frequencies (at end of RT), which persisted after RT. No differences were observed for air or bone conduction. None of the other assays displayed time- or dose-dependent changes. Dose-effect analyses revealed an ED50 (dose at which a 50% incidence is expected) for significant changes in hearing thresholds (15 dB) in the range of 20-25 Gy, with large confidence limits. Conclusions: Radiation effects on hearing ability were confined to threshold audiogram values, which started during the treatment without reversibility during 6 months postradiotherapy.« less

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

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

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

2014-06-01

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

MODELING THE INTERACTION THRESHOLD: THE BREAK-POINT BETWEEN ADDITIVITY AND NON-ADDITIVITY

EPA Science Inventory

Dose-dependent changes in toxicity mechanisms of single chemicals may take place along the full dose-response spectrum. At high doses, the possibility exists for some steps in the principle mechanism of toxicity to shift to other mechanisms. The possibility of mechanism shifts fo...

LNT IS THE BEST WE CAN DO - TO-DAY

EPA Science Inventory

Abstract

The form of the dose-response curve for radiation-induced cancers, particularly at low doses, is the subject of an ongoing and spirited debate. The present review describes the current data base and basis for establishing a low dose, linear no threshold (LNT) mode...

Can adaptive threshold-based metabolic tumor volume (MTV) and lean body mass corrected standard uptake value (SUL) predict prognosis in head and neck cancer patients treated with definitive radiotherapy/chemoradiotherapy?

PubMed

Akagunduz, Ozlem Ozkaya; Savas, Recep; Yalman, Deniz; Kocacelebi, Kenan; Esassolak, Mustafa

2015-11-01

To evaluate the predictive value of adaptive threshold-based metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax) and maximum lean body mass corrected SUV (SULmax) measured on pretreatment positron emission tomography and computed tomography (PET/CT) imaging in head and neck cancer patients treated with definitive radiotherapy/chemoradiotherapy. Pretreatment PET/CT of the 62 patients with locally advanced head and neck cancer who were treated consecutively between May 2010 and February 2013 were reviewed retrospectively. The maximum FDG uptake of the primary tumor was defined according to SUVmax and SULmax. Multiple threshold levels between 60% and 10% of the SUVmax and SULmax were tested with intervals of 5% to 10% in order to define the most suitable threshold value for the metabolic activity of each patient's tumor (adaptive threshold). MTV was calculated according to this value. We evaluated the relationship of mean values of MTV, SUVmax and SULmax with treatment response, local recurrence, distant metastasis and disease-related death. Receiver-operating characteristic (ROC) curve analysis was done to obtain optimal predictive cut-off values for MTV and SULmax which were found to have a predictive value. Local recurrence-free (LRFS), disease-free (DFS) and overall survival (OS) were examined according to these cut-offs. Forty six patients had complete response, 15 had partial response, and 1 had stable disease 6 weeks after the completion of treatment. Median follow-up of the entire cohort was 18 months. Of 46 complete responders 10 had local recurrence, and of 16 partial or no responders 10 had local progression. Eighteen patients died. Adaptive threshold-based MTV had significant predictive value for treatment response (p=0.011), local recurrence/progression (p=0.050), and disease-related death (p=0.024). SULmax had a predictive value for local recurrence/progression (p=0.030). ROC curves analysis revealed a cut-off value of 14.00 mL for MTV and 10.15 for SULmax. Three-year LRFS and DFS rates were significantly lower in patients with MTV ≥ 14.00 mL (p=0.026, p=0.018 respectively), and SULmax≥10.15 (p=0.017, p=0.022 respectively). SULmax did not have a significant predictive value for OS whereas MTV had (p=0.025). Adaptive threshold-based MTV and SULmax could have a role in predicting local control and survival in head and neck cancer patients. Copyright © 2015 Elsevier Inc. All rights reserved.

TTCs for oral exposure: Identification of outliers in Cramer class I, II and III using the combined database of RepDose (FhG), Toxbase (TNO), Munro and ToxRefDB (USEPA)

EPA Science Inventory

The Thresholds of Toxicological Concern (TTC) are generic human exposure threshold for structural groups of chemicals below which no risk to human health is assumed and therefore no further testing is needed. Different thresholds have been developed for oral exposure e.g. for gen...

Adaptive Dose Painting by Numbers for Head-and-Neck Cancer

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

Duprez, Frederic, E-mail: frederic.duprez@ugent.be; De Neve, Wilfried; De Gersem, Werner

Purpose: To investigate the feasibility of adaptive intensity-modulated radiation therapy (IMRT) using dose painting by numbers (DPBN) for head-and-neck cancer. Methods and Materials: Each patient's treatment used three separate treatment plans: fractions 1-10 used a DPBN ([{sup 18}-F]fluoro-2-deoxy-D-glucose positron emission tomography [{sup 18}F-FDG-PET]) voxel intensity-based IMRT plan based on a pretreatment {sup 18}F-FDG-PET/computed tomography (CT) scan; fractions 11-20 used a DPBN plan based on a {sup 18}F-FDG-PET/CT scan acquired after the eighth fraction; and fractions 21-32 used a conventional (uniform dose) IMRT plan. In a Phase I trial, two dose prescription levels were tested: a median dose of 80.9 Gymore » to the high-dose clinical target volume (CTV{sub highdose}) (dose level I) and a median dose of 85.9 Gy to the gross tumor volume (GTV) (dose level II). Between February 2007 and August 2009, 7 patients at dose level I and 14 patients at dose level II were enrolled. Results: All patients finished treatment without a break, and no Grade 4 acute toxicity was observed. Treatment adaptation (i.e., plans based on the second {sup 18}F-FDG-PET/CT scan) reduced the volumes for the GTV (41%, p = 0.01), CTV{sub highdose} (18%, p = 0.01), high-dose planning target volume (14%, p = 0.02), and parotids (9-12%, p < 0.05). Because the GTV was much smaller than the CTV{sub highdose} and target adaptation, further dose escalation at dose level II resulted in less severe toxicity than that observed at dose level I. Conclusion: To our knowledge, this represents the first clinical study that combines adaptive treatments with dose painting by numbers. Treatment as described above is feasible.« less

Edge detection based on adaptive threshold b-spline wavelet for optical sub-aperture measuring

NASA Astrophysics Data System (ADS)

Zhang, Shiqi; Hui, Mei; Liu, Ming; Zhao, Zhu; Dong, Liquan; Liu, Xiaohua; Zhao, Yuejin

2015-08-01

In the research of optical synthetic aperture imaging system, phase congruency is the main problem and it is necessary to detect sub-aperture phase. The edge of the sub-aperture system is more complex than that in the traditional optical imaging system. And with the existence of steep slope for large-aperture optical component, interference fringe may be quite dense when interference imaging. Deep phase gradient may cause a loss of phase information. Therefore, it's urgent to search for an efficient edge detection method. Wavelet analysis as a powerful tool is widely used in the fields of image processing. Based on its properties of multi-scale transform, edge region is detected with high precision in small scale. Longing with the increase of scale, noise is reduced in contrary. So it has a certain suppression effect on noise. Otherwise, adaptive threshold method which sets different thresholds in various regions can detect edge points from noise. Firstly, fringe pattern is obtained and cubic b-spline wavelet is adopted as the smoothing function. After the multi-scale wavelet decomposition of the whole image, we figure out the local modulus maxima in gradient directions. However, it also contains noise, and thus adaptive threshold method is used to select the modulus maxima. The point which greater than threshold value is boundary point. Finally, we use corrosion and expansion deal with the resulting image to get the consecutive boundary of image.

Extraction of Extended Small-Scale Objects in Digital Images

NASA Astrophysics Data System (ADS)

Volkov, V. Y.

2015-05-01

Detection and localization problem of extended small-scale objects with different shapes appears in radio observation systems which use SAR, infra-red, lidar and television camera. Intensive non-stationary background is the main difficulty for processing. Other challenge is low quality of images, blobs, blurred boundaries; in addition SAR images suffer from a serious intrinsic speckle noise. Statistics of background is not normal, it has evident skewness and heavy tails in probability density, so it is hard to identify it. The problem of extraction small-scale objects is solved here on the basis of directional filtering, adaptive thresholding and morthological analysis. New kind of masks is used which are open-ended at one side so it is possible to extract ends of line segments with unknown length. An advanced method of dynamical adaptive threshold setting is investigated which is based on isolated fragments extraction after thresholding. Hierarchy of isolated fragments on binary image is proposed for the analysis of segmentation results. It includes small-scale objects with different shape, size and orientation. The method uses extraction of isolated fragments in binary image and counting points in these fragments. Number of points in extracted fragments is normalized to the total number of points for given threshold and is used as effectiveness of extraction for these fragments. New method for adaptive threshold setting and control maximises effectiveness of extraction. It has optimality properties for objects extraction in normal noise field and shows effective results for real SAR images.

SU-E-T-397: Evaluation of Planned Dose Distributions by Monte Carlo (0.5%) and Ray Tracing Algorithm for the Spinal Tumors with CyberKnife

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

Cho, H; Brindle, J; Hepel, J

2015-06-15

Purpose: To analyze and evaluate dose distribution between Ray Tracing (RT) and Monte Carlo (MC) algorithms of 0.5% uncertainty on a critical structure of spinal cord and gross target volume and planning target volume. Methods: Twenty four spinal tumor patients were treated with stereotactic body radiotherapy (SBRT) by CyberKnife in 2013 and 2014. The MC algorithm with 0.5% of uncertainty is used to recalculate the dose distribution for the treatment plan of the patients using the same beams, beam directions, and monitor units (MUs). Results: The prescription doses are uniformly larger for MC plans than RT except one case. Upmore » to a factor of 1.19 for 0.25cc threshold volume and 1.14 for 1.2cc threshold volume of dose differences are observed for the spinal cord. Conclusion: The MC recalculated dose distributions are larger than the original MC calculations for the spinal tumor cases. Based on the accuracy of the MC calculations, more radiation dose might be delivered to the tumor targets and spinal cords with the increase prescription dose.« less

Robust crop and weed segmentation under uncontrolled outdoor illumination

USDA-ARS?s Scientific Manuscript database

A new machine vision for weed detection was developed from RGB color model images. Processes included in the algorithm for the detection were excessive green conversion, threshold value computation by statistical analysis, adaptive image segmentation by adjusting the threshold value, median filter, ...

Introducing an on-line adaptive procedure for prostate image guided intensity modulate proton therapy.

PubMed

Zhang, M; Westerly, D C; Mackie, T R

2011-08-07

With on-line image guidance (IG), prostate shifts relative to the bony anatomy can be corrected by realigning the patient with respect to the treatment fields. In image guided intensity modulated proton therapy (IG-IMPT), because the proton range is more sensitive to the material it travels through, the realignment may introduce large dose variations. This effect is studied in this work and an on-line adaptive procedure is proposed to restore the planned dose to the target. A 2D anthropomorphic phantom was constructed from a real prostate patient's CT image. Two-field laterally opposing spot 3D-modulation and 24-field full arc distal edge tracking (DET) plans were generated with a prescription of 70 Gy to the planning target volume. For the simulated delivery, we considered two types of procedures: the non-adaptive procedure and the on-line adaptive procedure. In the non-adaptive procedure, only patient realignment to match the prostate location in the planning CT was performed. In the on-line adaptive procedure, on top of the patient realignment, the kinetic energy for each individual proton pencil beam was re-determined from the on-line CT image acquired after the realignment and subsequently used for delivery. Dose distributions were re-calculated for individual fractions for different plans and different delivery procedures. The results show, without adaptive, that both the 3D-modulation and the DET plans experienced delivered dose degradation by having large cold or hot spots in the prostate. The DET plan had worse dose degradation than the 3D-modulation plan. The adaptive procedure effectively restored the planned dose distribution in the DET plan, with delivered prostate D(98%), D(50%) and D(2%) values less than 1% from the prescription. In the 3D-modulation plan, in certain cases the adaptive procedure was not effective to reduce the delivered dose degradation and yield similar results as the non-adaptive procedure. In conclusion, based on this 2D phantom study, by updating the proton pencil beam energy from the on-line image after realignment, this on-line adaptive procedure is necessary and effective for the DET-based IG-IMPT. Without dose re-calculation and re-optimization, it could be easily incorporated into the clinical workflow.

Introducing an on-line adaptive procedure for prostate image guided intensity modulate proton therapy

NASA Astrophysics Data System (ADS)

Zhang, M.; Westerly, D. C.; Mackie, T. R.

2011-08-01

With on-line image guidance (IG), prostate shifts relative to the bony anatomy can be corrected by realigning the patient with respect to the treatment fields. In image guided intensity modulated proton therapy (IG-IMPT), because the proton range is more sensitive to the material it travels through, the realignment may introduce large dose variations. This effect is studied in this work and an on-line adaptive procedure is proposed to restore the planned dose to the target. A 2D anthropomorphic phantom was constructed from a real prostate patient's CT image. Two-field laterally opposing spot 3D-modulation and 24-field full arc distal edge tracking (DET) plans were generated with a prescription of 70 Gy to the planning target volume. For the simulated delivery, we considered two types of procedures: the non-adaptive procedure and the on-line adaptive procedure. In the non-adaptive procedure, only patient realignment to match the prostate location in the planning CT was performed. In the on-line adaptive procedure, on top of the patient realignment, the kinetic energy for each individual proton pencil beam was re-determined from the on-line CT image acquired after the realignment and subsequently used for delivery. Dose distributions were re-calculated for individual fractions for different plans and different delivery procedures. The results show, without adaptive, that both the 3D-modulation and the DET plans experienced delivered dose degradation by having large cold or hot spots in the prostate. The DET plan had worse dose degradation than the 3D-modulation plan. The adaptive procedure effectively restored the planned dose distribution in the DET plan, with delivered prostate D98%, D50% and D2% values less than 1% from the prescription. In the 3D-modulation plan, in certain cases the adaptive procedure was not effective to reduce the delivered dose degradation and yield similar results as the non-adaptive procedure. In conclusion, based on this 2D phantom study, by updating the proton pencil beam energy from the on-line image after realignment, this on-line adaptive procedure is necessary and effective for the DET-based IG-IMPT. Without dose re-calculation and re-optimization, it could be easily incorporated into the clinical workflow.

An adaptive detector and channel estimator for deep space optical communications

NASA Technical Reports Server (NTRS)

Mukai, R.; Arabshahi, P.; Yan, T. Y.

2001-01-01

This paper will discuss the design and testing of both the channel parameter identification system, and the adaptive threshold system, and illustrate their advantages and performance under simulated channel degradation conditions.

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.

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

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

None

1973-01-01

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

An F1-extended one-generation reproductive toxicity study in Crl:CD(SD) rats with 2,4-dichlorophenoxyacetic acid.

PubMed

Marty, Mary Sue; Neal, Barbara H; Zablotny, Carol L; Yano, Barry L; Andrus, Amanda K; Woolhiser, Michael R; Boverhof, Darrell R; Saghir, Shakil A; Perala, Adam W; Passage, Julie K; Lawson, Marie A; Bus, James S; Lamb, James C; Hammond, Larry

2013-12-01

2,4-Dichlorophenoxyacetic acid (2,4-D) was assessed for systemic toxicity, reproductive toxicity, developmental neurotoxicity (DNT), developmental immunotoxicity (DIT), and endocrine toxicity. CD rats (27/sex/dose) were exposed to 0, 100, 300, 600 (female), or 800 (male) ppm 2,4-D in diet. Nonlinear toxicokinetic behavior was shown at high doses; the renal clearance saturation threshold for 2,4-D was exceeded markedly in females and slightly exceeded in males. Exposure was 4 weeks premating, 7 weeks postmating for P1 males and through lactation for P1 females. F1 offspring were examined for survival and development, and at weaning, pups were divided in cohorts, by sex and dose, and by systemic toxicity (10), DNT (10), DIT (20), and reproductive toxicity (≥ 23). Remaining weanlings were evaluated for systemic toxicity and neuropathology (10-12). Body weight decreased during lactation in high-dose P1 females and in F1 pups. Kidney was the primary target organ, with slight degeneration of proximal convoluted tubules observed in high-dose P1 males and in high-dose F1 males and females. A slight intergenerational difference in kidney toxicity was attributed to increased intake of 2,4-D in F1 offspring. Decreased weanling testes weights and delayed preputial separation in F1 males were attributed to decreased body weights. Endocrine-related effects were limited to slight thyroid hormone changes and adaptive histopathology in high-dose GD 17 dams seen only at a nonlinear toxicokinetic dose. 2,4-D did not cause reproductive toxicity, DNT, or DIT. The "No Observed Adverse Effect Level" for systemic toxicity was 300 ppm in both males (16.6 mg/kg/day) and females (20.6 mg/kg/day), which is approximately 6700- to 93 000-fold higher than that reported for 2,4-D exposures in human biomonitoring studies.

An F1-Extended One-Generation Reproductive Toxicity Study in Crl:CD(SD) Rats With 2,4-Dichlorophenoxyacetic Acid

PubMed Central

Marty, Mary Sue

2013-01-01

2,4-Dichlorophenoxyacetic acid (2,4-D) was assessed for systemic toxicity, reproductive toxicity, developmental neurotoxicity (DNT), developmental immunotoxicity (DIT), and endocrine toxicity. CD rats (27/sex/dose) were exposed to 0, 100, 300, 600 (female), or 800 (male) ppm 2,4-D in diet. Nonlinear toxicokinetic behavior was shown at high doses; the renal clearance saturation threshold for 2,4-D was exceeded markedly in females and slightly exceeded in males. Exposure was 4 weeks premating, 7 weeks postmating for P1 males and through lactation for P1 females. F1 offspring were examined for survival and development, and at weaning, pups were divided in cohorts, by sex and dose, and by systemic toxicity (10), DNT (10), DIT (20), and reproductive toxicity (≥ 23). Remaining weanlings were evaluated for systemic toxicity and neuropathology (10–12). Body weight decreased during lactation in high-dose P1 females and in F1 pups. Kidney was the primary target organ, with slight degeneration of proximal convoluted tubules observed in high-dose P1 males and in high-dose F1 males and females. A slight intergenerational difference in kidney toxicity was attributed to increased intake of 2,4-D in F1 offspring. Decreased weanling testes weights and delayed preputial separation in F1 males were attributed to decreased body weights. Endocrine-related effects were limited to slight thyroid hormone changes and adaptive histopathology in high-dose GD 17 dams seen only at a nonlinear toxicokinetic dose. 2,4-D did not cause reproductive toxicity, DNT, or DIT. The “No Observed Adverse Effect Level” for systemic toxicity was 300 ppm in both males (16.6mg/kg/day) and females (20.6mg/kg/day), which is approximately 6700- to 93 000-fold higher than that reported for 2,4-D exposures in human biomonitoring studies. PMID:24072463

THE EFFECTS OF VARIATIONS IN THE CONCENTRATION OF OXYGEN AND OF GLUCOSE ON DARK ADAPTATION

PubMed Central

McFarland, R. A.; Forbes, W. H.

1940-01-01

In this study we have analyzed the effects of variations in the concentrations of oxygen and of blood sugar on light sensitivity; i.e. dark adaptation. The experiments were carried out in an air-conditioned light-proof chamber where the concentrations of oxygen could be changed by dilution with nitrogen or by inhaling oxygen from a cylinder. The blood sugar was lowered by the injection of insulin and raised by the ingestion of glucose. The dark adaptation curves were plotted from data secured with an apparatus built according to specifications outlined by Hecht and Shlaer. During each experiment, observations were first made in normal air with the subject under basal conditions followed by one, and in most instances two, periods under the desired experimental conditions involving either anoxia or hyper- or hypoglycemia or variations in both the oxygen tension and blood sugar at the same time. 1. Dark adaptation curves were plotted (threshold against time) in normal air and compared with those obtained while inhaling lowered concentrations of oxygen. A decrease in sensitivity was observed with lowered oxygen tensions. Both the rod and cone portions of the curves were influenced in a similar way. These effects were counteracted by inhaling oxygen, the final rod thresholds returning to about the level of the normal base line in air or even below it within 2 to 3 minutes. The impairment was greatest for those with a poorer tolerance for low O2. Both the inter- and intra-individual variability in thresholds increased significantly at the highest altitude. 2. In a second series of tests control curves were obtained in normal air. Then while each subject remained dark adapted, the concentrations of oxygen were gradually decreased. The regeneration of visual purple was apparently complete during the 40 minutes of dark adaptation, yet in each case the thresholds continued to rise in direct proportion to the degree of anoxia. The inhalation of oxygen from a cylinder quickly counteracted the effects for the thresholds returned to the original control level within 2 to 3 minutes. 3. In experiments where the blood sugar was raised by the ingestion of glucose in normal air, no significant changes in the thresholds were observed except when the blood sugar was rapidly falling toward the end of the glucose tolerance tests. However, when glucose was ingested at the end of an experiment in low oxygen, while the subject remained dark adapted, the effects of the anoxia were largely counteracted within 6 to 8 minutes. 4. The influence of low blood sugar on light sensitivity was then studied by injecting insulin. The thresholds were raised as soon as the effects of the insulin produced a fall in the blood sugar. When the subjects inhaled oxygen the thresholds were lowered. Then when the oxygen was withdrawn so that the subject was breathing normal air, the thresholds rose again within 1 to 2 minutes. Finally, if the blood sugar was raised by ingesting glucose, the average threshold fell to the original control level or even below it. 5. The combined effects of low oxygen and low blood sugar on light sensitivity were studied in one subject (W. F.). These effects appeared to be greater than when a similar degree of anoxia or hypoglycemia was brought about separately. 6. In a series of experiments on ten subjects the dark adaptation curves were obtained both in the basal state and after a normal breakfast. In nine of the ten subjects, the food increased the sensitivity of the subjects to light. 7. The experiments reported above lend support to the hypothesis that both anoxia and hypoglycemia produce their effects on light sensitivity in essentially the same way; namely, by slowing the oxidative processes. Consequently the effects of anoxia may be ameliorated by giving glucose and the effects of hypoglycemia by inhaling oxygen. In our opinion, the changes may be attributed directly to the effects on the nervous tissue of the visual mechanism and the brain rather than on the photochemical processes of the retina. PMID:19873200

Monopolar Detection Thresholds Predict Spatial Selectivity of Neural Excitation in Cochlear Implants: Implications for Speech Recognition

PubMed Central

2016-01-01

The objectives of the study were to (1) investigate the potential of using monopolar psychophysical detection thresholds for estimating spatial selectivity of neural excitation with cochlear implants and to (2) examine the effect of site removal on speech recognition based on the threshold measure. Detection thresholds were measured in Cochlear Nucleus® device users using monopolar stimulation for pulse trains that were of (a) low rate and long duration, (b) high rate and short duration, and (c) high rate and long duration. Spatial selectivity of neural excitation was estimated by a forward-masking paradigm, where the probe threshold elevation in the presence of a forward masker was measured as a function of masker-probe separation. The strength of the correlation between the monopolar thresholds and the slopes of the masking patterns systematically reduced as neural response of the threshold stimulus involved interpulse interactions (refractoriness and sub-threshold adaptation), and spike-rate adaptation. Detection threshold for the low-rate stimulus most strongly correlated with the spread of forward masking patterns and the correlation reduced for long and high rate pulse trains. The low-rate thresholds were then measured for all electrodes across the array for each subject. Subsequently, speech recognition was tested with experimental maps that deactivated five stimulation sites with the highest thresholds and five randomly chosen ones. Performance with deactivating the high-threshold sites was better than performance with the subjects’ clinical map used every day with all electrodes active, in both quiet and background noise. Performance with random deactivation was on average poorer than that with the clinical map but the difference was not significant. These results suggested that the monopolar low-rate thresholds are related to the spatial neural excitation patterns in cochlear implant users and can be used to select sites for more optimal speech recognition performance. PMID:27798658

The threshold vs LNT showdown: Dose rate findings exposed flaws in the LNT model part 2. How a mistake led BEIR I to adopt LNT.

PubMed

Calabrese, Edward J

2017-04-01

This paper reveals that nearly 25 years after the National Academy of Sciences (NAS), Biological Effects of Ionizing Radiation (BEIR) I Committee (1972) used Russell's dose-rate data to support the adoption of the linear-no-threshold (LNT) dose response model for genetic and cancer risk assessment, Russell acknowledged a significant under-reporting of the mutation rate of the historical control group. This error, which was unknown to BEIR I, had profound implications, leading it to incorrectly adopt the LNT model, which was a decision that profoundly changed the course of risk assessment for radiation and chemicals to the present. Copyright © 2016 Elsevier Inc. All rights reserved.

A method to quantify infectious airborne pathogens at concentrations below the threshold of quantification by culture

PubMed Central

Cutler, Timothy D.; Wang, Chong; Hoff, Steven J.; Zimmerman, Jeffrey J.

2013-01-01

In aerobiology, dose-response studies are used to estimate the risk of infection to a susceptible host presented by exposure to a specific dose of an airborne pathogen. In the research setting, host- and pathogen-specific factors that affect the dose-response continuum can be accounted for by experimental design, but the requirement to precisely determine the dose of infectious pathogen to which the host was exposed is often challenging. By definition, quantification of viable airborne pathogens is based on the culture of micro-organisms, but some airborne pathogens are transmissible at concentrations below the threshold of quantification by culture. In this paper we present an approach to the calculation of exposure dose at microbiologically unquantifiable levels using an application of the “continuous-stirred tank reactor (CSTR) model” and the validation of this approach using rhodamine B dye as a surrogate for aerosolized microbial pathogens in a dynamic aerosol toroid (DAT). PMID:24082399

QUEST+: A general multidimensional Bayesian adaptive psychometric method.

PubMed

Watson, Andrew B

2017-03-01

QUEST+ is a Bayesian adaptive psychometric testing method that allows an arbitrary number of stimulus dimensions, psychometric function parameters, and trial outcomes. It is a generalization and extension of the original QUEST procedure and incorporates many subsequent developments in the area of parametric adaptive testing. With a single procedure, it is possible to implement a wide variety of experimental designs, including conventional threshold measurement; measurement of psychometric function parameters, such as slope and lapse; estimation of the contrast sensitivity function; measurement of increment threshold functions; measurement of noise-masking functions; Thurstone scale estimation using pair comparisons; and categorical ratings on linear and circular stimulus dimensions. QUEST+ provides a general method to accelerate data collection in many areas of cognitive and perceptual science.

Method and apparatus for detection of catalyst failure on-board a motor vehicle using a dual oxygen sensor and an algorithm

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

Clemmens, W.B.; Koupal, J.W.; Sabourin, M.A.

1993-07-20

Apparatus is described for detecting motor vehicle exhaust gas catalytic converter deterioration comprising a first exhaust gas oxygen sensor adapted for communication with an exhaust stream before passage of the exhaust stream through a catalytic converter and a second exhaust gas oxygen sensor adapted for communication with the exhaust stream after passage of the exhaust stream through the catalytic converter, an on-board vehicle computational means, said computational means adapted to accept oxygen content signals from the before and after catalytic converter oxygen sensors and adapted to generate signal threshold values, said computational means adapted to compare over repeated time intervalsmore » the oxygen content signals to the signal threshold values and to store the output of the compared oxygen content signals, and in response after a specified number of time intervals for a specified mode of motor vehicle operation to determine and indicate a level of catalyst deterioration.« less

Threshold-adaptive canny operator based on cross-zero points

NASA Astrophysics Data System (ADS)

Liu, Boqi; Zhang, Xiuhua; Hong, Hanyu

2018-03-01

Canny edge detection[1] is a technique to extract useful structural information from different vision objects and dramatically reduce the amount of data to be processed. It has been widely applied in various computer vision systems. There are two thresholds have to be settled before the edge is segregated from background. Usually, by the experience of developers, two static values are set as the thresholds[2]. In this paper, a novel automatic thresholding method is proposed. The relation between the thresholds and Cross-zero Points is analyzed, and an interpolation function is deduced to determine the thresholds. Comprehensive experimental results demonstrate the effectiveness of proposed method and advantageous for stable edge detection at changing illumination.

Pretreatment of low dose radiation reduces radiation-induced apoptosis in mouse lymphoma (EL4) cells.

PubMed

Kim, J H; Hyun, S J; Yoon, M Y; Ji, Y H; Cho, C K; Yoo, S Y

1997-06-01

Induction of an adaptive response to ionizing radiation in mouse lymphoma (EL4) cells was studied by using cell survival fraction and apoptotic nucleosomal DNA fragmentation as biological end points. Cells in early log phase were pre-exposed to low dose of gamma-rays (0.01 Gy) 4 or 20 hrs prior to high dose gamma-ray (4, 8 and 12 Gy for cell survival fraction analysis; 8 Gy for DNA fragmentation analysis) irradiation. Then cell survival fractions and the extent of DNA fragmentation were measured. Significant adaptive response, increase in cell survival fraction and decrease in the extent of DNA fragmentation were induced when low and high dose gamma-ray irradiation time interval was 4 hr. Addition of protein or RNA synthesis inhibitor, cycloheximide or 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRFB), respectively during adaptation period, the period from low dose gamma-ray irradiation to high dose gamma-ray irradiation, was able to inhibit the induction of adaptive response, which is the reduction of the extent DNA fragmentation in irradiated EL4 cells. These data suggest that the induction of adaptive response to ionizing radiation in EL4 cells required both protein and RNA synthesis.

Adaptation and Sensitization to Proteotoxic Stress

PubMed Central

Leak, Rehana K.

2014-01-01

Although severe stress can elicit toxicity, mild stress often elicits adaptations. Here we review the literature on stress-induced adaptations versus stress sensitization in models of neurodegenerative diseases. We also describe our recent findings that chronic proteotoxic stress can elicit adaptations if the dose is low but that high-dose proteotoxic stress sensitizes cells to subsequent challenges. In these experiments, long-term, low-dose proteasome inhibition elicited protection in a superoxide dismutase-dependent manner. In contrast, acute, high-dose proteotoxic stress sensitized cells to subsequent proteotoxic challenges by eliciting catastrophic loss of glutathione. However, even in the latter model of synergistic toxicity, several defensive proteins were upregulated by severe proteotoxicity. This led us to wonder whether high-dose proteotoxic stress can elicit protection against subsequent challenges in astrocytes, a cell type well known for their resilience. In support of this new hypothesis, we found that the astrocytes that survived severe proteotoxicity became harder to kill. The adaptive mechanism was glutathione dependent. If these findings can be generalized to the human brain, similar endogenous adaptations may help explain why neurodegenerative diseases are so delayed in appearance and so slow to progress. In contrast, sensitization to severe stress may explain why defenses eventually collapse in vulnerable neurons. PMID:24659932

Assessment of the anticonvulsant potency of various benzylamide derivatives in the mouse maximal electroshock-induced seizure threshold model.

PubMed

Świąder, Mariusz J; Paruszewski, Ryszard; Łuszczki, Jarogniew J

2016-04-01

The aim of this study was to assess the anticonvulsant potency of 6 various benzylamide derivatives [i.e., nicotinic acid benzylamide (Nic-BZA), picolinic acid 2-fluoro-benzylamide (2F-Pic-BZA), picolinic acid benzylamide (Pic-BZA), (RS)-methyl-alanine-benzylamide (Me-Ala-BZA), isonicotinic acid benzylamide (Iso-Nic-BZA), and (R)-N-methyl-proline-benzylamide (Me-Pro-BZA)] in the threshold for maximal electroshock (MEST)-induced seizures in mice. Electroconvulsions (seizure activity) were produced in mice by means of a current (sine-wave, 50Hz, 500V, strength from 4 to 18mA, ear-clip electrodes, 0.2-s stimulus duration, tonic hindlimb extension taken as the endpoint). Nic-BZA, 2F-Pic-BZA, Pic-BZA, Me-Ala-BZA, Iso-Nic-BZA, and Me-Pro-BZA administered systemically (ip) in a dose-dependent manner increase the threshold for maximal electroconvulsions in mice. Linear regression analysis of Nic-BZA, 2F-Pic-BZA, Pic-BZA, MeAla-BZA, IsoNic-BZA, and Me-Pro-BZA doses and their corresponding threshold increases allowed determining threshold increasing doses by 20% (TID20 values) that elevate the threshold in drug-treated animals over the threshold in control animals. The experimentally derived TID20 values in the MEST test for Nic-BZA, 2F-Pic-BZA, Pic-BZA, Me-Ala-BZA, Iso-Nic-BZA, and Me-Pro-BZA were 7.45mg/kg, 7.72mg/kg, 8.74mg/kg, 15.11mg/kg, 21.95mg/kg and 28.06mg/kg, respectively. The studied benzylamide derivatives can be arranged with respect to their anticonvulsant potency in the MEST test as follows: Nic-BZA>2F-Pic-BZA>Pic-BZA>Me-Ala-BZA>Iso-Nic-BZA>Me-Pro-BZA. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

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.

Local noise reduction for emphysema scoring in low-dose CT images

NASA Astrophysics Data System (ADS)

Schilham, Arnold; Prokop, Mathias; Gietema, Hester; van Ginneken, Bram

2005-04-01

Computed Tomography (CT) has become the new reference standard for quantification of emphysema. The most popular measure for emphysema derived from CT is the Pixel Index (PI), which expresses the fraction of the lung volume with abnormally low intensity values. As PI is calculated from a single, fixed threshold on intensity, this measure is strongly influenced by noise. This effect shows up clearly when comparing the PI score for a high-dose scan to the PI score for a low-dose (i.e. noisy) scan of the same subject. This paper presents a class of noise filters that make use of a local noise estimate to specify the filtering strength: Local Noise Variance Weighted Averaging (LNVWA). The performance of the filter is assessed by comparing high-dose and low-dose PI scores for 11 subjects. LNVWA improves the reproducibility of high-dose PI scores: For an emphysema threshold of -910 HU, the root-mean-square difference in PI score drops from 10% of the lung volume to 3.3% of the lung volume if LNVWA is used.

Low-Dose N,N-Dimethylformamide Exposure and Liver Injuries in a Cohort of Chinese Leather Industry Workers.

PubMed

Qi, Cong; Gu, Yiyang; Sun, Qing; Gu, Hongliang; Xu, Bo; Gu, Qing; Xiao, Jing; Lian, Yulong

2017-05-01

We assessed the risk of liver injuries following low doses of N,N-dimethylformamide (DMF) below threshold limit values (20 mg/m) among leather industry workers and comparison groups. A cohort of 429 workers from a leather factory and 466 non-exposed subjects in China were followed for 4 years. Poisson regression and piece-wise linear regression were used to examine the relationship between DMF and liver injury. Workers exposed to a cumulative dose of DMF were significantly more likely than non-exposed workers to develop liver injury. A nonlinear relationship between DMF and liver injury was observed, and a threshold of the cumulative DMF dose for liver injury was 7.30 (mg/m) year. The findings indicate the importance of taking action to reduce DMF occupational exposure limits for promoting worker health.

Extended range radiation dose-rate monitor

DOEpatents

Valentine, Kenneth H.

1988-01-01

An extended range dose-rate monitor is provided which utilizes the pulse pileup phenomenon that occurs in conventional counting systems to alter the dynamic response of the system to extend the dose-rate counting range. The current pulses from a solid-state detector generated by radiation events are amplified and shaped prior to applying the pulses to the input of a comparator. The comparator generates one logic pulse for each input pulse which exceeds the comparator reference threshold. These pulses are integrated and applied to a meter calibrated to indicate the measured dose-rate in response to the integrator output. A portion of the output signal from the integrator is fed back to vary the comparator reference threshold in proportion to the output count rate to extend the sensitive dynamic detection range by delaying the asymptotic approach of the integrator output toward full scale as measured by the meter.

The impact of different algorithms for ideal body weight on screening for hydroxychloroquine retinopathy in women.

PubMed

Browning, David J; Lee, Chong; Rotberg, David

2014-01-01

To determine how algorithms for ideal body weight (IBW) affect hydroxychloroquine dosing in women. This was a retrospective study of 520 patients screened for hydroxychloroquine retinopathy. Charts were reviewed for sex, height, weight, and daily dose. The outcome measures were ranges of IBW across algorithms; rates of potentially toxic dosing; height thresholds below which 400 mg/d dosing is potentially toxic; and rates for which actual body weight (ABW) was less than IBW. Women made up 474 (91%) of the patients. The IBWs for a height varied from 30-34 pounds (13.6-15.5 kg) across algorithms. The threshold heights below which toxic dosing occurred varied from 62-70 inches (157.5-177.8 cm). Different algorithms placed 16%-98% of women in the toxic dosing range. The proportion for whom dosing should have been based on ABW rather than IBW ranged from 5%-31% across algorithms. Although hydroxychloroquine dosing should be based on the lesser of ABW and IBW, there is no consensus about the definition of IBW. The Michaelides algorithm is associated with the most frequent need to adjust dosing; the Metropolitan Life Insurance, large frame, mean value table with the least frequent need. No evidence indicates that one algorithm is superior to others.

Effects of striatal ΔFosB overexpression and ketamine on social defeat stress-induced anhedonia in mice.

PubMed

Donahue, Rachel J; Muschamp, John W; Russo, Scott J; Nestler, Eric J; Carlezon, William A

2014-10-01

Chronic social defeat stress (CSDS) produces persistent behavioral adaptations in mice. In many behavioral assays, it can be difficult to determine if these adaptations reflect core signs of depression. We designed studies to characterize the effects of CSDS on sensitivity to reward because anhedonia (reduced sensitivity to reward) is a defining characteristic of depressive disorders in humans. We also examined the effects of striatal ΔFosB overexpression and the N-methyl-D-aspartate receptor antagonist ketamine, both of which promote resilience, on CSDS-induced alterations in reward function and social interaction. Intracranial self-stimulation (ICSS) was used to quantify CSDS-induced changes in reward function. Mice were implanted with lateral hypothalamic electrodes, and ICSS thresholds were measured after each of 10 daily CSDS sessions and during a 5-day recovery period. We also examined if acute intraperitoneal administration of ketamine (2.5-20 mg/kg) reverses CSDS-induced effects on reward or, in separate mice, social interaction. ICSS thresholds were increased by CSDS, indicating decreases in the rewarding impact of lateral hypothalamic stimulation (anhedonia). This effect was attenuated in mice overexpressing ∆FosB in striatum, consistent with pro-resilient actions of this transcription factor. High, but not low, doses of ketamine administered after completion of the CSDS regimen attenuated social avoidance in defeated mice, although this effect was transient. Ketamine did not block CSDS-induced anhedonia in the ICSS test. This study found that CSDS triggers persistent anhedonia and confirms that ΔFosB overexpression produces stress resilience. The findings of this study also indicate that acute administration of ketamine fails to attenuate CSDS-induced anhedonia despite reducing other depression-related behavioral abnormalities. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Contrast adaptation induced by defocus - a possible error signal for emmetropization?

PubMed

Ohlendorf, Arne; Schaeffel, Frank

2009-01-01

To describe some features of contrast adaptation as induced by imposed positive or negative defocus. To study its time course and selectivity for the sign of the imposed defocus. Contrast adaptation, CA (here referred to as any change in supra-threshold contrast sensitivity) was induced by presenting a movie to the subjects on a computer screen at 1m distance for 10min, while the right eye was defocused by a trial lens (+4D (n=25); -4D (n=10); -2D (n=11 subjects). The PowerRefractor was used to track accommodation binocularly. Contrast sensitivity at threshold was measured by a method of adjustment with a Gabor patch of 1deg angular subtense, filled with 3.22cyc/deg sine wave grating presented on a computer screen at 1m distance on gray background (33cd/m(2)). Supra-threshold contrast sensitivity was quantified by an interocular contrast matching task, in which the subject had to match the contrast of the sine wave grating seen with the right eye with the contrast of a grating with fixed contrast of 0.1. (1) Contrast sensitivity thresholds were not lowered by previous viewing of defocused movies. (2) By wearing positive lenses, the supra-threshold contrast sensitivity in the right eye was raised by about 30% and remained elevated for at least 2min until baseline was reached after about 5min. (3) CA was induced only by positive, but not by negative lenses, even after the distance of the computer screen was taken into account (1m, equivalent to +1D). In five subjects, binocular accommodation was tracked over the full adaptation period. Accommodation appeared to focus the eye not wearing a lens, but short transient switches in focus to the lens wearing eye could not be entirely excluded. Transient contrast adaptation was found at 3.22cyc/deg when positive lenses were worn but not with negative lenses. This asymmetry is intriguing. While it may represent an epiphenomenon of physiological optics, further experiments are necessary to determine whether it could also trace back to differences in CA with defocus of different sign.

Ultra-low dose naltrexone enhances cannabinoid-induced antinociception.

PubMed

Paquette, Jay; Olmstead, Mary C; Olmstead, Mary

2005-12-01

Both opioids and cannabinoids have inhibitory effects at micromolar doses, which are mediated by activated receptors coupling to Gi/o-proteins. Surprisingly, the analgesic effects of opioids are enhanced by ultra-low doses (nanomolar to picomolar) of the opioid antagonist, naltrexone. As opioid and cannabinoid systems interact, this study investigated whether ultra-low dose naltrexone also influences cannabinoid-induced antinociception. Separate groups of Long-Evans rats were tested for antinociception following an injection of vehicle, a sub-maximal dose of the cannabinoid agonist WIN 55 212-2, naltrexone (an ultra-low or a high dose) or a combination of WIN 55 212-2 and naltrexone doses. Tail-flick latencies were recorded for 3 h, at 10-min intervals for the first hour, and at 15-min intervals thereafter. Ultra-low dose naltrexone elevated WIN 55 212-2-induced tail flick thresholds without extending its duration of action. This enhancement was replicated in animals receiving intraperitoneal or intravenous injections. A high dose of naltrexone had no effect on WIN 55 212-2-induced tail flick latencies, but a high dose of the cannabinoid 1 receptor antagonist SR 141716 blocked the elevated tail-flick thresholds produced by WIN 55 212-2+ultra-low dose naltrexone. These data suggest a mechanism of cannabinoid-opioid interaction whereby activated opioid receptors that couple to Gs-proteins may attenuate cannabinoid-induced antinociception and/or motor functioning.

Biological mechanisms of non-linear dose-response for respirable mineral fibers.

PubMed

Cox, Louis Anthony Tony

2018-06-19

Sufficiently high and prolonged inhalation exposures to some respirable elongated mineral particles (REMPs), notably including amphibole asbestos fibers, can increase risk of inflammation-mediated diseases including malignant mesothelioma, pleural diseases, fibrosis, and lung cancer. Chronic inflammation involves ongoing activation of the NLRP3 inflammasome, which enables immune cells to produce potent proinflammatory cytokines IL-1β and IL-18. Reactive oxygen species (ROS) (in particular, mitochondrial ROS) contribute to NRLP3 activation via a well-elucidated mechanism involving oxidation of reduced thioredoxin and association of thioredoxin-interacting protein with NLRP3. Lysosomal destabilization, efflux of cytosolic potassium ions and influx of calcium ions, signals from damaged mitochondria, both translational and post-translational controls, and prion-like polymerization have increasingly clear roles in regulating NLRP3 activation. As the molecular biology of inflammation-mediated responses to REMP exposure becomes clearer, a practical question looms: What do these mechanisms imply for the shape of the dose-response function relating exposure concentrations and durations for EMPs to risk of pathological responses? Dose-response thresholds or threshold-like nonlinearities can arise from (a) Cooperativity in assembly of supramolecular signaling complexes; (b) Positive feedback loops and bistability in regulatory networks; (c) Overwhelming of defensive barriers maintaining homeostasis; and (d) Damage thresholds, as in lysosome destabilization-induced activation of NLRP3. Each of these mechanisms holds for NLRP3 activation in response to stimuli such as REMP exposures. It is therefore timely to consider the implications of these advances in biological understanding for human health risk assessment with dose-response thresholds. Copyright © 2018. Published by Elsevier Inc.

Functional liver image guided hepatic therapy (FLIGHT) with hepatobiliary iminodiacetic acid (HIDA) scans.

PubMed

Long, David E; Tann, Mark; Huang, Ke Colin; Bartlett, Gregory; Galle, James O; Furukawa, Yukie; Maluccio, Mary; Cox, John A; Kong, Feng-Ming Spring; Ellsworth, Susannah G

2018-05-01

Hepatobiliary iminodiacetic acid (HIDA) scans provide global and regional assessments of liver function that can serve as a road map for functional avoidance in stereotactic body radiation therapy (SBRT) planning. Functional liver image guided hepatic therapy (FLIGHT), an innovative planning technique, is described and compared with standard planning using functional dose-volume histograms. Thresholds predicting for decompensation during follow up are evaluated. We studied 17 patients who underwent HIDA scans before SBRT. All SBRT cases were replanned using FLIGHT. The following dosimetric endpoints were compared for FLIGHT versus standard SBRT planning: functional residual capacity <15 Gy (FRC 15 HIDA), mean liver dose (MLD), equivalent uniform dose (EUD), and functional EUD (FEUD). Receiver operating characteristics curves were used to evaluate whether baseline HIDA values, standard cirrhosis scoring, and/or dosimetric data predicted clinical decompensation. Compared with standard planning, FLIGHT significantly improved FRC 15 HIDA (mean improvement: 5.3%) as well as MLD, EUD, and FEUD (P < .05). Considerable interindividual variations in the extent of benefit were noted. Decompensation during follow-up was associated with baseline global HIDA <2.915%/min/m 2 , FRC 15 HIDA <2.11%/min/m 2 , and MELD ≥11 (P < .05). FLIGHT with HIDA-based parameters may complement blood chemistry-based assessments of liver function and facilitate individualized, adaptive liver SBRT planning. Copyright © 2018. Published by Elsevier Inc.

Passive activity observation (PAO) method to estimate outdoor thermal adaptation in public space: case studies in Australian cities.

PubMed

Sharifi, Ehsan; Boland, John

2018-06-18

Outdoor thermal comfort is influenced by people's climate expectations, perceptions and adaptation capacity. Varied individual response to comfortable or stressful thermal environments results in a deviation between actual outdoor thermal activity choices and those predicted by thermal comfort indices. This paper presents a passive activity observation (PAO) method for estimating contextual limits of outdoor thermal adaptation. The PAO method determines which thermal environment result in statistically meaningful changes may occur in outdoor activity patterns, and it estimates thresholds of outdoor thermal neutrality and limits of thermal adaptation in public space based on activity observation and microclimate field measurement. Applications of the PAO method have been demonstrated in Adelaide, Melbourne and Sydney, where outdoor activities were analysed against outdoor thermal comfort indices between 2013 and 2014. Adjusted apparent temperature (aAT), adaptive predicted mean vote (aPMV), outdoor standard effective temperature (OUT_SET), physiological equivalent temperature (PET) and universal thermal comfort index (UTCI) are calculated from the PAO data. Using the PAO method, the high threshold of outdoor thermal neutrality was observed between 24 °C for optional activities and 34 °C for necessary activities (UTCI scale). Meanwhile, the ultimate limit of thermal adaptation in uncontrolled public spaces is estimated to be between 28 °C for social activities and 48 °C for necessary activities. Normalised results indicate that city-wide high thresholds for outdoor thermal neutrality vary from 25 °C in Melbourne to 26 °C in Sydney and 30 °C in Adelaide. The PAO method is a relatively fast and localised method for measuring limits of outdoor thermal adaptation and effectively informs urban design and policy making in the context of climate change.

In-vivo singlet oxygen threshold doses for PDT

PubMed Central

Zhu, Timothy C.; Kim, Michele M.; Liang, Xing; Finlay, Jarod C.; Busch, Theresa M.

2015-01-01

Objective Dosimetry of singlet oxygen (1O2) is of particular interest because it is the major cytotoxic agent causing biological effects for type-II photosensitizers during photodynamic therapy (PDT). An in-vivo model to determine the singlet oxygen threshold dose, [1O2]rx,sh, for PDT was developed. Material and methods An in-vivo radiation-induced fibrosarcoma (RIF) tumor mouse model was used to correlate the radius of necrosis to the calculation based on explicit PDT dosimetry of light fluence distribution, tissue optical properties, and photosensitizer concentrations. Inputs to the model include five photosensitizer-specific photochemical parameters along with [1O2]rx,sh. Photosensitizer-specific model parameters were determined for benzoporphyrin derivative monoacid ring A (BPD) and compared with two other type-II photosensitizers, Photofrin® and m-tetrahydroxyphenylchlorin (mTHPC) from the literature. Results The mean values (standard deviation) of the in-vivo [1O2]rx,sh are approximately 0.56 (0.26) and 0.72 (0.21) mM (or 3.6×107 and 4.6×107 singlet oxygen per cell to reduce the cell survival to 1/e) for Photofrin® and BPD, respectively, assuming that the fraction of generated singlet oxygen that interacts with the cell is 1. While the values for the photochemical parameters (ξ, σ, g, β) used for BPD were preliminary and may need further refinement, there is reasonable confidence for the values of the singlet oxygen threshold doses. Discussion In comparison, the [1O2]rx,sh value derived from in-vivo mouse study was reported to be 0.4 mM for mTHPC-PDT. However, the singlet oxygen required per cell is reported to be 9×108 per cell per 1/e fractional kill in an in-vitro mTHPC-PDT study on a rat prostate cancer cell line (MLL cells) and is reported to be 7.9 mM for a multicell in-vitro EMT6/Ro spheroid model for mTHPC-PDT. A theoretical analysis is provided to relate the number of in-vitro singlet oxygen required per cell to reach cell killing of 1/e to in-vivo singlet oxygen threshold dose (in mM). The sensitivity of threshold singlet oxygen dose for our experiment is examined. The possible influence of vascular vs. apoptotic cell killing mechanisms on the singlet oxygen threshold dose is discussed by comparing [1O2]rx,sh for BPD with 3 hr and 15 min drug-light-intervals, with the later being known to have a dominantly vascular effect. Conclusions The experimental results of threshold singlet oxygen concentration in an in-vivo RIF tumor model for Photofrin®, BPD, and mTHPC are about 20 times smaller than those observed in vitro. These results are consistent with knowledge that factors other than singlet oxygen-mediated tumor cell killing can contribute to PDT damage in-vivo. PMID:25927018

In-vivo singlet oxygen threshold doses for PDT.

PubMed

Zhu, Timothy C; Kim, Michele M; Liang, Xing; Finlay, Jarod C; Busch, Theresa M

2015-02-01

Dosimetry of singlet oxygen ( 1 O 2 ) is of particular interest because it is the major cytotoxic agent causing biological effects for type-II photosensitizers during photodynamic therapy (PDT). An in-vivo model to determine the singlet oxygen threshold dose, [ 1 O 2 ] rx,sh , for PDT was developed. An in-vivo radiation-induced fibrosarcoma (RIF) tumor mouse model was used to correlate the radius of necrosis to the calculation based on explicit PDT dosimetry of light fluence distribution, tissue optical properties, and photosensitizer concentrations. Inputs to the model include five photosensitizer-specific photochemical parameters along with [ 1 O 2 ] rx,sh . Photosensitizer-specific model parameters were determined for benzoporphyrin derivative monoacid ring A (BPD) and compared with two other type-II photosensitizers, Photofrin ® and m-tetrahydroxyphenylchlorin (mTHPC) from the literature. The mean values (standard deviation) of the in-vivo [ 1 O 2 ] rx,sh are approximately 0.56 (0.26) and 0.72 (0.21) mM (or 3.6×10 7 and 4.6×10 7 singlet oxygen per cell to reduce the cell survival to 1/e) for Photofrin ® and BPD, respectively, assuming that the fraction of generated singlet oxygen that interacts with the cell is 1. While the values for the photochemical parameters (ξ, σ, g , β) used for BPD were preliminary and may need further refinement, there is reasonable confidence for the values of the singlet oxygen threshold doses. In comparison, the [ 1 O 2 ] rx,sh value derived from in-vivo mouse study was reported to be 0.4 mM for mTHPC-PDT. However, the singlet oxygen required per cell is reported to be 9×10 8 per cell per 1/ e fractional kill in an in-vitro mTHPC-PDT study on a rat prostate cancer cell line (MLL cells) and is reported to be 7.9 mM for a multicell in-vitro EMT6/Ro spheroid model for mTHPC-PDT. A theoretical analysis is provided to relate the number of in-vitro singlet oxygen required per cell to reach cell killing of 1/ e to in-vivo singlet oxygen threshold dose (in mM). The sensitivity of threshold singlet oxygen dose for our experiment is examined. The possible influence of vascular vs. apoptotic cell killing mechanisms on the singlet oxygen threshold dose is discussed by comparing [ 1 O 2 ] rx,sh for BPD with 3 hr and 15 min drug-light-intervals, with the later being known to have a dominantly vascular effect. The experimental results of threshold singlet oxygen concentration in an in-vivo RIF tumor model for Photofrin ® , BPD, and mTHPC are about 20 times smaller than those observed in vitro . These results are consistent with knowledge that factors other than singlet oxygen-mediated tumor cell killing can contribute to PDT damage in-vivo .

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

Fukada, Junichi, E-mail: fukada@rad.med.keio.ac.jp; Shigematsu, Naoyuki; Takeuchi, Hiroya

Purpose: We investigated clinical and treatment-related factors as predictors of symptomatic pericardial effusion in esophageal cancer patients after concurrent chemoradiation therapy. Methods and Materials: We reviewed 214 consecutive primary esophageal cancer patients treated with concurrent chemoradiation therapy between 2001 and 2010 in our institute. Pericardial effusion was detected on follow-up computed tomography. Symptomatic effusion was defined as effusion ≥grade 3 according to Common Terminology Criteria for Adverse Events v4.0 criteria. Percent volume irradiated with 5 to 65 Gy (V5-V65) and mean dose to the pericardium were evaluated employing dose-volume histograms. To evaluate dosimetry for patients treated with two-dimensional planning inmore » the earlier period (2001-2005), computed tomography data at diagnosis were transferred to a treatment planning system to reconstruct three-dimensional plans without modification. Optimal dosimetric thresholds for symptomatic pericardial effusion were calculated by receiver operating characteristic curves. Associating clinical and treatment-related risk factors for symptomatic pericardial effusion were detected by univariate and multivariate analyses. Results: The median follow-up was 29 (range, 6-121) months for eligible 167 patients. Symptomatic pericardial effusion was observed in 14 (8.4%) patients. Dosimetric analyses revealed average values of V30 to V45 for the pericardium and mean pericardial doses were significantly higher in patients with symptomatic pericardial effusion than in those with asymptomatic pericardial effusion (P<.05). Pericardial V5 to V55 and mean pericardial doses were significantly higher in patients with symptomatic pericardial effusion than in those without pericardial effusion (P<.001). Mean pericardial doses of 36.5 Gy and V45 of 58% were selected as optimal cutoff values for predicting symptomatic pericardial effusion. Multivariate analysis identified mean pericardial dose as the strongest risk factor for symptomatic pericardial effusion. Conclusions: Dose-volume thresholds for the pericardium facilitate predicting symptomatic pericardial effusion. Mean pericardial dose was selected based not only on the optimal dose-volume threshold but also on the most significant risk factor for symptomatic pericardial effusion.« less

High-intensity corneal collagen crosslinking with riboflavin and UVA in rat cornea.

PubMed

Zhu, Yirui; Reinach, Peter S; Zhu, Hanlei; Tan, Qiufan; Zheng, Qinxiang; Qu, Jia; Chen, Wei

2017-01-01

Corneal collagen cross-linking (CXL) halts human corneal ectasias progression by increasing stromal mechanical stiffness. Although some reports describe that this procedure is effective in dealing with some infectious and immunologic corneal thinning diseases, there is a need for more animal models whose corneal thickness more closely resemble those occurring in these patients. To meet this need, we describe here high-intensity protocols that are safe and effective for obtaining CXL in rat corneas. Initially, a range of potentially effective UVA doses were evaluated based on their effectiveness in increasing tissue enzymatic resistance to dissolution. At UVA doses higher than a threshold level of 0.54 J/cm2, resistance to enzymatic digestion increased relative to that in non-irradiated corneas. Based on the theoretical threshold CXL dose, a CXL regimen was established in which the UVA tissue irradiance was 9 mW/cm2, which was delivered at doses of either 2.16, 2.7 or 3.24 J/cm2. Their dose dependent effects were evaluated on ocular surface morphological integrity, keratocyte apoptotic frequency, tissue thickness and endothelial cell layer density. Doses of 2.16 and 2.7 J/cm2 transiently decreased normal corneal transparency and increased thickness. These effects were fully reversed after 14 days. In contrast, 3.24 J/cm2 had more irreversible side effects. Three days after treatment, apoptotic frequency in the CXL-2.16 group was lower than that at higher doses. Endothelial cell losses remained evident only in the CXL-3.24 group at 42 days posttreatment. Stromal fiber thickening was evident in all the CXL-treated groups. We determined both the threshold UVA dose using the high-intensity CXL procedure and identified an effective dose range that provides optimal CXL with minimal transient side effects in the rat cornea. These results may help to provide insight into how to improve the CXL outcome in patients afflicted with a severe corneal thinning disease.

Symptomatic pericardial effusion after chemoradiation therapy in esophageal cancer patients.

PubMed

Fukada, Junichi; Shigematsu, Naoyuki; Takeuchi, Hiroya; Ohashi, Toshio; Saikawa, Yoshiro; Takaishi, Hiromasa; Hanada, Takashi; Shiraishi, Yutaka; Kitagawa, Yuko; Fukuda, Keiichi

2013-11-01

We investigated clinical and treatment-related factors as predictors of symptomatic pericardial effusion in esophageal cancer patients after concurrent chemoradiation therapy. We reviewed 214 consecutive primary esophageal cancer patients treated with concurrent chemoradiation therapy between 2001 and 2010 in our institute. Pericardial effusion was detected on follow-up computed tomography. Symptomatic effusion was defined as effusion ≥grade 3 according to Common Terminology Criteria for Adverse Events v4.0 criteria. Percent volume irradiated with 5 to 65 Gy (V5-V65) and mean dose to the pericardium were evaluated employing dose-volume histograms. To evaluate dosimetry for patients treated with two-dimensional planning in the earlier period (2001-2005), computed tomography data at diagnosis were transferred to a treatment planning system to reconstruct three-dimensional plans without modification. Optimal dosimetric thresholds for symptomatic pericardial effusion were calculated by receiver operating characteristic curves. Associating clinical and treatment-related risk factors for symptomatic pericardial effusion were detected by univariate and multivariate analyses. The median follow-up was 29 (range, 6-121) months for eligible 167 patients. Symptomatic pericardial effusion was observed in 14 (8.4%) patients. Dosimetric analyses revealed average values of V30 to V45 for the pericardium and mean pericardial doses were significantly higher in patients with symptomatic pericardial effusion than in those with asymptomatic pericardial effusion (P<.05). Pericardial V5 to V55 and mean pericardial doses were significantly higher in patients with symptomatic pericardial effusion than in those without pericardial effusion (P<.001). Mean pericardial doses of 36.5 Gy and V45 of 58% were selected as optimal cutoff values for predicting symptomatic pericardial effusion. Multivariate analysis identified mean pericardial dose as the strongest risk factor for symptomatic pericardial effusion. Dose-volume thresholds for the pericardium facilitate predicting symptomatic pericardial effusion. Mean pericardial dose was selected based not only on the optimal dose-volume threshold but also on the most significant risk factor for symptomatic pericardial effusion. Copyright © 2013 Elsevier Inc. All rights reserved.

A STATISTICAL MODELING METHODOLOGY FOR THE DETECTION, QUANTIFICATION, AND PREDICTION OF ECOLOGICAL THRESHOLDS

EPA Science Inventory

This study will provide a general methodology for integrating threshold information from multiple species ecological metrics, allow for prediction of changes of alternative stable states, and provide a risk assessment tool that can be applied to adaptive management. The integr...

Incorporating adaptive responses into future projections of coral bleaching.

PubMed

Logan, Cheryl A; Dunne, John P; Eakin, C Mark; Donner, Simon D

2014-01-01

Climate warming threatens to increase mass coral bleaching events, and several studies have projected the demise of tropical coral reefs this century. However, recent evidence indicates corals may be able to respond to thermal stress though adaptive processes (e.g., genetic adaptation, acclimatization, and symbiont shuffling). How these mechanisms might influence warming-induced bleaching remains largely unknown. This study compared how different adaptive processes could affect coral bleaching projections. We used the latest bias-corrected global sea surface temperature (SST) output from the NOAA/GFDL Earth System Model 2 (ESM2M) for the preindustrial period through 2100 to project coral bleaching trajectories. Initial results showed that, in the absence of adaptive processes, application of a preindustrial climatology to the NOAA Coral Reef Watch bleaching prediction method overpredicts the present-day bleaching frequency. This suggests that corals may have already responded adaptively to some warming over the industrial period. We then modified the prediction method so that the bleaching threshold either permanently increased in response to thermal history (e.g., simulating directional genetic selection) or temporarily increased for 2-10 years in response to a bleaching event (e.g., simulating symbiont shuffling). A bleaching threshold that changes relative to the preceding 60 years of thermal history reduced the frequency of mass bleaching events by 20-80% compared with the 'no adaptive response' prediction model by 2100, depending on the emissions scenario. When both types of adaptive responses were applied, up to 14% more reef cells avoided high-frequency bleaching by 2100. However, temporary increases in bleaching thresholds alone only delayed the occurrence of high-frequency bleaching by ca. 10 years in all but the lowest emissions scenario. Future research should test the rate and limit of different adaptive responses for coral species across latitudes and ocean basins to determine if and how much corals can respond to increasing thermal stress.

Deep reinforcement learning for automated radiation adaptation in lung cancer.

PubMed

Tseng, Huan-Hsin; Luo, Yi; Cui, Sunan; Chien, Jen-Tzung; Ten Haken, Randall K; Naqa, Issam El

2017-12-01

To investigate deep reinforcement learning (DRL) based on historical treatment plans for developing automated radiation adaptation protocols for nonsmall cell lung cancer (NSCLC) patients that aim to maximize tumor local control at reduced rates of radiation pneumonitis grade 2 (RP2). In a retrospective population of 114 NSCLC patients who received radiotherapy, a three-component neural networks framework was developed for deep reinforcement learning (DRL) of dose fractionation adaptation. Large-scale patient characteristics included clinical, genetic, and imaging radiomics features in addition to tumor and lung dosimetric variables. First, a generative adversarial network (GAN) was employed to learn patient population characteristics necessary for DRL training from a relatively limited sample size. Second, a radiotherapy artificial environment (RAE) was reconstructed by a deep neural network (DNN) utilizing both original and synthetic data (by GAN) to estimate the transition probabilities for adaptation of personalized radiotherapy patients' treatment courses. Third, a deep Q-network (DQN) was applied to the RAE for choosing the optimal dose in a response-adapted treatment setting. This multicomponent reinforcement learning approach was benchmarked against real clinical decisions that were applied in an adaptive dose escalation clinical protocol. In which, 34 patients were treated based on avid PET signal in the tumor and constrained by a 17.2% normal tissue complication probability (NTCP) limit for RP2. The uncomplicated cure probability (P+) was used as a baseline reward function in the DRL. Taking our adaptive dose escalation protocol as a blueprint for the proposed DRL (GAN + RAE + DQN) architecture, we obtained an automated dose adaptation estimate for use at ∼2/3 of the way into the radiotherapy treatment course. By letting the DQN component freely control the estimated adaptive dose per fraction (ranging from 1-5 Gy), the DRL automatically favored dose escalation/de-escalation between 1.5 and 3.8 Gy, a range similar to that used in the clinical protocol. The same DQN yielded two patterns of dose escalation for the 34 test patients, but with different reward variants. First, using the baseline P+ reward function, individual adaptive fraction doses of the DQN had similar tendencies to the clinical data with an RMSE = 0.76 Gy; but adaptations suggested by the DQN were generally lower in magnitude (less aggressive). Second, by adjusting the P+ reward function with higher emphasis on mitigating local failure, better matching of doses between the DQN and the clinical protocol was achieved with an RMSE = 0.5 Gy. Moreover, the decisions selected by the DQN seemed to have better concordance with patients eventual outcomes. In comparison, the traditional temporal difference (TD) algorithm for reinforcement learning yielded an RMSE = 3.3 Gy due to numerical instabilities and lack of sufficient learning. We demonstrated that automated dose adaptation by DRL is a feasible and a promising approach for achieving similar results to those chosen by clinicians. The process may require customization of the reward function if individual cases were to be considered. However, development of this framework into a fully credible autonomous system for clinical decision support would require further validation on larger multi-institutional datasets. © 2017 American Association of Physicists in Medicine.

A heuristic model of stone comminution in shock wave lithotripsy

PubMed Central

Smith, Nathan B.; Zhong, Pei

2013-01-01

A heuristic model is presented to describe the overall progression of stone comminution in shock wave lithotripsy (SWL), accounting for the effects of shock wave dose and the average peak pressure, P+(avg), incident on the stone during the treatment. The model is developed through adaptation of the Weibull theory for brittle fracture, incorporating threshold values in dose and P+(avg) that are required to initiate fragmentation. The model is validated against experimental data of stone comminution from two stone types (hard and soft BegoStone) obtained at various positions in lithotripter fields produced by two shock wave sources of different beam width and pulse profile both in water and in 1,3-butanediol (which suppresses cavitation). Subsequently, the model is used to assess the performance of a newly developed acoustic lens for electromagnetic lithotripters in comparison with its original counterpart both under static and simulated respiratory motion. The results have demonstrated the predictive value of this heuristic model in elucidating the physical basis for improved performance of the new lens. The model also provides a rationale for the selection of SWL treatment protocols to achieve effective stone comminution without elevating the risk of tissue injury. PMID:23927195

TU-AB-303-12: Towards Inter and Intra Fraction Plan Adaptation for the MR-Linac

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

Kontaxis, C; Bol, G; Lagendijk, J

Purpose: To develop a new sequencer for IMRT that during treatment can account for anatomy changes provided by online and real-time MRI. This sequencer employs a novel inter and intra fraction scheme that converges to the prescribed dose without a final segment weight optimization (SWO) and enables immediate optimization and delivery of radiation adapted to the deformed anatomy. Methods: The sequencer is initially supplied with a voxel-based dose prescription and during the optimization iteratively generates segments that provide this prescribed dose. Every iteration selects the best segment for the current anatomy state, calculates the dose it will deliver, warps itmore » back to the reference prescription grid and subtracts it from the remaining prescribed dose. This process continues until a certain percentage of dose or a number of segments has been delivered. The anatomy changes that occur during treatment require that convergence is achieved without a final SWO. This is resolved by adding the difference between the prescribed and delivered dose up to this fraction to the prescription of the subsequent fraction. This process is repeated for all fractions of the treatment. Results: Two breast cases were selected to stress test the pipeline by producing artificial inter and intra fraction anatomy deformations using a combination of incrementally applied rigid transformations. The dose convergence of the adaptive scheme over the entire treatment, relative to the prescribed dose, was on average 8.6% higher than the static plans delivered to the respective deformed anatomies and only 1.6% less than the static segment weighted plans on the static anatomy. Conclusion: This new adaptive sequencing strategy enables dose convergence without the need of SWO while adapting the plan to intermediate anatomies, which is a prerequisite for online plan adaptation. We are now testing our pipeline on prostate cases using clinical anatomy deformation data from our department. This work is financially supported by Elekta AB, Stockholm, Sweden.« less

Method of Improved Fuzzy Contrast Combined Adaptive Threshold in NSCT for Medical Image Enhancement

PubMed Central

Yang, Jie; Kasabov, Nikola

2017-01-01

Noises and artifacts are introduced to medical images due to acquisition techniques and systems. This interference leads to low contrast and distortion in images, which not only impacts the effectiveness of the medical image but also seriously affects the clinical diagnoses. This paper proposes an algorithm for medical image enhancement based on the nonsubsampled contourlet transform (NSCT), which combines adaptive threshold and an improved fuzzy set. First, the original image is decomposed into the NSCT domain with a low-frequency subband and several high-frequency subbands. Then, a linear transformation is adopted for the coefficients of the low-frequency component. An adaptive threshold method is used for the removal of high-frequency image noise. Finally, the improved fuzzy set is used to enhance the global contrast and the Laplace operator is used to enhance the details of the medical images. Experiments and simulation results show that the proposed method is superior to existing methods of image noise removal, improves the contrast of the image significantly, and obtains a better visual effect. PMID:28744464

Free testosterone as marker of adaptation to medium-intensive exercise.

PubMed

Shkurnikov, M U; Donnikov, A E; Akimov, E B; Sakharov, D A; Tonevitsky, A G

2008-09-01

A 4-week study of adaptation reserves of the body was carried out during medium intensive exercise (medium intensive training: 60-80% threshold anaerobic metabolism). Two groups of athletes were singled out by the results of pulsometry analysis: with less than 20% work duration at the level above the 80% threshold anaerobic metabolism and with more than 20% work duration at the level above 80% threshold anaerobic metabolism. No appreciable differences between the concentrations of total testosterone, growth hormone, and cortisol before and after exercise in the groups with different percentage of anaerobic work duration were detected. In group 1 the concentrations of free testosterone did not change throughout the period of observation in comparison with the levels before training. In group 2, the level of free testosterone increased in comparison with the basal level: from 0.61+/-0.12 nmol/liter at the end of week 1 to 0.98+/-0.11 nmol/liter at the end of week 4 (p<0.01). The results indicate that the level of free testosterone can be used for evaluating the degree of athlete's adaptation to medium intensive exercise.

Advanced p-MOSFET Ionizing-Radiation Dosimeter

NASA Technical Reports Server (NTRS)

Buehler, Martin G.; Blaes, Brent R.

1994-01-01

Circuit measures total dose of ionizing radiation in terms of shift in threshold gate voltage of doped-channel metal oxide/semiconductor field-effect transistor (p-MOSFET). Drain current set at temperature-independent point to increase accuracy in determination of radiation dose.

T Cell Activation Thresholds are Affected by Gravitational

NASA Technical Reports Server (NTRS)

Adams, Charley; Gonzalez, M.; Nelman-Gonzalez, M.

1999-01-01

T cells stimulated in space flight by various mitogenic signals show a dramatic reduction in proliferation and expression of early activation markers. Similar results are also obtained in a ground based model of microgravity, clinorotation, which provides a vector-averaged reduction of the apparent gravity on cells without significant shear force. Here we demonstrate that T cell inhibition is due to an increase in the required threshold for activation. Dose response curves indicate that cells activated during clinorotation require higher stimulation to achieve the same level of activation, as measured by CD69 expression. Interleukin 2 receptor expression, and DNA synthesis. The amount of stimulation necessary for 50% activation is 5 fold in the clinostat relative to static. Correlation of TCR internalization with activation also exhibit a dramatic right shift in clinorotation, demonstrating unequivocally that signal transduction mechanism independent of TCR triggering account for the increased activation threshold. Previous results from space flight experiments are consistent with the dose response curves obtained for clinorotation. Activation thresholds are important aspects of T cell memory, autoimmunity and tolerance Clinorotation is a useful, noninvasive tool for the study of cellular and biochemical event regulating T cell activation threshold and the effects of gravitation forces on these systems.

Biological PET-guided adaptive radiotherapy for dose escalation in head and neck cancer: a systematic review.

PubMed

Hamming-Vrieze, Olga; Navran, Arash; Al-Mamgani, Abrahim; Vogel, Wouter V

2018-06-04

In recent years, the possibility of adapting radiotherapy to changes in biological tissue parameters has emerged. It is hypothesized that early identification of radio-resistant parts of the tumor during treatment provides the possibility to adjust the radiotherapy plan to improve outcome. The aim of this systematic literature review was to evaluate the current state of the art of biological PET-guided adaptive radiotherapy, focusing on dose escalation to radio-resistant tumor. A structured literature search was done to select clinical trials including patients with head and neck cancer of the oral cavity, oropharynx, hypopharynx or larynx, with a PET performed during treatment used to develop biological adaptive radiotherapy by i) delineation of sub-volumes suitable for adaptive re-planning, ii) in silico adaptive treatment planning or iii) treatment of patients with PET based dose escalated adaptive radiotherapy. Nineteen articles were selected, 12 articles analyzing molecular imaging signal during treatment and 7 articles focused on biological adaptive treatment planning, of which two were clinical trials. Studied biological pathways include metabolism (FDG), hypoxia (MISO, FAZA and HX4) and proliferation (FLT). In the development of biological dose adaptation in radiotherapy for head-neck tumors, many aspects of the procedure remain ambiguous. Patient selection, tracer selection for detection of the radio-resistant sub-volumes, timing of adaptive radiotherapy, workflow and treatment planning aspects are discussed in a clinical context.

An automated, quantitative, and case-specific evaluation of deformable image registration in computed tomography images

NASA Astrophysics Data System (ADS)

Kierkels, R. G. J.; den Otter, L. A.; Korevaar, E. W.; Langendijk, J. A.; van der Schaaf, A.; Knopf, A. C.; Sijtsema, N. M.

2018-02-01

A prerequisite for adaptive dose-tracking in radiotherapy is the assessment of the deformable image registration (DIR) quality. In this work, various metrics that quantify DIR uncertainties are investigated using realistic deformation fields of 26 head and neck and 12 lung cancer patients. Metrics related to the physiologically feasibility (the Jacobian determinant, harmonic energy (HE), and octahedral shear strain (OSS)) and numerically robustness of the deformation (the inverse consistency error (ICE), transitivity error (TE), and distance discordance metric (DDM)) were investigated. The deformable registrations were performed using a B-spline transformation model. The DIR error metrics were log-transformed and correlated (Pearson) against the log-transformed ground-truth error on a voxel level. Correlations of r  ⩾  0.5 were found for the DDM and HE. Given a DIR tolerance threshold of 2.0 mm and a negative predictive value of 0.90, the DDM and HE thresholds were 0.49 mm and 0.014, respectively. In conclusion, the log-transformed DDM and HE can be used to identify voxels at risk for large DIR errors with a large negative predictive value. The HE and/or DDM can therefore be used to perform automated quality assurance of each CT-based DIR for head and neck and lung cancer patients.

Is the sky the limit? On the expansion threshold of a species' range.

PubMed

Polechová, Jitka

2018-06-15

More than 100 years after Grigg's influential analysis of species' borders, the causes of limits to species' ranges still represent a puzzle that has never been understood with clarity. The topic has become especially important recently as many scientists have become interested in the potential for species' ranges to shift in response to climate change-and yet nearly all of those studies fail to recognise or incorporate evolutionary genetics in a way that relates to theoretical developments. I show that range margins can be understood based on just two measurable parameters: (i) the fitness cost of dispersal-a measure of environmental heterogeneity-and (ii) the strength of genetic drift, which reduces genetic diversity. Together, these two parameters define an 'expansion threshold': adaptation fails when genetic drift reduces genetic diversity below that required for adaptation to a heterogeneous environment. When the key parameters drop below this expansion threshold locally, a sharp range margin forms. When they drop below this threshold throughout the species' range, adaptation collapses everywhere, resulting in either extinction or formation of a fragmented metapopulation. Because the effects of dispersal differ fundamentally with dimension, the second parameter-the strength of genetic drift-is qualitatively different compared to a linear habitat. In two-dimensional habitats, genetic drift becomes effectively independent of selection. It decreases with 'neighbourhood size'-the number of individuals accessible by dispersal within one generation. Moreover, in contrast to earlier predictions, which neglected evolution of genetic variance and/or stochasticity in two dimensions, dispersal into small marginal populations aids adaptation. This is because the reduction of both genetic and demographic stochasticity has a stronger effect than the cost of dispersal through increased maladaptation. The expansion threshold thus provides a novel, theoretically justified, and testable prediction for formation of the range margin and collapse of the species' range.

Six weeks of a polarized training-intensity distribution leads to greater physiological and performance adaptations than a threshold model in trained cyclists.

PubMed

Neal, Craig M; Hunter, Angus M; Brennan, Lorraine; O'Sullivan, Aifric; Hamilton, D Lee; De Vito, Giuseppe; Galloway, Stuart D R

2013-02-15

This study was undertaken to investigate physiological adaptation with two endurance-training periods differing in intensity distribution. In a randomized crossover fashion, separated by 4 wk of detraining, 12 male cyclists completed two 6-wk training periods: 1) a polarized model [6.4 (±1.4 SD) h/wk; 80%, 0%, and 20% of training time in low-, moderate-, and high-intensity zones, respectively]; and 2) a threshold model [7.5 (±2.0 SD) h/wk; 57%, 43%, and 0% training-intensity distribution]. Before and after each training period, following 2 days of diet and exercise control, fasted skeletal muscle biopsies were obtained for mitochondrial enzyme activity and monocarboxylate transporter (MCT) 1 and 4 expression, and morning first-void urine samples were collected for NMR spectroscopy-based metabolomics analysis. Endurance performance (40-km time trial), incremental exercise, peak power output (PPO), and high-intensity exercise capacity (95% maximal work rate to exhaustion) were also assessed. Endurance performance, PPOs, lactate threshold (LT), MCT4, and high-intensity exercise capacity all increased over both training periods. Improvements were greater following polarized rather than threshold for PPO [mean (±SE) change of 8 (±2)% vs. 3 (±1)%, P < 0.05], LT [9 (±3)% vs. 2 (±4)%, P < 0.05], and high-intensity exercise capacity [85 (±14)% vs. 37 (±14)%, P < 0.05]. No changes in mitochondrial enzyme activities or MCT1 were observed following training. A significant multilevel, partial least squares-discriminant analysis model was obtained for the threshold model but not the polarized model in the metabolomics analysis. A polarized training distribution results in greater systemic adaptation over 6 wk in already well-trained cyclists. Markers of muscle metabolic adaptation are largely unchanged, but metabolomics markers suggest different cellular metabolic stress that requires further investigation.

[Effects of sildenafil citrate on mice hearing].

PubMed

Luo, Xiaoqin; Guo, Xuyao; Chen, Lin; Chen, Xiaohong; Zhang, Xueyuan; Yuan, Wei

2014-06-01

The purpose of this investigation was to study the effects of the Sildenafil citrate on mice hearing. Seven-week-old adult male Kunming mice were used. The mice were randomly divided into four groups with 10 mice in each group.Sildenafil groups were orally administered daily with sildenafil [0.1 mg/(kg·d), 1 mg/(kg·d), 10 mg/(kg·d)] and control group was orally administered with normal saline. Then mice were tested for auditory brainstem response (ABR) to observe the changes of ABR's thresholds at before administration and 1, 5, 10, 15, 20 day afterwards. The mice basilar membrane samples were studied by immunofluorescent labeling.High performance liquid chromatography was used for determination the concentration of sildenafil in endolymph of mice cochlea. Statistical analysis was performed using SPSS 13.0. After 30 min following administration, the Sildenafil in endolymph of mice cochlear could be assayed by high performance liquid chromatography, and it was dose-related.Sildenafil increased the hearing thresholds with the time of administration. Hearing thresholds increased significantly in the sildenafil group at 20 d compared to the control group (P < 0.05). After administered high dose of Sildenafil, on the 20th day, the ABR thresholds average threshold was (60.0 ± 10.0) dBnHL, and the control group was (14.5 ± 6.0) dBnHL.Hair cells damages in the base ring of cochlea could be observed in experimental group in a concentration-dependent manner. Sildenafil can pass through blood-labyrinth barrier to the inner ear, and doses of sildenafil administration can induce hearing impairment in mice.

Standard and reduced radiation dose liver CT images: adaptive statistical iterative reconstruction versus model-based iterative reconstruction-comparison of findings and image quality.

PubMed

Shuman, William P; Chan, Keith T; Busey, Janet M; Mitsumori, Lee M; Choi, Eunice; Koprowicz, Kent M; Kanal, Kalpana M

2014-12-01

To investigate whether reduced radiation dose liver computed tomography (CT) images reconstructed with model-based iterative reconstruction ( MBIR model-based iterative reconstruction ) might compromise depiction of clinically relevant findings or might have decreased image quality when compared with clinical standard radiation dose CT images reconstructed with adaptive statistical iterative reconstruction ( ASIR adaptive statistical iterative reconstruction ). With institutional review board approval, informed consent, and HIPAA compliance, 50 patients (39 men, 11 women) were prospectively included who underwent liver CT. After a portal venous pass with ASIR adaptive statistical iterative reconstruction images, a 60% reduced radiation dose pass was added with MBIR model-based iterative reconstruction images. One reviewer scored ASIR adaptive statistical iterative reconstruction image quality and marked findings. Two additional independent reviewers noted whether marked findings were present on MBIR model-based iterative reconstruction images and assigned scores for relative conspicuity, spatial resolution, image noise, and image quality. Liver and aorta Hounsfield units and image noise were measured. Volume CT dose index and size-specific dose estimate ( SSDE size-specific dose estimate ) were recorded. Qualitative reviewer scores were summarized. Formal statistical inference for signal-to-noise ratio ( SNR signal-to-noise ratio ), contrast-to-noise ratio ( CNR contrast-to-noise ratio ), volume CT dose index, and SSDE size-specific dose estimate was made (paired t tests), with Bonferroni adjustment. Two independent reviewers identified all 136 ASIR adaptive statistical iterative reconstruction image findings (n = 272) on MBIR model-based iterative reconstruction images, scoring them as equal or better for conspicuity, spatial resolution, and image noise in 94.1% (256 of 272), 96.7% (263 of 272), and 99.3% (270 of 272), respectively. In 50 image sets, two reviewers (n = 100) scored overall image quality as sufficient or good with MBIR model-based iterative reconstruction in 99% (99 of 100). Liver SNR signal-to-noise ratio was significantly greater for MBIR model-based iterative reconstruction (10.8 ± 2.5 [standard deviation] vs 7.7 ± 1.4, P < .001); there was no difference for CNR contrast-to-noise ratio (2.5 ± 1.4 vs 2.4 ± 1.4, P = .45). For ASIR adaptive statistical iterative reconstruction and MBIR model-based iterative reconstruction , respectively, volume CT dose index was 15.2 mGy ± 7.6 versus 6.2 mGy ± 3.6; SSDE size-specific dose estimate was 16.4 mGy ± 6.6 versus 6.7 mGy ± 3.1 (P < .001). Liver CT images reconstructed with MBIR model-based iterative reconstruction may allow up to 59% radiation dose reduction compared with the dose with ASIR adaptive statistical iterative reconstruction , without compromising depiction of findings or image quality. © RSNA, 2014.

The effect of low-dose experimental zearalenone intoxication on the immunoexpression of estrogen receptors in the ovaries of pre-pubertal bitches.

PubMed

Gajecka, M

2012-01-01

Zearalenone is an estrogenic mycotoxin that often contaminates plant material used in the production of feeds for companion animals. Small daily doses of ingested zearalenone--a competitive substrate modulating the activity of enzymes participating in estrogen biosynthesis at the pre-receptor level--can induce subclinical symptoms of hyperestrogenism in bitches. The objective of this study was to determine the effects of low zearalenone doses on the presence of estrogen receptors in the ovaries of pre-pubertal Beagle bitches. The bitches were divided into three groups of 10 animals each: experimental group I--50 microg zearalenone/kg body weight administered once daily per os; experimental group II--75 microg zearalenone/kg body weight administered once daily per os; control group--placebo containing no ZEN administered per os. The animals were ovariorectomized at the end of the experiment, at 112 days of age. Estrogen receptors were detected in ovarian specimens by immunohistochemical methods. The results revealed an absence of estrogen receptors alpha in all groups. In both experimental groups a decrease in the positive response of estrogen receptors beta in specified structures of ovaries was observed. Very low alpha-zearalenol levels probably attested to the slowing down (hypostimulation) of the biotransformation process. Overall, zearalenone intoxication led to hyperestrogenism during a specific developmental stage of pre-pubertal bitches. As regards hormesis, the threshold dose of zearalenone (adaptive capability) was exceeded in the ovaries of experimental group II animals. The results obtained in both experimental groups suggest that long-term exposure to low-dose zearalenone intoxication decreased the degree of estrogen receptors beta staining in particular structures of ovaries in the experimental bitches, which initiated epigenetic modification mechanisms that inhibited ovarian development.

Comparison of the anticonvulsant potency of various diuretic drugs in the maximal electroshock-induced seizure threshold test in mice.

PubMed

Załuska, Katarzyna; Kondrat-Wróbel, Maria W; Łuszczki, Jarogniew J

2018-05-01

The coexistence of seizures and arterial hypertension requires an adequate and efficacious treatment involving both protection from seizures and reduction of high arterial blood pressure. Accumulating evidence indicates that some diuretic drugs (with a well-established position in the treatment of arterial hypertension) also possess anticonvulsant properties in various experimental models of epilepsy. The aim of this study was to assess the anticonvulsant potency of 6 commonly used diuretic drugs (i.e., amiloride, ethacrynic acid, furosemide, hydrochlorothiazide, indapamide, and spironolactone) in the maximal electroshock-induced seizure threshold (MEST) test in mice. Doses of the studied diuretics and their corresponding threshold increases were linearly related, allowing for the determination of doses which increase the threshold for electroconvulsions in drug-treated animals by 20% (TID20 values) over the threshold in control animals. Amiloride, hydrochlorothiazide and indapamide administered systemically (intraperitoneally - i.p.) increased the threshold for maximal electroconvulsions in mice, and the experimentally-derived TID20 values in the maximal electroshock seizure threshold test were 30.2 mg/kg for amiloride, 68.2 mg/kg for hydrochlorothiazide and 3.9 mg/kg for indapamide. In contrast, ethacrynic acid (up to 100 mg/kg), furosemide (up to 100 mg/kg) and spironolactone (up to 50 mg/kg) administered i.p. had no significant impact on the threshold for electroconvulsions in mice. The studied diuretics can be arranged with respect to their anticonvulsant potency in the MEST test as follows: indapamide > amiloride > hydrochlorothiazide. No anticonvulsant effects were observed for ethacrynic acid, furosemide or spironolactone in the MEST test in mice.

Cancer risk at low doses of ionizing radiation: artificial neural networks inference from atomic bomb survivors

PubMed Central

Sasaki, Masao S.; Tachibana, Akira; Takeda, Shunichi

2014-01-01

Cancer risk at low doses of ionizing radiation remains poorly defined because of ambiguity in the quantitative link to doses below 0.2 Sv in atomic bomb survivors in Hiroshima and Nagasaki arising from limitations in the statistical power and information available on overall radiation dose. To deal with these difficulties, a novel nonparametric statistics based on the ‘integrate-and-fire’ algorithm of artificial neural networks was developed and tested in cancer databases established by the Radiation Effects Research Foundation. The analysis revealed unique features at low doses that could not be accounted for by nominal exposure dose, including (i) the presence of a threshold that varied with organ, gender and age at exposure, and (ii) a small but significant bumping increase in cancer risk at low doses in Nagasaki that probably reflects internal exposure to 239Pu. The threshold was distinct from the canonical definition of zero effect in that it was manifested as negative excess relative risk, or suppression of background cancer rates. Such a unique tissue response at low doses of radiation exposure has been implicated in the context of the molecular basis of radiation–environment interplay in favor of recently emerging experimental evidence on DNA double-strand break repair pathway choice and its epigenetic memory by histone marking. PMID:24366315

Cancer risk at low doses of ionizing radiation: artificial neural networks inference from atomic bomb survivors.

PubMed

Sasaki, Masao S; Tachibana, Akira; Takeda, Shunichi

2014-05-01

Cancer risk at low doses of ionizing radiation remains poorly defined because of ambiguity in the quantitative link to doses below 0.2 Sv in atomic bomb survivors in Hiroshima and Nagasaki arising from limitations in the statistical power and information available on overall radiation dose. To deal with these difficulties, a novel nonparametric statistics based on the 'integrate-and-fire' algorithm of artificial neural networks was developed and tested in cancer databases established by the Radiation Effects Research Foundation. The analysis revealed unique features at low doses that could not be accounted for by nominal exposure dose, including (i) the presence of a threshold that varied with organ, gender and age at exposure, and (ii) a small but significant bumping increase in cancer risk at low doses in Nagasaki that probably reflects internal exposure to (239)Pu. The threshold was distinct from the canonical definition of zero effect in that it was manifested as negative excess relative risk, or suppression of background cancer rates. Such a unique tissue response at low doses of radiation exposure has been implicated in the context of the molecular basis of radiation-environment interplay in favor of recently emerging experimental evidence on DNA double-strand break repair pathway choice and its epigenetic memory by histone marking.

Quantitative assessment of anatomical change using a virtual proton depth radiograph for adaptive head and neck proton therapy.

PubMed

Wang, Peng; Yin, Lingshu; Zhang, Yawei; Kirk, Maura; Song, Gang; Ahn, Peter H; Lin, Alexander; Gee, James; Dolney, Derek; Solberg, Timothy D; Maughan, Richard; McDonough, James; Teo, Boon-Keng Kevin

2016-03-08

The aim of this work is to demonstrate the feasibility of using water-equivalent thickness (WET) and virtual proton depth radiographs (PDRs) of intensity corrected cone-beam computed tomography (CBCT) to detect anatomical change and patient setup error to trigger adaptive head and neck proton therapy. The planning CT (pCT) and linear accelerator (linac) equipped CBCTs acquired weekly during treatment of a head and neck patient were used in this study. Deformable image registration (DIR) was used to register each CBCT with the pCT and map Hounsfield units (HUs) from the planning CT (pCT) onto the daily CBCT. The deformed pCT is referred as the corrected CBCT (cCBCT). Two dimensional virtual lateral PDRs were generated using a ray-tracing technique to project the cumulative WET from a virtual source through the cCBCT and the pCT onto a virtual plane. The PDRs were used to identify anatomic regions with large variations in the proton range between the cCBCT and pCT using a threshold of 3 mm relative difference of WET and 3 mm search radius criteria. The relationship between PDR differences and dose distribution is established. Due to weight change and tumor response during treatment, large variations in WETs were observed in the relative PDRs which corresponded spatially with an increase in the number of failing points within the GTV, especially in the pharynx area. Failing points were also evident near the posterior neck due to setup variations. Differences in PDRs correlated spatially to differences in the distal dose distribution in the beam's eye view. Virtual PDRs generated from volumetric data, such as pCTs or CBCTs, are potentially a useful quantitative tool in proton therapy. PDRs and WET analysis may be used to detect anatomical change from baseline during treatment and trigger further analysis in adaptive proton therapy.

High thresholds for avoidance of sonar by free-ranging long-finned pilot whales (Globicephala melas).

PubMed

Antunes, R; Kvadsheim, P H; Lam, F P A; Tyack, P L; Thomas, L; Wensveen, P J; Miller, P J O

2014-06-15

The potential effects of exposing marine mammals to military sonar is a current concern. Dose-response relationships are useful for predicting potential environmental impacts of specific operations. To reveal behavioral response thresholds of exposure to sonar, we conducted 18 exposure/control approaches to 6 long-finned pilot whales. Source level and proximity of sonar transmitting one of two frequency bands (1-2 kHz and 6-7 kHz) were increased during exposure sessions. The 2-dimensional movement tracks were analyzed using a changepoint method to identify the avoidance response thresholds which were used to estimate dose-response relationships. No support for an effect of sonar frequency or previous exposures on the probability of response was found. Estimated response thresholds at which 50% of population show avoidance (SPLmax=170 dB re 1 μPa, SELcum=173 dB re 1 μPa(2) s) were higher than previously found for other cetaceans. The US Navy currently uses a generic dose-response relationship to predict the responses of cetaceans to naval active sonar, which has been found to underestimate behavioural impacts on killer whales and beaked whales. The navy curve appears to match more closely our results with long-finned pilot whales, though it might underestimate the probability of avoidance for pilot-whales at long distances from sonar sources. Copyright © 2014 Elsevier Ltd. All rights reserved.

Adaptive Spot Detection With Optimal Scale Selection in Fluorescence Microscopy Images.

PubMed

Basset, Antoine; Boulanger, Jérôme; Salamero, Jean; Bouthemy, Patrick; Kervrann, Charles

2015-11-01

Accurately detecting subcellular particles in fluorescence microscopy is of primary interest for further quantitative analysis such as counting, tracking, or classification. Our primary goal is to segment vesicles likely to share nearly the same size in fluorescence microscopy images. Our method termed adaptive thresholding of Laplacian of Gaussian (LoG) images with autoselected scale (ATLAS) automatically selects the optimal scale corresponding to the most frequent spot size in the image. Four criteria are proposed and compared to determine the optimal scale in a scale-space framework. Then, the segmentation stage amounts to thresholding the LoG of the intensity image. In contrast to other methods, the threshold is locally adapted given a probability of false alarm (PFA) specified by the user for the whole set of images to be processed. The local threshold is automatically derived from the PFA value and local image statistics estimated in a window whose size is not a critical parameter. We also propose a new data set for benchmarking, consisting of six collections of one hundred images each, which exploits backgrounds extracted from real microscopy images. We have carried out an extensive comparative evaluation on several data sets with ground-truth, which demonstrates that ATLAS outperforms existing methods. ATLAS does not need any fine parameter tuning and requires very low computation time. Convincing results are also reported on real total internal reflection fluorescence microscopy images.

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

Zhang, P; Kuo, L; Yorke, E

Purpose: To develop a biological modeling strategy which incorporates the response observed on the mid-treatment PET/CT into a dose escalation design for adaptive radiotherapy of non-small-cell lung cancer. Method: FDG-PET/CT was acquired midway through standard fractionated treatment and registered to pre-treatment planning PET/CT to evaluate radiation response of lung cancer. Each mid-treatment PET voxel was assigned the median SUV inside a concentric 1cm-diameter sphere to account for registration and imaging uncertainties. For each voxel, the planned radiation dose, pre- and mid-treatment SUVs were used to parameterize the linear-quadratic model, which was then utilized to predict the SUV distribution after themore » full prescribed dose. Voxels with predicted post-treatment SUV≥2 were identified as the resistant target (response arm). An adaptive simultaneous integrated boost was designed to escalate dose to the resistant target as high as possible, while keeping prescription dose to the original target and lung toxicity intact. In contrast, an adaptive target volume was delineated based only on the intensity of mid-treatment PET/CT (intensity arm), and a similar adaptive boost plan was optimized. The dose escalation capability of the two approaches was compared. Result: Images of three patients were used in this planning study. For one patient, SUV prediction indicated complete response and no necessary dose escalation. For the other two, resistant targets defined in the response arm were multifocal, and on average accounted for 25% of the pre-treatment target, compared to 67% in the intensity arm. The smaller response arm targets led to a 6Gy higher mean target dose in the adaptive escalation design. Conclusion: This pilot study suggests that adaptive dose escalation to a biologically resistant target predicted from a pre- and mid-treatment PET/CT may be more effective than escalation based on the mid-treatment PET/CT alone. More plans and ultimately clinical protocols are needed to validate this approach. MSKCC has a research agreement with Varian Medical System.« less

Weight-adapted iodinated contrast media administration in abdomino-pelvic CT: Can image quality be maintained?

PubMed

Perrin, E; Jackson, M; Grant, R; Lloyd, C; Chinaka, F; Goh, V

2018-02-01

In many centres, a fixed method of contrast-media administration is used for CT regardless of patient body habitus. The aim of this trial was to assess contrast enhancement of the aorta, portal vein, liver and spleen during abdomino-pelvic CT imaging using a weight-adapted contrast media protocol compared to the current fixed dose method. Thirty-nine oncology patients, who had previously undergone CT abdomino-pelvic imaging at the institution using a fixed contrast media dose, were prospectively imaged using a weight-adapted contrast media dose (1.4 ml/kg). The two sets of images were assessed for contrast enhancement levels (HU) at locations in the liver, aorta, portal vein and spleen during portal-venous enhancement phase. The t-test was used to compare the difference in results using a non-inferiority margin of 10 HU. When the contrast dose was tailored to patient weight, contrast enhancement levels were shown to be non-inferior to the fixed dose method (liver p < 0.001; portal vein p = 0.003; aorta p = 0.001; spleen p = 0.001). As a group, patients received a total contrast dose reduction of 165 ml using the weight-adapted method compared to the fixed dose method, with a mean cost per patient of £6.81 and £7.19 respectively. Using a weight-adapted method of contrast media administration was shown to be non-inferior to a fixed dose method of contrast media administration. Patients weighing 76 kg, or less, received a lower contrast dose which may have associated cost savings. A weight-adapted contrast media protocol should be implemented for portal-venous phase abdomino-pelvic CT for oncology patients with adequate renal function (>70 ml/min/1.73 m 2 ). Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Accurate tissue characterization in low-dose CT imaging with pure iterative reconstruction.

PubMed

Murphy, Kevin P; McLaughlin, Patrick D; Twomey, Maria; Chan, Vincent E; Moloney, Fiachra; Fung, Adrian J; Chan, Faimee E; Kao, Tafline; O'Neill, Siobhan B; Watson, Benjamin; O'Connor, Owen J; Maher, Michael M

2017-04-01

We assess the ability of low-dose hybrid iterative reconstruction (IR) and 'pure' model-based IR (MBIR) images to maintain accurate Hounsfield unit (HU)-determined tissue characterization. Standard-protocol (SP) and low-dose modified-protocol (MP) CTs were contemporaneously acquired in 34 Crohn's disease patients referred for CT. SP image reconstruction was via the manufacturer's recommendations (60% FBP, filtered back projection; 40% ASiR, Adaptive Statistical iterative Reconstruction; SP-ASiR40). MP data sets underwent four reconstructions (100% FBP; 40% ASiR; 70% ASiR; MBIR). Three observers measured tissue volumes using HU thresholds for fat, soft tissue and bone/contrast on each data set. Analysis was via SPSS. Inter-observer agreement was strong for 1530 datapoints (rs > 0.9). MP-MBIR tissue volume measurement was superior to other MP reconstructions and closely correlated with the reference SP-ASiR40 images for all tissue types. MP-MBIR superiority was most marked for fat volume calculation - close SP-ASiR40 and MP-MBIR Bland-Altman plot correlation was seen with the lowest average difference (336 cm 3 ) when compared with other MP reconstructions. Hounsfield unit-determined tissue volume calculations from MP-MBIR images resulted in values comparable to SP-ASiR40 calculations and values that are superior to MP-ASiR images. Accuracy of estimation of volume of tissues (e.g. fat) using segmentation software on low-dose CT images appears optimal when reconstructed with pure IR. © 2016 The Royal Australian and New Zealand College of Radiologists.

Spot Weight Adaptation for Moving Target in Spot Scanning Proton Therapy.

PubMed

Morel, Paul; Wu, Xiaodong; Blin, Guillaume; Vialette, Stéphane; Flynn, Ryan; Hyer, Daniel; Wang, Dongxu

2015-01-01

This study describes a real-time spot weight adaptation method in spot-scanning proton therapy for moving target or moving patient, so that the resultant dose distribution closely matches the planned dose distribution. The method proposed in this study adapts the weight (MU) of the delivering pencil beam to that of the target spot; it will actually hit during patient/target motion. The target spot that a certain delivering pencil beam may hit relies on patient monitoring and/or motion modeling using four-dimensional (4D) CT. After the adapted delivery, the required total weight [Monitor Unit (MU)] for this target spot is then subtracted from the planned value. With continuous patient motion and continuous spot scanning, the planned doses to all target spots will eventually be all fulfilled. In a proof-of-principle test, a lung case was presented with realistic temporal and motion parameters; the resultant dose distribution using spot weight adaptation was compared to that without using this method. The impact of the real-time patient/target position tracking or prediction was also investigated. For moderate motion (i.e., mean amplitude 0.5 cm), D95% to the planning target volume (PTV) was only 81.5% of the prescription (RX) dose; with spot weight adaptation PTV D95% achieves 97.7% RX. For large motion amplitude (i.e., 1.5 cm), without spot weight adaptation PTV D95% is only 42.9% of RX; with spot weight adaptation, PTV D95% achieves 97.7% RX. Larger errors in patient/target position tracking or prediction led to worse final target coverage; an error of 3 mm or smaller in patient/target position tracking is preferred. The proposed spot weight adaptation method was able to deliver the planned dose distribution and maintain target coverage when patient motion was involved. The successful implementation of this method would rely on accurate monitoring or prediction of patient/target motion.

Image guidance doses delivered during radiotherapy: Quantification, management, and reduction: Report of the AAPM Therapy Physics Committee Task Group 180.

PubMed

Ding, George X; Alaei, Parham; Curran, Bruce; Flynn, Ryan; Gossman, Michael; Mackie, T Rock; Miften, Moyed; Morin, Richard; Xu, X George; Zhu, Timothy C

2018-05-01

With radiotherapy having entered the era of image guidance, or image-guided radiation therapy (IGRT), imaging procedures are routinely performed for patient positioning and target localization. The imaging dose delivered may result in excessive dose to sensitive organs and potentially increase the chance of secondary cancers and, therefore, needs to be managed. This task group was charged with: a) providing an overview on imaging dose, including megavoltage electronic portal imaging (MV EPI), kilovoltage digital radiography (kV DR), Tomotherapy MV-CT, megavoltage cone-beam CT (MV-CBCT) and kilovoltage cone-beam CT (kV-CBCT), and b) providing general guidelines for commissioning dose calculation methods and managing imaging dose to patients. We briefly review the dose to radiotherapy (RT) patients resulting from different image guidance procedures and list typical organ doses resulting from MV and kV image acquisition procedures. We provide recommendations for managing the imaging dose, including different methods for its calculation, and techniques for reducing it. The recommended threshold beyond which imaging dose should be considered in the treatment planning process is 5% of the therapeutic target dose. Although the imaging dose resulting from current kV acquisition procedures is generally below this threshold, the ALARA principle should always be applied in practice. Medical physicists should make radiation oncologists aware of the imaging doses delivered to patients under their care. Balancing ALARA with the requirement for effective target localization requires that imaging dose be managed based on the consideration of weighing risks and benefits to the patient. © 2018 American Association of Physicists in Medicine.

Dosimetric benefit of adaptive re-planning in pancreatic cancer stereotactic body radiotherapy

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

Li, Yongbao; Center for Advanced Radiotherapy Technologies University of California San Diego, La Jolla, CA; Department of Radiation Oncology, University of California San Diego, La Jolla, CA

Stereotactic body radiotherapy (SBRT) shows promise in unresectable pancreatic cancer, though this treatment modality has high rates of normal tissue toxicity. This study explores the dosimetric utility of daily adaptive re-planning with pancreas SBRT. We used a previously developed supercomputing online re-planning environment (SCORE) to re-plan 10 patients with pancreas SBRT. Tumor and normal tissue contours were deformed from treatment planning computed tomographies (CTs) and transferred to daily cone-beam CT (CBCT) scans before re-optimizing each daily treatment plan. We compared the intended radiation dose, the actual radiation dose, and the optimized radiation dose for the pancreas tumor planning target volumemore » (PTV) and the duodenum. Treatment re-optimization improved coverage of the PTV and reduced dose to the duodenum. Within the PTV, the actual hot spot (volume receiving 110% of the prescription dose) decreased from 4.5% to 0.5% after daily adaptive re-planning. Within the duodenum, the volume receiving the prescription dose decreased from 0.9% to 0.3% after re-planning. It is noteworthy that variation in the amount of air within a patient's stomach substantially changed dose to the PTV. Adaptive re-planning with pancreas SBRT has the ability to improve dose to the tumor and decrease dose to the nearby duodenum, thereby reducing the risk of toxicity.« less

Adaptive, dose-finding phase 2 trial evaluating the safety and efficacy of ABT-089 in mild to moderate Alzheimer disease.

PubMed

Lenz, Robert A; Pritchett, Yili L; Berry, Scott M; Llano, Daniel A; Han, Shu; Berry, Donald A; Sadowsky, Carl H; Abi-Saab, Walid M; Saltarelli, Mario D

2015-01-01

ABT-089, an α4β2 neuronal nicotinic receptor partial agonist, was evaluated for efficacy and safety in mild to moderate Alzheimer disease patients receiving stable doses of acetylcholinesterase inhibitors. This phase 2 double-blind, placebo-controlled, proof-of-concept, and dose-finding study adaptively randomized patients to receive ABT-089 (5, 10, 15, 20, 30, or 35 mg once daily) or placebo for 12 weeks. The primary efficacy endpoint was the Alzheimer's Disease Assessment Scale, cognition subscale (ADAS-Cog) total score. A Bayesian response-adaptive randomization algorithm dynamically assigned allocation probabilities based on interim ADAS-Cog total scores. A normal dynamic linear model for dose-response relationships and a longitudinal model for predicting final ADAS-cog score were employed in the algorithm. Stopping criteria for futility or success were defined. The futility stopping criterion was met, terminating the study with 337 patients randomized. No dose-response relationship was observed and no dose demonstrated statistically significant improvement over placebo on ADAS-Cog or any secondary endpoint. ABT-089 was well tolerated at all dose levels. When administered as adjunctive therapy to acetylcholinesterase inhibitors, ABT-089 was not efficacious in mild to moderate Alzheimer disease. The adaptive study design enabled the examination of a broad dose range, enabled rapid determination of futility, and reduced patient exposure to nonefficacious doses of the investigational compound.

SU-F-J-194: Development of Dose-Based Image Guided Proton Therapy Workflow

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

Pham, R; Sun, B; Zhao, T

Purpose: To implement image-guided proton therapy (IGPT) based on daily proton dose distribution. Methods: Unlike x-ray therapy, simple alignment based on anatomy cannot ensure proper dose coverage in proton therapy. Anatomy changes along the beam path may lead to underdosing the target, or overdosing the organ-at-risk (OAR). With an in-room mobile computed tomography (CT) system, we are developing a dose-based IGPT software tool that allows patient positioning and treatment adaption based on daily dose distributions. During an IGPT treatment, daily CT images are acquired in treatment position. After initial positioning based on rigid image registration, proton dose distribution is calculatedmore » on daily CT images. The target and OARs are automatically delineated via deformable image registration. Dose distributions are evaluated to decide if repositioning or plan adaptation is necessary in order to achieve proper coverage of the target and sparing of OARs. Besides online dose-based image guidance, the software tool can also map daily treatment doses to the treatment planning CT images for offline adaptive treatment. Results: An in-room helical CT system is commissioned for IGPT purposes. It produces accurate CT numbers that allow proton dose calculation. GPU-based deformable image registration algorithms are developed and evaluated for automatic ROI-delineation and dose mapping. The online and offline IGPT functionalities are evaluated with daily CT images of the proton patients. Conclusion: The online and offline IGPT software tool may improve the safety and quality of proton treatment by allowing dose-based IGPT and adaptive proton treatments. Research is partially supported by Mevion Medical Systems.« less

Pain thresholds, supra-threshold pain and lidocaine sensitivity in patients with erythromelalgia, including the I848Tmutation in NaV 1.7.

PubMed

Helås, T; Sagafos, D; Kleggetveit, I P; Quiding, H; Jönsson, B; Segerdahl, M; Zhang, Z; Salter, H; Schmelz, M; Jørum, E

2017-09-01

Nociceptive thresholds and supra-threshold pain ratings as well as their reduction upon local injection with lidocaine were compared between healthy subjects and patients with erythromelalgia (EM). Lidocaine (0.25, 0.50, 1.0 or 10 mg/mL) or placebo (saline) was injected intradermally in non-painful areas of the lower arm, in a randomized, double-blind manner, to test the effect on dynamic and static mechanical sensitivity, mechanical pain sensitivity, thermal thresholds and supra-threshold heat pain sensitivity. Heat pain thresholds and pain ratings to supra-threshold heat stimulation did not differ between EM-patients (n = 27) and controls (n = 25), neither did the dose-response curves for lidocaine. Only the subgroup of EM-patients with mutations in sodium channel subunits Na V 1.7, 1.8 or 1.9 (n = 8) had increased lidocaine sensitivity for supra-threshold heat stimuli, contrasting lower sensitivity to strong mechanical stimuli. This pattern was particularly clear in the two patients carrying the Na V 1.7 I848T mutations in whom lidocaine's hyperalgesic effect on mechanical pain sensitivity contrasted more effective heat analgesia. Heat pain thresholds are not sensitized in EM patients, even in those with gain-of-function mutations in Na V 1.7. Differential lidocaine sensitivity was overt only for noxious stimuli in the supra-threshold range suggesting that sensitized supra-threshold encoding is important for the clinical pain phenotype in EM in addition to lower activation threshold. Intracutaneous lidocaine dose-dependently blocked nociceptive sensations, but we did not identify EM patients with particular high lidocaine sensitivity that could have provided valuable therapeutic guidance. Acute pain thresholds and supra-threshold heat pain in controls and patients with erythromelalgia do not differ and have the same lidocaine sensitivity. Acute heat pain thresholds even in EM patients with the Na V 1.7 I848T mutation are normal and only nociceptor sensitivity to intradermal lidocaine is changed. Only in EM patients with mutations in Na V 1.7, 1.8 or 1.9 supra-threshold heat and mechanical pain shows differential lidocaine sensitivity as compared to controls. © 2017 European Pain Federation - EFIC®.

Effects of intrathecal or intracerebroventricular administration of nonsteroidal anti-inflammatory drugs on a C-fiber reflex in rats.

PubMed

Bustamante, D; Paeile, C; Willer, J C; Le Bars, D

1997-06-01

A C-fiber reflex elicited by electrical stimulation within the territory of the sural nerve was recorded from the ipsilateral biceps femoris muscle in anesthetized rats. The temporal evolution of the response was studied using a constant stimulus intensity (3 times threshold), and recruitment curves were built by varying the stimulus intensity from 0 to 7 times threshold. The intrathecal (i.t.) but not i.c.v. administration of aspirin, indomethacin, ketoprofen and lysine clonixinate resulted in dose-dependent depressions of the C-fiber reflex. In contrast, saline was ineffective. Regardless of the route of administration, the drugs never produced disturbances in heart rate and/or acid-base equilibrium. When a constant level of stimulation was used, 500 microg of aspirin i.t. induced a blockade of the reflex immediately after the injection, followed by a partial recovery. Indomethacin produced a stable depression, which reached 80 to 90% with an i.t. dose of 500 microg. Ketoprofen and lysine clonixinate produced a more stable effect; the highest doses (500 microg) produced a steady-state depression of approximately 50% for approximately 30 min. When the recruitment curves were built with a range of nociceptive stimulus intensities, all of the drugs except for indomethacin produced a dose-dependent decrease in the slopes and the areas under the recruitment curves without major modifications in the thresholds; indomethacin also induced a significant dose-related increase in the threshold. The orders of potency for both stimulation paradigms with the i.t. route were the same, namely aspirin > indomethacin > lysine clonixinate > or = ketoprofen. It is concluded that nonsteroidal anti-inflammatory drugs elicit significant antinociceptive effects at a spinal level, which do not depend on the existence of a hyperalgesic or inflammatory state. Such effects were not seen after injections within the lateral ventricle.

Chaotic Signal Denoising Based on Hierarchical Threshold Synchrosqueezed Wavelet Transform

NASA Astrophysics Data System (ADS)

Wang, Wen-Bo; Jing, Yun-yu; Zhao, Yan-chao; Zhang, Lian-Hua; Wang, Xiang-Li

2017-12-01

In order to overcoming the shortcoming of single threshold synchrosqueezed wavelet transform(SWT) denoising method, an adaptive hierarchical threshold SWT chaotic signal denoising method is proposed. Firstly, a new SWT threshold function is constructed based on Stein unbiased risk estimation, which is two order continuous derivable. Then, by using of the new threshold function, a threshold process based on the minimum mean square error was implemented, and the optimal estimation value of each layer threshold in SWT chaotic denoising is obtained. The experimental results of the simulating chaotic signal and measured sunspot signals show that, the proposed method can filter the noise of chaotic signal well, and the intrinsic chaotic characteristic of the original signal can be recovered very well. Compared with the EEMD denoising method and the single threshold SWT denoising method, the proposed method can obtain better denoising result for the chaotic signal.

Antinociceptive effects of long-acting nalbuphine decanoate after intramuscular administration to Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Sanchez-Migallon Guzman, David; Braun, Jana M; Steagall, Paulo V M; Keuler, Nicholas S; Heath, Timothy D; Krugner-Higby, Lisa A; Brown, Carolyn S; Paul-Murphy, Joanne R

2013-02-01

To evaluate the thermal antinociceptive effects and duration of action of nalbuphine decanoate after IM administration to Hispaniolan Amazon parrots (Amazona ventralis). 10 healthy adult Hispaniolan Amazon parrots of unknown sex. Nalbuphine decanoate (33.7 mg/kg) or saline (0.9% NaCl) solution was administered IM in a randomized complete crossover experimental design (periods 1 and 2). Foot withdrawal threshold to a noxious thermal stimulus was used to evaluate responses. Baseline thermal withdrawal threshold was recorded 1 hour before drug or saline solution administration, and thermal foot withdrawal threshold measurements were repeated 1, 2, 3, 6, 12, 24, 48, and 72 hours after drug administration. Nalbuphine decanoate administered IM at a dose of 33.7 mg/kg significantly increased thermal foot withdrawal threshold, compared with results after administration of saline solution during period 2, and also caused a significant change in withdrawal threshold for up to 12 hours, compared with baseline values. Nalbuphine decanoate increased the foot withdrawal threshold to a noxious thermal stimulus in Hispaniolan Amazon parrots for up to 12 hours and provided a longer duration of action than has been reported for other nalbuphine formulations. Further studies with other types of nociceptive stimulation, dosages, and dosing intervals as well as clinical trials are needed to fully evaluate the analgesic effects of nalbuphine decanoate in psittacine birds.

A new laser pain threshold model detects a faster onset of action from a liquid formulation of 1 g paracetamol than an equivalent tablet formulation

PubMed Central

Sutton, J A; Gillin, W P; Grattan, T J; Clarke, G D; Kilminster, S G

2002-01-01

Aims To discover whether a new infra-red laser method could detect a change in pain threshold after as mild an analgesic as paracetamol and whether an effervescent liquid formulation produced a faster onset of action than tablets. Methods This double-blind, placebo controlled randomized study used a portable, infra-red laser to measure ‘first pain’ thresholds on the nondominant forearm in 12 normal volunteers before and after 1 g of paracetamol or placebo. The mean of six recordings was determined three times before dosing, the first being used as a familiarization procedure, and 14 times after dosing. Results We detected a small (2%), statistically significant difference in pain threshold between a liquid formulation of paracetamol and placebo at 30 and 60 min (P = 0.004 and P = 0.001), but not between tablets and placebo. Liquid also increased the threshold significantly compared with tablets at 60 min (P = 0.01). Conclusions To detect such a small increase in pain threshold requires a highly consistent measure and the coefficient of variation was 2% for the study overall, surprisingly low for a subjective phenomenon. The reasons for this include minimizing reflectance by blacking the skin, using a nonhairy site, averaging six data points at each sample time and controlling closely the ambient conditions and the subjects’ preparation for studies. PMID:11849194

Determining a threshold sub-acute dose leading to minimal physiological alterations following prolonged exposure to the nerve agent VX in rats.

PubMed

Bloch-Shilderman, E; Rabinovitz, I; Egoz, I; Yacov, G; Allon, N; Nili, U

2018-02-01

VX, a potent inhibitor of cholinesterase (ChE), is considered as one of the most toxic, persistent and least volatile nerve agents. VX is absorbed in various environmental surfaces and is gradually released long after its initial dispersal. Its toxicity is mainly caused by disrupting central and peripheral cholinergic nervous system activity, leading to potential long-term detrimental effects on health. The primary objective of the present study was to assess the threshold VX dose leading to minimal physiological alterations following prolonged VX exposure. Characterization of such a threshold is crucial for dealing with unresolved operative dilemmas such as when it is safe enough to resettle a population that has been evacuated from a VX-contaminated area. Rats, continuously exposed to various doses of VX (0.225-45 µg/kg/day) for 4 weeks via implanted mini-osmotic pumps, showed a dose-dependent and continuous decrease in ChE activity in whole blood, brain and muscles, ranging between 20 and 100%. Exposure to 13.5 µg/kg/day led to a stable low ChE activity level (~ 20%), accompanied by transient and negligible electrocorticogram spectral power transformations, especially in the theta and alpha brain wave frequencies, and a significant decrease in total brain M2 receptor density. These changes were neither accompanied by observable signs of intoxication nor by changes in motor function, circadian rhythm or TSPO level (a reliable marker of brain damage). Following exposure to lower doses of 2.25 and 0.225 µg/kg/day, the only change measured was a reduction in ChE activity of 60 and 20%, respectively. Based on these results, we delineate ChE inhibition as the physiological measure most susceptible to alterations following prolonged VX exposure, and determine for the first time the threshold sub-acute VX dose for minimal physiological effects (up to 20% reduction in ChE activity) in the rat as 0.225 µg/kg/day.

Salicylate-induced changes in auditory thresholds of adolescent and adult rats.

PubMed

Brennan, J F; Brown, C A; Jastreboff, P J

1996-01-01

Shifts in auditory intensity thresholds after salicylate administration were examined in postweanling and adult pigmented rats at frequencies ranging from 1 to 35 kHz. A total of 132 subjects from both age levels were tested under two-way active avoidance or one-way active avoidance paradigms. Estimated thresholds were inferred from behavioral responses to presentations of descending and ascending series of intensities for each test frequency value. Reliable threshold estimates were found under both avoidance conditioning methods, and compared to controls, subjects at both age levels showed threshold shifts at selective higher frequency values after salicylate injection, and the extent of shifts was related to salicylate dose level.

Cumulative effects from repeated exposures to ultraviolet radiation

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

Kaidbey, K.H.; Kligman, A.M.

Repeated exposures to subliminal doses of UVR, given at 24-hr intervals, resulted in a lowering of the erythema threshold dose. At erythemogenically equivalent doses, UV-A was the most effective and UV-C the least. A similar and more pronounced effect was observed following repeated exposures to subthreshold doses of UV-A and topically applied 8-methoxypsoralen. These findings provide quantitative evidence for the cumulative nature of acute UVR damage in human skin.

Vitamin D supplementation increases calcium absorption without a threshold effect

USDA-ARS?s Scientific Manuscript database

The maximal calcium absorption in response to vitamin D has been proposed as a biomarker for vitamin D sufficiency. Our objective was to determine whether there is a threshold beyond which increasing doses of vitamin D, or concentrations of serum 25-hydroxyvitamin D [25(OH)D], no longer increase cal...

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

PubMed

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

2016-11-01

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

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

PubMed Central

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

2016-01-01

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

A group sequential adaptive treatment assignment design for proof of concept and dose selection in headache trials.

PubMed

Hall, David B; Meier, Ulrich; Diener, Hans-Cristoph

2005-06-01

The trial objective was to test whether a new mechanism of action would effectively treat migraine headaches and to select a dose range for further investigation. The motivation for a group sequential, adaptive, placebo-controlled trial design was (1) limited information about where across the range of seven doses to focus attention, (2) a need to limit sample size for a complicated inpatient treatment and (3) a desire to reduce exposure of patients to ineffective treatment. A design based on group sequential and up and down designs was developed and operational characteristics were explored by trial simulation. The primary outcome was headache response at 2 h after treatment. Groups of four treated and two placebo patients were assigned to one dose. Adaptive dose selection was based on response rates of 60% seen with other migraine treatments. If more than 60% of treated patients responded, then the next dose was the next lower dose; otherwise, the dose was increased. A stopping rule of at least five groups at the target dose and at least four groups at that dose with more than 60% response was developed to ensure that a selected dose would be statistically significantly (p=0.05) superior to placebo. Simulations indicated good characteristics in terms of control of type 1 error, sufficient power, modest expected sample size and modest bias in estimation. The trial design is attractive for phase 2 clinical trials when response is acute and simple, ideally binary, placebo comparator is required, and patient accrual is relatively slow allowing for the collection and processing of results as a basis for the adaptive assignment of patients to dose groups. The acute migraine trial based on this design was successful in both proof of concept and dose range selection.

Diethylene glycol-induced toxicities show marked threshold dose response in rats

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

Landry, Greg M., E-mail: Landry.Greg@mayo.edu; Dunning, Cody L., E-mail: cdunni@lsuhsc.edu; Abreo, Fleurette, E-mail: fabreo@lsuhsc.edu

Diethylene glycol (DEG) exposure poses risks to human health because of widespread industrial use and accidental exposures from contaminated products. To enhance the understanding of the mechanistic role of metabolites in DEG toxicity, this study used a dose response paradigm to determine a rat model that would best mimic DEG exposure in humans. Wistar and Fischer-344 (F-344) rats were treated by oral gavage with 0, 2, 5, or 10 g/kg DEG and blood, kidney and liver tissues were collected at 48 h. Both rat strains treated with 10 g/kg DEG had equivalent degrees of metabolic acidosis, renal toxicity (increased BUNmore » and creatinine and cortical necrosis) and liver toxicity (increased serum enzyme levels, centrilobular necrosis and severe glycogen depletion). There was no liver or kidney toxicity at the lower DEG doses (2 and 5 g/kg) regardless of strain, demonstrating a steep threshold dose response. Kidney diglycolic acid (DGA), the presumed nephrotoxic metabolite of DEG, was markedly elevated in both rat strains administered 10 g/kg DEG, but no DGA was present at 2 or 5 g/kg, asserting its necessary role in DEG-induced toxicity. These results indicate that mechanistically in order to produce toxicity, metabolism to and significant target organ accumulation of DGA are required and that both strains would be useful for DEG risk assessments. - Highlights: • DEG produces a steep threshold dose response for kidney injury in rats. • Wistar and F-344 rats do not differ in response to DEG-induced renal injury. • The dose response for renal injury closely mirrors that for renal DGA accumulation. • Results demonstrate the importance of DGA accumulation in producing kidney injury.« less

Benefits of adaptive radiation therapy in lung cancer as a function of replanning frequency

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

Dial, Christian; Weiss, Elisabeth; Hugo, Geoffrey D., E-mail: gdhugo@vcu.edu

Purpose: To quantify the potential benefit associated with daily replanning in lung cancer in terms of normal tissue dose sparing and to characterize the tradeoff between adaptive benefit and replanning frequency. Methods: A set of synthetic images and contours, derived from weekly active breathing control images of 12 patients who underwent radiation therapy treatment for nonsmall cell lung cancer, is generated for each fraction of treatment using principal component analysis in a way that preserves temporal anatomical trends (e.g., tumor regression). Daily synthetic images and contours are used to simulate four different treatment scenarios: (1) a “no-adapt” scenario that simulatesmore » delivery of an initial plan throughout treatment, (2) a “midadapt” scenario that implements a single replan for fraction 18, (3) a “weekly adapt” scenario that simulates weekly adaptations, and (4) a “full-adapt” scenario that simulates daily replanning. An initial intensity modulated radiation therapy plan is created for each patient and replanning is carried out in an automated fashion by reoptimizing beam apertures and weights. Dose is calculated on each image and accumulated to the first in the series using deformable mappings utilized in synthetic image creation for comparison between simulated treatments. Results: Target coverage was maintained and cord tolerance was not exceeded for any of the adaptive simulations. Average reductions in mean lung dose (MLD) and volume of lung receiving 20 Gy or more (V20{sub lung}) were 65 ± 49 cGy (p = 0.000 01) and 1.1% ± 1.2% (p = 0.0006), respectively, for all patients. The largest reduction in MLD for a single patient was 162 cGy, which allowed an isotoxic escalation of the target dose of 1668 cGy. Average reductions in cord max dose, mean esophageal dose (MED), dose received by 66% of the heart (D66{sub heart}), and dose received by 33% of the heart (D33{sub heart}), were 158 ± 280, 117 ± 121, 37 ± 77, and 99 ± 120 cGy, respectively. Average incremental reductions in MLD for the midadapt, weekly adapt, and full-adapt treatments were 38, 18, and 8 cGy, respectively. Incremental reductions in MED for the same treatments were 57, 37, and 23 cGy. Reductions in MLD and MED for the full-adapt treatment were correlated with the absolute decrease in the planning target volume (r = 0.34 and r = 0.26). Conclusions: Adaptive radiation therapy for lung cancer yields clinically relevant reductions in normal tissue doses for frequencies of adaptation ranging from a single replan up to daily replanning. Increased frequencies of adaptation result in additional benefit while magnitude of benefit decreases.« less

Calibration of coronary calcium scores determined using iterative image reconstruction (AIDR 3D) at 120, 100, and 80 kVp

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

Blobel, Joerg, E-mail: Joerg.Blobel@toshiba-medical.eu; Mews, Juergen; Schuijf, Joanne D.

Purpose: Computed tomography (CT) radiation dose reduction is frequently achieved by applying lower tube voltages and using iterative reconstruction (IR). For calcium scoring, the reference protocol at 120 kVp with filtered back projection (FBP) is still used, because kVp and IR may influence the Agatston score (AS) and volume score (VS). The authors present a two-step method to optimize dose: first, to determine the lowest feasible exposure and highest noise thresholds; second, to define a calibration method that ensures that the AS and VS are similar to the reference protocol. Methods: AS and VS were measured for an anthropomorphic thoracicmore » phantom that includes a calcium calibration module. The phantom was scanned on a 320-row CT scanner, at tube voltages of 120 kVp using FBP, and 120, 100, and 80 kVp using adaptive iterative dose reduction (AIDR 3D) reconstruction. The minimum CTDIs were determined based on three objective quality criteria. Calibration was performed to estimate adjusted CT number thresholds for the lower kVp acquisitions. Finally, the accuracies of the total and individual insert scores at dose level close to the minimum CTDI level were investigated and compared to low (FBP{sub LD} − 120) and high (FBP{sub HD} − 120) dose reference protocols (based on ten repeated acquisitions for each group). Results: IR allows the exposure to be reduced by 69% at 120 kVp, with no significant effect on the total scores when averaged over all included dose steps and compared to FBP-120 (AS: 693 vs 699, p = 0.182; VS: 588 vs 587 mm{sup 3}, p = 0.569). Also when averaged over ten repeated scans and compared to FBP{sub HD} − 120 (AS: 709 vs 704, p = 0.435; VS: 604 vs 601 mm{sup 3}, p = 0.479), there is no statistical significant effect. Reducing the peak tube voltage allows even greater dose reductions: 73% at 100 kVp and 76% at 80 kVp. The calibrated CT number thresholds for analysis at 120, 100, and 80 kVp were, respectively, 130, 133, and 160 HU for the Agatston score, and 130, 132, and 140 HU for the volume score. Following the calibration, the mean scores of the four groups with dose variation were not significantly different from the reference protocol, at 100 kVp (AS: 698 vs 699, p = 0.818; VS: 584 vs 587 mm{sup 3}, p = 0.365) or at 80 kVp (AS: 698 vs 699, p = 0.996; VS: 586 vs 587 mm{sup 3}, p = 0.827). Similarly, there was no significant score difference with FBP{sub LD} − 120 during repeated scanning: 100 kVp (AS: 690 vs 694, p = 0.394; VS: 579 vs 585 mm{sup 3}, p = 0.168) and 80 kVp (AS: 703 vs 694, p = 0.115; VS: 588 vs 585 mm{sup 3}, p = 0.613). Compared to FBP{sub HD} − 120 group, the relative score deviation for the accuracy of the 400 and 800 mg/cm{sup 3} HA inserts with 3 and 5 mm diameter is less than 7%. However, the relative deviation of the smaller 1 mm inserts is poorer (up to 41% deviations for scores <3). Conclusions: With iterative reconstruction using AIDR 3D, deviations of the total Agatston and volume scores remain within 4% of the reference protocol. The 1 mm inserts were detected as calcification, but scores less than ten tend to be underestimated. Following the calibration process, the application of IR in combination with reduced tube voltages allows up to 76% lower radiation dose.« less

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.

The anticonvulsant action of AHR-11748 on kindled amygdaloid seizures in rats.

PubMed

Albertson, T E; Walby, W F

1987-03-01

The anticonvulsant effectiveness of AHR-11748 (3-[3-(trifluoromethyl)phenoxy]-1-azetidinecarboxamide) was evaluated in the kindled amygdaloid seizure model in rats. Doses of AHR-11748 that did not cause prestimulation toxicity significantly attenuated elicited afterdischarge durations and the severity of the accompanying behavioral convulsive response in previously kindled rats. AHR-11748 (25-100 mg/kg i.p.) was evaluated at 30 min in previously kindled rats using both threshold (20 microA increments) and suprathreshold (400 microA) paradigms. AHR-11748 (50-100.mg/kg) reduced suprathreshold elicited after discharges and seizure severity. Utilizing a suprathreshold kindling paradigm, the maximum anticonvulsant effectiveness for the 100 mg/kg i.p. dose of AHR-11748 was seen at 180 min. AHR-11748 significantly elevated seizure thresholds only at the 100 mg/kg dose. AHR-11748 (25-100 mg/kg) significantly reduced the severity of threshold elicited seizures. When AHR-11748 (50 and 100 mg/kg i.p.) was administered daily during kindling acquisition, the number of daily trials necessary to complete kindling significantly increased. A reduction in both the duration and the severity of the responses induced by the daily stimulations during the acquisition period was seen with AHR-11748 treatment. This study has demonstrated that AHR-11748 significantly modifies both the acquisition of kindling and the fully kindled amygdaloid seizures at doses that do not cause behavioral toxicity.

A new edge detection algorithm based on Canny idea

NASA Astrophysics Data System (ADS)

Feng, Yingke; Zhang, Jinmin; Wang, Siming

2017-10-01

The traditional Canny algorithm has poor self-adaptability threshold, and it is more sensitive to noise. In order to overcome these drawbacks, this paper proposed a new edge detection method based on Canny algorithm. Firstly, the media filtering and filtering based on the method of Euclidean distance are adopted to process it; secondly using the Frei-chen algorithm to calculate gradient amplitude; finally, using the Otsu algorithm to calculate partial gradient amplitude operation to get images of thresholds value, then find the average of all thresholds that had been calculated, half of the average is high threshold value, and the half of the high threshold value is low threshold value. Experiment results show that this new method can effectively suppress noise disturbance, keep the edge information, and also improve the edge detection accuracy.

Comparison of the effects of the alpha-2 agonists detomidine, romifidine and xylazine on nociceptive withdrawal reflex and temporal summation in horses.

PubMed

Rohrbach, Helene; Korpivaara, Toni; Schatzmann, Urs; Spadavecchia, Claudia

2009-07-01

To evaluate and compare the antinociceptive effects of the three alpha-2 agonists, detomidine, romifidine and xylazine at doses considered equipotent for sedation, using the nociceptive withdrawal reflex (NWR) and temporal summation model in standing horses. Prospective, blinded, randomized cross-over study. Ten healthy adult horses weighing 527-645 kg and aged 11-21 years old. Electrical stimulation was applied to the digital nerves to evoke NWR and temporal summation in the left thoracic limb and pelvic limb of each horse. Electromyographic reflex activity was recorded from the common digital extensor and the cranial tibial muscles. After baseline measurements a single bolus dose of detomidine, 0.02 mg kg(-1), romifidine 0.08 mg kg(-1), or xylazine, 1 mg kg(-1), was administered intravenously (IV). Determinations of NWR and temporal summation thresholds were repeated at 10, 20, 30, 40, 60, 70, 90, 100, 120 and 130 minutes after test-drug administration alternating the thoracic limb and the pelvic limb. Depth of sedation was assessed before measurements at each time point. Behavioural reaction was observed and recorded following each stimulation. The administration of detomidine, romifidine and xylazine significantly increased the current intensities necessary to evoke NWR and temporal summation in thoracic limbs and pelvic limbs of all horses compared with baseline. Xylazine increased NWR thresholds over baseline values for 60 minutes, while detomidine and romifidine increased NWR thresholds over baseline for 100 and 120 minutes, respectively. Temporal summation thresholds were significantly increased for 40, 70 and 130 minutes after xylazine, detomidine and romifidine, respectively. Detomidine, romifidine and xylazine, administered IV at doses considered equipotent for sedation, significantly increased NWR and temporal summation thresholds, used as a measure of antinociceptive activity. The extent of maximal increase of NWR and temporal summation thresholds was comparable, while the duration of action was drug-specific.

Nefopam, a Non-sedative Benzoxazocine Analgesic, Selectively Reduces the Shivering Threshold

PubMed Central

Alfonsi, Pascal; Adam, Frederic; Passard, Andrea; Guignard, Bruno; Sessler, Daniel I.; Chauvin, Marcel

2005-01-01

Background The analgesic nefopam does not compromise ventilation, is minimally sedating, and is effective as a treatment for postoperative shivering. We evaluated the effects of nefopam on the major thermoregulatory responses in humans: sweating, vasoconstriction, and shivering. Methods Nine volunteers were studied on three randomly assigned days: 1) control (Saline), 2) nefopam at a target plasma concentration of 35 ng/ml (Small Dose), and 3) nefopam at a target concentration of 70 ng/ml (Large Dose, ≈20 mg total). Each day, skin and core temperatures were increased to provoke sweating and then reduced to elicit peripheral vasoconstriction and shivering. We determined the thresholds (triggering core temperature at a designated skin temperature of 34°C) by mathematically compensating for changes in skin temperature using the established linear cutaneous contributions to control of each response. Results Nefopam did not significantly modify the slopes for sweating (0.0 ± 4.9°C·μg−1·ml; r2 = 0.73 ± 0.32) or vasoconstriction (−3.6 ± 5.0°C·μg−1·ml; r2=−0.47± 0.41). In contrast, nefopam significantly reduced the slope of shivering (−16.8 ± 9.3°C·μg−1·ml; r2 = 0.92 ± 0.06). Large-Dose nefopam thus reduced the shivering threshold by 0.9 ± 0.4°C (P<0.001) without any discernable effect on the sweating or vasoconstriction thresholds. Conclusions Most drugs with thermoregulatory actions — including anesthetics, sedatives, and opioids — synchronously reduce the vasoconstriction and shivering thresholds. Nefopam however reduced only the shivering threshold. This pattern has not previously been reported for a centrally acting drug. That pharmacologic modulation of vasoconstriction and shivering can be separated is of clinical and physiologic interest. PMID:14695722

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

PubMed Central

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

2003-01-01

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

Threshold dose for behavioral discrimination of cigarette nicotine content in menthol vs. non-menthol smokers.

PubMed

Perkins, Kenneth A; Kunkle, Nicole; Karelitz, Joshua L

2017-04-01

The lowest threshold content (or "dose") of nicotine discriminated in cigarettes may differ due to menthol preference. Menthol and non-menthol Spectrum research cigarettes differing in nicotine content were used to determine discrimination thresholds. Dependent smokers preferring menthol (n = 40) or non-menthol (n = 21) brands were tested on ability to discriminate cigarettes (matched for their menthol preference) with nicotine contents of 16-17, 11-12, 5, 2, and 1 mg/g, one per session, from an "ultra-low" cigarette with 0.4 mg/g. Controlled exposure to each cigarette was four puffs/trial, and the number of sessions was determined by the lowest nicotine content they could discriminate on >80% of trials (i.e., ≥5 of 6). We also assessed subjective perceptions and behavioral choice between cigarettes to relate them to discrimination responses. Controlling for Fagerstrom Test of Nicotine Dependence score, discrimination thresholds were more likely to be at higher nicotine content cigarettes for menthol vs. non-menthol smokers (p < .005), with medians of 16 vs. 11 mg/g, respectively. Compared to the ultra-low, threshold and subthreshold (next lowest) cigarettes differed on most perceptions and puff choice, but menthol preference did not alter these associations. Notably, threshold cigarettes did, but subthreshold did not, increase choice over the ultra-low. Threshold for discriminating nicotine via smoking may be generally higher for menthol vs. non-menthol smokers. More research is needed to identify why menthol smoking is related to higher nicotine thresholds and to verify that cigarettes unable to be discriminated do not support reinforcement.

The absolute threshold of cone vision

PubMed Central

Koeing, Darran; Hofer, Heidi

2013-01-01

We report measurements of the absolute threshold of cone vision, which has been previously underestimated due to sub-optimal conditions or overly strict subjective response criteria. We avoided these limitations by using optimized stimuli and experimental conditions while having subjects respond within a rating scale framework. Small (1′ fwhm), brief (34 msec), monochromatic (550 nm) stimuli were foveally presented at multiple intensities in dark-adapted retina for 5 subjects. For comparison, 4 subjects underwent similar testing with rod-optimized stimuli. Cone absolute threshold, that is, the minimum light energy for which subjects were just able to detect a visual stimulus with any response criterion, was 203 ± 38 photons at the cornea, ∼0.47 log units lower than previously reported. Two-alternative forced-choice measurements in a subset of subjects yielded consistent results. Cone thresholds were less responsive to criterion changes than rod thresholds, suggesting a limit to the stimulus information recoverable from the cone mosaic in addition to the limit imposed by Poisson noise. Results were consistent with expectations for detection in the face of stimulus uncertainty. We discuss implications of these findings for modeling the first stages of human cone vision and interpreting psychophysical data acquired with adaptive optics at the spatial scale of the receptor mosaic. PMID:21270115

Evaluation of delivered dose for a clinical daily adaptive plan selection strategy for bladder cancer radiotherapy.

PubMed

Lutkenhaus, Lotte J; Visser, Jorrit; de Jong, Rianne; Hulshof, Maarten C C M; Bel, Arjan

2015-07-01

To account for variable bladder size during bladder cancer radiotherapy, a daily plan selection strategy was implemented. The aim of this study was to calculate the actually delivered dose using an adaptive strategy, compared to a non-adaptive approach. Ten patients were treated to the bladder and lymph nodes with an adaptive full bladder strategy. Interpolated delineations of bladder and tumor on a full and empty bladder CT scan resulted in five PTVs for which VMAT plans were created. Daily cone beam CT (CBCT) scans were used for plan selection. Bowel, rectum and target volumes were delineated on these CBCTs, and delivered dose for these was calculated using both the adaptive plan, and a non-adaptive plan. Target coverage for lymph nodes improved using an adaptive strategy. The full bladder strategy spared the healthy part of the bladder from a high dose. Average bowel cavity V30Gy and V40Gy significantly reduced with 60 and 69ml, respectively (p<0.01). Other parameters for bowel and rectum remained unchanged. Daily plan selection compared to a non-adaptive strategy yielded similar bladder coverage and improved coverage for lymph nodes, with a significant reduction in bowel cavity V30Gy and V40Gy only, while other sparing was limited. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effect of a single dose of dextromethorphan on psychomotor performance and working memory capacity.

PubMed

Al-Kuraishy, Hayder M; Al-Gareeb, Ali I; Ashor, Ammar Waham

2012-04-01

Previous studies show that the prolonged use of dextromethorphan produces cognitive deterioration in humans. The aim of this study was to investigate the effect of a single dose of dextroemthrophan on psychomotor performance and working memory capacity. This is a randomized, double-blind, controlled, and prospective study. Thirty-six (17 women, 19 men) medical students enrolled in the study; half of them (7 women, 11 men) were given placebo, while the other half (10 women, 8 men) received dextromethorphan. The choice reaction time, critical flicker fusion threshold, and N-back working memory task were measured before and after 2 h of taking the drugs. Dextromethorphan showed a significant deterioration in the 3-back working memory task (P<0.05). No significant changes were seen as regards the choice reaction time components (total, recognition, motor) and critical flicker fusion threshold (P>0.05). On the other hand, placebo showed no significant changes as regards the choice reaction time, critical flicker fusion threshold, and N-back working memory task (P>0.05). A single dose of dextromethorphan has no effect on attention and arousal but may significantly impair the working memory capacity.

Is the bitter rejection response always adaptive?

PubMed

Glendinning, J I

1994-12-01

The bitter rejection response consists of a suite of withdrawal reflexes and negative affective responses. It is generally assumed to have evolved as a way to facilitate avoidance of foods that are poisonous because they usually taste bitter to humans. Using previously published studies, the present paper examines the relationship between bitterness and toxicity in mammals, and then assesses the ecological costs and benefits of the bitter rejection response in carnivorous, omnivorous, and herbivorous (grazing and browsing) mammals. If the bitter rejection response accurately predicts the potential toxicity of foods, then one would expect the threshold for the response to be lower for highly toxic compounds than for nontoxic compounds. The data revealed no such relationship. Bitter taste thresholds varied independently of toxicity thresholds, indicating that the bitter rejection response is just as likely to be elicited by a harmless bitter food as it is by a harmful one. Thus, it is not necessarily in an animal's best interest to have an extremely high or low bitter threshold. Based on this observation, it was hypothesized that the adaptiveness of the bitter rejection response depends upon the relative occurrence of bitter and potentially toxic compounds in an animal's diet. Animals with a relatively high occurrence of bitter and potentially toxic compounds in their diet (e.g., browsing herbivores) were predicted to have evolved a high bitter taste threshold and tolerance to dietary poisons. Such an adaptation would be necessary because a browser cannot "afford" to reject all foods that are bitter and potentially toxic without unduly restricting its dietary options. At the other extreme, animals that rarely encounter bitter and potentially toxic compounds in their diet (e.g., carnivores) were predicted to have evolved a low bitter threshold. Carnivores could "afford" to utilize such a stringent rejection mechanism because foods containing bitter and potentially toxic compounds constitute a small portion of their diet. Since the low bitter threshold would reduce substantially the risk of ingesting anything poisonous, carnivores were also expected to have a relatively low tolerance to dietary poisons. This hypothesis was supported by a comparison involving 30 mammal species, in which a suggestive relationship was found between quinine hydrochloride sensitivity and trophic group, with carnivores > omnivores > grazers > browsers. Further support for the hypothesis was provided by a comparison across browsers and grazers in terms of the production of tannin-binding salivary proteins, which probably represent an adaptation for reducing the bitterness and astringency of tannins.(ABSTRACT TRUNCATED AT 400 WORDS)

Comparison of an adaptive local thresholding method on CBCT and µCT endodontic images

NASA Astrophysics Data System (ADS)

Michetti, Jérôme; Basarab, Adrian; Diemer, Franck; Kouame, Denis

2018-01-01

Root canal segmentation on cone beam computed tomography (CBCT) images is difficult because of the noise level, resolution limitations, beam hardening and dental morphological variations. An image processing framework, based on an adaptive local threshold method, was evaluated on CBCT images acquired on extracted teeth. A comparison with high quality segmented endodontic images on micro computed tomography (µCT) images acquired from the same teeth was carried out using a dedicated registration process. Each segmented tooth was evaluated according to volume and root canal sections through the area and the Feret’s diameter. The proposed method is shown to overcome the limitations of CBCT and to provide an automated and adaptive complete endodontic segmentation. Despite a slight underestimation (-4, 08%), the local threshold segmentation method based on edge-detection was shown to be fast and accurate. Strong correlations between CBCT and µCT segmentations were found both for the root canal area and diameter (respectively 0.98 and 0.88). Our findings suggest that combining CBCT imaging with this image processing framework may benefit experimental endodontology, teaching and could represent a first development step towards the clinical use of endodontic CBCT segmentation during pulp cavity treatment.

Multiratio fusion change detection with adaptive thresholding

NASA Astrophysics Data System (ADS)

Hytla, Patrick C.; Balster, Eric J.; Vasquez, Juan R.; Neuroth, Robert M.

2017-04-01

A ratio-based change detection method known as multiratio fusion (MRF) is proposed and tested. The MRF framework builds on other change detection components proposed in this work: dual ratio (DR) and multiratio (MR). The DR method involves two ratios coupled with adaptive thresholds to maximize detected changes and minimize false alarms. The use of two ratios is shown to outperform the single ratio case when the means of the image pairs are not equal. MR change detection builds on the DR method by including negative imagery to produce four total ratios with adaptive thresholds. Inclusion of negative imagery is shown to improve detection sensitivity and to boost detection performance in certain target and background cases. MRF further expands this concept by fusing together the ratio outputs using a routine in which detections must be verified by two or more ratios to be classified as a true changed pixel. The proposed method is tested with synthetically generated test imagery and real datasets with results compared to other methods found in the literature. DR is shown to significantly outperform the standard single ratio method. MRF produces excellent change detection results that exhibit up to a 22% performance improvement over other methods from the literature at low false-alarm rates.

Excel-Based Tool for Pharmacokinetically Guided Dose Adjustment of Paclitaxel.

PubMed

Kraff, Stefanie; Lindauer, Andreas; Joerger, Markus; Salamone, Salvatore J; Jaehde, Ulrich

2015-12-01

Neutropenia is a frequent and severe adverse event in patients receiving paclitaxel chemotherapy. The time above a paclitaxel threshold concentration of 0.05 μmol/L (Tc > 0.05 μmol/L) is a strong predictor for paclitaxel-associated neutropenia and has been proposed as a target pharmacokinetic (PK) parameter for paclitaxel therapeutic drug monitoring and dose adaptation. Up to now, individual Tc > 0.05 μmol/L values are estimated based on a published PK model of paclitaxel by using the software NONMEM. Because many clinicians are not familiar with the use of NONMEM, an Excel-based dosing tool was developed to allow calculation of paclitaxel Tc > 0.05 μmol/L and give clinicians an easy-to-use tool. Population PK parameters of paclitaxel were taken from a published PK model. An Alglib VBA code was implemented in Excel 2007 to compute differential equations for the paclitaxel PK model. Maximum a posteriori Bayesian estimates of the PK parameters were determined with the Excel Solver using individual drug concentrations. Concentrations from 250 patients were simulated receiving 1 cycle of paclitaxel chemotherapy. Predictions of paclitaxel Tc > 0.05 μmol/L as calculated by the Excel tool were compared with NONMEM, whereby maximum a posteriori Bayesian estimates were obtained using the POSTHOC function. There was a good concordance and comparable predictive performance between Excel and NONMEM regarding predicted paclitaxel plasma concentrations and Tc > 0.05 μmol/L values. Tc > 0.05 μmol/L had a maximum bias of 3% and an error on precision of <12%. The median relative deviation of the estimated Tc > 0.05 μmol/L values between both programs was 1%. The Excel-based tool can estimate the time above a paclitaxel threshold concentration of 0.05 μmol/L with acceptable accuracy and precision. The presented Excel tool allows reliable calculation of paclitaxel Tc > 0.05 μmol/L and thus allows target concentration intervention to improve the benefit-risk ratio of the drug. The easy use facilitates therapeutic drug monitoring in clinical routine.

The effects of a repeated dose of a recombinant humanized anti-cocaine monoclonal antibody on cocaine self-administration in rats.

PubMed

Wetzel, Hanna N; Tsibulsky, Vladimir L; Norman, Andrew B

2016-11-01

Immunotherapy has shown potential as a treatment for cocaine abuse. The humanized recombinant anti-cocaine monoclonal antibody (mAb) with the preclinical designation h2E2 has been shown to decrease cocaine concentrations in the brain in rats, but its effects on cocaine self-administration behavior have never been tested. The amount of cocaine needed to reinstate self-administration behavior (priming threshold) was calculated and the inter-injection intervals at unit doses of 0.3μmol/kg and 3μmol/kg during maintained self-administration were measured over a five-week baseline period. Rats trained to self-administer cocaine were infused with two doses of h2E2 (120mg/kg i.v.) 35days apart. Priming threshold and inter-injection intervals were measured for 35days after both injections. After both injections of h2E2, priming thresholds were significantly increased (3-fold) compared to expected baseline and then gradually declined over 35days. A significant decrease (15-33%) in inter-injection intervals during maintained self-administration was also observed following both h2E2 infusions at the lower dose, and after the first injection at the higher dose. No significant decreases in body weight were observed after either injection, indicating a lack of toxicity following a second injection. These data predict that the safety and effectiveness of h2E2 will be maintained after multiple treatments of this potential immunotherapy for cocaine abuse. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The effects of a repeated dose of a recombinant humanized anti-cocaine monoclonal antibody on cocaine self-administration in rats

PubMed Central

Wetzel, Hanna N.; Tsibulsky, Vladimir L.; Norman, Andrew B.

2016-01-01

Background Immunotherapy has shown potential as a treatment for cocaine abuse. The humanized recombinant anti-cocaine monoclonal antibody (mAb) with the preclinical designation h2E2 has been shown to decrease cocaine concentrations in the brain in rats, but its effects on cocaine self-administration behavior have never been tested. Methods The amount of cocaine needed to reinstate self-administration behavior (priming threshold) was calculated and the inter-injection intervals at unit doses of 0.3 μmol/kg and 3 μmol/kg during maintained self-administration were measured over a five-week baseline period. Rats trained to self-administer cocaine were infused with two doses of h2E2 (120 mg/kg i.v.) 35 days apart. Priming threshold and inter-injection intervals were measured for 35 days after both injections. Results After both injections of h2E2, priming thresholds were significantly increased (3-fold) compared to expected baseline and then gradually declined over 35 days. A significant decrease (15–33%) in inter-injection intervals during maintained self-administration was also observed following both h2E2 at the lower dose, and after the first injection at the higher dose. No significant decreases in body weight were observed after either injection, indicating a lack of toxicity following a second injection. Conclusions These data predict that the safety and efficacy of h2E2 will be maintained after multiple treatments of this potential immunotherapy for cocaine abuse. PMID:27736682

Delivery of nicotine in an extract of a smokeless tobacco product reduces its reinforcement-attenuating and discriminative stimulus effects in rats

PubMed Central

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

2012-01-01

Rationale Animal models of tobacco addiction rely on administration of nicotine alone or nicotine combined with isolated constituents. Models using tobacco extracts derived from tobacco products and containing a range of tobacco constituents might more accurately simulate tobacco exposure in humans. Objective To compare the effects of nicotine alone and an aqueous smokeless tobacco extract in several addiction-related animal behavioral models. Methods Nicotine alone and nicotine dose-equivalent concentrations of extract were compared in terms of their acute effects on intracranial self-stimulation (ICSS) thresholds, discriminative stimulus effects, and effects on locomotor activity. Results Similar levels of nicotine and minor alkaloids were achieved using either artificial saliva or saline for extraction, supporting the clinical relevance of the saline extracts used in these studies. Extract produced reinforcement-enhancing (ICSS threshold-decreasing) effects similar to those of nicotine alone at low to moderate nicotine doses, but reduced reinforcement-attenuating (ICSS threshold-increasing) effects at a high nicotine dose. In rats trained to discriminate nicotine alone from saline, intermediate extract doses did not substitute for the training dose as well as nicotine alone. Locomotor stimulant effects and nicotine distribution to brain were similar following administration of extract or nicotine alone. Conclusions The reinforcement-attenuating and discriminative stimulus effects of nicotine delivered in an extract of a commercial smokeless tobacco product differed from those of nicotine alone. Extracts of tobacco products may be useful for evaluating the abuse liability of those products and understanding the role of non-nicotine constituents in tobacco addiction. PMID:21960181

Delivery of nicotine in an extract of a smokeless tobacco product reduces its reinforcement-attenuating and discriminative stimulus effects in rats.

PubMed

Harris, Andrew C; Stepanov, Irina; Pentel, Paul R; Lesage, Mark G

2012-04-01

Animal models of tobacco addiction rely on administration of nicotine alone or nicotine combined with isolated constituents. Models using tobacco extracts derived from tobacco products and containing a range of tobacco constituents might more accurately simulate tobacco exposure in humans. To compare the effects of nicotine alone and an aqueous smokeless tobacco extract in several addiction-related animal behavioral models. Nicotine alone and nicotine dose-equivalent concentrations of extract were compared in terms of their acute effects on intracranial self-stimulation (ICSS) thresholds, discriminative stimulus effects, and effects on locomotor activity. Similar levels of nicotine and minor alkaloids were achieved using either artificial saliva or saline for extraction, supporting the clinical relevance of the saline extracts used in these studies. Extract produced reinforcement-enhancing (ICSS threshold-decreasing) effects similar to those of nicotine alone at low to moderate nicotine doses, but reduced reinforcement-attenuating (ICSS threshold-increasing) effects at a high nicotine dose. In rats trained to discriminate nicotine alone from saline, intermediate extract doses did not substitute for the training dose as well as nicotine alone. Locomotor stimulant effects and nicotine distribution to brain were similar following administration of extract or nicotine alone. The reinforcement-attenuating and discriminative stimulus effects of nicotine delivered in an extract of a commercial smokeless tobacco product differed from those of nicotine alone. Extracts of tobacco products may be useful for evaluating the abuse liability of those products and understanding the role of non-nicotine constituents in tobacco addiction.

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

PubMed Central

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

2013-01-01

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

Dosimetric and radiobiological consequences of computed tomography-guided adaptive strategies for intensity modulated radiation therapy of the prostate.

PubMed

Battista, Jerry J; Johnson, Carol; Turnbull, David; Kempe, Jeff; Bzdusek, Karl; Van Dyk, Jacob; Bauman, Glenn

2013-12-01

To examine a range of scenarios for image-guided adaptive radiation therapy of prostate cancer, including different schedules for megavoltage CT imaging, patient repositioning, and dose replanning. We simulated multifraction dose distributions with deformable registration using 35 sets of megavoltage CT scans of 13 patients. We computed cumulative dose-volume histograms, from which tumor control probabilities and normal tissue complication probabilities (NTCPs) for rectum were calculated. Five-field intensity modulated radiation therapy (IMRT) with 18-MV x-rays was planned to achieve an isocentric dose of 76 Gy to the clinical target volume (CTV). The differences between D95, tumor control probability, V70Gy, and NTCP for rectum, for accumulated versus planned dose distributions, were compared for different target volume sizes, margins, and adaptive strategies. The CTV D95 for IMRT treatment plans, averaged over 13 patients, was 75.2 Gy. Using the largest CTV margins (10/7 mm), the D95 values accumulated over 35 fractions were within 2% of the planned value, regardless of the adaptive strategy used. For tighter margins (5 mm), the average D95 values dropped to approximately 73.0 Gy even with frequent repositioning, and daily replanning was necessary to correct this deficit. When personalized margins were applied to an adaptive CTV derived from the first 6 treatment fractions using the STAPLE (Simultaneous Truth and Performance Level Estimation) algorithm, target coverage could be maintained using a single replan 1 week into therapy. For all approaches, normal tissue parameters (rectum V(70Gy) and NTCP) remained within acceptable limits. The frequency of adaptive interventions depends on the size of the CTV combined with target margins used during IMRT optimization. The application of adaptive target margins (<5 mm) to an adaptive CTV determined 1 week into therapy minimizes the need for subsequent dose replanning. Copyright © 2013 Elsevier Inc. All rights reserved.

Predictors of the nicotine reinforcement threshold, compensation, and elasticity of demand in a rodent model of nicotine reduction policy.

PubMed

Grebenstein, Patricia E; Burroughs, Danielle; Roiko, Samuel A; Pentel, Paul R; LeSage, Mark G

2015-06-01

The FDA is considering reducing the nicotine content in tobacco products as a population-based strategy to reduce tobacco addiction. Research is needed to determine the threshold level of nicotine needed to maintain smoking and the extent of compensatory smoking that could occur during nicotine reduction. Sources of variability in these measures across sub-populations also need to be identified so that policies can take into account the risks and benefits of nicotine reduction in vulnerable populations. The present study examined these issues in a rodent nicotine self-administration model of nicotine reduction policy to characterize individual differences in nicotine reinforcement thresholds, degree of compensation, and elasticity of demand during progressive reduction of the unit nicotine dose. The ability of individual differences in baseline nicotine intake and nicotine pharmacokinetics to predict responses to dose reduction was also examined. Considerable variability in the reinforcement threshold, compensation, and elasticity of demand was evident. High baseline nicotine intake was not correlated with the reinforcement threshold, but predicted less compensation and less elastic demand. Higher nicotine clearance predicted low reinforcement thresholds, greater compensation, and less elastic demand. Less elastic demand also predicted lower reinforcement thresholds. These findings suggest that baseline nicotine intake, nicotine clearance, and the essential value of nicotine (i.e. elasticity of demand) moderate the effects of progressive nicotine reduction in rats and warrant further study in humans. They also suggest that smokers with fast nicotine metabolism may be more vulnerable to the risks of nicotine reduction. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Predictors of the nicotine reinforcement threshold, compensation, and elasticity of demand in a rodent model of nicotine reduction policy*

PubMed Central

Grebenstein, Patricia E.; Burroughs, Danielle; Roiko, Samuel A.; Pentel, Paul R.; LeSage, Mark G.

2015-01-01

Background The FDA is considering reducing the nicotine content in tobacco products as a population-based strategy to reduce tobacco addiction. Research is needed to determine the threshold level of nicotine needed to maintain smoking and the extent of compensatory smoking that could occur during nicotine reduction. Sources of variability in these measures across sub-populations also need to be identified so that policies can take into account the risks and benefits of nicotine reduction in vulnerable populations. Methods The present study examined these issues in a rodent nicotine self- administration model of nicotine reduction policy to characterize individual differences in nicotine reinforcement thresholds, degree of compensation, and elasticity of demand during progressive reduction of the unit nicotine dose. The ability of individual differences in baseline nicotine intake and nicotine pharmacokinetics to predict responses to dose reduction was also examined. Results Considerable variability in the reinforcement threshold, compensation, and elasticity of demand was evident. High baseline nicotine intake was not correlated with the reinforcement threshold, but predicted less compensation and less elastic demand. Higher nicotine clearance predicted low reinforcement thresholds, greater compensation, and less elastic demand. Less elastic demand also predicted lower reinforcement thresholds. Conclusions These findings suggest that baseline nicotine intake, nicotine clearance, and the essential value of nicotine (i.e. elasticity of demand) moderate the effects of progressive nicotine reduction in rats and warrant further study in humans. They also suggest that smokers with fast nicotine metabolism may be more vulnerable to the risks of nicotine reduction. PMID:25891231

Psychophysical chromatic mechanisms in macaque monkey.

PubMed

Stoughton, Cleo M; Lafer-Sousa, Rosa; Gagin, Galina; Conway, Bevil R

2012-10-24

Chromatic mechanisms have been studied extensively with psychophysical techniques in humans, but the number and nature of the mechanisms are still controversial. Appeals to monkey neurophysiology are often used to sort out the competing claims and to test hypotheses arising from the experiments in humans, but psychophysical chromatic mechanisms have never been assessed in monkeys. Here we address this issue by measuring color-detection thresholds in monkeys before and after chromatic adaptation, employing a standard approach used to determine chromatic mechanisms in humans. We conducted separate experiments using adaptation configured as either flickering full-field colors or heterochromatic gratings. Full-field colors would favor activity within the visual system at or before the arrival of retinal signals to V1, before the spatial transformation of color signals by the cortex. Conversely, gratings would favor activity within the cortex where neurons are often sensitive to spatial chromatic structure. Detection thresholds were selectively elevated for the colors of full-field adaptation when it modulated along either of the two cardinal chromatic axes that define cone-opponent color space [L vs M or S vs (L + M)], providing evidence for two privileged cardinal chromatic mechanisms implemented early in the visual-processing hierarchy. Adaptation with gratings produced elevated thresholds for colors of the adaptation regardless of its chromatic makeup, suggesting a cortical representation comprised of multiple higher-order mechanisms each selective for a different direction in color space. The results suggest that color is represented by two cardinal channels early in the processing hierarchy and many chromatic channels in brain regions closer to perceptual readout.

Dark adaptation and the retinoid cycle of vision.

PubMed

Lamb, T D; Pugh, E N

2004-05-01

Following exposure of our eye to very intense illumination, we experience a greatly elevated visual threshold, that takes tens of minutes to return completely to normal. The slowness of this phenomenon of "dark adaptation" has been studied for many decades, yet is still not fully understood. Here we review the biochemical and physical processes involved in eliminating the products of light absorption from the photoreceptor outer segment, in recycling the released retinoid to its original isomeric form as 11-cis retinal, and in regenerating the visual pigment rhodopsin. Then we analyse the time-course of three aspects of human dark adaptation: the recovery of psychophysical threshold, the recovery of rod photoreceptor circulating current, and the regeneration of rhodopsin. We begin with normal human subjects, and then analyse the recovery in several retinal disorders, including Oguchi disease, vitamin A deficiency, fundus albipunctatus, Bothnia dystrophy and Stargardt disease. We review a large body of evidence showing that the time-course of human dark adaptation and pigment regeneration is determined by the local concentration of 11-cis retinal, and that after a large bleach the recovery is limited by the rate at which 11-cis retinal is delivered to opsin in the bleached rod outer segments. We present a mathematical model that successfully describes a wide range of results in human and other mammals. The theoretical analysis provides a simple means of estimating the relative concentration of free 11-cis retinal in the retina/RPE, in disorders exhibiting slowed dark adaptation, from analysis of psychophysical measurements of threshold recovery or from analysis of pigment regeneration kinetics.

ABT-627, an endothelin ET(A) receptor-selective antagonist, attenuates tactile allodynia in a diabetic rat model of neuropathic pain.

PubMed

Jarvis, M F; Wessale, J L; Zhu, C Z; Lynch, J J; Dayton, B D; Calzadilla, S V; Padley, R J; Opgenorth, T J; Kowaluk, E A

2000-01-24

Tactile allodynia, the enhanced perception of pain in response to normally non-painful stimulation, represents a common complication of diabetic neuropathy. The activation of endothelin ET(A) receptors has been implicated in diabetes-induced reductions in peripheral neurovascularization and concomitant endoneurial hypoxia. Endothelin receptor activation has also been shown to alter the peripheral and central processing of nociceptive information. The present study was conducted to evaluate the antinociceptive effects of the novel endothelin ET(A) receptor-selective antagonist, 2R-(4-methoxyphenyl)-4S-(1,3-benzodioxol-5-yl)-1-(N, N-di(n-butyl)aminocarbonyl-methyl)-pyrrolidine-3R-carboxylic acid (ABT-627), in the streptozotocin-induced diabetic rat model of neuropathic pain. Rats were injected with 75 mg/kg streptozotocin (i. p.), and drug effects were assessed 8-12 weeks following streptozotocin treatment to allow for stabilization of blood glucose levels (>/=240 mg/dl) and tactile allodynia thresholds (

Automated size-specific CT dose monitoring program: assessing variability in CT dose.

PubMed

Christianson, Olav; Li, Xiang; Frush, Donald; Samei, Ehsan

2012-11-01

The potential health risks associated with low levels of ionizing radiation have created a movement in the radiology community to optimize computed tomography (CT) imaging protocols to use the lowest radiation dose possible without compromising the diagnostic usefulness of the images. Despite efforts to use appropriate and consistent radiation doses, studies suggest that a great deal of variability in radiation dose exists both within and between institutions for CT imaging. In this context, the authors have developed an automated size-specific radiation dose monitoring program for CT and used this program to assess variability in size-adjusted effective dose from CT imaging. The authors radiation dose monitoring program operates on an independent health insurance portability and accountability act compliant dosimetry server. Digital imaging and communication in medicine routing software is used to isolate dose report screen captures and scout images for all incoming CT studies. Effective dose conversion factors (k-factors) are determined based on the protocol and optical character recognition is used to extract the CT dose index and dose-length product. The patient's thickness is obtained by applying an adaptive thresholding algorithm to the scout images and is used to calculate the size-adjusted effective dose (ED(adj)). The radiation dose monitoring program was used to collect data on 6351 CT studies from three scanner models (GE Lightspeed Pro 16, GE Lightspeed VCT, and GE Definition CT750 HD) and two institutions over a one-month period and to analyze the variability in ED(adj) between scanner models and across institutions. No significant difference was found between computer measurements of patient thickness and observer measurements (p = 0.17), and the average difference between the two methods was less than 4%. Applying the size correction resulted in ED(adj) that differed by up to 44% from effective dose estimates that were not adjusted by patient size. Additionally, considerable differences were noted in ED(adj) distributions between scanners, with scanners employing iterative reconstruction exhibiting significantly lower ED(adj) (range: 9%-64%). Finally, a significant difference (up to 59%) in ED(adj) distributions was observed between institutions, indicating the potential for dose reduction. The authors developed a robust automated size-specific radiation dose monitoring program for CT. Using this program, significant differences in ED(adj) were observed between scanner models and across institutions. This new dose monitoring program offers a unique tool for improving quality assurance and standardization both within and across institutions.

Automated size-specific CT dose monitoring program: Assessing variability in CT dose

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

Christianson, Olav; Li Xiang; Frush, Donald

2012-11-15

Purpose: The potential health risks associated with low levels of ionizing radiation have created a movement in the radiology community to optimize computed tomography (CT) imaging protocols to use the lowest radiation dose possible without compromising the diagnostic usefulness of the images. Despite efforts to use appropriate and consistent radiation doses, studies suggest that a great deal of variability in radiation dose exists both within and between institutions for CT imaging. In this context, the authors have developed an automated size-specific radiation dose monitoring program for CT and used this program to assess variability in size-adjusted effective dose from CTmore » imaging. Methods: The authors radiation dose monitoring program operates on an independent health insurance portability and accountability act compliant dosimetry server. Digital imaging and communication in medicine routing software is used to isolate dose report screen captures and scout images for all incoming CT studies. Effective dose conversion factors (k-factors) are determined based on the protocol and optical character recognition is used to extract the CT dose index and dose-length product. The patient's thickness is obtained by applying an adaptive thresholding algorithm to the scout images and is used to calculate the size-adjusted effective dose (ED{sub adj}). The radiation dose monitoring program was used to collect data on 6351 CT studies from three scanner models (GE Lightspeed Pro 16, GE Lightspeed VCT, and GE Definition CT750 HD) and two institutions over a one-month period and to analyze the variability in ED{sub adj} between scanner models and across institutions. Results: No significant difference was found between computer measurements of patient thickness and observer measurements (p= 0.17), and the average difference between the two methods was less than 4%. Applying the size correction resulted in ED{sub adj} that differed by up to 44% from effective dose estimates that were not adjusted by patient size. Additionally, considerable differences were noted in ED{sub adj} distributions between scanners, with scanners employing iterative reconstruction exhibiting significantly lower ED{sub adj} (range: 9%-64%). Finally, a significant difference (up to 59%) in ED{sub adj} distributions was observed between institutions, indicating the potential for dose reduction. Conclusions: The authors developed a robust automated size-specific radiation dose monitoring program for CT. Using this program, significant differences in ED{sub adj} were observed between scanner models and across institutions. This new dose monitoring program offers a unique tool for improving quality assurance and standardization both within and across institutions.« less

Reliability of gamma-irradiated n-channel ZnO thin-film transistors: electronic and interface properties

NASA Astrophysics Data System (ADS)

Lee, Kin Kiong; Wang, Danna; Shinobu, Onoda; Ohshima, Takeshi

2018-04-01

Radiation-induced charge trapping and interface traps in n-channel ZnO thin film transistors are characterised as a function of total dose and irradiation bias following exposure to gamma-rays. Devices were irradiated up to ∼60 kGy(SiO?) and the electrical characteristic exhibits two distinct regimes. In the first regime, up to a total dose of 40 kGy(SiO?), the threshold voltage increases positively. However, in the second regime with irradiation greater than 40 kGy(SiO?), the threshold voltage moves in the opposite direction. This reversal of threshold voltage is attributed to the influence of the radiation-induced interface and oxide- charge, in which both have opposite polarity, on the electrical performance of the transistors. In the first regime, the generation of the oxide- charge is initially greater than the density of interface traps and caused a positive shift. In the second regime, when the total doses were greater than 40 kGy(SiO?), the radiation-induced interface traps are greater than the density of oxide- charge and caused the threshold voltage to switch direction. Further, the generated interface traps contributed to the degradation of the effective channel mobility, whereas the density of traps at the grain-boundaries did not increase significantly upon irradiation. Isothermal annealing of the devices at 363 K results in a reduction in the trap density and an improvement of the effective channel mobility to ∼90% of its pre-irradiation value.

Evaluation and Application of Enhancements to the Performance of the ASDE-3 Radar in Heavy Rain

DOT National Transportation Integrated Search

1982-03-01

This report presents the results of a study performed by the Transportation Systems Center (TSC) to evaluate two proposed enhancements to the performance of the ASDE-3 Radar in heavy rain: Adaptive gain and adaptive clutter thresholding, (operating w...

Adaptive 4d Psi-Based Change Detection

NASA Astrophysics Data System (ADS)

Yang, Chia-Hsiang; Soergel, Uwe

2018-04-01

In a previous work, we proposed a PSI-based 4D change detection to detect disappearing and emerging PS points (3D) along with their occurrence dates (1D). Such change points are usually caused by anthropic events, e.g., building constructions in cities. This method first divides an entire SAR image stack into several subsets by a set of break dates. The PS points, which are selected based on their temporal coherences before or after a break date, are regarded as change candidates. Change points are then extracted from these candidates according to their change indices, which are modelled from their temporal coherences of divided image subsets. Finally, we check the evolution of the change indices for each change point to detect the break date that this change occurred. The experiment validated both feasibility and applicability of our method. However, two questions still remain. First, selection of temporal coherence threshold associates with a trade-off between quality and quantity of PS points. This selection is also crucial for the amount of change points in a more complex way. Second, heuristic selection of change index thresholds brings vulnerability and causes loss of change points. In this study, we adapt our approach to identify change points based on statistical characteristics of change indices rather than thresholding. The experiment validates this adaptive approach and shows increase of change points compared with the old version. In addition, we also explore and discuss optimal selection of temporal coherence threshold.

Perception of Self-Motion and Regulation of Walking Speed in Young-Old Adults.

PubMed

Lalonde-Parsi, Marie-Jasmine; Lamontagne, Anouk

2015-07-01

Whether a reduced perception of self-motion contributes to poor walking speed adaptations in older adults is unknown. In this study, speed discrimination thresholds (perceptual task) and walking speed adaptations (walking task) were compared between young (19-27 years) and young-old individuals (63-74 years), and the relationship between the performance on the two tasks was examined. Participants were evaluated while viewing a virtual corridor in a helmet-mounted display. Speed discrimination thresholds were determined using a staircase procedure. Walking speed modulation was assessed on a self-paced treadmill while exposed to different self-motion speeds ranging from 0.25 to 2 times the participants' comfortable speed. For each speed, participants were instructed to match the self-motion speed described by the moving corridor. On the walking task, participants displayed smaller walking speed errors at comfortable walking speeds compared with slower of faster speeds. The young-old adults presented larger speed discrimination thresholds (perceptual experiment) and larger walking speed errors (walking experiment) compared with young adults. Larger walking speed errors were associated with higher discrimination thresholds. The enhanced performance on the walking task at comfortable speed suggests that intersensory calibration processes are influenced by experience, hence optimized for frequently encountered conditions. The altered performance of the young-old adults on the perceptual and walking tasks, as well as the relationship observed between the two tasks, suggest that a poor perception of visual motion information may contribute to the poor walking speed adaptations that arise with aging.

SU-F-T-201: Acceleration of Dose Optimization Process Using Dual-Loop Optimization Technique for Spot Scanning Proton Therapy

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

Hirayama, S; Fujimoto, R

Purpose: The purpose was to demonstrate a developed acceleration technique of dose optimization and to investigate its applicability to the optimization process in a treatment planning system (TPS) for proton therapy. Methods: In the developed technique, the dose matrix is divided into two parts, main and halo, based on beam sizes. The boundary of the two parts is varied depending on the beam energy and water equivalent depth by utilizing the beam size as a singular threshold parameter. The optimization is executed with two levels of iterations. In the inner loop, doses from the main part are updated, whereas dosesmore » from the halo part remain constant. In the outer loop, the doses from the halo part are recalculated. We implemented this technique to the optimization process in the TPS and investigated the dependence on the target volume of the speedup effect and applicability to the worst-case optimization (WCO) in benchmarks. Results: We created irradiation plans for various cubic targets and measured the optimization time varying the target volume. The speedup effect was improved as the target volume increased, and the calculation speed increased by a factor of six for a 1000 cm3 target. An IMPT plan for the RTOG benchmark phantom was created in consideration of ±3.5% range uncertainties using the WCO. Beams were irradiated at 0, 45, and 315 degrees. The target’s prescribed dose and OAR’s Dmax were set to 3 Gy and 1.5 Gy, respectively. Using the developed technique, the calculation speed increased by a factor of 1.5. Meanwhile, no significant difference in the calculated DVHs was found before and after incorporating the technique into the WCO. Conclusion: The developed technique could be adapted to the TPS’s optimization. The technique was effective particularly for large target cases.« less

Sex differences in nicotine self-administration in rats during progressive unit dose reduction: implications for nicotine regulation policy.

PubMed

Grebenstein, Patricia; Burroughs, Danielle; Zhang, Yan; LeSage, Mark G

2013-12-01

Reducing the nicotine content in tobacco products is being considered by the FDA as a policy to reduce the addictiveness of tobacco products. Understanding individual differences in response to nicotine reduction will be critical to developing safe and effective policy. Animal and human research demonstrating sex differences in the reinforcing effects of nicotine suggests that males and females may respond differently to nicotine-reduction policies. However, no studies have directly examined sex differences in the effects of nicotine unit-dose reduction on nicotine self-administration (NSA) in animals. The purpose of the present study was to examine this issue in a rodent self-administration model. Male and female rats were trained to self-administer nicotine (0.06mg/kg) under an FR 3 schedule during daily 23h sessions. Rats were then exposed to saline extinction and reacquisition of NSA, followed by weekly reductions in the unit dose (0.03 to 0.00025mg/kg) until extinction levels of responding were achieved. Males and females were compared with respect to baseline levels of intake, resistance to extinction, degree of compensatory increases in responding during dose reduction, and the threshold reinforcing unit dose of nicotine. Exponential demand-curve analysis was also conducted to compare the sensitivity of males and females to increases in the unit price (FR/unit dose) of nicotine (i.e., elasticity of demand or reinforcing efficacy). Females exhibited significantly higher baseline intake and less compensation than males. However, there were no sex differences in the reinforcement threshold or elasticity of demand. Dose-response relationships were very well described by the exponential demand function (r(2) values>0.96 for individual subjects). These findings suggest that females may exhibit less compensatory smoking in response to nicotine reduction policies, even though their nicotine reinforcement threshold and elasticity of demand may not differ from males. Copyright © 2013 Elsevier Inc. All rights reserved.

Predicting Nonauditory Adverse Radiation Effects Following Radiosurgery for Vestibular Schwannoma: A Volume and Dosimetric Analysis

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

Hayhurst, Caroline; Monsalves, Eric; Bernstein, Mark

2012-04-01

Purpose: To define clinical and dosimetric predictors of nonauditory adverse radiation effects after radiosurgery for vestibular schwannoma treated with a 12 Gy prescription dose. Methods: We retrospectively reviewed our experience of vestibular schwannoma patients treated between September 2005 and December 2009. Two hundred patients were treated at a 12 Gy prescription dose; 80 had complete clinical and radiological follow-up for at least 24 months (median, 28.5 months). All treatment plans were reviewed for target volume and dosimetry characteristics; gradient index; homogeneity index, defined as the maximum dose in the treatment volume divided by the prescription dose; conformity index; brainstem; andmore » trigeminal nerve dose. All adverse radiation effects (ARE) were recorded. Because the intent of our study was to focus on the nonauditory adverse effects, hearing outcome was not evaluated in this study. Results: Twenty-seven (33.8%) patients developed ARE, 5 (6%) developed hydrocephalus, 10 (12.5%) reported new ataxia, 17 (21%) developed trigeminal dysfunction, 3 (3.75%) had facial weakness, and 1 patient developed hemifacial spasm. The development of edema within the pons was significantly associated with ARE (p = 0.001). On multivariate analysis, only target volume is a significant predictor of ARE (p = 0.001). There is a target volume threshold of 5 cm3, above which ARE are more likely. The treatment plan dosimetric characteristics are not associated with ARE, although the maximum dose to the 5th nerve is a significant predictor of trigeminal dysfunction, with a threshold of 9 Gy. The overall 2-year tumor control rate was 96%. Conclusions: Target volume is the most important predictor of adverse radiation effects, and we identified the significant treatment volume threshold to be 5 cm3. We also established through our series that the maximum tolerable dose to the 5th nerve is 9 Gy.« less

Randomised field trial to evaluate serological response after foot-and-mouth disease vaccination in Turkey.

PubMed

Knight-Jones, T J D; Bulut, A N; Gubbins, S; Stärk, K D C; Pfeiffer, D U; Sumption, K J; Paton, D J

2015-02-04

Despite years of biannual mass vaccination of cattle, foot-and-mouth disease (FMD) remains uncontrolled in Anatolian Turkey. To evaluate protection after mass vaccination we measured post-vaccination antibodies in a cohort of cattle (serotypes O, A and Asia-1). To obtain results reflecting typical field protection, participants were randomly sampled from across Central and Western Turkey after routine vaccination. Giving two-doses one month apart is recommended when cattle are first vaccinated against FMD. However, due to cost and logistics, this is not routinely performed in Turkey, and elsewhere. Nested within the cohort, we conducted a randomised trial comparing post-vaccination antibodies after a single-dose versus a two-dose primary vaccination course. Four to five months after vaccination, only a third of single-vaccinated cattle had antibody levels above a threshold associated with protection. A third never reached this threshold, even at peak response one month after vaccination. It was not until animals had received three vaccine doses in their lifetime, vaccinating every six months, that most (64% to 86% depending on serotype) maintained antibody levels above this threshold. By this time cattle would be >20 months old with almost half the population below this age. Consequently, many vaccinated animals will be unprotected for much of the year. Compared to a single-dose, a primary vaccination course of two-doses greatly improved the level and duration of immunity. We concluded that the FMD vaccination programme in Anatolian Turkey did not produce the high levels of immunity required. Higher potency vaccines are now used throughout Turkey, with a two-dose primary course in certain areas. Monitoring post-vaccination serology is an important component of evaluation for FMD vaccination programmes. However, consideration must be given to which antigens are present in the test, the vaccine and the field virus. Differences between these antigens affect the relationship between antibody titre and protection. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Acute toxicity, histopathology, and coagulopathy in American kestrels (Falco sparverius) following administration of the rodenticie diphacinone

USGS Publications Warehouse

Rattner, Barnett A.; Horak, Katherine E.; Warner, Sarah E.; Day, Daniel D.; Meteyer, Carol U.; Voler, Steven F.; Eisemann, John D.; Johnston, John J.

2011-01-01

The acute oral toxicity of the anticoagulant rodenticide diphacinone was found to be over 20 times greater in American kestrels (Falco sparverius; median lethal dose 96.8 mg/kg body weight) compared with Northern bobwhite (Colinus virginianus) and mallards (Anas platyrhynchos). Modest evidence of internal bleeding was observed at necropsy, although histological examination of heart, liver, kidney, lung, intestine, and skeletal muscle revealed hemorrhage over a wide range of doses (35.1-675 mg/kg). Residue analysis suggests that the half-life of diphacinone in the liver of kestrels that survived was relatively short, with the majority of the dose cleared within 7 d of exposure. Several precise and sensitive clotting assays (prothrombin time, Russell's viper venom time, thrombin clotting time) were adapted for use in this species, and oral administration of diphacinone at 50 mg/kg increased prothrombin time and Russell?s viper venom time at 48 and 96 h postdose compared with controls. Prolongation of in vitro clotting time reflects impaired coagulation complex activity, and generally corresponded with the onset of overt signs of toxicity and lethality. In view of the toxicity and risk evaluation data derived from American kestrels, the involvement of diphacinone in some raptor mortality events, and the paucity of threshold effects data following short-term dietary exposure for birds of prey, additional feeding trials with captive raptors are warranted to characterize more fully the risk of secondary poisoning.

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

Risk equivalent of exposure versus dose of radiation

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

Bond, V.P.

This report describes a risk analysis study of low-dose irradiation and the resulting biological effects on a cell. The author describes fundamental differences between the effects of high-level exposure (HLE) and low-level exposure (LLE). He stresses that the concept of absorbed dose to an organ is not a dose but a level of effect produced by a particular number of particles. He discusses the confusion between a linear-proportional representation of dose limits and a threshold-curvilinear representation, suggesting that a LLE is a composite of both systems. (TEM)

Experiences with an adaptive design for a dose-finding study in patients with osteoarthritis.

PubMed

Miller, Frank; Björnsson, Marcus; Svensson, Ola; Karlsten, Rolf

2014-03-01

Dose-finding studies in non-oncology areas are usually conducted in Phase II of the development process of a new potential medicine and it is key to choose a good design for such a study, as the results will decide if and how to proceed to Phase III. The present article has focus on the design of a dose-finding study for pain in osteoarthritis patients treated with the TRPV1 antagonist AZD1386. We describe different design alternatives in the planning of this study, the reasoning for choosing the adaptive design and experiences with conduct and interim analysis. Three alternatives were proposed: one single dose-finding study with parallel design, a programme with a smaller Phase IIa study followed by a Phase IIb dose-finding study, and an adaptive dose-finding study. We describe these alternatives in detail and explain why the adaptive design was chosen for the study. We give insights in design aspects of the adaptive study, which need to be pre-planned, like interim decision criteria, statistical analysis method and setup of a Data Monitoring Committee. Based on the interim analysis it was recommended to stop the study for futility since AZD1386 showed no significant pain decrease based on the primary variable. We discuss results and experiences from the conduct of the study with the novel design approach. Huge cost savings have been done compared to if the option with one dose-finding design for Phase II had been chosen. However, we point out several challenges with this approach. Copyright © 2014 Elsevier Inc. All rights reserved.

PEG spacer gel and adaptive planning vs single plan in external prostate radiotherapy—clinical dosimetry evaluation

PubMed Central

2015-01-01

Objective: Spacer gel is used to reduce the rectal dose in prostate radiotherapy. It is injected to increase the distance between the prostate and rectum. During the course of external radiotherapy treatment, physiological changes in rectal volume exist. When using polyethylene glycol material, such as DuraSeal® (Covidien, Mansfield, MA), gel resorption also occurs. Together, these factors alter the original dose plan distribution. Methods: External dose planning and calculations were simulated using images acquired from 10 patients who were treated with brachytherapy and gel. The CT series was taken relative to gel injection: pre 1 day, post 1 day, post 1 month and post 2 months. Adaptive planning was compared with a single plan. Results: Adaptive planning shows better results compared with the single plan used in the total treatment course; however, the effect is minor. Conclusion: Gel usage is clearly favourable to rectal DVH. Using adaptive planning with gel improves rectal DVH but is not necessary according to this study. Advances in knowledge: Spacer gel is used in prostate radiotherapy to increase distance between the prostate and the rectum, thus reducing the rectal doses. During the treatment course, gel resorption exists which affects the rectal doses. The usefulness of adaptive planning to compensate this resorption effect has not been studied before. PMID:26370300

Measurement of skin dose from cone-beam computed tomography imaging.

PubMed

Akyalcin, Sercan; English, Jeryl D; Abramovitch, Kenneth M; Rong, Xiujiang J

2013-10-09

To measure surface skin dose from various cone-beam computed tomography (CBCT) scanners using point-dosimeters. A head anthropomorphic phantom was used with nanoDOT optically stimulated luminescence (OSL) dosimeters (Landauer Corp., Glenwood, IL) attached to various anatomic landmarks. The phantom was scanned using multiple exposure protocols for craniofacial evaluations in three different CBCT units and a conventional x-ray imaging system. The dosimeters were calibrated for each of the scan protocols on the different imaging systems. Peak skin dose and surface doses at the eye lens, thyroid, submandibular and parotid gland levels were measured. The measured skin doses ranged from 0.09 to 4.62 mGy depending on dosimeter positions and imaging systems. The average surface doses to the lens locations were ~4.0 mGy, well below the threshold for cataractogenesis (500 mGy). The results changed accordingly with x-ray tube output (mAs and kV) and also were sensitive to scan field of view (SFOV). As compared to the conventional panoramic and cephalometric imaging system, doses from all three CBCT systems were at least an order of magnitude higher. Peak skin dose and surface doses at the eye lens, thyroid, and salivary gland levels measured from the CBCT imaging systems were lower than the thresholds to induce deterministic effects. However, our findings do not justify the routine use of CBCT imaging in orthodontics considering the lifetime-attributable risk to the individual.

Measurement of skin dose from cone-beam computed tomography imaging

PubMed Central

2013-01-01

Objective To measure surface skin dose from various cone-beam computed tomography (CBCT) scanners using point-dosimeters. Materials & methods A head anthropomorphic phantom was used with nanoDOT optically stimulated luminescence (OSL) dosimeters (Landauer Corp., Glenwood, IL) attached to various anatomic landmarks. The phantom was scanned using multiple exposure protocols for craniofacial evaluations in three different CBCT units and a conventional x-ray imaging system. The dosimeters were calibrated for each of the scan protocols on the different imaging systems. Peak skin dose and surface doses at the eye lens, thyroid, submandibular and parotid gland levels were measured. Results The measured skin doses ranged from 0.09 to 4.62 mGy depending on dosimeter positions and imaging systems. The average surface doses to the lens locations were ~4.0 mGy, well below the threshold for cataractogenesis (500 mGy). The results changed accordingly with x-ray tube output (mAs and kV) and also were sensitive to scan field of view (SFOV). As compared to the conventional panoramic and cephalometric imaging system, doses from all three CBCT systems were at least an order of magnitude higher. Conclusions Peak skin dose and surface doses at the eye lens, thyroid, and salivary gland levels measured from the CBCT imaging systems were lower than the thresholds to induce deterministic effects. However, our findings do not justify the routine use of CBCT imaging in orthodontics considering the lifetime-attributable risk to the individual. PMID:24192155

An adaptive design for updating the threshold value of a continuous biomarker

PubMed Central

Spencer, Amy V.; Harbron, Chris; Mander, Adrian; Wason, James; Peers, Ian

2017-01-01

Potential predictive biomarkers are often measured on a continuous scale, but in practice, a threshold value to divide the patient population into biomarker ‘positive’ and ‘negative’ is desirable. Early phase clinical trials are increasingly using biomarkers for patient selection, but at this stage, it is likely that little will be known about the relationship between the biomarker and the treatment outcome. We describe a single-arm trial design with adaptive enrichment, which can increase power to demonstrate efficacy within a patient subpopulation, the parameters of which are also estimated. Our design enables us to learn about the biomarker and optimally adjust the threshold during the study, using a combination of generalised linear modelling and Bayesian prediction. At the final analysis, a binomial exact test is carried out, allowing the hypothesis that ‘no population subset exists in which the novel treatment has a desirable response rate’ to be tested. Through extensive simulations, we are able to show increased power over fixed threshold methods in many situations without increasing the type-I error rate. We also show that estimates of the threshold, which defines the population subset, are unbiased and often more precise than those from fixed threshold studies. We provide an example of the method applied (retrospectively) to publically available data from a study of the use of tamoxifen after mastectomy by the German Breast Study Group, where progesterone receptor is the biomarker of interest. PMID:27417407

Thresholds for conservation and management: structured decision making as a conceptual framework

USGS Publications Warehouse

Nichols, James D.; Eaton, Mitchell J.; Martin, Julien; Edited by Guntenspergen, Glenn R.

2014-01-01

changes in system dynamics. They are frequently incorporated into ecological models used to project system responses to management actions. Utility thresholds are components of management objectives and are values of state or performance variables at which small changes yield substantial changes in the value of the management outcome. Decision thresholds are values of system state variables at which small changes prompt changes in management actions in order to reach specified management objectives. Decision thresholds are derived from the other components of the decision process.We advocate a structured decision making (SDM) approach within which the following components are identified: objectives (possibly including utility thresholds), potential actions, models (possibly including ecological thresholds), monitoring program, and a solution algorithm (which produces decision thresholds). Adaptive resource management (ARM) is described as a special case of SDM developed for recurrent decision problems that are characterized by uncertainty. We believe that SDM, in general, and ARM, in particular, provide good approaches to conservation and management. Use of SDM and ARM also clarifies the distinct roles of ecological thresholds, utility thresholds, and decision thresholds in informed decision processes.

Evaluation of a software module for adaptive treatment planning and re-irradiation.

PubMed

Richter, Anne; Weick, Stefan; Krieger, Thomas; Exner, Florian; Kellner, Sonja; Polat, Bülent; Flentje, Michael

2017-12-28

The aim of this work is to validate the Dynamic Planning Module in terms of usability and acceptance in the treatment planning workflow. The Dynamic Planning Module was used for decision making whether a plan adaptation was necessary within one course of radiation therapy. The Module was also used for patients scheduled for re-irradiation to estimate the dose in the pretreated region and calculate the accumulated dose to critical organs at risk. During one year, 370 patients were scheduled for plan adaptation or re-irradiation. All patient cases were classified according to their treated body region. For a sub-group of 20 patients treated with RT for lung cancer, the dosimetric effect of plan adaptation during the main treatment course was evaluated in detail. Changes in tumor volume, frequency of re-planning and the time interval between treatment start and plan adaptation were assessed. The Dynamic Planning Tool was used in 20% of treated patients per year for both approaches nearly equally (42% plan adaptation and 58% re-irradiation). Most cases were assessed for the thoracic body region (51%) followed by pelvis (21%) and head and neck cases (10%). The sub-group evaluation showed that unintended plan adaptation was performed in 38% of the scheduled cases. A median time span between first day of treatment and necessity of adaptation of 17 days (range 4-35 days) was observed. PTV changed by 12 ± 12% on average (maximum change 42%). PTV decreased in 18 of 20 cases due to tumor shrinkage and increased in 2 of 20 cases. Re-planning resulted in a reduction of the mean lung dose of the ipsilateral side in 15 of 20 cases. The experience of one year showed high acceptance of the Dynamic Planning Module in our department for both physicians and medical physicists. The re-planning can potentially reduce the accumulated dose to the organs at risk and ensure a better target volume coverage. In the re-irradiation situation, the Dynamic Planning Tool was used to consider the pretreatment dose, to adapt the actual treatment schema more specifically and to review the accumulated dose.

The Key Events Dose-Response Framework: A cross-Disciplinary Mode-of-Action Based Approach to Examining Does-Response and Thresholds

EPA Science Inventory

the ILSI Research Foundation conveded a cross-disciplinary working group to examine current approaches for assessing dose-response and identifying safe levels of intake or exposure for four categoreis of bioactive agents: food allergens, nutrients, pathogenic microorganisms, and ...

Gender and dose dependent ovalbumin induced hypersensitivity responses in murine model of food allergy

USDA-ARS?s Scientific Manuscript database

While federal regulations mandate the labeling of major food allergens, allowable food allergen thresholds have yet to be determined. Therefore the aim of this project was to identify the lowest egg allergen ovalbumin (OVA) dose causing hypersensitization using a validated murine model. Mice were or...

Gender and dose dependent ovalbumin induced hypersensitivity responses in murine model of food allergy

USDA-ARS?s Scientific Manuscript database

While federal regulations mandate the labeling of major food allergens, allowable food allergen thresholds have yet to be determined. Therefore the aim of this project was to identify the lowest egg allergen ovalbumin (OVA) dose causing hypersensitization using a validated murine model. Mice were o...

Increased seizure susceptibility and other toxicity symptoms following acute sulforaphane treatment in mice.

PubMed

Socała, Katarzyna; Nieoczym, Dorota; Kowalczuk-Vasilev, Edyta; Wyska, Elżbieta; Wlaź, Piotr

2017-07-01

Activation of Nrf2 with sulforaphane has recently gained attention as a new therapeutic approach in the treatment of many diseases, including epilepsy. As a plant-derived compound, sulforaphane is considered to be safe and well-tolerated. It is widely consumed, also by patients suffering from seizure and taking antiepileptic drugs, but no toxicity profile of sulforaphane exists. Since many natural remedies and dietary supplements may increase seizure risk and potentially interact with antiepileptic drugs, the aim of our study was to investigate the acute effects of sulforaphane on seizure thresholds and activity of some first- and second-generation antiepileptic drugs in mice. In addition, some preliminary toxicity profile of sulforaphane in mice after intraperitoneal injection was evaluated. The LD 50 value of sulforaphane in mice was estimated at 212.67mg/kg, while the TD 50 value - at 191.58mg/kg. In seizure tests, sulforaphane at the highest dose tested (200mg/kg) significantly decreased the thresholds for the onset of the first myoclonic twitch and generalized clonic seizure in the iv PTZ test as well as the threshold for the 6Hz-induced psychomotor seizure. At doses of 10-200mg/kg, sulforaphane did not affect the threshold for the iv PTZ-induced forelimb tonus or the threshold for maximal electroshock-induced hindlimb tonus. Interestingly, sulforaphane (at 100mg/kg) potentiated the anticonvulsant efficacy of carbamazepine in the maximal electroshock seizure test. This interaction could have been pharmacokinetic in nature, as sulforaphane increased concentrations of carbamazepine in both serum and brain tissue. The toxicity study showed that high doses of sulforaphane produced marked sedation (at 150-300mg/kg), hypothermia (at 150-300mg/kg), impairment of motor coordination (at 200-300mg/kg), decrease in skeletal muscle strength (at 250-300mg/kg), and deaths (at 200-300mg/kg). Moreover, blood analysis showed leucopenia in mice injected with sulforaphane at 200mg/kg. In conclusion, since sulforaphane was proconvulsant at a toxic dose, the safety profile and the risk-to-benefit ratio of sulforaphane usage in epileptic patients should be further evaluated. Copyright © 2017 Elsevier Inc. All rights reserved.

Ultraviolet radiation exposure triggers neurokinin-1 receptor upregulation in ocular tissues in vivo.

PubMed

Gross, Janine; Wegener, Alfred R; Kronschlaeger, Martin; Holz, Frank G; Schönfeld, Carl-Ludwig; Meyer, Linda M

2018-04-26

The purpose of this study was to investigate the neurokinin receptor-1 (NKR-1) protein expression in ocular tissues before and after supra-cataract threshold ultraviolet radiation (UVR-B peak at 312 nm) exposure in vivo in a mouse model. Six-week-old C57Bl/6 mice were unilaterally exposed to a single (2.9 kJ/m 2 ) and an above 3-fold UVR-B cataract threshold dose (9.4 kJ/m 2 ) of UVR. UVR-exposure (λpeak = 312 nm) was performed in mydriasis using a Bio-Spectra exposure system. After latency periods of 3 and 7 days, eyes were fixed in 4% paraformaldehyde, embedded in paraffin, sectioned and stained with fluorescence coupled antibody for NKR-1 and DAPI for cell nuclei staining. Control animals received only anesthesia but no UVR-exposure. Cataract development was documented with a Leica dark-field microscope and quantified as integrated optical density (IOD). NKR-1 is ubiquitously present in ocular tissues. An above 3-fold cataract threshold dose of UV-radiation induced NKR-1 upregulation after days 3 and 7 in the epithelium and endothelium of the cornea, the endothelial cells of the iris vessels, the pigmented epithelium/stroma of the ciliary body, the lens epithelium, pronounced in the nuclear bow region and the inner plexiform layer of the retina. A significant upregulation of NKR-1 could not be provoked with a single cataract threshold dose (2.9 kJ/m 2 UVR-B) ultraviolet irradiation. All exposed eyes developed anterior subcapsular cataracts. Neurokinin-1 receptor is present ubiquitously in ocular tissues including the lens epithelium and the nuclear bow region of the lens. UV-radiation exposure to an above 3-fold UVR-B cataract threshold dose triggers NKR-1 upregulation in the eye in vivo. The involvement of inflammation in ultraviolet radiation induced cataract and the role of neuroinflammatory peptides such as substance P and its receptor, NKR-1, might have been underestimated to date. Copyright © 2018. Published by Elsevier Ltd.

An electric field induced in the retina and brain at threshold magnetic flux density causing magnetophosphenes.

PubMed

Hirata, Akimasa; Takano, Yukinori; Fujiwara, Osamu; Dovan, Thanh; Kavet, Robert

2011-07-07

For magnetic field exposures at extremely low frequencies, the electrostimulatory response with the lowest threshold is the magnetophosphene, a response that corresponds to an adult exposed to a 20 Hz magnetic field of nominally 8.14 mT. In the IEEE standard C95.6 (2002), the corresponding in situ field in the retinal locus of an adult-sized ellipsoidal was calculated to be 53 mV m(-1). However, the associated dose in the retina and brain at a high level of resolution in anatomically correct human models is incompletely characterized. Furthermore, the dose maxima in tissue computed with voxel human models are prone to staircasing errors, particularly for the low-frequency dosimetry. In the analyses presented in this paper, analytical and quasi-static finite-difference time-domain (FDTD) solutions were first compared for a three-layer sphere exposed to a uniform 50 Hz magnetic field. Staircasing errors in the FDTD results were observed at the tissue interface, and were greatest at the skin-air boundary. The 99th percentile value was within 3% of the analytic maximum, depending on model resolution, and thus may be considered a close approximation of the analytic maximum. For the adult anatomical model, TARO, exposed to a uniform magnetic field, the differences in the 99th percentile value of in situ electric fields for 2 mm and 1 mm voxel models were at most several per cent. For various human models exposed at the magnetophosphene threshold at three orthogonal field orientations, the in situ electric field in the brain was between 10% and 70% greater than the analytical IEEE threshold of 53 mV m(-1), and in the retina was lower by roughly 50% for two horizontal orientations (anterior-posterior and lateral), and greater by about 15% for a vertically oriented field. Considering a reduction factor or safety factors of several folds applied to electrostimulatory thresholds, the 99th percentile dose to a tissue calculated with voxel human models may be used as an estimate of the tissue's maximum dose.

Seamless Phase IIa/IIb and enhanced dose-finding adaptive design.

PubMed

Yuan, Jiacheng; Pang, Herbert; Tong, Tiejun; Xi, Dong; Guo, Wenzhao; Mesenbrink, Peter

2016-01-01

In drug development, when the drug class has a relatively well-defined path to regulatory approval and the enrollment is slow with certain patient populations, one may want to consider combining studies of different phases. This article considers combining a proof of concept (POC) study and a dose-finding (DF) study with a control treatment. Conventional DF study designs sometimes are not efficient, or do not have a high probability to find the optimal dose(s) for Phase III trials. This article seeks more efficient DF strategies that allow the economical testing of more doses. Hypothetical examples are simulated to compare the proposed adaptive design vs. the conventional design based on different models of the overall quantitative representation of efficacy, safety, and tolerability. The results show that the proposed adaptive design tests more active doses with higher power and comparable or smaller sample size in a shorter overall study duration for POC and DF, compared with a conventional design.

Advanced Computational Approaches for Characterizing Stochastic Cellular Responses to Low Dose, Low Dose Rate Exposures

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

Scott, Bobby, R., Ph.D.

2003-06-27

OAK - B135 This project final report summarizes modeling research conducted in the U.S. Department of Energy (DOE), Low Dose Radiation Research Program at the Lovelace Respiratory Research Institute from October 1998 through June 2003. The modeling research described involves critically evaluating the validity of the linear nonthreshold (LNT) risk model as it relates to stochastic effects induced in cells by low doses of ionizing radiation and genotoxic chemicals. The LNT model plays a central role in low-dose risk assessment for humans. With the LNT model, any radiation (or genotoxic chemical) exposure is assumed to increase one¡¯s risk of cancer.more » Based on the LNT model, others have predicted tens of thousands of cancer deaths related to environmental exposure to radioactive material from nuclear accidents (e.g., Chernobyl) and fallout from nuclear weapons testing. Our research has focused on developing biologically based models that explain the shape of dose-response curves for low-dose radiation and genotoxic chemical-induced stochastic effects in cells. Understanding the shape of the dose-response curve for radiation and genotoxic chemical-induced stochastic effects in cells helps to better understand the shape of the dose-response curve for cancer induction in humans. We have used a modeling approach that facilitated model revisions over time, allowing for timely incorporation of new knowledge gained related to the biological basis for low-dose-induced stochastic effects in cells. Both deleterious (e.g., genomic instability, mutations, and neoplastic transformation) and protective (e.g., DNA repair and apoptosis) effects have been included in our modeling. Our most advanced model, NEOTRANS2, involves differing levels of genomic instability. Persistent genomic instability is presumed to be associated with nonspecific, nonlethal mutations and to increase both the risk for neoplastic transformation and for cancer occurrence. Our research results, based on applications of NEOTRANS2, indicate that nonlinear threshold-type, dose-response relationships for excess stochastic effects (problematic nonlethal mutations, neoplastic transformation) should be expected after exposure to low linear energy transfer (LET) gamma rays or gamma rays in combination with high-LET alpha radiation. Similar thresholds are expected for low-dose-rate low-LET beta irradiation. We attribute the thresholds to low-dose, low-LET radiation induced protection against spontaneous mutations and neoplastic transformations. The protection is presumed mainly to involve selective elimination of problematic cells via apoptosis. Low-dose, low-LET radiation is presumed to trigger wide-area cell signaling, which in turn leads to problematic bystander cells (e.g., mutants, neoplastically transformed cells) selectively undergoing apoptosis. Thus, this protective bystander effect leads to selective elimination of problematic cells (a tissue cleansing process in vivo). However, this protective bystander effects is a different process from low-dose stimulation of the immune system. Low-dose, low-LET radiation stimulation of the immune system may explain why thresholds for inducing excess cancer appear much larger (possibly more than 100-fold larger) than thresholds for inducing excess mutations and neoplastic transformations, when the dose rate is low. For ionizing radiation, the current risk assessment paradigm is such that the relative risk (RR) is always ¡Ý 1, no matter how small the dose. Our research results indicate that for low-dose or low-dose-rate, low-LET irradiation, RR < 1 may be more the rule than the exception. Directly tied to the current RR paradigm are the billion-dollar cleanup costs for radionuclide-contaminated DOE sites. Our research results suggest that continued use of the current RR paradigm for which RR ¡Ý 1 could cause more harm than benefit to society (e.g., by spreading unwarranted fear about phantom excess risks associated with low-dose low-LET radiation). Such phantom risks also may arise from risk assessments conducted for combined exposure to low- and high-LET radiations when based on the LNT or other models that exclude RR < 1. Our results for high-LET radiation are consistent with the LNT hypothesis but only where there is no additional low-LET contribution (e.g., gamma rays) to the total dose. For high-LET neutron sources, gamma rays arise (especially in vivo) for large mammals such as humans from neutron interactions with tissue. The gamma rays might provide some protection from low-dose-related stochastic effects via inducing the protective bystander apoptosis effect that is considered to contribute to tissue cleansing via removal of problematic cells.« less

Noradrenaline decreases spike voltage threshold and induces electrographic sharp waves in turtle medial cortex in vitro.

PubMed

Lorenzo, Daniel; Velluti, Julio C

2004-01-01

The noradrenergic modulation of neuronal properties has been described at different levels of the mammalian brain. Although the anatomical characteristics of the noradrenergic system are well known in reptiles, functional data are scarce. In our study the noradrenergic modulation of cortical electrogenesis in the turtle medial cortex was studied in vitro using a combination of field and intracellular recordings. Turtle EEG consists of a low voltage background interspersed by spontaneous large sharp waves (LSWs). Noradrenaline (NA, 5-40 microM) induced (or enhanced) the generation of LSWs in a dose-dependent manner. Pharmacological experiments suggest the participation of alpha and beta receptors in this effect. In medial cortex neurons NA induced a hyperpolarization of the resting potential and a decrease of input resistance. Both effects were observed also after TTX treatment. Noradrenaline increased the response of the cells to depolarizing pulses, resulting in an upward shift of the frequency/current relation. In most cells the excitability change was mediated by a decrease of the spike voltage threshold resulting in the reduction of the amount of depolarization needed to fire the cell (voltage threshold minus resting potential). As opposed to the mechanisms reported in mammalian neurons, no changes in the frequency adaptation or the post-train afterhyperpolarization were observed. The NA effects at the cellular level were not reproduced by noradrenergic agonists. Age- and species-dependent properties in the pharmacology of adrenergic receptors could be involved in this result. Cellular effects of NA in turtle cortex are similar to those described in mammals, although the increase in cellular excitability seems to be mediated by a different mechanism. Copyright 2004 S. Karger AG, Basel

SU-F-J-32: Do We Need KV Imaging During CBCT Based Patient Set-Up for Lung Radiation Therapy?

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

Gopal, A; Zhou, J; Prado, K

Purpose: To evaluate the role of 2D kilovoltage (kV) imaging to complement cone beam CT (CBCT) imaging in a shift threshold based image guided radiation therapy (IGRT) strategy for conventional lung radiotherapy. Methods: A retrospective study was conducted by analyzing IGRT couch shift trends for 15 patients that received lung radiation therapy to evaluate the benefit of performing orthogonal kV imaging prior to CBCT imaging. Herein, a shift threshold based IGRT protocol was applied, which would mandate additional CBCT verification if the applied patient shifts exceeded 3 mm to avoid intraobserver variability in CBCT registration and to confirm table shifts.more » For each patient, two IGRT strategies: kV + CBCT and CBCT alone, were compared and the recorded patient shifts were categorized into whether additional CBCT acquisition would have been mandated or not. The effectiveness of either strategy was gauged by the likelihood of needing additional CBCT imaging for accurate patient set-up. Results: The use of CBCT alone was 6 times more likely to require an additional CBCT than KV+CBCT, for a 3 mm shift threshold (88% vs 14%). The likelihood of additional CBCT verification generally increased with lower shift thresholds, and was significantly lower when kV+CBCT was used (7% with 5 mm shift threshold, 36% with 2 mm threshold), than with CBCT alone (61% with 5 mm shift threshold, 97% with 2 mm threshold). With CBCT alone, treatment time increased by 2.2 min and dose increased by 1.9 cGy per fraction on average due to additional CBCT with a 3mm shift threshold. Conclusion: The benefit of kV imaging to screen for gross misalignments led to more accurate CBCT based patient localization compared with using CBCT alone. The subsequently reduced need for additional CBCT verification will minimize treatment time and result in less overall patient imaging dose.« less

Adaptive thresholding algorithm based on SAR images and wind data to segment oil spills along the northwest coast of the Iberian Peninsula.

PubMed

Mera, David; Cotos, José M; Varela-Pet, José; Garcia-Pineda, Oscar

2012-10-01

Satellite Synthetic Aperture Radar (SAR) has been established as a useful tool for detecting hydrocarbon spillage on the ocean's surface. Several surveillance applications have been developed based on this technology. Environmental variables such as wind speed should be taken into account for better SAR image segmentation. This paper presents an adaptive thresholding algorithm for detecting oil spills based on SAR data and a wind field estimation as well as its implementation as a part of a functional prototype. The algorithm was adapted to an important shipping route off the Galician coast (northwest Iberian Peninsula) and was developed on the basis of confirmed oil spills. Image testing revealed 99.93% pixel labelling accuracy. By taking advantage of multi-core processor architecture, the prototype was optimized to get a nearly 30% improvement in processing time. Copyright © 2012 Elsevier Ltd. All rights reserved.

Central and rear-edge populations can be equally vulnerable to warming

NASA Astrophysics Data System (ADS)

Bennett, Scott; Wernberg, Thomas; Arackal Joy, Bijo; de Bettignies, Thibaut; Campbell, Alexandra H.

2015-12-01

Rear (warm) edge populations are often considered more susceptible to warming than central (cool) populations because of the warmer ambient temperatures they experience, but this overlooks the potential for local variation in thermal tolerances. Here we provide conceptual models illustrating how sensitivity to warming is affected throughout a species' geographical range for locally adapted and non-adapted populations. We test these models for a range-contracting seaweed using observations from a marine heatwave and a 12-month experiment, translocating seaweeds among central, present and historic range edge locations. Growth, reproductive development and survivorship display different temperature thresholds among central and rear-edge populations, but share a 2.5 °C anomaly threshold. Range contraction, therefore, reflects variation in local anomalies rather than differences in absolute temperatures. This demonstrates that warming sensitivity can be similar throughout a species geographical range and highlights the importance of incorporating local adaptation and acclimatization into climate change vulnerability assessments.

Hematopoietic responses under protracted exposures to low daily dose gamma irradiation

NASA Astrophysics Data System (ADS)

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

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

Feasibility of online IMPT adaptation using fast, automatic and robust dose restoration

NASA Astrophysics Data System (ADS)

Bernatowicz, Kinga; Geets, Xavier; Barragan, Ana; Janssens, Guillaume; Souris, Kevin; Sterpin, Edmond

2018-04-01

Intensity-modulated proton therapy (IMPT) offers excellent dose conformity and healthy tissue sparing, but it can be substantially compromised in the presence of anatomical changes. A major dosimetric effect is caused by density changes, which alter the planned proton range in the patient. Three different methods, which automatically restore an IMPT plan dose on a daily CT image were implemented and compared: (1) simple dose restoration (DR) using optimization objectives of the initial plan, (2) voxel-wise dose restoration (vDR), and (3) isodose volume dose restoration (iDR). Dose restorations were calculated for three different clinical cases, selected to test different capabilities of the restoration methods: large range adaptation, complex dose distributions and robust re-optimization. All dose restorations were obtained in less than 5 min, without manual adjustments of the optimization settings. The evaluation of initial plans on repeated CTs showed large dose distortions, which were substantially reduced after restoration. In general, all dose restoration methods improved DVH-based scores in propagated target volumes and OARs. Analysis of local dose differences showed that, although all dose restorations performed similarly in high dose regions, iDR restored the initial dose with higher precision and accuracy in the whole patient anatomy. Median dose errors decreased from 13.55 Gy in distorted plan to 9.75 Gy (vDR), 6.2 Gy (DR) and 4.3 Gy (iDR). High quality dose restoration is essential to minimize or eventually by-pass the physician approval of the restored plan, as long as dose stability can be assumed. Motion (as well as setup and range uncertainties) can be taken into account by including robust optimization in the dose restoration. Restoring clinically-approved dose distribution on repeated CTs does not require new ROI segmentation and is compatible with an online adaptive workflow.

Adaptive semantic tag mining from heterogeneous clinical research texts.

PubMed

Hao, T; Weng, C

2015-01-01

To develop an adaptive approach to mine frequent semantic tags (FSTs) from heterogeneous clinical research texts. We develop a "plug-n-play" framework that integrates replaceable unsupervised kernel algorithms with formatting, functional, and utility wrappers for FST mining. Temporal information identification and semantic equivalence detection were two example functional wrappers. We first compared this approach's recall and efficiency for mining FSTs from ClinicalTrials.gov to that of a recently published tag-mining algorithm. Then we assessed this approach's adaptability to two other types of clinical research texts: clinical data requests and clinical trial protocols, by comparing the prevalence trends of FSTs across three texts. Our approach increased the average recall and speed by 12.8% and 47.02% respectively upon the baseline when mining FSTs from ClinicalTrials.gov, and maintained an overlap in relevant FSTs with the base- line ranging between 76.9% and 100% for varying FST frequency thresholds. The FSTs saturated when the data size reached 200 documents. Consistent trends in the prevalence of FST were observed across the three texts as the data size or frequency threshold changed. This paper contributes an adaptive tag-mining framework that is scalable and adaptable without sacrificing its recall. This component-based architectural design can be potentially generalizable to improve the adaptability of other clinical text mining methods.

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

Evidence supporting radiation hormesis in atomic bomb survivor cancer mortality data.

PubMed

Doss, Mohan

2012-12-01

A recent update on the atomic bomb survivor cancer mortality data has concluded that excess relative risk (ERR) for solid cancers increases linearly with dose and that zero dose is the best estimate for the threshold, apparently validating the present use of the linear no threshold (LNT) model for estimating the cancer risk from low dose radiation. A major flaw in the standard ERR formalism for estimating cancer risk from radiation (and other carcinogens) is that it ignores the potential for a large systematic bias in the measured baseline cancer mortality rate, which can have a major effect on the ERR values. Cancer rates are highly variable from year to year and between adjacent regions and so the likelihood of such a bias is high. Calculations show that a correction for such a bias can lower the ERRs in the atomic bomb survivor data to negative values for intermediate doses. This is consistent with the phenomenon of radiation hormesis, providing a rational explanation for the decreased risk of cancer observed at intermediate doses for which there is no explanation based on the LNT model. The recent atomic bomb survivor data provides additional evidence for radiation hormesis in humans.

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

PubMed Central

Upton, A C

1983-01-01

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

Induction prednisone dosing for childhood nephrotic syndrome: how low should we go?

PubMed

Sibley, Matthew; Roshan, Abishek; Alshami, Alanoud; Catapang, Marisa; Jöbsis, Jasper J; Kwok, Trevor; Polderman, Nonnie; Sibley, Jennifer; Matsell, Douglas G; Mammen, Cherry

2018-05-22

Historically, children with nephrotic syndrome (NS) across British Columbia (BC), Canada have been cared for without formal standardization of induction prednisone dosing. We hypothesized that local historical practice variation in induction dosing was wide and that children treated with lower doses had worse relapsing outcomes. This retrospective cohort study included 92 NS patients from BC Children's Hospital (1990-2010). We excluded secondary causes of NS, age < 1 year at diagnosis, steroid resistance, and incomplete induction due to early relapse. We explored cumulative induction dose and defined dosing quartiles. Relapsing outcomes above and below each quartile threshold were compared including total relapses in 2 years, time to first relapse, and proportions developing frequently relapsing NS (FRNS) or starting a steroid-sparing agent (SSA). Cumulative prednisone was widely distributed with approximated median, 1st, and 3rd quartile doses of 2500, 2000, and 3000 mg/m 2 respectively. Doses ≤ 2000 mg/m 2 showed significantly higher relapses (4.2 vs 2.7), shorter time to first relapse (61 vs 175 days), and higher SSA use (36 vs 14%) compared to higher doses. Doses ≤ 2500 mg/m 2 also showed significantly more relapses (3.9 vs 2.2), quicker first relapse (79 vs 208 days), and higher FRNS (37 vs 17%) and SSA use (28 vs 11%). Relapsing outcomes lacked statistical difference in ≤ 3000 vs > 3000 mg/m 2 doses. Results strongly justify our development of a standardized, province-wide NS clinical pathway to reduce practice variation and minimize under-treatment. The lowest induction prednisone dosing threshold to minimize future relapsing risks is likely between 2000 and 2500 mg/m 2 . Further prospective studies are warranted.

Effect of Temporal Pattern of Radiation in Intensity Modulated Radiotherapy on Cell Cycle Progression and Apoptosis of ACHN Renal Cell Carcinoma Cell Line.

PubMed

Khorramizadeh, Maryam; Saberi, Alihossein; Tahmasebi-Birgani, Mohammadjavad; Shokrani, Parvaneh; Amouhedari, Alireza

The existence of a hypersensitive radiation response to doses below 1 Gy is well established for many normal and tumor cell lines. The aim of this study was to ascertain the impact of temporal pattern modeling IMRT on survival, cell cycle and apoptosis of human RCC cell line ACHN, so as to provide radiobiological basis for optimizing IMRT plans for this disease. The ACHN renal cell carcinoma cell line was used in this study. Impact of the triangle, V, small-large or large-small temporal patterns in the presence and absence of threshold dose of hyper-radiosensitivity at the beginning of patterns were studied using soft agarclonogenic assays. Cell cycle and apoptosis analysis were performed after irradiation with the temporal patterns. For triangle and small-large dose sequences, survival fraction was significantly reduced after irradiation with or without threshold dose of hyper-radiosensitivity at the beginning of the patterns. In all of the dose patterns, cell cycle distributions and the percentage of apoptotic cells at 24 h after irradiation with or without priming dose of hyper-radiosensitivity showed no significant difference. However, apoptotic cells were increased when beams with the smallest dose applied at the beginning of dose pattern like triangle and small-large dose sequence. These data show that the biologic effects of single fraction may differ in clinical settings depending on the size and sequence of the partial fractions. Doses at the beginning but not at the end of sequences may change cytotoxicity effects of radiation.

Cataract Avoidance With Proton Therapy in Ocular Melanomas.

PubMed

Thariat, Juliette; Jacob, Sophie; Caujolle, Jean-Pierre; Maschi, Celia; Baillif, Stéphanie; Angellier, Gaelle; Mathis, Thibaud; Rosier, Laurence; Carnicer, Adela; Hérault, Joel; Salleron, Julia

2017-10-01

The lens is a radiosensitive organ. Any dose of cephalic irradiation can give rise to radiation-induced cataracts. Contrary to other forms of radiotherapy, proton therapy (PT) can spare all or part of the lens due to accurate dose deposition. We investigated whether a lens-sparing approach was relevant to avoid cataracts in uveal melanoma patients. Patients were referred for PT from onco-ophthalmologists of private and academic institutions. Patients without preexisting cataracts or implants were entered in a prospective database. Dose thresholds responsible for cataracts were investigated in volumes of lens or lens periphery. Lens opacifications and de novo vision-impairing cataracts (VICs) had biannual follow up by ophthalmologists blinded to lens dose. Correlations between dose-volume relationships and VICs were assessed using univariate/multivariate regressions. Between 1991 and 2015, 1696 uveal melanoma patients were consecutively treated with PT. After a median follow up of 48 months, 14.4% and 8.7% of patients had cataracts and VIC within median times of 19 and 28 months, respectively. Median values of mean lens and lens periphery doses were 1.1 (radiobiologically effective [RBE] dose in photon-equivalent grays [GyRBE]) and 6.5 GyRBE, respectively. The lens received no dose in 25% of the patients. At an irradiated lens volume of ≤5%, there was no significantly increased risk for VIC below a dose of 10 GyRBE. A lens-sparing approach is feasible and results not only in reduced need for cataract surgery but also in better fundus-based tumor control. Reassessment of radioprotection rules for lens dose thresholds may follow.

Adaptive/nonadaptive proton radiation planning and outcomes in a phase II trial for locally advanced non-small cell lung cancer.

PubMed

Koay, Eugene J; Lege, David; Mohan, Radhe; Komaki, Ritsuko; Cox, James D; Chang, Joe Y

2012-12-01

To analyze dosimetric variables and outcomes after adaptive replanning of radiation therapy during concurrent high-dose protons and chemotherapy for locally advanced non-small cell lung cancer (NSCLC). Nine of 44 patients with stage III NSCLC in a prospective phase II trial of concurrent paclitaxel/carboplatin with proton radiation [74 Gy(RBE) in 37 fractions] had modifications to their original treatment plans after re-evaluation revealed changes that would compromise coverage of the target volume or violate dose constraints; plans for the other 35 patients were not changed. We compared patients with adaptive plans with those with nonadaptive plans in terms of dosimetry and outcomes. At a median follow-up of 21.2 months (median overall survival, 29.6 months), no differences were found in local, regional, or distant failure or overall survival between groups. Adaptive planning was used more often for large tumors that shrank to a greater extent (median, 107.1 cm(3) adaptive and 86.4 cm(3) nonadaptive; median changes in volume, 25.3% adaptive and 1.2% nonadaptive; P<.01). The median number of fractions delivered using adaptive planning was 13 (range, 4-22). Adaptive planning generally improved sparing of the esophagus (median absolute decrease in V(70), 1.8%; range, 0%-22.9%) and spinal cord (median absolute change in maximum dose, 3.7 Gy; range, 0-13.8 Gy). Without adaptive replanning, target coverage would have been compromised in 2 cases (57% and 82% coverage without adaptation vs 100% for both with adaptation); neither patient experienced local failure. Radiation-related grade 3 toxicity rates were similar between groups. Adaptive planning can reduce normal tissue doses and prevent target misses, particularly for patients with large tumors that shrink substantially during therapy. Adaptive plans seem to have acceptable toxicity and achieve similar local, regional, and distant control and overall survival, even in patients with larger tumors, vs nonadaptive plans. Copyright © 2012 Elsevier Inc. All rights reserved.

Interocular transfer of spatial adaptation is weak at low spatial frequencies.

PubMed

Baker, Daniel H; Meese, Tim S

2012-06-15

Adapting one eye to a high contrast grating reduces sensitivity to similar target gratings shown to the same eye, and also to those shown to the opposite eye. According to the textbook account, interocular transfer (IOT) of adaptation is around 60% of the within-eye effect. However, most previous studies on this were limited to using high spatial frequencies, sustained presentation, and criterion-dependent methods for assessing threshold. Here, we measure IOT across a wide range of spatiotemporal frequencies, using a criterion-free 2AFC method. We find little or no IOT at low spatial frequencies, consistent with other recent observations. At higher spatial frequencies, IOT was present, but weaker than previously reported (around 35%, on average, at 8c/deg). Across all conditions, monocular adaptation raised thresholds by around a factor of 2, and observers showed normal binocular summation, demonstrating that they were not binocularly compromised. These findings prompt a reassessment of our understanding of the binocular architecture implied by interocular adaptation. In particular, the output of monocular channels may be available to perceptual decision making at low spatial frequencies. Copyright © 2012 Elsevier Ltd. All rights reserved.

Caffeine, mental health, and psychiatric disorders.

PubMed

Lara, Diogo R

2010-01-01

Caffeine intake is so common that its pharmacological effects on the mind are undervalued. Since it is so readily available, individuals can adjust their own dose, time of administration and dose intervals of caffeine, according to the perceived benefits and side effects of each dose. This review focuses on human studies of caffeine in subjects with and without psychiatric disorders. Besides the possibility of mild drug dependence, caffeine may bring benefits that contribute to its widespread use. These benefits seem to be related to adaptation of mental energy to the context by increasing alertness, attention, and cognitive function (more evident in longer or more difficult tasks or situations of low arousal) and by elevating mood. Accordingly, moderate caffeine intake (< 6 cups/day) has been associated with less depressive symptoms, fewer cognitive failures, and lower risk of suicide. However, its putative therapeutic effects on depression and ADHD have been insufficiently studied. Conversely, in rare cases high doses of caffeine can induce psychotic and manic symptoms, and more commonly, anxiety. Patients with panic disorder and performance social anxiety disorder seem to be particularly sensitive to the anxiogenic effects of caffeine, whereas preliminary data suggests that it may be effective for some patients with obsessive compulsive disorder (OCD). The threshold for the anxiogenic effect of caffeine is influenced by a polymorphism of the A2A receptor. In summary, caffeine can be regarded as a pharmacological tool to increase energy and effortful behavior in daily activities. More populational (cross-sectional and prospective) and experimental studies are necessary to establish the role of caffeine intake in psychiatric disorders, especially its putative efficacy on depressive mood and cognitive/attentional disorders.

Organic thin film devices with stabilized threshold voltage and mobility, and method for preparing the devices

DOEpatents

Nastasi, Michael Anthony; Wang, Yongqiang; Fraboni, Beatrice; Cosseddu, Piero; Bonfiglio, Annalisa

2013-06-11

Organic thin film devices that included an organic thin film subjected to a selected dose of a selected energy of ions exhibited a stabilized mobility (.mu.) and threshold voltage (VT), a decrease in contact resistance R.sub.C, and an extended operational lifetime that did not degrade after 2000 hours of operation in the air.

Analysis of risk and predictors of brain radiation necrosis after radiosurgery.

PubMed

Zhuang, Hongqing; Zheng, Yi; Wang, Junjie; Chang, Joe Y; Wang, Xiaoguang; Yuan, Zhiyong; Wang, Ping

2016-02-16

In this study, we examined the factors contributing to brain radiation necrosis and its predictors of patients treated with Cyberknife radiosurgery. A total of 94 patients with primary or metastatic brain tumours having been treated with Cyberknife radiotherapy from Sep. 2006 to Oct. 2011 were collected and retrospectively analyzed. Skull based tracking was used to deliver radiation to 104 target sites. and the prescribed radiation doses ranged from 1200 to 4500 cGy in 1 to 8 fractions with a 60% to 87% isodose line. Radiation necrosis was confirmed by imaging or pathological examination. Associations between cerebral radiation necrosis and factors including diabetes, cardio-cerebrovascular disease, target volume, isodose line, prescribed dosage, number of fractions, combination with whole brain radiation and biologically equivalent dose (BED) were determined by logistic regression. ROC curves were created to measure the predictive accuracy of influence factors and identify the threshold for brain radiation necrosis. Our results showed that radiation necrosis occurred in 12 targets (11.54%). Brain radiation necrosis was associated by BED, combination with whole brain radiotherapy, and fractions (areas under the ROC curves = 0.892±0.0335, 0.650±0.0717, and 0.712±0.0637 respectively). Among these factors, only BED had the capability to predict brain radiation necrosis, and the threshold dose was 7410 cGy. In conclusion, BED is the most effective predictor of brain radiation necrosis, with a dose of 7410 cGy being identified as the threshold.

Measurand transient signal suppressor

NASA Technical Reports Server (NTRS)

Bozeman, Richard J., Jr. (Inventor)

1994-01-01

A transient signal suppressor for use in a controls system which is adapted to respond to a change in a physical parameter whenever it crosses a predetermined threshold value in a selected direction of increasing or decreasing values with respect to the threshold value and is sustained for a selected discrete time interval is presented. The suppressor includes a sensor transducer for sensing the physical parameter and generating an electrical input signal whenever the sensed physical parameter crosses the threshold level in the selected direction. A manually operated switch is provided for adapting the suppressor to produce an output drive signal whenever the physical parameter crosses the threshold value in the selected direction of increasing or decreasing values. A time delay circuit is selectively adjustable for suppressing the transducer input signal for a preselected one of a plurality of available discrete suppression time and producing an output signal only if the input signal is sustained for a time greater than the selected suppression time. An electronic gate is coupled to receive the transducer input signal and the timer output signal and produce an output drive signal for energizing a control relay whenever the transducer input is a non-transient signal which is sustained beyond the selected time interval.

Uncertainty Estimates of Psychoacoustic Thresholds Obtained from Group Tests

NASA Technical Reports Server (NTRS)

Rathsam, Jonathan; Christian, Andrew

2016-01-01

Adaptive psychoacoustic test methods, in which the next signal level depends on the response to the previous signal, are the most efficient for determining psychoacoustic thresholds of individual subjects. In many tests conducted in the NASA psychoacoustic labs, the goal is to determine thresholds representative of the general population. To do this economically, non-adaptive testing methods are used in which three or four subjects are tested at the same time with predetermined signal levels. This approach requires us to identify techniques for assessing the uncertainty in resulting group-average psychoacoustic thresholds. In this presentation we examine the Delta Method of frequentist statistics, the Generalized Linear Model (GLM), the Nonparametric Bootstrap, a frequentist method, and Markov Chain Monte Carlo Posterior Estimation and a Bayesian approach. Each technique is exercised on a manufactured, theoretical dataset and then on datasets from two psychoacoustics facilities at NASA. The Delta Method is the simplest to implement and accurate for the cases studied. The GLM is found to be the least robust, and the Bootstrap takes the longest to calculate. The Bayesian Posterior Estimate is the most versatile technique examined because it allows the inclusion of prior information.

A globally convergent MC algorithm with an adaptive learning rate.

PubMed

Peng, Dezhong; Yi, Zhang; Xiang, Yong; Zhang, Haixian

2012-02-01

This brief deals with the problem of minor component analysis (MCA). Artificial neural networks can be exploited to achieve the task of MCA. Recent research works show that convergence of neural networks based MCA algorithms can be guaranteed if the learning rates are less than certain thresholds. However, the computation of these thresholds needs information about the eigenvalues of the autocorrelation matrix of data set, which is unavailable in online extraction of minor component from input data stream. In this correspondence, we introduce an adaptive learning rate into the OJAn MCA algorithm, such that its convergence condition does not depend on any unobtainable information, and can be easily satisfied in practical applications.

Evaluation of adaptive treatment planning for patients with non-small cell lung cancer

NASA Astrophysics Data System (ADS)

Zhong, Hualiang; Siddiqui, Salim M.; Movsas, Benjamin; Chetty, Indrin J.

2017-06-01

The purpose of this study was to develop metrics to evaluate uncertainties in deformable dose accumulation for patients with non-small cell lung cancer (NSCLC). Initial treatment plans (primary) and cone-beam CT (CBCT) images were retrospectively processed for seven NSCLC patients, who showed significant tumor regression during the course of treatment. Each plan was developed with IMRT for 2 Gy  ×  33 fractions. A B-spline-based DIR algorithm was used to register weekly CBCT images to a reference image acquired at fraction 21 and the resultant displacement vector fields (DVFs) were then modified using a finite element method (FEM). The doses were calculated on each of these CBCT images and mapped to the reference image using a tri-linear dose interpolation method, based on the B-spline and FEM-generated DVFs. Contours propagated from the planning image were adjusted to the residual tumor and OARs on the reference image to develop a secondary plan. For iso-prescription adaptive plans (relative to initial plans), mean lung dose (MLD) was reduced, on average from 17.3 Gy (initial plan) to 15.2, 14.5 and 14.8 Gy for the plans adapted using the rigid, B-Spline and FEM-based registrations. Similarly, for iso-toxic adaptive plans (considering MLD relative to initial plans) using the rigid, B-Spline and FEM-based registrations, the average doses were 69.9  ±  6.8, 65.7  ±  5.1 and 67.2  ±  5.6 Gy in the initial volume (PTV1), and 81.5  ±  25.8, 77.7  ±  21.6, and 78.9  ±  22.5 Gy in the residual volume (PTV21), respectively. Tumor volume reduction was correlated with dose escalation (for isotoxic plans, correlation coefficient  =  0.92), and with MLD reduction (for iso-fractional plans, correlation coefficient  =  0.85). For the case of the iso-toxic dose escalation, plans adapted with the B-Spline and FEM DVFs differed from the primary plan adapted with rigid registration by 2.8  ±  1.0 Gy and 1.8  ±  0.9 Gy in PTV1, and the mean difference between doses accumulated using the B-spline and FEM DVF’s was 1.1  ±  0.6 Gy. As a dose mapping-induced energy change, energy defect in the tumor volume was 20.8  ±  13.4% and 4.5  ±  2.4% for the B-spline and FEM-based dose accumulations, respectively. The energy defect of the B-Spline-based dose accumulation is significant in the tumor volume and highly correlated to the difference between the B-Spline and FEM-accumulated doses with their correlation coefficient equal to 0.79. Adaptive planning helps escalate target dose and spare normal tissue for patients with NSCLC, but deformable dose accumulation may have a significant loss of energy in regressed tumor volumes when using image intensity-based DIR algorithms. The metric of energy defect is a useful tool for evaluation of adaptive planning accuracy for lung cancer patients.

SU-F-J-57: Effectiveness of Daily CT-Based Three-Dimensional Image Guided and Adaptive Proton Therapy

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

Moriya, S; National Cancer Center, Kashiwa, Chiba; Tachibana, H

Purpose: Daily CT-based three-dimensional image-guided and adaptive (CTIGRT-ART) proton therapy system was designed and developed. We also evaluated the effectiveness of the CTIGRT-ART. Methods: Retrospective analysis was performed in three lung cancer patients: Proton treatment planning was performed using CT image datasets acquired by Toshiba Aquilion ONE. Planning target volume and surrounding organs were contoured by a well-trained radiation oncologist. Dose distribution was optimized using 180-deg. and 270-deg. two fields in passive scattering proton therapy. Well commissioned Simplified Monte Carlo algorithm was used as dose calculation engine. Daily consecutive CT image datasets was acquired by an in-room CT (Toshiba Aquilionmore » LB). In our in-house program, two image registrations for bone and tumor were performed to shift the isocenter using treatment CT image dataset. Subsequently, dose recalculation was performed after the shift of the isocenter. When the dose distribution after the tumor registration exhibits change of dosimetric parameter of CTV D90% compared to the initial plan, an additional process of was performed that the range shifter thickness was optimized. Dose distribution with CTV D90% for the bone registration, the tumor registration only and adaptive plan with the tumor registration was compared to the initial plan. Results: In the bone registration, tumor dose coverage was decreased by 16% on average (Maximum: 56%). The tumor registration shows better coverage than the bone registration, however the coverage was also decreased by 9% (Maximum: 22%) The adaptive plan shows similar dose coverage of the tumor (Average: 2%, Maximum: 7%). Conclusion: There is a high possibility that only image registration for bone and tumor may reduce tumor coverage. Thus, our proposed methodology of image guidance and adaptive planning using the range adaptation after tumor registration would be effective for proton therapy. This research is partially supported by Japan Agency for Medical Research and Development (AMED).« less

Comparison of in-air evoked potential and underwater behavioral hearing thresholds in four bottlenose dolphins (Tursiops truncatus).

PubMed

Finneran, James J; Houser, Dorian S

2006-05-01

Traditional behavioral techniques for hearing assessment in marine mammals are limited by the time and access required to train subjects. Electrophysiological methods, where passive electrodes are used to measure auditory evoked potentials (AEPs), are attractive alternatives to behavioral techniques; however, there have been few attempts to compare AEP and behavioral results for the same subject. In this study, behavioral and AEP hearing thresholds were compared in four bottlenose dolphins. AEP thresholds were measured in-air using a piezoelectric sound projector embedded in a suction cup to deliver amplitude modulated tones to the dolphin through the lower jaw. Evoked potentials were recorded noninvasively using surface electrodes. Adaptive procedures allowed AEP hearing thresholds to be estimated from 10 to 150 kHz in a single ear in about 45 min. Behavioral thresholds were measured in a quiet pool and in San Diego Bay. AEP and behavioral threshold estimates agreed closely as to the upper cutoff frequency beyond which thresholds increased sharply. AEP thresholds were strongly correlated with pool behavioral thresholds across the range of hearing; differences between AEP and pool behavioral thresholds increased with threshold magnitude and ranged from 0 to + 18 dB.

Low dose radiation interactions with the transformation growth factor (TFG)-beta pathway

NASA Astrophysics Data System (ADS)

Maslowski, Amy Jesse

A major limiting factor for long-term, deep-space missions is the radiation dose to astronauts. Because the dose to the astronauts is a mixed field of low- and high-LET radiation, there is a need to understand the effects of both radiation types on whole tissue; however, there are limited published data on the effects of high-LET (linear-energy-transfer) radiation on tissue. Thus, we designed a perfusion chamber system for rat trachea in order to mimic in vivo respiratory tissue. We successfully maintained the perfused tracheal tissue ex vivo in a healthy and viable condition for up to three days. In addition, this project studied the effects of high-LET Fe particles on the overall transformation growth factor (TGF)-beta response after TGF-beta inactivation and compared the results to the TGF-beta response post x-ray irradiation. It was found that a TGF-beta response could be measured in the perfused tracheal tissue, for x-ray and Fe particle irradiations, despite the high autofluorescent background intrinsic to tissue. However, after comparing the TGF-beta response of x-ray irradiation to High-Z-High-energy (HZE) irradiation, there was not a significant difference in radiation types. The TGF-beta response in x-ray and HZE irradiated perfusion chambers was also measured over time post irradiation. It was found that for 6 hour and 8 hour post irradiation, the TGF-beta response was higher for lower doses of radiation than for higher doses. This is in contrast to the 0 hour fixation which found the TGF-beta response to increase with increased dose. The inverse relationship found for 6 hour and 8 hour fixation times may indicate a threshold response for TGF-beta response; i.e., for low doses, a threshold of dose must be reached for an immediate TGF-beta response, otherwise the tissue responds more slowly to the irradiation damage. This result was unexpected and will require further investigation to determine if the threshold can be determined for the 250 kVp x-rays and 1 Gev Fe particles.

Cavitation and non-cavitation regime for large-scale ultrasonic standing wave particle separation systems--In situ gentle cavitation threshold determination and free radical related oxidation.

PubMed

Johansson, Linda; Singh, Tanoj; Leong, Thomas; Mawson, Raymond; McArthur, Sally; Manasseh, Richard; Juliano, Pablo

2016-01-01

We here suggest a novel and straightforward approach for liter-scale ultrasound particle manipulation standing wave systems to guide system design in terms of frequency and acoustic power for operating in either cavitation or non-cavitation regimes for ultrasound standing wave systems, using the sonochemiluminescent chemical luminol. We show that this method offers a simple way of in situ determination of the cavitation threshold for selected separation vessel geometry. Since the pressure field is system specific the cavitation threshold is system specific (for the threshold parameter range). In this study we discuss cavitation effects and also measure one implication of cavitation for the application of milk fat separation, the degree of milk fat lipid oxidation by headspace volatile measurements. For the evaluated vessel, 2 MHz as opposed to 1 MHz operation enabled operation in non-cavitation or low cavitation conditions as measured by the luminol intensity threshold method. In all cases the lipid oxidation derived volatiles were below the human sensory detection level. Ultrasound treatment did not significantly influence the oxidative changes in milk for either 1 MHz (dose of 46 kJ/L and 464 kJ/L) or 2 MHz (dose of 37 kJ/L and 373 kJ/L) operation. Copyright © 2015 Elsevier B.V. All rights reserved.

Methods for Reducing Normal Tissue Complication Probabilities in Oropharyngeal Cancer: Dose Reduction or Planning Target Volume Elimination

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

Samuels, Stuart E.; Eisbruch, Avraham; Vineberg, Karen

Purpose: Strategies to reduce the toxicities of head and neck radiation (ie, dysphagia [difficulty swallowing] and xerostomia [dry mouth]) are currently underway. However, the predicted benefit of dose and planning target volume (PTV) reduction strategies is unknown. The purpose of the present study was to compare the normal tissue complication probabilities (NTCP) for swallowing and salivary structures in standard plans (70 Gy [P70]), dose-reduced plans (60 Gy [P60]), and plans eliminating the PTV margin. Methods and Materials: A total of 38 oropharyngeal cancer (OPC) plans were analyzed. Standard organ-sparing volumetric modulated arc therapy plans (P70) were created and then modified by eliminatingmore » the PTVs and treating the clinical tumor volumes (CTVs) only (C70) or maintaining the PTV but reducing the dose to 60 Gy (P60). NTCP dose models for the pharyngeal constrictors, glottis/supraglottic larynx, parotid glands (PGs), and submandibular glands (SMGs) were analyzed. The minimal clinically important benefit was defined as a mean change in NTCP of >5%. The P70 NTCP thresholds and overlap percentages of the organs at risk with the PTVs (56-59 Gy, vPTV{sub 56}) were evaluated to identify the predictors for NTCP improvement. Results: With the P60 plans, only the ipsilateral PG (iPG) benefited (23.9% vs 16.2%; P<.01). With the C70 plans, only the iPG (23.9% vs 17.5%; P<.01) and contralateral SMG (cSMG) (NTCP 32.1% vs 22.9%; P<.01) benefited. An iPG NTCP threshold of 20% and 30% predicted NTCP benefits for the P60 and C70 plans, respectively (P<.001). A cSMG NTCP threshold of 30% predicted for an NTCP benefit with the C70 plans (P<.001). Furthermore, for the iPG, a vPTV{sub 56} >13% predicted benefit with P60 (P<.001) and C70 (P=.002). For the cSMG, a vPTV{sub 56} >22% predicted benefit with C70 (P<.01). Conclusions: PTV elimination and dose-reduction lowered the NTCP of the iPG, and PTV elimination lowered the NTCP of the cSMG. NTCP thresholds and the percentage of overlap of the PTV with organs at risk can predict which patients will benefit and inform future clinical trial design.« less

TU-AB-BRA-11: Indications for Online Adaptive Radiotherapy Based On Dosimetric Consequences of Interfractional Pancreas-To-Duodenum Motion in MRI-Guided Pancreatic Radiotherapy

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

Mittauer, K; Rosenberg, S; Geurts, M

Purpose: Dose limiting structures, such as the duodenum, render the treatment of pancreatic cancer challenging. In this multi-institutional study, we assess dosimetric differences caused by interfraction pancreas-to-duodenum motion using MR-IGRT to determine the potential impact of adaptive replanning. Methods: Ten patients from two institutions undergoing MRI-guided radiotherapy with conventional fractionation (n=5) or SBRT (n=5) for pancreatic cancer were included. Initial plans were limited by duodenal dose constraints of 50 Gy (0.5 cc)/31 Gy (0.1 cc) for conventional/SBRT with prescriptions of 30 Gy/5 fractions (SBRT) and 40–50 Gy/25 fractions (conventional). Daily volumetric MR images were acquired under treatment conditions on amore » clinical MR-IGRT system. The correlation was assessed between interfractional GTV-to-duodenum positional variation and daily recalculations of duodenal dose metrics. Positional variation was quantified as the interfraction difference in Hausdorff distance from simulation baseline (ΔHD) between the GTV and proximal duodenal surface, or volume overlap between GTV and duodenum for cases with HD{sub 0}=0 (GTV abutting duodenum). Adaptation was considered indicated when daily positional variations enabled dose escalation to the target while maintaining duodenal constraints. Results: For fractions with ΔHD>0 (n=14, SBRT only), the mean interfraction duodenum dose decrease from simulation to treatment was 44±53 cGy (maximum 136 cGy). A correlation was found between ΔHD and dosimetric difference (R{sup 2}=0.82). No correlation was found between volume of overlap and dosimetric difference (R{sup 2}=0.31). For 89% of fractions, the duodenum remained overlapped with the target and the duodenal dose difference was negligible. The maximum observed indication for adaptation was for interfraction ΔHD=11.6 mm with potential for adaptive dose escalation of 136 cGy. Conclusion: This assessment showed that Hausdorff distance was a reasonable metric to use to determine the indication for adaptation. Adaptation was potentially indicated in 11% of the treatments (fractions where GTV-to-duodenum distance increased from simulation), with a feasible average dose escalation of 7.0%. MB, LH, JO, RK, PP: research and/or travel funding from ViewRay Inc. PP: research grant from Varian Medical Systems and Philips Healthcare.« less

Adaptive Responses to Prochloraz Exposure That Alter Dose-Response and Time-Course Behaviors

EPA Science Inventory

Dose response and time-course (DRTC) are, along with exposure, the major determinants of health risk. Adaptive changes within exposed organisms in response to environmental stress are common, and alter DRTC behaviors to minimize the effects caused by stressors. In this project, ...

Determining the Critical Dose Threshold of Electron-Induced Electron Yield for Minimally Charged Highly Insulating Materials

NASA Astrophysics Data System (ADS)

Hoffmann, Ryan; Dennison, J. R.; Abbott, Jonathan

2006-03-01

When incident energetic electrons interact with a material, they excite electrons within the material to escape energies. The electron emission is quantified as the ratio of emitted electrons to incident particle flux, termed electron yield. Measuring the electron yield of insulators is difficult due to dynamic surface charge accumulation which directly affects landing energies and the potential barrier that emitted electrons must overcome. Our recent measurements of highly insulating materials have demonstrated significant changes in total yield curves and yield decay curves for very small electron doses equivalent to a trapped charge density of <10^10 electrons /cm^3. The Chung-Everhart theory provides a basic model for the behavior of the electron emission spectra which we relate to yield decay curves as charge is allowed to accumulate. Yield measurements as a function of dose for polyimide (Kapton^TM) and microcrystalline SiO2 will be presented. We use our data and model to address the question of whether there is a minimal dose threshold at which the accumulated charge no longer affects the yield.

Prediction of error rates in dose-imprinted memories on board CRRES by two different methods. [Combined Release and Radiation Effects Satellite

NASA Technical Reports Server (NTRS)

Brucker, G. J.; Stassinopoulos, E. G.

1991-01-01

An analysis of the expected space radiation effects on the single event upset (SEU) properties of CMOS/bulk memories onboard the Combined Release and Radiation Effects Satellite (CRRES) is presented. Dose-imprint data from ground test irradiations of identical devices are applied to the predictions of cosmic-ray-induced space upset rates in the memories onboard the spacecraft. The calculations take into account the effect of total dose on the SEU sensitivity of the devices as the dose accumulates in orbit. Estimates of error rates, which involved an arbitrary selection of a single pair of threshold linear energy transfer (LET) and asymptotic cross-section values, were compared to the results of an integration over the cross-section curves versus LET. The integration gave lower upset rates than the use of the selected values of the SEU parameters. Since the integration approach is more accurate and eliminates the need for an arbitrary definition of threshold LET and asymptotic cross section, it is recommended for all error rate predictions where experimental sigma-versus-LET curves are available.

Genetic deletion of the norepinephrine transporter decreases vulnerability to seizures

PubMed Central

Kaminski, Rafal M.; Shippenberg, Toni S.; Witkin, Jeffrey M.; Rocha, Beatriz A.

2005-01-01

Norepinephrine (NE) has been reported to modulate neuronal excitability and act as endogenous anticonvulsant. In the present study we used NE transporter knock-out mice (NET-KO), which are characterized by high levels of extracellular NE, to investigate the role of endogenous NE in seizure susceptibility. Seizure thresholds for cocaine (i.p.), pentylenetetrazol (i.v.) and kainic acid (i.v.) were compared in NET-KO, heterozygous (NET-HT) and wild type (NET-WT) female mice. The dose-response curve for cocaine-induced convulsions was significantly shifted to the right in NET-KO mice, indicating higher seizure thresholds. The threshold doses of pentylenetetrazol that induced clonic and tonic seizures were also significantly higher in NET-KO when compared to NET-WT mice. Similarly, NET-KO mice displayed higher resistance to convulsions engendered by kainic acid. For all drugs tested, the response of NET-HT mice was always intermediate. These data provide further support for a role of endogenous NE in the control of seizure susceptibility. PMID:15911120

The risk of radiation exposure to the eyes of the interventional pain physician.

PubMed

Fish, David E; Kim, Andrew; Ornelas, Christopher; Song, Sungchan; Pangarkar, Sanjog

2011-01-01

It is widely accepted that the use of medical imaging continues to grow across the globe as does the concern for radiation safety. The danger of lens opacities and cataract formation related to radiation exposure is well documented in the medical literature. However, there continues to be controversy regarding actual dose thresholds of radiation exposure and whether these thresholds are still relevant to cataract formation. Eye safety and the risk involved for the interventional pain physician is not entirely clear. Given the available literature on measured radiation exposure to the interventionist, and the controversy regarding dose thresholds, it is our current recommendation that the interventional pain physician use shielded eyewear. As the breadth of interventional procedures continues to grow, so does the radiation risk to the interventional pain physician. In this paper, we attempt to outline the risk of cataract formation in the scope of practice of an interventional pain physician and describe techniques that may help reduce them.

The Risk of Radiation Exposure to the Eyes of the Interventional Pain Physician

PubMed Central

Fish, David E.; Kim, Andrew; Ornelas, Christopher; Song, Sungchan; Pangarkar, Sanjog

2011-01-01

It is widely accepted that the use of medical imaging continues to grow across the globe as does the concern for radiation safety. The danger of lens opacities and cataract formation related to radiation exposure is well documented in the medical literature. However, there continues to be controversy regarding actual dose thresholds of radiation exposure and whether these thresholds are still relevant to cataract formation. Eye safety and the risk involved for the interventional pain physician is not entirely clear. Given the available literature on measured radiation exposure to the interventionist, and the controversy regarding dose thresholds, it is our current recommendation that the interventional pain physician use shielded eyewear. As the breadth of interventional procedures continues to grow, so does the radiation risk to the interventional pain physician. In this paper, we attempt to outline the risk of cataract formation in the scope of practice of an interventional pain physician and describe techniques that may help reduce them. PMID:22091381

Radiation Resistance of the U(Al, Si)3 Alloy: Ion-Induced Disordering

PubMed Central

Yaniv, Gili; Horak, Pavel; Vacik, Jiri; Mykytenko, Natalia; Rafailov, Gennady; Dahan, Itzchak; Fuks, David; Kiv, Arik

2018-01-01

During the exploitation of nuclear reactors, various U-Al based ternary intermetallides are formed in the fuel-cladding interaction layer. Structure and physical properties of these intermetallides determine the radiation resistance of cladding and, ultimately, the reliability and lifetime of the nuclear reactor. In current research, U(Al, Si)3 composition was studied as a potential constituent of an interaction layer. Phase content of the alloy of an interest was ordered U(Al, Si)3, structure of which was reported earlier, and pure Al (constituting less than 20 vol % of the alloy). This alloy was investigated prior and after the irradiation performed by Ar ions at 30 keV. The irradiation was performed on the transmission electron microscopy (TEM, JEOL, Japan) samples, characterized before and after the irradiation process. Irradiation induced disorder accompanied by stress relief. Furthermore, it was found that there is a dose threshold for disordering of the crystalline matter in the irradiated region. Irradiation at doses equal or higher than this threshold resulted in almost solely disordered phase. Using the program “Stopping and Range of Ions in Matter” (SRIM), the parameters of penetration of Ar ions into the irradiated samples were estimated. Based on these estimations, the dose threshold for ion-induced disordering of the studied material was assessed. PMID:29393870

Radiation Resistance of the U(Al, Si)₃ Alloy: Ion-Induced Disordering.

PubMed

Meshi, Louisa; Yaniv, Gili; Horak, Pavel; Vacik, Jiri; Mykytenko, Natalia; Rafailov, Gennady; Dahan, Itzchak; Fuks, David; Kiv, Arik

2018-02-02

During the exploitation of nuclear reactors, various U-Al based ternary intermetallides are formed in the fuel-cladding interaction layer. Structure and physical properties of these intermetallides determine the radiation resistance of cladding and, ultimately, the reliability and lifetime of the nuclear reactor. In current research, U(Al, Si)₃ composition was studied as a potential constituent of an interaction layer. Phase content of the alloy of an interest was ordered U(Al, Si)₃, structure of which was reported earlier, and pure Al (constituting less than 20 vol % of the alloy). This alloy was investigated prior and after the irradiation performed by Ar ions at 30 keV. The irradiation was performed on the transmission electron microscopy (TEM, JEOL, Japan) samples, characterized before and after the irradiation process. Irradiation induced disorder accompanied by stress relief. Furthermore, it was found that there is a dose threshold for disordering of the crystalline matter in the irradiated region. Irradiation at doses equal or higher than this threshold resulted in almost solely disordered phase. Using the program "Stopping and Range of Ions in Matter" (SRIM), the parameters of penetration of Ar ions into the irradiated samples were estimated. Based on these estimations, the dose threshold for ion-induced disordering of the studied material was assessed.

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

Koay, Eugene J.; Lege, David; Mohan, Radhe

Purpose: To analyze dosimetric variables and outcomes after adaptive replanning of radiation therapy during concurrent high-dose protons and chemotherapy for locally advanced non-small cell lung cancer (NSCLC). Methods and Materials: Nine of 44 patients with stage III NSCLC in a prospective phase II trial of concurrent paclitaxel/carboplatin with proton radiation [74 Gy(RBE) in 37 fractions] had modifications to their original treatment plans after re-evaluation revealed changes that would compromise coverage of the target volume or violate dose constraints; plans for the other 35 patients were not changed. We compared patients with adaptive plans with those with nonadaptive plans in termsmore » of dosimetry and outcomes. Results: At a median follow-up of 21.2 months (median overall survival, 29.6 months), no differences were found in local, regional, or distant failure or overall survival between groups. Adaptive planning was used more often for large tumors that shrank to a greater extent (median, 107.1 cm{sup 3} adaptive and 86.4 cm{sup 3} nonadaptive; median changes in volume, 25.3% adaptive and 1.2% nonadaptive; P<.01). The median number of fractions delivered using adaptive planning was 13 (range, 4-22). Adaptive planning generally improved sparing of the esophagus (median absolute decrease in V{sub 70}, 1.8%; range, 0%-22.9%) and spinal cord (median absolute change in maximum dose, 3.7 Gy; range, 0-13.8 Gy). Without adaptive replanning, target coverage would have been compromised in 2 cases (57% and 82% coverage without adaptation vs 100% for both with adaptation); neither patient experienced local failure. Radiation-related grade 3 toxicity rates were similar between groups. Conclusions: Adaptive planning can reduce normal tissue doses and prevent target misses, particularly for patients with large tumors that shrink substantially during therapy. Adaptive plans seem to have acceptable toxicity and achieve similar local, regional, and distant control and overall survival, even in patients with larger tumors, vs nonadaptive plans.« less

The Role of Parametric Assumptions in Adaptive Bayesian Estimation

ERIC Educational Resources Information Center

Alcala-Quintana, Rocio; Garcia-Perez, Miguel A.

2004-01-01

Variants of adaptive Bayesian procedures for estimating the 5% point on a psychometric function were studied by simulation. Bias and standard error were the criteria to evaluate performance. The results indicated a superiority of (a) uniform priors, (b) model likelihood functions that are odd symmetric about threshold and that have parameter…

An electrophysiological investigation of the receptor apparatus of the duck's bill

PubMed Central

Gregory, J. E.

1973-01-01

1. The properties of receptors in the duck's bill have been studied by recording from units isolated by dissecting fine filaments from the maxillary and ophthalmic nerves. 2. The units studied were divisible into three groups, phasic mechanoreceptors responsive to vibration, thermoreceptive units, and high threshold mechanoreceptors. 3. Vibration-sensitive mechanoreceptors (113 units) had small receptive fields, showed a rapidly adapting discharge to mechanical stimulation of the bill, were sensitive to vibratory but not to thermal stimuli and showed no background discharge. 4. Temperature receptors (twenty-one units) were insensitive to mechanical stimulation and showed a temperature-dependent background discharge. Sudden cooling produced a transient increase in discharge frequency. 5. High threshold mechanosensitive units (eight units) gave a slowly adapting discharge to strong mechanical stimulation and were insensitive to vibratory and thermal stimulation. 6. It is concluded that the low-threshold, vibration-sensitive responses come from Herbst corpuscles. No specific function can yet be assigned to the Grandry corpuscles. PMID:4689962

The NTID speech recognition test: NSRT(®).

PubMed

Bochner, Joseph H; Garrison, Wayne M; Doherty, Karen A

2015-07-01

The purpose of this study was to collect and analyse data necessary for expansion of the NSRT item pool and to evaluate the NSRT adaptive testing software. Participants were administered pure-tone and speech recognition tests including W-22 and QuickSIN, as well as a set of 323 new NSRT items and NSRT adaptive tests in quiet and background noise. Performance on the adaptive tests was compared to pure-tone thresholds and performance on other speech recognition measures. The 323 new items were subjected to Rasch scaling analysis. Seventy adults with mild to moderately severe hearing loss participated in this study. Their mean age was 62.4 years (sd = 20.8). The 323 new NSRT items fit very well with the original item bank, enabling the item pool to be more than doubled in size. Data indicate high reliability coefficients for the NSRT and moderate correlations with pure-tone thresholds (PTA and HFPTA) and other speech recognition measures (W-22, QuickSIN, and SRT). The adaptive NSRT is an efficient and effective measure of speech recognition, providing valid and reliable information concerning respondents' speech perception abilities.

Differentially Private Histogram Publication For Dynamic Datasets: An Adaptive Sampling Approach

PubMed Central

Li, Haoran; Jiang, Xiaoqian; Xiong, Li; Liu, Jinfei

2016-01-01

Differential privacy has recently become a de facto standard for private statistical data release. Many algorithms have been proposed to generate differentially private histograms or synthetic data. However, most of them focus on “one-time” release of a static dataset and do not adequately address the increasing need of releasing series of dynamic datasets in real time. A straightforward application of existing histogram methods on each snapshot of such dynamic datasets will incur high accumulated error due to the composibility of differential privacy and correlations or overlapping users between the snapshots. In this paper, we address the problem of releasing series of dynamic datasets in real time with differential privacy, using a novel adaptive distance-based sampling approach. Our first method, DSFT, uses a fixed distance threshold and releases a differentially private histogram only when the current snapshot is sufficiently different from the previous one, i.e., with a distance greater than a predefined threshold. Our second method, DSAT, further improves DSFT and uses a dynamic threshold adaptively adjusted by a feedback control mechanism to capture the data dynamics. Extensive experiments on real and synthetic datasets demonstrate that our approach achieves better utility than baseline methods and existing state-of-the-art methods. PMID:26973795

Thyroid Cancer Following Childhood Low-Dose Radiation Exposure: A Pooled Analysis of Nine Cohorts.

PubMed

Lubin, Jay H; Adams, M Jacob; Shore, Roy; Holmberg, Erik; Schneider, Arthur B; Hawkins, Michael M; Robison, Leslie L; Inskip, Peter D; Lundell, Marie; Johansson, Robert; Kleinerman, Ruth A; de Vathaire, Florent; Damber, Lena; Sadetzki, Siegal; Tucker, Margaret; Sakata, Ritsu; Veiga, Lene H S

2017-07-01

The increased use of diagnostic and therapeutic procedures that involve radiation raises concerns about radiation effects, particularly in children and the radiosensitive thyroid gland. Evaluation of relative risk (RR) trends for thyroid radiation doses <0.2 gray (Gy); evidence of a threshold dose; and possible modifiers of the dose-response, e.g., sex, age at exposure, time since exposure. Pooled data from nine cohort studies of childhood external radiation exposure and thyroid cancer with individualized dose estimates, ≥1000 irradiated subjects or ≥10 thyroid cancer cases, with data limited to individuals receiving doses <0.2 Gy. Cohorts included the following: childhood cancer survivors (n = 2); children treated for benign diseases (n = 6); and children who survived the atomic bombings in Japan (n = 1). There were 252 cases and 2,588,559 person-years in irradiated individuals and 142 cases and 1,865,957 person-years in nonirradiated individuals. There were no interventions. Incident thyroid cancers. For both <0.2 and <0.1 Gy, RRs increased with thyroid dose (P < 0.01), without significant departure from linearity (P = 0.77 and P = 0.66, respectively). Estimates of threshold dose ranged from 0.0 to 0.03 Gy, with an upper 95% confidence bound of 0.04 Gy. The increasing dose-response trend persisted >45 years after exposure, was greater at younger age at exposure and younger attained age, and was similar by sex and number of treatments. Our analyses reaffirmed linearity of the dose response as the most plausible relationship for "as low as reasonably achievable" assessments for pediatric low-dose radiation-associated thyroid cancer risk. Copyright © 2017 Endocrine Society

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.

Evidence for dose-additive effects of pyrethroids on motor activity in rats.

PubMed

Wolansky, Marcelo J; Gennings, Chris; DeVito, Michael J; Crofton, Kevin M

2009-10-01

Pyrethroids are neurotoxic insecticides used in a variety of indoor and outdoor applications. Previous research characterized the acute dose-effect functions for 11 pyrethroids administered orally in corn oil (1 mL/kg) based on assessment of motor activity. We used a mixture of these 11 pyrethroids and the same testing paradigm used in single-compound assays to test the hypothesis that cumulative neurotoxic effects of pyrethroid mixtures can be predicted using the default dose-addition theory. Mixing ratios of the 11 pyrethroids in the tested mixture were based on the ED30 (effective dose that produces a 30% decrease in response) of the individual chemical (i.e., the mixture comprised equipotent amounts of each pyrethroid). The highest concentration of each individual chemical in the mixture was less than the threshold for inducing behavioral effects. Adult male rats received acute oral exposure to corn oil (control) or dilutions of the stock mixture solution. The mixture of 11 pyrethroids was administered either simultaneously (2 hr before testing) or after a sequence based on times of peak effect for the individual chemicals (4, 2, and 1 hr before testing). A threshold additivity model was fit to the single-chemical data to predict the theoretical dose-effect relationship for the mixture under the assumption of dose additivity. When subthreshold doses of individual chemicals were combined in the mixtures, we found significant dose-related decreases in motor activity. Further, we found no departure from the predicted dose-additive curve regardless of the mixture dosing protocol used. In this article we present the first in vivo evidence on pyrethroid cumulative effects supporting the default assumption of dose addition.

Modelling PK/QT relationships from Phase I dose-escalation trials for drug combinations and developing quantitative risk assessments of clinically relevant QT prolongations.

PubMed

Sinclair, Karen; Kinable, Els; Grosch, Kai; Wang, Jixian

2016-05-01

In current industry practice, it is difficult to assess QT effects at potential therapeutic doses based on Phase I dose-escalation trials in oncology due to data scarcity, particularly in combinations trials. In this paper, we propose to use dose-concentration and concentration-QT models jointly to model the exposures and effects of multiple drugs in combination. The fitted models then can be used to make early predictions for QT prolongation to aid choosing recommended dose combinations for further investigation. The models consider potential correlation between concentrations of test drugs and potential drug-drug interactions at PK and QT levels. In addition, this approach allows for the assessment of the probability of QT prolongation exceeding given thresholds of clinical significance. The performance of this approach was examined via simulation under practical scenarios for dose-escalation trials for a combination of two drugs. The simulation results show that invaluable information of QT effects at therapeutic dose combinations can be gained by the proposed approaches. Early detection of dose combinations with substantial QT prolongation is evaluated effectively through the CIs of the predicted peak QT prolongation at each dose combination. Furthermore, the probability of QT prolongation exceeding a certain threshold is also computed to support early detection of safety signals while accounting for uncertainty associated with data from Phase I studies. While the prediction of QT effects is sensitive to the dose escalation process, the sensitivity and limited sample size should be considered when providing support to the decision-making process for further developing certain dose combinations. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Anatomical robust optimization to account for nasal cavity filling variation during intensity-modulated proton therapy: a comparison with conventional and adaptive planning strategies

NASA Astrophysics Data System (ADS)

van de Water, Steven; Albertini, Francesca; Weber, Damien C.; Heijmen, Ben J. M.; Hoogeman, Mischa S.; Lomax, Antony J.

2018-01-01

The aim of this study is to develop an anatomical robust optimization method for intensity-modulated proton therapy (IMPT) that accounts for interfraction variations in nasal cavity filling, and to compare it with conventional single-field uniform dose (SFUD) optimization and online plan adaptation. We included CT data of five patients with tumors in the sinonasal region. Using the planning CT, we generated for each patient 25 ‘synthetic’ CTs with varying nasal cavity filling. The robust optimization method available in our treatment planning system ‘Erasmus-iCycle’ was extended to also account for anatomical uncertainties by including (synthetic) CTs with varying patient anatomy as error scenarios in the inverse optimization. For each patient, we generated treatment plans using anatomical robust optimization and, for benchmarking, using SFUD optimization and online plan adaptation. Clinical target volume (CTV) and organ-at-risk (OAR) doses were assessed by recalculating the treatment plans on the synthetic CTs, evaluating dose distributions individually and accumulated over an entire fractionated 50 GyRBE treatment, assuming each synthetic CT to correspond to a 2 GyRBE fraction. Treatment plans were also evaluated using actual repeat CTs. Anatomical robust optimization resulted in adequate CTV doses (V95%  ⩾  98% and V107%  ⩽  2%) if at least three synthetic CTs were included in addition to the planning CT. These CTV requirements were also fulfilled for online plan adaptation, but not for the SFUD approach, even when applying a margin of 5 mm. Compared with anatomical robust optimization, OAR dose parameters for the accumulated dose distributions were on average 5.9 GyRBE (20%) higher when using SFUD optimization and on average 3.6 GyRBE (18%) lower for online plan adaptation. In conclusion, anatomical robust optimization effectively accounted for changes in nasal cavity filling during IMPT, providing substantially improved CTV and OAR doses compared with conventional SFUD optimization. OAR doses can be further reduced by using online plan adaptation.

A de-noising algorithm based on wavelet threshold-exponential adaptive window width-fitting for ground electrical source airborne transient electromagnetic signal

NASA Astrophysics Data System (ADS)

Ji, Yanju; Li, Dongsheng; Yu, Mingmei; Wang, Yuan; Wu, Qiong; Lin, Jun

2016-05-01

The ground electrical source airborne transient electromagnetic system (GREATEM) on an unmanned aircraft enjoys considerable prospecting depth, lateral resolution and detection efficiency, etc. In recent years it has become an important technical means of rapid resources exploration. However, GREATEM data are extremely vulnerable to stationary white noise and non-stationary electromagnetic noise (sferics noise, aircraft engine noise and other human electromagnetic noises). These noises will cause degradation of the imaging quality for data interpretation. Based on the characteristics of the GREATEM data and major noises, we propose a de-noising algorithm utilizing wavelet threshold method and exponential adaptive window width-fitting. Firstly, the white noise is filtered in the measured data using the wavelet threshold method. Then, the data are segmented using data window whose step length is even logarithmic intervals. The data polluted by electromagnetic noise are identified within each window based on the discriminating principle of energy detection, and the attenuation characteristics of the data slope are extracted. Eventually, an exponential fitting algorithm is adopted to fit the attenuation curve of each window, and the data polluted by non-stationary electromagnetic noise are replaced with their fitting results. Thus the non-stationary electromagnetic noise can be effectively removed. The proposed algorithm is verified by the synthetic and real GREATEM signals. The results show that in GREATEM signal, stationary white noise and non-stationary electromagnetic noise can be effectively filtered using the wavelet threshold-exponential adaptive window width-fitting algorithm, which enhances the imaging quality.

Searching for signposts: Adaptive planning thresholds in long-term water supply projections for the Western U.S.

NASA Astrophysics Data System (ADS)

Robinson, B.; Herman, J. D.

2017-12-01

Long-term water supply planning is challenged by highly uncertain streamflow projections across climate models and emissions scenarios. Recent studies have devised infrastructure and policy responses that can withstand or adapt to an ensemble of scenarios, particularly those outside the envelope of historical variability. An important aspect of this process is whether the proposed thresholds for adaptation (i.e., observations that trigger a response) truly represent a trend toward future change. Here we propose an approach to connect observations of annual mean streamflow with long-term projections by filtering GCM-based streamflow ensembles. Visualizations are developed to investigate whether observed changes in mean annual streamflow can be linked to projected changes in end-of-century mean and variance relative to the full ensemble. A key focus is identifying thresholds that point to significant long-term changes in the distribution of streamflow (+/- 20% or greater) as early as possible. The analysis is performed on 87 sites in the Western United States, using streamflow ensembles through 2100 from a recent study by the U.S. Bureau of Reclamation. Results focus on three primary questions: (1) how many years of observed data are needed to identify the most extreme scenarios, and by what year can they be identified? (2) are these features different between sites? and (3) using this analysis, do observed flows to date at each site point to significant long-term changes? This study addresses the challenge of severe uncertainty in long-term streamflow projections by identifying key thresholds that can be observed to support water supply planning.

Fundus-controlled two-color dark adaptometry with the Microperimeter MP1.

PubMed

Bowl, Wadim; Stieger, Knut; Lorenz, Birgit

2015-06-01

The aim of this study was to provide fundus-controlled two-color adaptometry with an existing device. A quick and easy approach extends the application possibilities of a commercial fundus-controlled perimeter. An external filter holder was placed in front the objective lens of the MP1 (Nidek, Italy) and fitted with filters to modify background, stimulus intensity, and color. Prior to dark adaptometry, the subject's visual sensitivity profile was measured for red and blue stimuli to determine whether rods or cones or both mediated the absolute threshold. After light adaptation, 20 healthy subjects were investigated with a pattern covering six spots at the posterior pole of the retina up to 45 min of dark adaptation. Thresholds were determined using a 200 ms red Goldmann IV and a blue Goldmann II stimulus. The pre-test sensitivity showed a typical distribution of values along the meridian, with high peripheral light increment sensitivity (LIS) and low central LIS for rods and the reverse for cones. After bleach, threshold recovery had a classic biphasic shape. The absolute threshold was reached after approximately 10 min for the red and 15 min for the blue stimulus. Two-color fundus-controlled adaptometry with a commercial MP1 without internal changes to the device provides a quick and easy examination of rod and cone function during dark adaptation at defined retinal loci of the posterior pole. This innovative method will be helpful to measure rod vs. cone function at known loci of the posterior pole in early stages of retinal degenerations.

Outlier detection for particle image velocimetry data using a locally estimated noise variance

NASA Astrophysics Data System (ADS)

Lee, Yong; Yang, Hua; Yin, ZhouPing

2017-03-01

This work describes an adaptive spatial variable threshold outlier detection algorithm for raw gridded particle image velocimetry data using a locally estimated noise variance. This method is an iterative procedure, and each iteration is composed of a reference vector field reconstruction step and an outlier detection step. We construct the reference vector field using a weighted adaptive smoothing method (Garcia 2010 Comput. Stat. Data Anal. 54 1167-78), and the weights are determined in the outlier detection step using a modified outlier detector (Ma et al 2014 IEEE Trans. Image Process. 23 1706-21). A hard decision on the final weights of the iteration can produce outlier labels of the field. The technical contribution is that the spatial variable threshold motivation is embedded in the modified outlier detector with a locally estimated noise variance in an iterative framework for the first time. It turns out that a spatial variable threshold is preferable to a single spatial constant threshold in complicated flows such as vortex flows or turbulent flows. Synthetic cellular vortical flows with simulated scattered or clustered outliers are adopted to evaluate the performance of our proposed method in comparison with popular validation approaches. This method also turns out to be beneficial in a real PIV measurement of turbulent flow. The experimental results demonstrated that the proposed method yields the competitive performance in terms of outlier under-detection count and over-detection count. In addition, the outlier detection method is computational efficient and adaptive, requires no user-defined parameters, and corresponding implementations are also provided in supplementary materials.

Dose measurement based on threshold shift in MOSFET arrays in commercial SRAMS

NASA Technical Reports Server (NTRS)

Scheick, L. Z.; Swift, G.

2002-01-01

A new method using an array of MOS transistors isdescribed for measuring dose absorbed from ionizingradiation. Using the array of MOSFETs in a SRAM, a direct measurement of the number of MOS cells which change as a function of applied bias on the SRAM. Since the input and output of a SRAM used as a dosimeter is completely digital, the measurement of dose is easily accessible by a remote processing system.

Adaptation of exercise ventilation during an actively-induced hyperthermia following passive heat acclimation.

PubMed

Beaudin, Andrew E; Clegg, Miriam E; Walsh, Michael L; White, Matthew D

2009-09-01

Hyperthermia-induced hyperventilation has been proposed to be a human thermolytic thermoregulatory response and to contribute to the disproportionate increase in exercise ventilation (VE) relative to metabolic needs during high-intensity exercise. In this study it was hypothesized that VE would adapt similar to human eccrine sweating (E(SW)) following a passive heat acclimation (HA). All participants performed an incremental exercise test on a cycle ergometer from rest to exhaustion before and after a 10-day passive exposure for 2 h/day to either 50 degrees C and 20% relative humidity (RH) (n = 8, Acclimation group) or 24 degrees C and 32% RH (n = 4, Control group). Attainment of HA was confirmed by a significant decrease (P = 0.025) of the esophageal temperature (T(es)) threshold for the onset of E(SW) and a significantly elevated E(SW) (P < or = 0.040) during the post-HA exercise tests. HA also gave a significant decrease in resting T(es) (P = 0.006) and a significant increase in plasma volume (P = 0.005). Ventilatory adaptations during exercise tests following HA included significantly decreased T(es) thresholds (P < or = 0.005) for the onset of increases in the ventilatory equivalents for O(2) (VE/VO(2)) and CO(2) (VE/VCO(2)) and a significantly increased VE (P < or = 0.017) at all levels of T(es). Elevated VE was a function of a significantly greater tidal volume (P = 0.003) at lower T(es) and of breathing frequency (P < or = 0.005) at higher T(es). Following HA, the ventilatory threshold was uninfluenced and the relationships between VO(2) and either VE/VO(2) or VE/VCO(2) did not explain the resulting hyperventilation. In conclusion, the results support that exercise VE following passive HA responds similarly to E(SW), and the mechanism accounting for this adaptation is independent of changes of the ventilatory threshold or relationships between VO(2) with each of VE/VO(2) and VE/VCO(2).

Influence of Host Quality and Temperature on the Biology of Diaeretiella rapae (Hymenoptera: Braconidae, Aphidiinae).

PubMed

Souza, M F; Veloso, L F A; Sampaio, M V; Davis, J A

2017-08-01

Biological features of Diaeretiella rapae (McIntosh), an aphid parasitoid, are conditioned by temperature and host. However, studies of host quality changes due to temperature adaptability have not been performed previously. Therefore, this study evaluated the adaptability of Lipaphis pseudobrassicae (Davis) and Myzus persicae (Sulzer) to high temperature, high temperature effect on their quality as hosts for D. rapae, and on parasitoid's thermal threshold. Aphid development, survivorship, fecundity, and longevity were compared at 19 °C and 28 °C. Host quality in different temperatures was determined through evaluation of parasitoid biology. Thermal threshold of D. rapae was determined using development time data. At 28 °C, development time, rate of immature survival, and total fecundity rates were greater in L. pseudobrassicae than in M. persicae. Development time of D. rapae in L. pseudobrassicae was shorter than that in M. persicae at 28 °C and 31 °C for females and at 31 °C for males. The thermal threshold of D. rapae was 6.38 °C and 3.33 °C for females and 4.45 °C and 3.63 °C for males developed on L. pseudobrassicae and M. persicae, respectively. Diaeretiella rapae size gain was greater in L. pseudobrassicae than that in M. persicae at 25 °C and 28 °C. Lipaphis pseudobrassicae showed better adaptation than M. persicae to elevated temperatures, which resulted in a better quality host for D. rapae at temperatures of 28 °C and 31 °C and a higher lower thermal threshold when the parasitoid developed within L. pseudobrassicae. The host's adaptation to high temperatures is a determinant of host quality for the parasitoid at that same climatic condition. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Mouse current vocalization threshold measured with a neurospecific nociception assay: The effect of sex, morphine, and isoflurane

PubMed Central

Spornick, Nicholas; Guptill, Virginia; Koziol, Deloris; Wesley, Robert; Finkel, Julia; Quezado, Zenaide M.N.

2012-01-01

Sine-wave electrical stimulation at frequencies 2000, 250, and 5 Hz to respectively evaluate Aβ, Aδ, and C sensory neurons has recently been added to the armamentarium used to evaluate sensory neurons. We developed an automated nociception assay using sine-wave stimulation methodology to determine current vocalization threshold in response to 2000, 250, and 5 Hz and examine the effects of sex, analgesics, and anesthetics in mice. At baseline, males had significantly higher mean current vocalization thresholds compared with female mice at 2000, 250, and 5 Hz (p ≤ 0.019). By 1 h after intrathecal injections of morphine there were significant increases in current vocalization threshold percent changes from baseline that varied with doses (p = 0.0001) and frequency used (p < 0.0001). Specifically, with increasing doses of morphine, there were significantly greater increases in current vocalization threshold percent changes from baseline in response to 5 Hz compared with 250 and 2000 Hz stimulation in a significantly ordered pattern: 5 Hz > 250 Hz (p < 0.0001) and 250 Hz > 2000 Hz (p = 0.0002). Forty-five minutes after exposure, there were no effects of isoflurane on current vocalization thresholds at any frequency. Therefore, our findings suggest that this automated nociception assay using sine-wave stimulation in mice, can be valuable for measurements of the effects of sex, opioids, and anesthetics on the response to electrical stimuli that preferentially stimulate Aβ, Aδ, and C-sensory fibers in vivo. This investigation suggests the validation of this assay and supports its use to examine mechanisms of nociception in mice. PMID:21864576

Optimal Design for the Precise Estimation of an Interaction Threshold: The Impact of Exposure to a Mixture of 18 Polyhalogenated Aromatic Hydrocarbons

PubMed Central

Yeatts, Sharon D.; Gennings, Chris; Crofton, Kevin M.

2014-01-01

Traditional additivity models provide little flexibility in modeling the dose–response relationships of the single agents in a mixture. While the flexible single chemical required (FSCR) methods allow greater flexibility, its implicit nature is an obstacle in the formation of the parameter covariance matrix, which forms the basis for many statistical optimality design criteria. The goal of this effort is to develop a method for constructing the parameter covariance matrix for the FSCR models, so that (local) alphabetic optimality criteria can be applied. Data from Crofton et al. are provided as motivation; in an experiment designed to determine the effect of 18 polyhalogenated aromatic hydrocarbons on serum total thyroxine (T4), the interaction among the chemicals was statistically significant. Gennings et al. fit the FSCR interaction threshold model to the data. The resulting estimate of the interaction threshold was positive and within the observed dose region, providing evidence of a dose-dependent interaction. However, the corresponding likelihood-ratio-based confidence interval was wide and included zero. In order to more precisely estimate the location of the interaction threshold, supplemental data are required. Using the available data as the first stage, the Ds-optimal second-stage design criterion was applied to minimize the variance of the hypothesized interaction threshold. Practical concerns associated with the resulting design are discussed and addressed using the penalized optimality criterion. Results demonstrate that the penalized Ds-optimal second-stage design can be used to more precisely define the interaction threshold while maintaining the characteristics deemed important in practice. PMID:22640366

Sex differences in nicotine self-administration in rats during progressive unit dose reduction: Implications for nicotine regulation policy

PubMed Central

Grebenstein, Patricia; Burroughs, Danielle; Zhang, Yan; LeSage, Mark G.

2013-01-01

Reducing the nicotine content in tobacco products is being considered by the FDA as a policy to reduce the addictiveness of tobacco products. Understanding individual differences in response to nicotine reduction will be critical to developing safe and effective policy. Animal and human research demonstrating sex differences in the reinforcing effects of nicotine suggests that males and females may respond differently to nicotine-reduction policies. However, no studies have directly examined sex differences in the effects of nicotine unit-dose reduction on nicotine self-administration (NSA) in animals. The purpose of the present study was to examine this issue in a rodent self-administration model. Male and female rats were trained to self-administer nicotine (0.06 mg/kg) under an FR 3 schedule during daily 23 h sessions. Rats were then exposed to saline extinction and reacquisition of NSA, followed by weekly reductions in the unit dose (0.03 to 0.00025 mg/kg) until extinction levels of responding were achieved. Males and females were compared with respect to baseline levels of intake, resistance to extinction, degree of compensatory increases in responding during dose reduction, and the threshold reinforcing unit dose of nicotine. Exponential demand-curve analysis was also conducted to compare the sensitivity of males and females to increases in the unit price (FR/unit dose) of nicotine (i.e., elasticity of demand or reinforcing efficacy). Females exhibited significantly higher baseline intake and less compensation than males. However, there were no sex differences in the reinforcement threshold or elasticity of demand. Dose–response relationships were very well described by the exponential demand function (r2 values > 0.96 for individual subjects). These findings suggest that females may exhibit less compensatory smoking in response to nicotine reduction policies, even though their nicotine reinforcement threshold and elasticity of demand may not differ from males. PMID:24201048

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...

Evaluation and comparison of 50 Hz current threshold of electrocutaneous sensations using different methods

PubMed Central

Lindenblatt, G.; Silny, J.

2006-01-01

Leakage currents, tiny currents flowing from an everyday-life appliance through the body to the ground, can cause a non-adequate perception (called electrocutaneous sensation, ECS) or even pain and should be avoided. Safety standards for low-frequency range are based on experimental results of current thresholds of electrocutaneous sensations, which however show a wide range between about 50 μA (rms) and 1000 μA (rms). In order to be able to explain these differences, the perception threshold was measured repeatedly in experiments with test persons under identical experimental setup, but by means of different methods (measuring strategies), namely: direct adjustment, classical threshold as amperage of 50% perception probability, and confidence rating procedure of signal detection theory. The current is injected using a 1 cm2 electrode at the highly touch sensitive part of the index fingertip. These investigations show for the first time that the threshold of electrocutaneous sensations is influenced both by adaptation to the non-adequate stimulus and individual, emotional factors. Therefore, classical methods, on which the majority of the safety investigations are based, cannot be used to determine a leakage current threshold. The confidence rating procedure of the modern signal detection theory yields a value of 179.5 μA (rms) at 50 Hz power supply net frequency as the lower end of the 95% confidence range considering the variance in the investigated group. This value is expected to be free of adaptation influences, and is distinctly lower than the European limits and supports the stricter regulations of Canada and USA. PMID:17111461

An adaptive design for updating the threshold value of a continuous biomarker.

PubMed

Spencer, Amy V; Harbron, Chris; Mander, Adrian; Wason, James; Peers, Ian

2016-11-30

Potential predictive biomarkers are often measured on a continuous scale, but in practice, a threshold value to divide the patient population into biomarker 'positive' and 'negative' is desirable. Early phase clinical trials are increasingly using biomarkers for patient selection, but at this stage, it is likely that little will be known about the relationship between the biomarker and the treatment outcome. We describe a single-arm trial design with adaptive enrichment, which can increase power to demonstrate efficacy within a patient subpopulation, the parameters of which are also estimated. Our design enables us to learn about the biomarker and optimally adjust the threshold during the study, using a combination of generalised linear modelling and Bayesian prediction. At the final analysis, a binomial exact test is carried out, allowing the hypothesis that 'no population subset exists in which the novel treatment has a desirable response rate' to be tested. Through extensive simulations, we are able to show increased power over fixed threshold methods in many situations without increasing the type-I error rate. We also show that estimates of the threshold, which defines the population subset, are unbiased and often more precise than those from fixed threshold studies. We provide an example of the method applied (retrospectively) to publically available data from a study of the use of tamoxifen after mastectomy by the German Breast Study Group, where progesterone receptor is the biomarker of interest. © 2016 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.

Visual adaptation and the amplitude spectra of radiological images.

PubMed

Kompaniez-Dunigan, Elysse; Abbey, Craig K; Boone, John M; Webster, Michael A

2018-01-01

We examined how visual sensitivity and perception are affected by adaptation to the characteristic amplitude spectra of X-ray mammography images. Because of the transmissive nature of X-ray photons, these images have relatively more low-frequency variability than natural images, a difference that is captured by a steeper slope of the amplitude spectrum (~ - 1.5) compared to the ~ 1/f (slope of - 1) spectra common to natural scenes. Radiologists inspecting these images are therefore exposed to a different balance of spectral components, and we measured how this exposure might alter spatial vision. Observers (who were not radiologists) were adapted to images of normal mammograms or the same images sharpened by filtering the amplitude spectra to shallower slopes. Prior adaptation to the original mammograms significantly biased judgments of image focus relative to the sharpened images, demonstrating that the images are sufficient to induce substantial after-effects. The adaptation also induced strong losses in threshold contrast sensitivity that were selective for lower spatial frequencies, though these losses were very similar to the threshold changes induced by the sharpened images. Visual search for targets (Gaussian blobs) added to the images was also not differentially affected by adaptation to the original or sharper images. These results complement our previous studies examining how observers adapt to the textural properties or phase spectra of mammograms. Like the phase spectrum, adaptation to the amplitude spectrum of mammograms alters spatial sensitivity and visual judgments about the images. However, unlike the phase spectrum, adaptation to the amplitude spectra did not confer a selective performance advantage relative to more natural spectra.

Increased seizure susceptibility and other toxicity symptoms following acute sulforaphane treatment in mice

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

Socała, Katarzyna, E-mail: ksocala@op.pl

Activation of Nrf2 with sulforaphane has recently gained attention as a new therapeutic approach in the treatment of many diseases, including epilepsy. As a plant-derived compound, sulforaphane is considered to be safe and well-tolerated. It is widely consumed, also by patients suffering from seizure and taking antiepileptic drugs, but no toxicity profile of sulforaphane exists. Since many natural remedies and dietary supplements may increase seizure risk and potentially interact with antiepileptic drugs, the aim of our study was to investigate the acute effects of sulforaphane on seizure thresholds and activity of some first- and second-generation antiepileptic drugs in mice. Inmore » addition, some preliminary toxicity profile of sulforaphane in mice after intraperitoneal injection was evaluated. The LD{sub 50} value of sulforaphane in mice was estimated at 212.67 mg/kg, while the TD{sub 50} value – at 191.58 mg/kg. In seizure tests, sulforaphane at the highest dose tested (200 mg/kg) significantly decreased the thresholds for the onset of the first myoclonic twitch and generalized clonic seizure in the iv PTZ test as well as the threshold for the 6 Hz-induced psychomotor seizure. At doses of 10–200 mg/kg, sulforaphane did not affect the threshold for the iv PTZ-induced forelimb tonus or the threshold for maximal electroshock-induced hindlimb tonus. Interestingly, sulforaphane (at 100 mg/kg) potentiated the anticonvulsant efficacy of carbamazepine in the maximal electroshock seizure test. This interaction could have been pharmacokinetic in nature, as sulforaphane increased concentrations of carbamazepine in both serum and brain tissue. The toxicity study showed that high doses of sulforaphane produced marked sedation (at 150–300 mg/kg), hypothermia (at 150–300 mg/kg), impairment of motor coordination (at 200–300 mg/kg), decrease in skeletal muscle strength (at 250–300 mg/kg), and deaths (at 200–300 mg/kg). Moreover, blood analysis showed leucopenia in mice injected with sulforaphane at 200 mg/kg. In conclusion, since sulforaphane was proconvulsant at a toxic dose, the safety profile and the risk-to-benefit ratio of sulforaphane usage in epileptic patients should be further evaluated. - Highlights: • Sulforaphane, an Nrf2 activator, is proconvulsant at toxic doses in mice. • Sulforaphane at 100 mg/kg produces a pharmacokinetic interaction with carbamazepine. • Sulforaphane has an LD{sub 50} of 212.67 mg/kg in mice (after ip administration). • The risk-to-benefit ratio of sulforaphane needs further evaluation.« less

SU-E-J-135: Feasibility of Using Quantitative Cone Beam CT for Proton Adaptive Planning

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

Jingqian, W; Wang, Q; Zhang, X

2015-06-15

Purpose: To investigate the feasibility of using scatter corrected cone beam CT (CBCT) for proton adaptive planning. Methods: Phantom study was used to evaluate the CT number difference between the planning CT (pCT), quantitative CBCT (qCBCT) with scatter correction and calibrated Hounsfield units using adaptive scatter kernel superposition (ASKS) technique, and raw CBCT (rCBCT). After confirming the CT number accuracy, prostate patients, each with a pCT and several sets of weekly CBCT, were investigated for this study. Spot scanning proton treatment plans were independently generated on pCT, qCBCT and rCBCT. The treatment plans were then recalculated on all images. Dose-volume-histogrammore » (DVH) parameters and gamma analysis were used to compare between dose distributions. Results: Phantom study suggested that Hounsfield unit accuracy for different materials are within 20 HU for qCBCT and over 250 HU for rCBCT. For prostate patients, proton dose could be calculated accurately on qCBCT but not on rCBCT. When the original plan was recalculated on qCBCT, tumor coverage was maintained when anatomy was consistent with pCT. However, large dose variance was observed when patient anatomy change. Adaptive plan using qCBCT was able to recover tumor coverage and reduce dose to normal tissue. Conclusion: It is feasible to use qu antitative CBCT (qCBCT) with scatter correction and calibrated Hounsfield units for proton dose calculation and adaptive planning in proton therapy. Partly supported by Varian Medical Systems.« less

The influence of the image registration method on the adaptive radiotherapy. A proof of the principle in a selected case of prostate IMRT.

PubMed

Berenguer, Roberto; de la Vara, Victoria; Lopez-Honrubia, Veronica; Nuñez, Ana Teresa; Rivera, Miguel; Villas, Maria Victoria; Sabater, Sebastia

2018-01-01

To analyse the influence of the image registration method on the adaptive radiotherapy of an IMRT prostate treatment, and to compare the dose accumulation according to 3 different image registration methods with the planned dose. The IMRT prostate patient was CT imaged 3 times throughout his treatment. The prostate, PTV, rectum and bladder were segmented on each CT. A Rigid, a deformable (DIR) B-spline and a DIR with landmarks registration algorithms were employed. The difference between the accumulated doses and planned doses were evaluated by the gamma index. The Dice coefficient and Hausdorff distance was used to evaluate the overlap between volumes, to quantify the quality of the registration. When comparing adaptive vs no adaptive RT, the gamma index calculation showed large differences depending on the image registration method (as much as 87.6% in the case of DIR B-spline). The quality of the registration was evaluated using an index such as the Dice coefficient. This showed that the best result was obtained with DIR with landmarks compared with the rest and it was always above 0.77, reported as a recommended minimum value for prostate studies in a multi-centre review. Apart from showing the importance of the application of an adaptive RT protocol in a particular treatment, this work shows that the election of the registration method is decisive in the result of the adaptive radiotherapy and dose accumulation. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

A spatially encoded dose difference maximal intensity projection map for patient dose evaluation: A new first line patient quality assurance tool

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

Hu Weigang; Graff, Pierre; Boettger, Thomas

2011-04-15

Purpose: To develop a spatially encoded dose difference maximal intensity projection (DD-MIP) as an online patient dose evaluation tool for visualizing the dose differences between the planning dose and dose on the treatment day. Methods: Megavoltage cone-beam CT (MVCBCT) images acquired on the treatment day are used for generating the dose difference index. Each index is represented by different colors for underdose, acceptable, and overdose regions. A maximal intensity projection (MIP) algorithm is developed to compress all the information of an arbitrary 3D dose difference index into a 2D DD-MIP image. In such an algorithm, a distance transformation is generatedmore » based on the planning CT. Then, two new volumes representing the overdose and underdose regions of the dose difference index are encoded with the distance transformation map. The distance-encoded indices of each volume are normalized using the skin distance obtained on the planning CT. After that, two MIPs are generated based on the underdose and overdose volumes with green-to-blue and green-to-red lookup tables, respectively. Finally, the two MIPs are merged with an appropriate transparency level and rendered in planning CT images. Results: The spatially encoded DD-MIP was implemented in a dose-guided radiotherapy prototype and tested on 33 MVCBCT images from six patients. The user can easily establish the threshold for the overdose and underdose. A 3% difference between the treatment and planning dose was used as the threshold in the study; hence, the DD-MIP shows red or blue color for the dose difference >3% or {<=}3%, respectively. With such a method, the overdose and underdose regions can be visualized and distinguished without being overshadowed by superficial dose differences. Conclusions: A DD-MIP algorithm was developed that compresses information from 3D into a single or two orthogonal projections while hinting the user whether the dose difference is on the skin surface or deeper.« less

A voxel-based investigation for MRI-only radiotherapy of the brain using ultra short echo times

NASA Astrophysics Data System (ADS)

Edmund, Jens M.; Kjer, Hans M.; Van Leemput, Koen; Hansen, Rasmus H.; Andersen, Jon AL; Andreasen, Daniel

2014-12-01

Radiotherapy (RT) based on magnetic resonance imaging (MRI) as the only modality, so-called MRI-only RT, would remove the systematic registration error between MR and computed tomography (CT), and provide co-registered MRI for assessment of treatment response and adaptive RT. Electron densities, however, need to be assigned to the MRI images for dose calculation and patient setup based on digitally reconstructed radiographs (DRRs). Here, we investigate the geometric and dosimetric performance for a number of popular voxel-based methods to generate a so-called pseudo CT (pCT). Five patients receiving cranial irradiation, each containing a co-registered MRI and CT scan, were included. An ultra short echo time MRI sequence for bone visualization was used. Six methods were investigated for three popular types of voxel-based approaches; (1) threshold-based segmentation, (2) Bayesian segmentation and (3) statistical regression. Each approach contained two methods. Approach 1 used bulk density assignment of MRI voxels into air, soft tissue and bone based on logical masks and the transverse relaxation time T2 of the bone. Approach 2 used similar bulk density assignments with Bayesian statistics including or excluding additional spatial information. Approach 3 used a statistical regression correlating MRI voxels with their corresponding CT voxels. A similar photon and proton treatment plan was generated for a target positioned between the nasal cavity and the brainstem for all patients. The CT agreement with the pCT of each method was quantified and compared with the other methods geometrically and dosimetrically using both a number of reported metrics and introducing some novel metrics. The best geometrical agreement with CT was obtained with the statistical regression methods which performed significantly better than the threshold and Bayesian segmentation methods (excluding spatial information). All methods agreed significantly better with CT than a reference water MRI comparison. The mean dosimetric deviation for photons and protons compared to the CT was about 2% and highest in the gradient dose region of the brainstem. Both the threshold based method and the statistical regression methods showed the highest dosimetrical agreement. Generation of pCTs using statistical regression seems to be the most promising candidate for MRI-only RT of the brain. Further, the total amount of different tissues needs to be taken into account for dosimetric considerations regardless of their correct geometrical position.

Evaluation of a multi-arm multi-stage Bayesian design for phase II drug selection trials - an example in hemato-oncology.

PubMed

Jacob, Louis; Uvarova, Maria; Boulet, Sandrine; Begaj, Inva; Chevret, Sylvie

2016-06-02

Multi-Arm Multi-Stage designs aim at comparing several new treatments to a common reference, in order to select or drop any treatment arm to move forward when such evidence already exists based on interim analyses. We redesigned a Bayesian adaptive design initially proposed for dose-finding, focusing our interest in the comparison of multiple experimental drugs to a control on a binary criterion measure. We redesigned a phase II clinical trial that randomly allocates patients across three (one control and two experimental) treatment arms to assess dropping decision rules. We were interested in dropping any arm due to futility, either based on historical control rate (first rule) or comparison across arms (second rule), and in stopping experimental arm due to its ability to reach a sufficient response rate (third rule), using the difference of response probabilities in Bayes binomial trials between the treated and control as a measure of treatment benefit. Simulations were then conducted to investigate the decision operating characteristics under a variety of plausible scenarios, as a function of the decision thresholds. Our findings suggest that one experimental treatment was less efficient than the control and could have been dropped from the trial based on a sample of approximately 20 instead of 40 patients. In the simulation study, stopping decisions were reached sooner for the first rule than for the second rule, with close mean estimates of response rates and small bias. According to the decision threshold, the mean sample size to detect the required 0.15 absolute benefit ranged from 63 to 70 (rule 3) with false negative rates of less than 2 % (rule 1) up to 6 % (rule 2). In contrast, detecting a 0.15 inferiority in response rates required a sample size ranging on average from 23 to 35 (rules 1 and 2, respectively) with a false positive rate ranging from 3.6 to 0.6 % (rule 3). Adaptive trial design is a good way to improve clinical trials. It allows removing ineffective drugs and reducing the trial sample size, while maintaining unbiased estimates. Decision thresholds can be set according to predefined fixed error decision rates. ClinicalTrials.gov Identifier: NCT01342692 .

Phase I trial of stereotactic MR-guided online adaptive radiation therapy (SMART) for the treatment of oligometastatic or unresectable primary malignancies of the abdomen.

PubMed

Henke, Lauren; Kashani, Rojano; Robinson, Clifford; Curcuru, Austen; DeWees, Todd; Bradley, Jeffrey; Green, Olga; Michalski, Jeff; Mutic, Sasa; Parikh, Parag; Olsen, Jeffrey

2018-03-01

SBRT is used to treat oligometastatic or unresectable primary abdominal malignancies, although ablative dose delivery is limited by proximity of organs-at-risk (OAR). Stereotactic, magnetic resonance (MR)-guided online-adaptive radiotherapy (SMART) may improve SBRT's therapeutic ratio. This prospective Phase I trial assessed feasibility and potential advantages of SMART to treat abdominal malignancies. Twenty patients with oligometastatic or unresectable primary liver (n = 10) and non-liver (n = 10) abdominal malignancies underwent SMART. Initial plans prescribed 50 Gy/5 fractions (BED 100 Gy) with goal 95% PTV coverage by 95% of prescription, subject to hard OAR constraints. Daily real-time online-adaptive plans were created as needed, based on daily setup MR-image-set tumor/OAR "anatomy-of-the-day" to preserve hard OAR constraints, escalate PTV dose, or both. Treatment times, patient outcomes, and dosimetric comparisons between initial and adaptive plans were prospectively recorded. Online adaptive plans were created at time of treatment for 81/97 fractions, due to initial plan violation of OAR constraints (61/97) or observed opportunity for PTV dose escalation (20/97). Plan adaptation increased PTV coverage in 64/97 fractions. Zero Grade ≥ 3 acute (<6 months) treatment-related toxicities were observed. SMART is clinically deliverable and safe, allowing PTV dose escalation and/or simultaneous OAR sparing compared to non-adaptive abdominal SBRT. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Determination of minimal steady-state plasma level of diazepam causing seizure threshold elevation in rats.

PubMed

Dhir, Ashish; Rogawski, Michael A

2018-05-01

Diazepam, administered by the intravenous, oral, or rectal routes, is widely used for the management of acute seizures. Dosage forms for delivery of diazepam by other routes of administration, including intranasal, intramuscular, and transbuccal, are under investigation. In predicting what dosages are necessary to terminate seizures, the minimal exposure required to confer seizure protection must be known. Here we administered diazepam by continuous intravenous infusion to obtain near-steady-state levels, which allowed an assessment of the minimal levels that elevate seizure threshold. The thresholds for various behavioral seizure signs (myoclonic jerk, clonus, and tonus) were determined with the timed intravenous pentylenetetrazol seizure threshold test in rats. Diazepam was administered to freely moving animals by continuous intravenous infusion via an indwelling jugular vein cannula. Blood samples for assay of plasma levels of diazepam and metabolites were recovered via an indwelling cannula in the contralateral jugular vein. The pharmacokinetic parameters of diazepam following a single 80-μg/kg intravenous bolus injection were determined using a noncompartmental pharmacokinetic approach. The derived parameters V d , CL, t 1/2α (distribution half-life) and t 1/2β (terminal half-life) for diazepam were, respectively, 608 mL, 22.1 mL/min, 13.7 minutes, and 76.8 minutes, respectively. Various doses of diazepam were continuously infused without or with an initial loading dose. At the end of the infusions, the thresholds for various behavioral seizure signs were determined. The minimal plasma diazepam concentration associated with threshold elevations was estimated at approximately 70 ng/mL. The active metabolites nordiazepam, oxazepam, and temazepam achieved levels that are expected to make only minor contributions to the threshold elevations. Diazepam elevates seizure threshold at steady-state plasma concentrations lower than previously recognized. The minimally effective plasma concentration provides a reference that may be considered when estimating the diazepam exposure required for acute seizure treatment. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

Pilot Study: Unique Response of Bone Tissue During an Investigation of Radio-Adaptive Effects in Mice

NASA Technical Reports Server (NTRS)

Sibonga, J. D.; Iwaniec, U.; Wu, H.

2011-01-01

PURPOSE: We obtained bone tissue to evaluate the collateral effects of experiments designed to investigate molecular mechanisms of radio-adaptation in a mouse model. Radio-adaptation describes a process by which the prior exposure to low dose radiation can protect against the toxic effect of a subsequent high dose exposure. In the radio-adaptation experiments, C57Bl/6 mice were exposed to either a Sham or a priming Low Dose (5 cGy) of Cs-137 gamma rays before being exposed to either a Sham or High Dose (6 Gy) 24 hours later. ANALYSIS: Bone tissue were obtained from two experiments where mice were sacrificed at 3 days (n=3/group, 12 total) and at 14 days (n=6/group, 24 total) following high dose exposure. Tissues were analyzed to 1) evaluate a radio-adaptive response in bone tissue and 2) describe cellular and microstructural effects for two skeletal sites with different rates of bone turnover. One tibia and one lumbar vertebrae (LV2), collected at the 3-day time-point, were analyzed by bone histomorphometry and micro-CT to evaluate the cellular response and any evidence of microarchitectural impact. Likewise, tibia and LV2, collected at the 14-day time-point, were analyzed by micro-CT alone to evaluate resulting changes to bone structure and microarchitecture. The data were analyzed by 2-way ANOVA to evaluate the effects of the priming low dose radiation, of the high dose radiation, and of any interaction between the priming low and high doses of radiation. Bone histomorphometry was performed in the cancellous bone (aka trabecular bone) compartments of the proximal tibial metaphysis and of LV2. RESULTS: Cellular Response @ 3 Days The priming Low Dose radiation decreased osteoblast-covered bone perimeter in the proximal tibia and the total cell density in the bone marrow in the LV2. High Dose radiation, regardless of prior exposure to priming dose, dramatically reduced total cell density in bone marrow of both the long bone and vertebra. However, in the proximal tibia, High Dose radiation increased the osteoclast-covered bone perimeters, the density of adipocytes in bone marrow, and the area of bone marrow occupied by fat cells -- while in the LV2, adipocytes were rare and not stimulated by High Dose radiation. In an unexpected response, High Dose radiation dramatically increased (10-fold) osteoblast-covered bone perimeter in the LV2.

Hypoalgesia in response to transcutaneous electrical nerve stimulation (TENS) depends on stimulation intensity.

PubMed

Moran, Fidelma; Leonard, Tracey; Hawthorne, Stephanie; Hughes, Ciara M; McCrum-Gardner, Evie; Johnson, Mark I; Rakel, Barbara A; Sluka, Kathleen A; Walsh, Deirdre M

2011-08-01

Transcutaneous electrical nerve stimulation (TENS) is an electrophysical modality used for pain management. This study investigated the dose response of different TENS intensities on experimentally induced pressure pain. One hundred and thirty TENS naïve healthy individuals (18-64 years old; 65 males, 65 females) were randomly allocated to 5 groups (n = 26 per group): Strong Non Painful TENS; Sensory Threshold TENS; Below Sensory Threshold TENS; No Current Placebo TENS; and Transient Placebo TENS. Active TENS (80 Hz) was applied to the forearm for 30 minutes. Transient Placebo TENS was applied for 42 seconds after which the current amplitude automatically reset to 0 mA. Pressure pain thresholds (PPT) were recorded from 2 points on the hand and forearm before and after TENS to measure hypoalgesia. There were significant differences between groups at both the hand and forearm (ANOVA; P = .005 and .002). At 30 minutes, there was a significant hypoalgesic effect in the Strong Non Painful TENS group compared to: Below Sensory Threshold TENS, No Current Placebo TENS and Transient Placebo TENS groups (P < .0001) at the forearm; Transient Placebo TENS and No Current Placebo TENS groups at the hand (P = .001). There was no significant difference between Strong Non Painful TENS and Sensory Threshold TENS groups. The area under the curve for the changes in PPT significantly correlated with the current amplitude (r(2) = .33, P = .003). These data therefore show that there is a dose-response effect of TENS with the largest effect occurring with the highest current amplitudes. This study shows a dose response for the intensity of TENS for pain relief with the strongest intensities showing the greatest effect; thus, we suggest that TENS intensity should be titrated to achieve the strongest possible intensity to achieve maximum pain relief. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

SU-E-T-110: An Investigation On Monitor Unit Threshold and Effects On IMPT Delivery in Proton Pencil Beam Planning System

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

Syh, J; Ding, X; Syh, J

2015-06-15

Purpose: An approved proton pencil beam scanning (PBS) treatment plan might not be able to deliver because of existed extremely low monitor unit per beam spot. A dual hybrid plan with higher efficiency of higher spot monitor unit and the efficacy of less number of energy layers were searched and optimized. The range of monitor unit threshold setting was investigated and the plan quality was evaluated by target dose conformity. Methods: Certain limitations and requirements need to be checks and tested before a nominal proton PBS treatment plan can be delivered. The plan needs to be met the machine characterization,more » specification in record and verification to deliver the beams. Minimal threshold of monitor unit, e.g. 0.02, per spot was set to filter the low counts and plan was re-computed. Further MU threshold increment was tested in sequence without sacrificing the plan quality. The number of energy layer was also alternated due to elimination of low count layer(s). Results: Minimal MU/spot threshold, spot spacing in each energy layer and total number of energy layer and the MU weighting of beam spots of each beam were evaluated. Plan optimization between increases of the spot MU (efficiency) and less energy layers of delivery (efficacy) was adjusted. 5% weighting limit of total monitor unit per beam was feasible. Scarce spreading of beam spots was not discouraging as long as target dose conformity within 3% criteria. Conclusion: Each spot size is equivalent to the relative dose in the beam delivery system. The energy layer is associated with the depth of the targeting tumor. Our work is crucial to maintain the best possible quality plan. To keep integrity of all intrinsic elements such as spot size, spot number, layer number and the carried weighting of spots in each layer is important in this study.« less

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.

Monitoring the eye lens: which dose quantity is adequate?

NASA Astrophysics Data System (ADS)

Behrens, R.; Dietze, G.

2010-07-01

Recent epidemiological studies suggest a rather low dose threshold (below 0.5 Gy) for the induction of a cataract of the eye lens. Some other studies even assume that there is no threshold at all. Therefore, protection measures have to be optimized and current dose limits for the eye lens may be reduced in the future. The question of which personal dose equivalent quantity is appropriate for monitoring the dose to the eye lens arises from this situation. While in many countries dosemeters calibrated in terms of the dose equivalent quantity Hp(0.07) have been seen as being adequate for monitoring the dose to the eye lens, this might be questionable in the case of reduced dose limits and, thus, it may become necessary to use the dose equivalent quantity Hp(3) for this purpose. To discuss this question, the dose conversion coefficients for the equivalent dose of the eye lens (in the following eye lens dose) were determined for realistic photon and beta radiation fields and compared with the values of the corresponding conversion coefficients for the different operational quantities. The values obtained lead to the following conclusions: in radiation fields where most of the dose comes from photons, especially x-rays, it is appropriate to use dosemeters calibrated in terms of Hp(0.07) on a slab phantom, while in other radiation fields (dominated by beta radiation or unknown contributions of photon and beta radiation) dosemeters calibrated in terms of Hp(3) on a slab phantom should be used. As an alternative, dosemeters calibrated in terms of Hp(0.07) on a slab phantom could also be used; however, in radiation fields containing beta radiation with the end point energy near 1 MeV, an overestimation of the eye lens dose by up to a factor of 550 is possible.

Monitoring the eye lens: which dose quantity is adequate?

PubMed

Behrens, R; Dietze, G

2010-07-21

Recent epidemiological studies suggest a rather low dose threshold (below 0.5 Gy) for the induction of a cataract of the eye lens. Some other studies even assume that there is no threshold at all. Therefore, protection measures have to be optimized and current dose limits for the eye lens may be reduced in the future. The question of which personal dose equivalent quantity is appropriate for monitoring the dose to the eye lens arises from this situation. While in many countries dosemeters calibrated in terms of the dose equivalent quantity H(p)(0.07) have been seen as being adequate for monitoring the dose to the eye lens, this might be questionable in the case of reduced dose limits and, thus, it may become necessary to use the dose equivalent quantity H(p)(3) for this purpose. To discuss this question, the dose conversion coefficients for the equivalent dose of the eye lens (in the following eye lens dose) were determined for realistic photon and beta radiation fields and compared with the values of the corresponding conversion coefficients for the different operational quantities. The values obtained lead to the following conclusions: in radiation fields where most of the dose comes from photons, especially x-rays, it is appropriate to use dosemeters calibrated in terms of H(p)(0.07) on a slab phantom, while in other radiation fields (dominated by beta radiation or unknown contributions of photon and beta radiation) dosemeters calibrated in terms of H(p)(3) on a slab phantom should be used. As an alternative, dosemeters calibrated in terms of H(p)(0.07) on a slab phantom could also be used; however, in radiation fields containing beta radiation with the end point energy near 1 MeV, an overestimation of the eye lens dose by up to a factor of 550 is possible.

TH-C-18A-08: A Management Tool for CT Dose Monitoring, Analysis, and Protocol Review

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

Wang, J; Chan, F; Newman, B

2014-06-15

Purpose: To develop a customizable tool for enterprise-wide managing of CT protocols and analyzing radiation dose information of CT exams for a variety of quality control applications Methods: All clinical CT protocols implemented on the 11 CT scanners at our institution were extracted in digital format. The original protocols had been preset by our CT management team. A commercial CT dose tracking software (DoseWatch,GE healthcare,WI) was used to collect exam information (exam date, patient age etc.), scanning parameters, and radiation doses for all CT exams. We developed a Matlab-based program (MathWorks,MA) with graphic user interface which allows to analyze themore » scanning protocols with the actual dose estimates, and compare the data to national (ACR,AAPM) and internal reference values for CT quality control. Results: The CT protocol review portion of our tool allows the user to look up the scanning and image reconstruction parameters of any protocol on any of the installed CT systems among about 120 protocols per scanner. In the dose analysis tool, dose information of all CT exams (from 05/2013 to 02/2014) was stratified on a protocol level, and within a protocol down to series level, i.e. each individual exposure event. This allows numerical and graphical review of dose information of any combination of scanner models, protocols and series. The key functions of the tool include: statistics of CTDI, DLP and SSDE, dose monitoring using user-set CTDI/DLP/SSDE thresholds, look-up of any CT exam dose data, and CT protocol review. Conclusion: our inhouse CT management tool provides radiologists, technologists and administration a first-hand near real-time enterprise-wide knowledge on CT dose levels of different exam types. Medical physicists use this tool to manage CT protocols, compare and optimize dose levels across different scanner models. It provides technologists feedback on CT scanning operation, and knowledge on important dose baselines and thresholds.« less

Thresholds for the perception of whole-body linear sinusoidal motion in the horizontal plane

NASA Technical Reports Server (NTRS)

Mah, Robert W.; Young, Laurence R.; Steele, Charles R.; Schubert, Earl D.

1989-01-01

An improved linear sled has been developed to provide precise motion stimuli without generating perceptible extraneous motion cues (a noiseless environment). A modified adaptive forced-choice method was employed to determine perceptual thresholds to whole-body linear sinusoidal motion in 25 subjects. Thresholds for the detection of movement in the horizontal plane were found to be lower than those reported previously. At frequencies of 0.2 to 0.5 Hz, thresholds were shown to be independent of frequency, while at frequencies of 1.0 to 3.0 Hz, thresholds showed a decreasing sensitivity with increasing frequency, indicating that the perceptual process is not sensitive to the rate change of acceleration of the motion stimulus. The results suggest that the perception of motion behaves as an integrating accelerometer with a bandwidth of at least 3 Hz.

Late cataractogenesis caused by particulate radiations and photons in long-lived mammalian species

NASA Technical Reports Server (NTRS)

Lett, J. T.; Lee, A. C.; Cox, A. B.; Wood, D. H.

1989-01-01

Radiation cataractogenesis induced by small acute doses of particulate radiations and photons in the New Zealand white rabbit (Oryctolagus cuniculus), the beagle dog (Canis familiaris) and the rhesus monkey (Macaca mulatta) is discussed in the context of the use of animal models to assess the radiation hazards faced by humans during lengthy sojourns in deep space. Attention is paid to (1) the importance of lifespan studies with long-lived species - the above animals have median lifespans in captivity of 5-7, 13-14 and 25 years, respectively; and (2) the magnitudes of possible dose thresholds for cataractogenesis from sparsely ionizing radiations and the modifications of those thresholds by the late degenerative phase of the phenomenon.

Application of adaptive design and decision making to a phase II trial of a phosphodiesterase inhibitor for the treatment of intermittent claudication.

PubMed

Lewis, Roger J; Connor, Jason T; Teerlink, John R; Murphy, James R; Cooper, Leslie T; Hiatt, William R; Brass, Eric P

2011-05-25

Claudication secondary to peripheral artery disease (PAD) is associated with substantial functional impairment. Phosphodiesterase (PDE) inhibitors have been shown to increase walking performance in these patients. K-134 is a selective PDE 3 inhibitor being developed as a potential treatment for claudication. The use of K-134, as with other PDE 3 inhibitors, in patients with PAD raises important safety and tolerability concerns, including the induction of cardiac ischemia, tachycardia, and hypotension. We describe the design, oversight, and implementation of an adaptive, phase II, dose-finding trial evaluating K-134 for the treatment of stable, intermittent claudication. The study design was a double-blind, multi-dose (25 mg, 50 mg, and 100 mg of K-134), randomized trial with both placebo and active comparator arms conducted in the United States and Russia. The primary objective of the study was to compare the highest tolerable dose of K-134 versus placebo using peak walking time after 26 weeks of therapy as the primary outcome. Study visits with intensive safety assessments were included early in the study period to provide data for adaptive decision making. The trial used an adaptive, dose-finding strategy to efficiently identify the highest dose(s) most likely to be safe and well tolerated, based on the side effect profiles observed within the trial, so that less promising doses could be abandoned. Protocol specified criteria for safety and tolerability endpoints were used and modeled prior to the adaptive decision making. The maximum target sample size was 85 subjects in each of the retained treatment arms. When 199 subjects had been randomized and 28-day data were available from 143, the Data Monitoring Committee (DMC) recommended termination of the lowest dose (25 mg) treatment arm. Safety evaluations performed during 14- and 28-day visits which included in-clinic dosing and assessments at peak drug concentrations provided core data for the DMC review. At the time of review, no subject in any of the five treatment arms (placebo, three K-134-containing arms, and cilostazol) had met pre-specified definitions for resting tachycardia or ischemic changes on exercise ECG. If, instead of dropping the 25-mg K-134 treatment arm, all arms had been continued to full enrollment, then approximately 43 additional research subjects would have been required to complete the trial. In this phase II, dose-finding trial of K-134 in the treatment of stable intermittent claudication, no concerning safety signals were seen at interim analysis, allowing the discontinuation of the lowest-dose-containing arm and the retention of the two highest-dose-containing arms. The adaptive design facilitated safe and efficient evaluation of K-134 in this high-risk cardiovascular population. ClinicalTrials.gov: NCT00783081.

Image-adaptive and robust digital wavelet-domain watermarking for images

NASA Astrophysics Data System (ADS)

Zhao, Yi; Zhang, Liping

2018-03-01

We propose a new frequency domain wavelet based watermarking technique. The key idea of our scheme is twofold: multi-tier solution representation of image and odd-even quantization embedding/extracting watermark. Because many complementary watermarks need to be hidden, the watermark image designed is image-adaptive. The meaningful and complementary watermark images was embedded into the original image (host image) by odd-even quantization modifying coefficients, which was selected from the detail wavelet coefficients of the original image, if their magnitudes are larger than their corresponding Just Noticeable Difference thresholds. The tests show good robustness against best-known attacks such as noise addition, image compression, median filtering, clipping as well as geometric transforms. Further research may improve the performance by refining JND thresholds.

Localization Transition Induced by Learning in Random Searches

NASA Astrophysics Data System (ADS)

Falcón-Cortés, Andrea; Boyer, Denis; Giuggioli, Luca; Majumdar, Satya N.

2017-10-01

We solve an adaptive search model where a random walker or Lévy flight stochastically resets to previously visited sites on a d -dimensional lattice containing one trapping site. Because of reinforcement, a phase transition occurs when the resetting rate crosses a threshold above which nondiffusive stationary states emerge, localized around the inhomogeneity. The threshold depends on the trapping strength and on the walker's return probability in the memoryless case. The transition belongs to the same class as the self-consistent theory of Anderson localization. These results show that similarly to many living organisms and unlike the well-studied Markovian walks, non-Markov movement processes can allow agents to learn about their environment and promise to bring adaptive solutions in search tasks.

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

Seals, Kevin F., E-mail: KSeals@mednet.ucla.edu; Lee, Edward W., E-mail: EdwardLee@mednet.ucla.edu; Cagnon, Christopher H., E-mail: CCagnon@mednet.ucla.edu

Extensive research supports an association between radiation exposure and cataractogenesis. New data suggests that radiation-induced cataracts may form stochastically, without a threshold and at low radiation doses. We first review data linking cataractogenesis with interventional work. We then analyze the lens dose typical of various procedures, factors modulating dose, and predicted annual dosages. We conclude by critically evaluating the literature describing techniques for lens protection, finding that leaded eyeglasses may offer inadequate protection and exploring the available data on alternative strategies for cataract prevention.

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

PubMed

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

2002-01-01

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

QUEST - A Bayesian adaptive psychometric method

NASA Technical Reports Server (NTRS)

Watson, A. B.; Pelli, D. G.

1983-01-01

An adaptive psychometric procedure that places each trial at the current most probable Bayesian estimate of threshold is described. The procedure takes advantage of the common finding that the human psychometric function is invariant in form when expressed as a function of log intensity. The procedure is simple, fast, and efficient, and may be easily implemented on any computer.

The method of constant stimuli is inefficient

NASA Technical Reports Server (NTRS)

Watson, Andrew B.; Fitzhugh, Andrew

1990-01-01

Simpson (1988) has argued that the method of constant stimuli is as efficient as adaptive methods of threshold estimation and has supported this claim with simulations. It is shown that Simpson's simulations are not a reasonable model of the experimental process and that more plausible simulations confirm that adaptive methods are much more efficient that the method of constant stimuli.

Opportunistic Access in Frequency Hopping Cognitive Radio Networks

DTIC Science & Technology

2014-03-27

thresholding MA multiple access MFSK M-ary frequency shift keying MIMO multiple-input/multiple-output OFDM orthogonal frequency-division multiplexing x...adaptive BER performance as a function of ISR with orthogonal frequency-division multiplexing ( OFDM ) interference present. . . . . . . . . . 41 4.15 Non...adaptive BER performance as a function of EB/N0 with OFDM interfer- ence present

Mechanisms for dose retention in conformal arsenic doping using a radial line slot antenna microwave plasma source

NASA Astrophysics Data System (ADS)

Ueda, Hirokazu; Ventzek, Peter L. G.; Oka, Masahiro; Kobayashi, Yuuki; Sugimoto, Yasuhiro

2015-06-01

Topographic structures such as Fin FETs and silicon nanowires for advanced gate fabrication require ultra-shallow high dose infusion of dopants into the silicon subsurface. Plasma doping meets this requirement by supplying a flux of inert ions and dopant radicals to the surface. However, the helium ion bombardment needed to infuse dopants into the fin surface can cause poor dose retention. This is due to the interaction between substrate damage and post doping process wet cleaning solutions required in the front end of line large-scale integration fabrication. We present findings from surface microscopy experiments that reveal the mechanism for dose retention in arsenic doped silicon fin samples using a microwave RLSA™ plasma source. Dilute aqueous hydrofluoric acid (DHF) cleans by themselves are incompatible with plasma doping processes because the films deposited over the dosed silicon and ion bombardment damaged silicon are readily removed. Oxidizing wet cleaning chemistries help retain the dose as silica rich over-layers are not significantly degraded. Furthermore, the dosed retention after a DHF clean following an oxidizing wet clean is unchanged. Still, the initial ion bombardment energy and flux are important. Large ion fluxes at energies below the sputter threshold and above the silicon damage threshold, before the silicon surface is covered by an amorphous mixed phase layer, allow for enhanced uptake of dopant into the silicon. The resulting dopant concentration is beyond the saturation limit of crystalline silicon.

Studies of the mortality of atomic bomb survivors, Report 14, 1950-2003: an overview of cancer and noncancer diseases.

PubMed

Ozasa, Kotaro; Shimizu, Yukiko; Suyama, Akihiko; Kasagi, Fumiyoshi; Soda, Midori; Grant, Eric J; Sakata, Ritsu; Sugiyama, Hiromi; Kodama, Kazunori

2012-03-01

This is the 14th report in a series of periodic general reports on mortality in the Life Span Study (LSS) cohort of atomic bomb survivors followed by the Radiation Effects Research Foundation to investigate the late health effects of the radiation from the atomic bombs. During the period 1950-2003, 58% of the 86,611 LSS cohort members with DS02 dose estimates have died. The 6 years of additional follow-up since the previous report provide substantially more information at longer periods after radiation exposure (17% more cancer deaths), especially among those under age 10 at exposure (58% more deaths). Poisson regression methods were used to investigate the magnitude of the radiation-associated risks, the shape of the dose response, and effect modification by gender, age at exposure, and attained age. The risk of all causes of death was positively associated with radiation dose. Importantly, for solid cancers the additive radiation risk (i.e., excess cancer cases per 10(4) person-years per Gy) continues to increase throughout life with a linear dose-response relationship. The sex-averaged excess relative risk per Gy was 0.42 [95% confidence interval (CI): 0.32, 0.53] for all solid cancer at age 70 years after exposure at age 30 based on a linear model. The risk increased by about 29% per decade decrease in age at exposure (95% CI: 17%, 41%). The estimated lowest dose range with a significant ERR for all solid cancer was 0 to 0.20 Gy, and a formal dose-threshold analysis indicated no threshold; i.e., zero dose was the best estimate of the threshold. The risk of cancer mortality increased significantly for most major sites, including stomach, lung, liver, colon, breast, gallbladder, esophagus, bladder and ovary, whereas rectum, pancreas, uterus, prostate and kidney parenchyma did not have significantly increased risks. An increased risk of non-neoplastic diseases including the circulatory, respiratory and digestive systems was observed, but whether these are causal relationships requires further investigation. There was no evidence of a radiation effect for infectious or external causes of death.

A self-adaptive algorithm for traffic sign detection in motion image based on color and shape features

NASA Astrophysics Data System (ADS)

Zhang, Ka; Sheng, Yehua; Gong, Zhijun; Ye, Chun; Li, Yongqiang; Liang, Cheng

2007-06-01

As an important sub-system in intelligent transportation system (ITS), the detection and recognition of traffic signs from mobile images is becoming one of the hot spots in the international research field of ITS. Considering the problem of traffic sign automatic detection in motion images, a new self-adaptive algorithm for traffic sign detection based on color and shape features is proposed in this paper. Firstly, global statistical color features of different images are computed based on statistics theory. Secondly, some self-adaptive thresholds and special segmentation rules for image segmentation are designed according to these global color features. Then, for red, yellow and blue traffic signs, the color image is segmented to three binary images by these thresholds and rules. Thirdly, if the number of white pixels in the segmented binary image exceeds the filtering threshold, the binary image should be further filtered. Fourthly, the method of gray-value projection is used to confirm top, bottom, left and right boundaries for candidate regions of traffic signs in the segmented binary image. Lastly, if the shape feature of candidate region satisfies the need of real traffic sign, this candidate region is confirmed as the detected traffic sign region. The new algorithm is applied to actual motion images of natural scenes taken by a CCD camera of the mobile photogrammetry system in Nanjing at different time. The experimental results show that the algorithm is not only simple, robust and more adaptive to natural scene images, but also reliable and high-speed on real traffic sign detection.

Separate channels for the analysis of the shape and the movement of moving visual stimulus.

PubMed

Tolhurst, D J

1973-06-01

1. The effects of temporal modulation on the properties of spatial frequency channels have been investigated using adaptation.2. Adapting to drifting sinusoidal gratings caused threshold elevation that was both spatial frequency and direction specific. Little systematic difference was found between the band widths of the elevation curves for drifting and stationary gratings.3. It was confirmed that adaptation fails to reveal channels at low spatial frequencies when stationary gratings are used. However, channels were revealed at frequencies at least as low as 0.66 c/deg when the test gratings were made to move. These channels are adapted only a little by stationary gratings, confirming their dependence on movement.4. The existence of movement-sensitive channels at low spatial frequencies explains the well known observation that temporal modulation greatly increases the sensitivity of the visual system to low spatial frequencies.5. Temporal modulation was effective at revealing these channels only when the flicker or movement of the test patterns was apparent to the observer; only at low spatial frequencies did patterns, modulated at low rates, actually appear to be temporarily modulated at threshold. At higher spatial frequencies, they were indistinguishable from stationary patterns until the contrast was some way above the detection threshold.6. It is suggested, therefore, that the movement-sensitive channels are responsible for signalling the occurrence of movement; the channels at higher spatial frequencies give no information about temporal changes. These two systems of channels are compared to the Y- and X-cells respectively of the cat.

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

Otake, M.; Schull, W.J.

This paper investigates the quantitative relationship of ionizing radiation to the occurrence of posterior lenticular opacities among the survivors of the atomic bombings of Hiroshima and Nagasaki suggested by the DS86 dosimetry system. DS86 doses are available for 1983 (93.4%) of the 2124 atomic bomb survivors analyzed in 1982. The DS86 kerma neutron component for Hiroshima survivors is much smaller than its comparable T65DR component, but still 4.2-fold higher (0.38 Gy at 6 Gy) than that in Nagasaki (0.09 Gy at 6 Gy). Thus, if the eye is especially sensitive to neutrons, there may yet be some useful information onmore » their effects, particularly in Hiroshima. The dose-response relationship has been evaluated as a function of the separately estimated gamma-ray and neutron doses. Among several different dose-response models without and with two thresholds, we have selected as the best model the one with the smallest x2 or the largest log likelihood value associated with the goodness of fit. The best fit is a linear gamma-linear neutron relationship which assumes different thresholds for the two types of radiation. Both gamma and neutron regression coefficients for the best fitting model are positive and highly significant for the estimated DS86 eye organ dose.« less

Anticoagulant effects of inhaled unfractionated heparin in the dog as determined by partial thromboplastin time and factor Xa activity.

PubMed

Manion, Jill S; Thomason, John M; Langston, Vernon C; Claude, Andrew K; Brooks, Marjory B; Mackin, Andrew J; Lunsford, Kari V

2016-01-01

To evaluate the anticoagulant effects of inhaled heparin in dogs. This study was conducted in 3 phases. In phase 1, bronchoalveolar lavage fluid (BALf) was collected to generate an in vitro calibration curve to relate heparin concentration to the activated partial thromboplastin time (aPTT). In phase 2, heparin was administered via nebulization to determine the threshold dose needed to prolong systemic aPTT. In phase 3, the local anticoagulant activity of inhaled heparin was determined by measurement of BALf anti-Xa activity and aPTT. University teaching hospital. Six healthy intact female Walker Hounds were used in this study. Two dogs were used for each phase. Inhaled unfractionated sodium heparin was administered in doses ranging from 50,000 to 200,000 IU. In vitro addition of heparin to BALf caused a prolongation in aPTT. Inhaled heparin at doses as high as 200,000 IU failed to prolong systemic aPTT, and a threshold dose could not be determined. No significant local anticoagulant effects were detected. Even at doses higher than those known to be effective in people, inhaled heparin appears to have no detectable local or systemic anticoagulant effects in dogs with the current delivery method. © Veterinary Emergency and Critical Care Society 2015.

Gastroprokinetic effect of a new benzamide derivative itopride and its action mechanisms in conscious dogs.

PubMed

Iwanaga, Y; Miyashita, N; Saito, T; Morikawa, K; Itoh, Z

1996-06-01

The novel benzamide derivative itopride was assayed for its effect on gastrointestinal motility in conscious dogs when it was administered intraduodenally (i.d.). Gastrointestinal motility was measured by means of chronically implanted force transducers, and itopride at a dose of 10 mg/kg, i.d. or more increased the gastric contractile force during the digestive state. Intraduodenal cisapride, domperidone and metoclopramide also stimulated gastric motility, and their threshold doses were 1, 3 and 1 mg/kg, respectively. Dopamine infusion (1 mg/kg/hr, i.v.) caused the postprandial gastric motility to disappear, but it was immediately restored by itopride at a dose of 3 mg/kg, i.d. With itopride at 1 and 3 mg/kg, i.d., acetylcholine (0.05 mg/kg/min)-induced contractions were greatly enhanced. In addition to its gastric stimulation, itopride at doses of 10-100 mg/kg, p.o. inhibited apomorphine (0.1 mg/kg, s.c.)-induced vomiting in dogs. In conclusion, intraduodenal itopride stimulates gastric motility through both anti-dopaminergic and anti-acetylcholinesterase actions. Its gastroprokinetic threshold dose was as large as 3-10 times those of cisapride, domperidone and metoclopramide. These findings suggest that itopride is an orally active gastroprokinetic with a moderate anti-emetic action.

The threshold number of protons to induce an adaptive response in zebrafish embryos.

PubMed

Choi, V W Y; Konishi, Teruaki; Oikawa, Masakazu; Cheng, S H; Yu, K N

2013-03-01

In this study, microbeam protons were used to provide the priming dose to induce an in vivo radioadaptive response (RAR) in the embryos of zebrafish, Danio rerio, against subsequent challenging doses provided by x-ray photons. The microbeam irradiation system (Single-Particle Irradiation System to Cell, acronym SPICE) at the National Institute of Radiological Sciences (NIRS), Japan, was employed. The embryos were dechorionated at 4 h post fertilisation (hpf) and irradiated at 5 hpf by microbeam protons. For each embryo, one irradiation point was chosen, to which 5, 10, 20, 30, 40, 50, 100, 200, 300 and 500 protons each with an energy of 3.4 MeV were delivered. The embryos were returned to the incubator until 10 hpf to further receive the challenging exposure, which was achieved using 2 Gy of x-ray irradiation, and then again returned to the incubator until 24 hpf for analyses. The levels of apoptosis in zebrafish embryos at 25 hpf were quantified through terminal dUTP transferase-mediated nick end-labelling (TUNEL) assay. The results revealed that at least 200 protons (with average radiation doses of about 300 and 650 mGy absorbed by an irradiated epithelial and deep cell, respectively) would be required to induce RAR in the zebrafish embryos in vivo. Our previous investigation showed that 5 protons delivered at 10 points on an embryo would already be sufficient to induce RAR in the zebrafish embryos. The difference was explained in terms of the radiation-induced bystander effect as well as the rescue effect.

Simulated Online Adaptive MR-Guided SBRT for the Treatment of Oligometastatic Disease of the Abdomen and Central Thorax: Characterization of Potential Advantages

PubMed Central

Henke, Lauren; Kashani, Rojano; Yang, Deshan; Zhao, Tianyu; Green, Olga; Olsen, Lindsey; Rodriguez, Vivian; Wooten, H. Omar; Li, H. Harold; Hu, Yanle; Bradley, Jeffrey; Robinson, Clifford; Parikh, Parag; Michalski, Jeff; Mutic, Sasa; Olsen, Jeffrey

2017-01-01

Purpose/Objectives Stereotactic body radiotherapy (SBRT) is increasingly used to treat oligometastatic or unresectable primary malignancy, although proximity of organs-at-risk (OAR) may limit delivery of sufficiently ablative dose. Magnetic resonance (MR)-based online-adaptive radiotherapy (ART) has potential to improve SBRT’s therapeutic ratio. This study characterizes potential advantages of online-adaptive MR-guided SBRT to treat oligometastatic disease of the non-liver abdomen and central thorax. Materials/Methods Ten patients treated with RT for unresectable primary or oligometastatic disease of the non-liver abdomen (n=5) or central thorax (n=5) underwent imaging throughout treatment on a clinical MR-IGRT system. SBRT plans were created based on tumor/OAR anatomy at initial CT simulation (PI) and simulated adaptive plans were created based on observed MR-image set tumor/OAR “anatomy-of-the-day” (PA). Each PA was planned under workflow constraints to simulate online-ART. Prescribed dose was 50Gy/5fractions with goal coverage of 95% PTV by 95% of the prescription, subject to hard OAR constraints. PI was applied to each MR dataset and compared to PA to evaluate changes in dose delivered to tumor/OARs, with dose escalation when possible. Results Hard OAR constraints were met for all PI based on anatomy from initial CT simulation, and all PA based on anatomy from each daily MR-image set. Application of the PI to anatomy-of-the-day caused OAR constraint violation in 19/30 cases. Adaptive planning increased PTV coverage in 21/30 cases, including 14 cases where hard OAR constraints were violated by the non-adaptive plan. For 9 PA cases, decreased PTV coverage was required to meet hard OAR constraints that would have been violated in a non-adaptive setting. Conclusions Online-adaptive MRI-guided SBRT may allow PTV dose escalation and/or simultaneous OAR sparing compared to non-adaptive SBRT. A prospective clinical trial is underway at our institution to evaluate clinical outcomes of this technique. PMID:27742541

Kalirin-7 Mediates Cocaine-Induced AMPA Receptor and Spine Plasticity, Enabling Incentive Sensitization

PubMed Central

Wang, Xiaoting; Cahill, Michael E.; Werner, Craig T.; Christoffel, Daniel J.; Golden, Sam A.; Xie, Zhong; Loweth, Jessica A.; Marinelli, Michela; Russo, Scott J.; Penzes, Peter

2013-01-01

It is well established that behavioral sensitization to cocaine is accompanied by increased spine density and AMPA receptor (AMPAR) transmission in the nucleus accumbens (NAc), but two major questions remain unanswered. Are these adaptations mechanistically coupled? And, given that they can be dissociated from locomotor sensitization, what is their functional significance? We tested the hypothesis that the guanine-nucleotide exchange factor Kalirin-7 (Kal-7) couples cocaine-induced AMPAR and spine upregulation and that these adaptations underlie sensitization of cocaine's incentive-motivational properties—the properties that make it “wanted.” Rats received eight daily injections of saline or cocaine. On withdrawal day 14, we found that Kal-7 levels and activation of its downstream effectors Rac-1 and PAK were increased in the NAc of cocaine-sensitized rats. Furthermore, AMPAR surface expression and spine density were increased, as expected. To determine whether these changes require Kal-7, a lentiviral vector expressing Kal-7 shRNA was injected into the NAc core before cocaine exposure. Knocking down Kal-7 abolished the AMPAR and spine upregulation normally seen during cocaine withdrawal. Despite the absence of these adaptations, rats with reduced Kal-7 levels developed locomotor sensitization. However, incentive sensitization, which was assessed by how rapidly rats learned to self-administer a threshold dose of cocaine, was severely impaired. These results identify a signaling pathway coordinating AMPAR and spine upregulation during cocaine withdrawal, demonstrate that locomotor and incentive sensitization involve divergent mechanisms, and link enhanced excitatory transmission in the NAc to incentive sensitization. PMID:23825406

Model-based adaptive phase I trial design of post-transplant decitabine maintenance in myelodysplastic syndrome.

PubMed

Han, Seunghoon; Kim, Yoo-Jin; Lee, Jongtae; Jeon, Sangil; Hong, Taegon; Park, Gab-Jin; Yoon, Jae-Ho; Yahng, Seung-Ah; Shin, Seung-Hwan; Lee, Sung-Eun; Eom, Ki-Seong; Kim, Hee-Je; Min, Chang-Ki; Lee, Seok; Yim, Dong-Seok

2015-10-23

This report focuses on the adaptive phase I trial design aimed to find the clinically applicable dose for decitabine maintenance treatment after allogeneic hematopoietic stem cell transplantation in patients with higher-risk myelodysplastic syndrome and secondary acute myeloid leukemia. The first cohort (three patients) was given the same initial daily dose of decitabine (5 mg/m(2)/day, five consecutive days with 4-week intervals). In all cohorts, the doses for Cycles 2 to 4 were individualized using pharmacokinetic-pharmacodynamic modeling and simulations. The goal of dose individualization was to determine the maximum dose for each patient at which the occurrence of grade 4 (CTC-AE) toxicities for both platelet and neutrophil counts could be avoided. The initial doses for the following cohorts were also estimated with the data from the previous cohorts in the same manner. In all but one patient (14 out of 15), neutrophil count was the dose-limiting factor throughout the cycles. In cycles where doses were individualized, the median neutrophil nadir observed was 1100/mm(3) (grade 2) and grade 4 toxicity occurred in 5.1 % of all cycles (while it occurred in 36.8 % where doses were not individualized). The initial doses estimated for cohorts 2 to 5 were 4, 5, 5.5, and 5 mg/m(2)/day, respectively. The median maintenance dose was 7 mg/m(2)/day. We determined the acceptable starting dose and individualized the maintenance dose for each patient, while minimizing the toxicity using the adaptive approach. Currently, 5 mg/m(2)/day is considered to be the most appropriate starting dose for the regimen studied. Clinicaltrials.gov NCT01277484.

The Sustained Influence of an Error on Future Decision-Making.

PubMed

Schiffler, Björn C; Bengtsson, Sara L; Lundqvist, Daniel

2017-01-01

Post-error slowing (PES) is consistently observed in decision-making tasks after negative feedback. Yet, findings are inconclusive as to whether PES supports performance accuracy. We addressed the role of PES by employing drift diffusion modeling which enabled us to investigate latent processes of reaction times and accuracy on a large-scale dataset (>5,800 participants) of a visual search experiment with emotional face stimuli. In our experiment, post-error trials were characterized by both adaptive and non-adaptive decision processes. An adaptive increase in participants' response threshold was sustained over several trials post-error. Contrarily, an initial decrease in evidence accumulation rate, followed by an increase on the subsequent trials, indicates a momentary distraction of task-relevant attention and resulted in an initial accuracy drop. Higher values of decision threshold and evidence accumulation on the post-error trial were associated with higher accuracy on subsequent trials which further gives credence to these parameters' role in post-error adaptation. Finally, the evidence accumulation rate post-error decreased when the error trial presented angry faces, a finding suggesting that the post-error decision can be influenced by the error context. In conclusion, we demonstrate that error-related response adaptations are multi-component processes that change dynamically over several trials post-error.

Cost-effectiveness of allopurinol and febuxostat for the management of gout.

PubMed

Jutkowitz, Eric; Choi, Hyon K; Pizzi, Laura T; Kuntz, Karen M

2014-11-04

Gout is the most common inflammatory arthritis in the United States. To evaluate the cost-effectiveness of urate-lowering treatment strategies for the management of gout. Markov model. Published literature and expert opinion. Patients for whom allopurinol or febuxostat is a suitable initial urate-lowering treatment. Lifetime. Health care payer. 5 urate-lowering treatment strategies were evaluated: no treatment; allopurinol- or febuxostat-only therapy; allopurinol-febuxostat sequential therapy; and febuxostat-allopurinol sequential therapy. Two dosing scenarios were investigated: fixed dose (80 mg of febuxostat daily, 0.80 success rate; 300 mg of allopurinol daily, 0.39 success rate) and dose escalation (≤120 mg of febuxostat daily, 0.82 success rate; ≤800 mg of allopurinol daily, 0.78 success rate). Discounted costs, discounted quality-adjusted life-years, and incremental cost-effectiveness ratios. In both dosing scenarios, allopurinol-only therapy was cost-saving. Dose-escalation allopurinol-febuxostat sequential therapy was more costly but more effective than dose-escalation allopurinol therapy, with an incremental cost-effectiveness ratio of $39 400 per quality-adjusted life-year. The relative rankings of treatments did not change. Our results were relatively sensitive to several potential variations of model assumptions; however, the cost-effectiveness ratios of dose escalation with allopurinol-febuxostat sequential therapy remained lower than the willingness-to-pay threshold of $109 000 per quality-adjusted life-year. Long-term outcome data for patients with gout, including medication adherence, are limited. Allopurinol single therapy is cost-saving compared with no treatment. Dose-escalation allopurinol-febuxostat sequential therapy is cost-effective compared with accepted willingness-to-pay thresholds. Agency for Healthcare Research and Quality.

Low-dose right unilateral electroconvulsive therapy (ECT): effectiveness of the first treatment.

PubMed

Lapidus, Kyle A B; Shin, Joseph S W; Pasculli, Rosa M; Briggs, Mimi C; Popeo, Dennis M; Kellner, Charles H

2013-06-01

Electroconvulsive therapy (ECT) is a widely used, highly effective antidepressant treatment. Except for the most severely ill patients, right unilateral (RUL) electrode placement is the most frequent initial treatment choice. In current practice, RUL ECT is administered at several multiples of seizure threshold (ST) based on reports that lower stimulus intensity results in lower response/remission rates. Many patients, as part of an initial dose titration to determine ST, will receive a single treatment with low-dose RUL ECT and subsequent treatments with a stimulus at a multiple of ST. To assess response to the first ECT. A retrospective analysis of charts from clinical practice at Mount Sinai Medical Center was performed. A single treatment with low-dose (presumably near ST) RUL ECT had a significant and immediate antidepressant effect in our sample of patients with major depression. We determined that this response is similar to that of patients receiving a single initial treatment with high-dose RUL ECT (at a multiple of ST). These data suggest, contrary to commonly held belief, that RUL ECT may be effective at a low stimulus dose. This argues against restimulating at 6 times ST in the initial session, based on the belief that the near-threshold seizure has no antidepressant efficacy. Our findings suggest a need for further investigation of cases in which low-dose RUL ECT may be an effective antidepressant treatment. Further prospective studies, including larger numbers of patients who receive randomized treatment with low- or high-dose RUL with longer follow-up, are indicated.

Validation of a Preclinical Spinal Safety Model: Effects of Intrathecal Morphine in the Neonatal Rat

PubMed Central

Westin, B. David; Walker, Suellen M.; Deumens, Ronald; Grafe, Marjorie; Yaksh, Tony L.

2010-01-01

Background Preclinical studies demonstrate increased neuroapoptosis after general anesthesia in early life. Neuraxial techniques may minimize potential risks, but there has been no systematic evaluation of spinal analgesic safety in developmental models. We aimed to validate a preclinical model for evaluating dose-dependent efficacy, spinal cord toxicity, and long term function following intrathecal morphine in the neonatal rat. Methods Lumbar intrathecal injections were performed in anesthetized rats aged postnatal day (P)3, 10 and 21. The relationship between injectate volume and segmental spread was assessed post mortem and by in-vivo imaging. To determine the antinociceptive dose, mechanical withdrawal thresholds were measured at baseline and 30 minutes following intrathecal morphine. To evaluate toxicity, doses up to the maximum tolerated were administered, and spinal cord histopathology, apoptosis and glial response were evaluated 1 and 7 days following P3 or P21 injection. Sensory thresholds and gait analysis were evaluated at P35. Results Intrathecal injection can be reliably performed at all postnatal ages and injectate volume influences segmental spread. Intrathecal morphine produced spinally-mediated analgesia at all ages with lower dose requirements in younger pups. High dose intrathecal morphine did not produce signs of spinal cord toxicity or alter long-term function. Conclusions The therapeutic ratio for intrathecal morphine (toxic dose / antinociceptive dose) was at least 300 at P3, and at least 20 at P21 (latter doses limited by side effects). This data provides relative efficacy and safety data for comparison with other analgesic preparations and contributes supporting evidence for the validity of this preclinical neonatal safety model. PMID:20526189

Validation of a preclinical spinal safety model: effects of intrathecal morphine in the neonatal rat.

PubMed

Westin, B David; Walker, Suellen M; Deumens, Ronald; Grafe, Marjorie; Yaksh, Tony L

2010-07-01

Preclinical studies demonstrate increased neuroapoptosis after general anesthesia in early life. Neuraxial techniques may minimize potential risks, but there has been no systematic evaluation of spinal analgesic safety in developmental models. We aimed to validate a preclinical model for evaluating dose-dependent efficacy, spinal cord toxicity, and long-term function after intrathecal morphine in the neonatal rat. Lumbar intrathecal injections were performed in anesthetized rats aged postnatal day (P) 3, 10, and 21. The relationship between injectate volume and segmental spread was assessed postmortem and by in vivo imaging. To determine the antinociceptive dose, mechanical withdrawal thresholds were measured at baseline and 30 min after intrathecal morphine. To evaluate toxicity, doses up to the maximum tolerated were administered, and spinal cord histopathology, apoptosis, and glial response were evaluated 1 and 7 days after P3 or P21 injection. Sensory thresholds and gait analysis were evaluated at P35. Intrathecal injection can be reliably performed at all postnatal ages and injectate volume influences segmental spread. Intrathecal morphine produced spinally mediated analgesia at all ages with lower dose requirements in younger pups. High-dose intrathecal morphine did not produce signs of spinal cord toxicity or alter long-term function. The therapeutic ratio for intrathecal morphine (toxic dose/antinociceptive dose) was at least 300 at P3 and at least 20 at P21 (latter doses limited by side effects). These data provide relative efficacy and safety for comparison with other analgesic preparations and contribute supporting evidence for the validity of this preclinical neonatal safety model.

Differential Effects of High Dose Magnetic Seizure Therapy (MST) and Electroconvulsive Shock (ECS) on Cognitive Function

PubMed Central

Spellman, Timothy; McClintock, Shawn M.; Terrace, Herbert; Luber, Bruce; Husain, Mustafa M.; Lisanby, Sarah H.

2008-01-01

Background Magnetic seizure therapy (MST) is under investigation as an alternative form of convulsive therapy that induces more focal seizures and spares cortical regions involved in memory. Using a newly expanded version of the Columbia University Primate Cognitive Profile, we compared the cognitive effects of high-dose MST delivered at 100 Hz (6X seizure threshold) with electroconvulsive shock (ECS) delivered at 2.5X seizure threshold. Methods Daily high-dose MST, ECS, and Sham (anesthesia-only) were administered for 4 weeks each in a within-subject cross-over design. Rhesus macaques (n = 3) were trained on five cognitive tasks assessing automatic memory, anterograde learning and memory, combined anterograde and retrograde simultaneous chaining, and spatial and serial working memory. Acutely following each intervention, monkeys were tested on the cognitive battery twice daily, separated by a 3-hour retention interval. Results Subjects were slower to complete criterion tasks (p’s<0.0001) following ECS, compared to sham and high-dose MST. Moreover, time to task-completion following high-dose MST did not differ from sham. Out of 6 measures of accuracy, treatment effects were found in 4; in all of these, ECS, but not MST, fared worse than Sham. On all accuracy and time to completion measurements, subjects performed as well as following high-dose MST as did subjects from a previous study on moderate-dose MST. Conclusion These findings provide evidence that high-dose MST results in benign acute cognitive side-effect profile relative to ECS, and are in line with our previous studies. PMID:18262171

Altered quantitative sensory testing outcome in subjects with opioid therapy.

PubMed

Chen, Lucy; Malarick, Charlene; Seefeld, Lindsey; Wang, Shuxing; Houghton, Mary; Mao, Jianren

2009-05-01

Preclinical studies have suggested that opioid exposure may induce a paradoxical decrease in the nociceptive threshold, commonly referred as opioid-induced hyperalgesia (OIH). While OIH may have implications in acute and chronic pain management, its clinical features remain unclear. Using an office-based quantitative sensory testing (QST) method, we compared pain threshold, pain tolerance, and the degree of temporal summation of the second pain in response to thermal stimulation among three groups of subjects: those with neither pain nor opioid therapy (group 1), with chronic pain but without opioid therapy (group 2), and with both chronic pain and opioid therapy (group 3). We also examined the possible correlation between QST responses to thermal stimulation and opioid dose, opioid treatment duration, opioid analgesic type, pain duration, or gender in group 3 subjects. As compared with both group 1 (n=41) and group 2 (n=41) subjects, group 3 subjects (n=58) displayed a decreased heat pain threshold and exacerbated temporal summation of the second pain to thermal stimulation. In contrast, there were no differences in cold or warm sensation among three groups. Among clinical factors, daily opioid dose consistently correlated with the decreased heat pain threshold and exacerbated temporal summation of the second pain in group 3 subjects. These results indicate that decreased heat pain threshold and exacerbated temporal summation of the second pain may be characteristic QST changes in subjects with opioid therapy. The data suggest that QST may be a useful tool in the clinical assessment of OIH.

Image quality, threshold contrast and mean glandular dose in CR mammography

NASA Astrophysics Data System (ADS)

Jakubiak, R. R.; Gamba, H. R.; Neves, E. B.; Peixoto, J. E.

2013-09-01

In many countries, computed radiography (CR) systems represent the majority of equipment used in digital mammography. This study presents a method for optimizing image quality and dose in CR mammography of patients with breast thicknesses between 45 and 75 mm. Initially, clinical images of 67 patients (group 1) were analyzed by three experienced radiologists, reporting about anatomical structures, noise and contrast in low and high pixel value areas, and image sharpness and contrast. Exposure parameters (kV, mAs and target/filter combination) used in the examinations of these patients were reproduced to determine the contrast-to-noise ratio (CNR) and mean glandular dose (MGD). The parameters were also used to radiograph a CDMAM (version 3.4) phantom (Artinis Medical Systems, The Netherlands) for image threshold contrast evaluation. After that, different breast thicknesses were simulated with polymethylmethacrylate layers and various sets of exposure parameters were used in order to determine optimal radiographic parameters. For each simulated breast thickness, optimal beam quality was defined as giving a target CNR to reach the threshold contrast of CDMAM images for acceptable MGD. These results were used for adjustments in the automatic exposure control (AEC) by the maintenance team. Using optimized exposure parameters, clinical images of 63 patients (group 2) were evaluated as described above. Threshold contrast, CNR and MGD for such exposure parameters were also determined. Results showed that the proposed optimization method was effective for all breast thicknesses studied in phantoms. The best result was found for breasts of 75 mm. While in group 1 there was no detection of the 0.1 mm critical diameter detail with threshold contrast below 23%, after the optimization, detection occurred in 47.6% of the images. There was also an average MGD reduction of 7.5%. The clinical image quality criteria were attended in 91.7% for all breast thicknesses evaluated in both patient groups. Finally, this study also concluded that the use of the AEC of the x-ray unit based on the constant dose to the detector may bring some difficulties to CR systems to operate under optimal conditions. More studies must be performed, so that the compatibility between systems and optimization methodologies can be evaluated, as well as this optimization method. Most methods are developed for phantoms, so comparative studies including clinical images must be developed.

Radiation Awareness for Endovascular Abdominal Aortic Aneurysm Repair in the Hybrid Operating Room. An Instant Patient Risk Chart for Daily Practice.

PubMed

de Ruiter, Quirina M; Gijsberts, Crystel M; Hazenberg, Constantijn E; Moll, Frans L; van Herwaarden, Joost A

2017-06-01

To determine which patient and C-arm characteristics are the strongest predictors of intraoperative patient radiation dose rates (DRs) during endovascular aneurysm repair (EVAR) procedures and create a patient risk chart. A retrospective analysis was performed of 74 EVAR procedures, including 16,889 X-ray runs using fixed C-arm imaging equipment. Four multivariate log-linear mixed models (with patient as a random effect) were constructed. Mean air kerma DR (DR AK , mGy/s) and the mean dose area product DR (DR DAP , mGycm 2 /s) were the outcome variables utilized for fluoroscopy as differentiated from digital subtraction angiography (DSA). These models were used to predict the maximum radiation duration allowed before a 2-Gy skin threshold (for DR AK ) or a 500-Gycm 2 threshold (for DR DAP ) was reached. The strongest predictor of DR AK and DR DAP for fluoroscopy imaging was the radiation protocol, with an increase of 200% when changing from "low" to "medium" and 410% from "low" to "normal." The strongest predictors of DR AK and DR DAP for DSA were C-arm angulation, with an increase of 47% per 30° of angulation, and body mass index (BMI), with an increase of 58% for every 5-point increase in BMI. Based on these models, a patient with a BMI of 30 kg/m 2 , combined with 45° of rotation and a field size of 800 cm 2 in the medium fluoroscopy protocol has a predicted DR AK of 0.39 mGy/s (or 85.5 minutes until the 2-Gy skin threshold is reached). While using comparable settings but switching the acquisition to a DSA with a "2 frames per second" protocol, the predicted DR AK will be 6.6 mGy/s (or 5.0 minutes until the 2-Gy threshold is reached). X-ray radiation DRs are constantly fluctuating during and between patients based on BMI, the protocols, C-arm position, and the image acquisitions that are used. An instant patient risk chart visualizes these radiation dose fluctuations and provides an overview of the expected duration of X-ray radiation, which can be used to predict when follow-up dose thresholds are reached during abdominal endovascular procedures.

Simulation of Healing Threshold in Strain-Induced Inflammation Through a Discrete Informatics Model.

PubMed

Ibrahim, Israr Bin M; Sarma O V, Sanjay; Pidaparti, Ramana M

2018-05-01

Respiratory diseases such as asthma and acute respiratory distress syndrome as well as acute lung injury involve inflammation at the cellular level. The inflammation process is very complex and is characterized by the emergence of cytokines along with other changes in cellular processes. Due to the complexity of the various constituents that makes up the inflammation dynamics, it is necessary to develop models that can complement experiments to fully understand inflammatory diseases. In this study, we developed a discrete informatics model based on cellular automata (CA) approach to investigate the influence of elastic field (stretch/strain) on the dynamics of inflammation and account for probabilistic adaptation based on statistical interpretation of existing experimental data. Our simulation model investigated the effects of low, medium, and high strain conditions on inflammation dynamics. Results suggest that the model is able to indicate the threshold of innate healing of tissue as a response to strain experienced by the tissue. When strain is under the threshold, the tissue is still capable of adapting its structure to heal the damaged part. However, there exists a strain threshold where healing capability breaks down. The results obtained demonstrate that the developed discrete informatics based CA model is capable of modeling and giving insights into inflammation dynamics parameters under various mechanical strain/stretch environments.

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

Nielsen, Michael A.; School of Information Technology and Electrical Engineering, University of Queensland, Brisbane, Queensland 4072; Dawson, Christopher M.

The one-way quantum computing model introduced by Raussendorf and Briegel [Phys. Rev. Lett. 86, 5188 (2001)] shows that it is possible to quantum compute using only a fixed entangled resource known as a cluster state, and adaptive single-qubit measurements. This model is the basis for several practical proposals for quantum computation, including a promising proposal for optical quantum computation based on cluster states [M. A. Nielsen, Phys. Rev. Lett. (to be published), quant-ph/0402005]. A significant open question is whether such proposals are scalable in the presence of physically realistic noise. In this paper we prove two threshold theorems which showmore » that scalable fault-tolerant quantum computation may be achieved in implementations based on cluster states, provided the noise in the implementations is below some constant threshold value. Our first threshold theorem applies to a class of implementations in which entangling gates are applied deterministically, but with a small amount of noise. We expect this threshold to be applicable in a wide variety of physical systems. Our second threshold theorem is specifically adapted to proposals such as the optical cluster-state proposal, in which nondeterministic entangling gates are used. A critical technical component of our proofs is two powerful theorems which relate the properties of noisy unitary operations restricted to act on a subspace of state space to extensions of those operations acting on the entire state space. We expect these theorems to have a variety of applications in other areas of quantum-information science.« less

Distinct DC subsets regulate adaptive Th1 and 2 responses during Trichuris muris infection.

PubMed

Demiri, M; Müller-Luda, K; Agace, W W; Svensson-Frej, M

2017-10-01

Low- and high-dose infections with the murine large intestinal nematode Trichuris muris are associated with induction of adaptive Th1 and Th2 responses, respectively, in mesenteric lymph nodes (MLN). Classical dendritic cells (cDC) accumulate in the large intestinal mucosa and MLN upon T. muris infection, yet their role in driving adaptive responses to infection remains largely unknown. We performed low- and high-dose T. muris infections of mice deficient in defined cDC subsets to investigate their role in induction of adaptive immune responses. Mice lacking IRF4-dependent cDC failed to clear a high-dose infection and displayed impaired Th2 responses. Conversely, mice lacking IRF8-dependent cDC cleared a low-dose infection and displayed an impaired Th1 response while increased production of Th2 cytokines. Finally, mice lacking both IRF4- and IRF8-dependent cDC were able to generate a Th2 response and clear a low-dose infection. Collectively, these results suggest that IRF4- and IRF8-dependent cDC act antagonistically during T. muris infection, and demonstrate that intestinal Th2 responses can be generated towards T. muris in the absence of IRF4-dependent cDC. © 2017 John Wiley & Sons Ltd.

An accelerator-based Boron Neutron Capture Therapy (BNCT) facility based on the 7Li(p,n)7Be

NASA Astrophysics Data System (ADS)

Musacchio González, Elizabeth; Martín Hernández, Guido

2017-09-01

BNCT (Boron Neutron Capture Therapy) is a therapeutic modality used to irradiate tumors cells previously loaded with the stable isotope 10B, with thermal or epithermal neutrons. This technique is capable of delivering a high dose to the tumor cells while the healthy surrounding tissue receive a much lower dose depending on the 10B biodistribution. In this study, therapeutic gain and tumor dose per target power, as parameters to evaluate the treatment quality, were calculated. The common neutron-producing reaction 7Li(p,n)7Be for accelerator-based BNCT, having a reaction threshold of 1880.4 keV, was considered as the primary source of neutrons. Energies near the reaction threshold for deep-seated brain tumors were employed. These calculations were performed with the Monte Carlo N-Particle (MCNP) code. A simple but effective beam shaping assembly (BSA) was calculated producing a high therapeutic gain compared to previously proposed facilities with the same nuclear reaction.

Determination of quality factors by microdosimetry

NASA Astrophysics Data System (ADS)

Al-Affan, I. A. M.; Watt, D. E.

1987-03-01

The application of microdose parameters for the specification of a revised scale of quality factors which would be applicable at low doses and dose rates is examined in terms of an original proposal by Rossi. Two important modifications are suggested to enable an absolute scale of quality factors to be constructed. Allowance should be made to allow for the dependence of the saturation threshold of lineal energy on the type of heavy charged particle. Also, an artificial saturation threshold should be introduced for electron tracks as a mean of modifying the measurements made in the microdosimeter to the more realistic site sizes of nanometer dimensions. The proposed absolute scale of quality factors nicely encompasses the high RBEs of around 3 observed at low doses for tritium β rays and is consistent with the recent recommendation of the ICRP that the quality factor for fast neutrons be increased by a factor of two, assuming that there is no biological repair for the reference radiation.

Evaluation of an adaptive detector collimation for prospectively ECG-triggered coronary CT angiography with third-generation dual-source CT.

PubMed

Messerli, Michael; Dewes, Patricia; Scholtz, Jan-Erik; Arendt, Christophe; Wildermuth, Simon; Vogl, Thomas J; Bauer, Ralf W

2018-05-01

To investigate the impact of an adaptive detector collimation on the dose parameters and accurateness of scan length adaption at prospectively ECG-triggered sequential cardiac CT with a wide-detector third-generation dual-source CT. Ideal scan lengths for human hearts were retrospectively derived from 103 triple-rule-out examinations. These measures were entered into the new scanner operated in prospectively ECG-triggered sequential cardiac scan mode with three different detector settings: (1) adaptive collimation, (2) fixed 64 × 0.6-mm collimation, and (3) fixed 96 × 0.6-mm collimation. Differences in effective scan length and deviation from the ideal scan length and dose parameters (CTDIvol, DLP) were documented. The ideal cardiac scan length could be matched by the adaptive collimation in every case while the mean scanned length was longer by 15.4% with the 64 × 0.6 mm and by 27.2% with the fixed 96 × 0.6-mm collimation. While the DLP was almost identical between the adaptive and the 64 × 0.6-mm collimation (83 vs. 89 mGycm at 120 kV), it was 62.7% higher with the 96 × 0.6-mm collimation (135 mGycm), p < 0.001. The adaptive detector collimation for prospectively ECG-triggered sequential acquisition allows for adjusting the scan length as accurate as this can only be achieved with a spiral acquisition. This technique allows keeping patient exposure low where patient dose would significantly increase with the traditional step-and-shoot mode. • Adaptive detector collimation allows keeping patient exposure low in cardiac CT. • With novel detectors the desired scan length can be accurately matched. • Differences in detector settings may cause 62.7% of excessive dose.

Skin dosimetry of patients during interventional cardiology procedures in the Czech Republic

NASA Astrophysics Data System (ADS)

Sukupova, Lucie; Novak, Leos

2008-01-01

The aim of the study is to determine distribution of air kerma-area product, fluoro time and number of frames values for the two most frequent procedures in the interventional cardiology, to reconstruct skin dose distributions for some patients undergoing coronarography and percutaneous transluminal coronary angioplasty procedures. Patient dose data were obtained from X-ray unit dose monitoring software report from one hospital and the reconstructions were performed in MATLAB. Dependence of maximum skin dose on air kerma-area product, fluoro time and number of frames was determined to assess trigger levels of these quantities, which can indicate possible exceeding of the 2 Gy skin dose threshold.