Caffeine dosing strategies to optimize alertness during sleep loss.
Vital-Lopez, Francisco G; Ramakrishnan, Sridhar; Doty, Tracy J; Balkin, Thomas J; Reifman, Jaques
2018-05-28
Sleep loss, which affects about one-third of the US population, can severely impair physical and neurobehavioural performance. Although caffeine, the most widely used stimulant in the world, can mitigate these effects, currently there are no tools to guide the timing and amount of caffeine consumption to optimize its benefits. In this work, we provide an optimization algorithm, suited for mobile computing platforms, to determine when and how much caffeine to consume, so as to safely maximize neurobehavioural performance at the desired time of the day, under any sleep-loss condition. The algorithm is based on our previously validated Unified Model of Performance, which predicts the effect of caffeine consumption on a psychomotor vigilance task. We assessed the algorithm by comparing the caffeine-dosing strategies (timing and amount) it identified with the dosing strategies used in four experimental studies, involving total and partial sleep loss. Through computer simulations, we showed that the algorithm yielded caffeine-dosing strategies that enhanced performance of the predicted psychomotor vigilance task by up to 64% while using the same total amount of caffeine as in the original studies. In addition, the algorithm identified strategies that resulted in equivalent performance to that in the experimental studies while reducing caffeine consumption by up to 65%. Our work provides the first quantitative caffeine optimization tool for designing effective strategies to maximize neurobehavioural performance and to avoid excessive caffeine consumption during any arbitrary sleep-loss condition. © 2018 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.
NASA Astrophysics Data System (ADS)
Nasef, Mohamed Mahmoud; Ahmad Ali, Amgad; Saidi, Hamdani; Ahmad, Arshad
2014-01-01
Modeling and optimization aspects of radiation induced grafting (RIG) of 4-vinylpyridine (4-VP) onto partially fluorinated polymers such as poly(ethylene-co-tetrafluoroethene) (ETFE) and poly(vinylidene fluoride) (PVDF) films were comparatively investigated using response surface method (RSM). The effects of independent parameters: absorbed dose, monomer concentration, grafting time and reaction temperature on the response, grafting yield (GY) were correlated through two quadratic models. The results of this work confirm that RSM is a reliable tool not only for optimization of the reaction parameters and prediction of GY in RIG processes, but also for the reduction of the number of the experiments, monomer consumption and absorbed dose leading to an improvement of the overall reaction cost.
Ng, S C; Habib, A S; Sodha, S; Carvalho, B; Sultan, P
2018-02-01
The optimal local-anaesthetic (LA) dose for transversus-abdominis-plane (TAP) block is unclear. In this meta-analysis, we aimed to determine whether TAP blocks for Caesarean delivery (CD) with low-dose (LD) LA demonstrated non-inferiority in terms of analgesic efficacy, compared with high-dose (HD) LA. A literature search was performed for randomised controlled trials examining the analgesic efficacy of TAP blocks vs control after CD. The different dosing used in these studies was classified as HD or LD (bupivacaine equivalents >50 or ≤50 mg per block side, respectively). The pooled results of each dose group vs control were indirectly compared using the Q test. The primary outcome was 24 h opioid consumption. Secondary outcomes included 6 and 24 h postoperative pain scores, time to first analgesia, 6 h opioid consumption, opioid-related side-effects, and maternal satisfaction. Fourteen studies consisting of 770 women (389 TAP and 381 control) were included. Compared with controls, the 24 h opioid consumption (milligram morphine equivalents) was lower in HD [mean difference (MD) 95% confidence interval (CI) -22.41 (-38.56, -6.26); P=0.007; I 2 =93%] and LD [MD 95% CI -16.29 (-29.74, -2.84); P=0.02; I 2 =98%] TAP groups. However, no differences were demonstrated between the HD and LD groups (P=0.57). There were also no differences between the HD and LD groups for the 6 h opioid consumption, time to first analgesia, 6 and 24 h pain scores, postoperative nausea and vomiting, pruritus, and maternal satisfaction. Low-dose TAP blocks for Caesarean delivery provide analgesia and opioid-sparing effects comparable with the high-dose blocks. This suggests that lower doses can be used to reduce local anaesthetic toxicity risk without compromising the analgesic efficacy. Copyright © 2017 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.
Schwingshackl, Lukas; Hoffmann, Georg; Lampousi, Anna-Maria; Knüppel, Sven; Iqbal, Khalid; Schwedhelm, Carolina; Bechthold, Angela; Schlesinger, Sabrina; Boeing, Heiner
2017-05-01
The aim of this systematic review and meta-analysis was to synthesize the knowledge about the relation between intake of 12 major food groups and risk of type 2 diabetes (T2D). We conducted a systematic search in PubMed, Embase, Medline (Ovid), Cochrane Central, and Google Scholar for prospective studies investigating the association between whole grains, refined grains, vegetables, fruits, nuts, legumes, eggs, dairy, fish, red meat, processed meat, and sugar-sweetened beverages (SSB) on risk of T2D. Summary relative risks were estimated using a random effects model by contrasting categories, and for linear and non-linear dose-response relationships. Six out of the 12 food-groups showed a significant relation with risk of T2D, three of them a decrease of risk with increasing consumption (whole grains, fruits, and dairy), and three an increase of risk with increasing consumption (red meat, processed meat, and SSB) in the linear dose-response meta-analysis. There was evidence of a non-linear relationship between fruits, vegetables, processed meat, whole grains, and SSB and T2D risk. Optimal consumption of risk-decreasing foods resulted in a 42% reduction, and consumption of risk-increasing foods was associated with a threefold T2D risk, compared to non-consumption. The meta-evidence was graded "low" for legumes and nuts; "moderate" for refined grains, vegetables, fruit, eggs, dairy, and fish; and "high" for processed meat, red meat, whole grains, and SSB. Among the investigated food groups, selecting specific optimal intakes can lead to a considerable change in risk of T2D.
Georgia fishery study: implications for dose calculations. Revision 1
DOE Office of Scientific and Technical Information (OSTI.GOV)
Turcotte, M.D.S.
Fish consumption will contribute a major portion of the estimated individual and population doses from L-Reactor liquid releases and Cs-137 remobilization in Steel Creek. It is therefore important that the values for fish consumption used in dose calculations be as realistic as possible. Since publication of the L-Reactor Environmental Information Document (EID), data have become available on sport fishing in the Savannah River. These data provide SRP with a site-specific sport fish harvest and consumption values for use in dose calculations. The Georgia fishery data support the total population fish consumption and calculated dose reported in the EID. The datamore » indicate, however, that both the EID average and maximum individual fish consumption have been underestimated, although each to a different degree. The average fish consumption value used in the EID is approximately 3% below the lower limit of the fish consumption range calculated using the Georgia data. Maximum fish consumption in the EID has been underestimated by approximately 60%, and doses to the maximum individual should also be recalculated. Future dose calculations should utilize an average adult fish consumption value of 11.3 kg/yr, and a maximum adult fish consumption value of 34 kg/yr. Consumption values for the teen and child age groups should be increased proportionally: (1) teen average = 8.5; maximum = 25.9 kg/yr; and (2) child average = 3.6; maximum = 11.2 kg/yr. 8 refs.« less
Global increase and geographic convergence in antibiotic consumption between 2000 and 2015
Van Boeckel, Thomas P.; Martinez, Elena M.; Pant, Suraj; Gandra, Sumanth; Levin, Simon A.; Goossens, Herman
2018-01-01
Tracking antibiotic consumption patterns over time and across countries could inform policies to optimize antibiotic prescribing and minimize antibiotic resistance, such as setting and enforcing per capita consumption targets or aiding investments in alternatives to antibiotics. In this study, we analyzed the trends and drivers of antibiotic consumption from 2000 to 2015 in 76 countries and projected total global antibiotic consumption through 2030. Between 2000 and 2015, antibiotic consumption, expressed in defined daily doses (DDD), increased 65% (21.1–34.8 billion DDDs), and the antibiotic consumption rate increased 39% (11.3–15.7 DDDs per 1,000 inhabitants per day). The increase was driven by low- and middle-income countries (LMICs), where rising consumption was correlated with gross domestic product per capita (GDPPC) growth (P = 0.004). In high-income countries (HICs), although overall consumption increased modestly, DDDs per 1,000 inhabitants per day fell 4%, and there was no correlation with GDPPC. Of particular concern was the rapid increase in the use of last-resort compounds, both in HICs and LMICs, such as glycylcyclines, oxazolidinones, carbapenems, and polymyxins. Projections of global antibiotic consumption in 2030, assuming no policy changes, were up to 200% higher than the 42 billion DDDs estimated in 2015. Although antibiotic consumption rates in most LMICs remain lower than in HICs despite higher bacterial disease burden, consumption in LMICs is rapidly converging to rates similar to HICs. Reducing global consumption is critical for reducing the threat of antibiotic resistance, but reduction efforts must balance access limitations in LMICs and take account of local and global resistance patterns. PMID:29581252
Prevalence of Tramadol Consumption in First Seizure Patients; a One-Year Cross-sectional Study
Asadi, Payman; Monsef Kasmaei, Vahid; Ziabari, Seyyed Zia; Zohrevandi, Behzad; Moadab Manesh, Aslan
2015-01-01
Introduction: Previous studies have shown that there is a probability of seizure even with therapeutic doses of tramadol. Yet, no accurate data exist regarding this problem in Iran. Therefore, the present study aimed to evaluate the prevalence of tramadol consumption in patients with first seizure referred to the emergency department (ED). Methods: In the present retrospective one-year cross-sectional study, all patients who were referred to the ED of Poursina Hospital, Rasht, Iran, with the complaint of first seizure were evaluated. Demographic data and data regarding history of tramadol consumption, duration, total dose, last dose, and time passed from the last dose of consumption were recorded and analyzed regarding the study questions using SPSS 20. Results: 383 (68.9%) out of the 556 patients referred to the ED, were experiencing their first seizure (mean age 26.43 ± 6.48 years; 70.5% male). 84 (21.9%) patients had recently used tramadol. History of seizure in the family of tramadol consumers was significantly lower (3.6% compared to 11%; p = 0.036). Mean total tramadol consumption dose in the last 24 hours was 140.17 ± 73.53 mg (range: 50-300 mg). Duration of tramadol consumption was less than 10 days in 84.5% (df: 2; χ2 = 96.1; p < 0.001). In addition, 62 (73.8%) patients had seizure within 6 hours of consumption (df: 3; χ2 = 29.5; p < 0.001). Conclusion: Results of the present study showed that 21.9% of the patients with first seizure had a history of tramadol consumption. Seizure following tramadol consumption is more prevalent in the initial 10 days and within 6 hours of consumption. In addition, it seems that lower doses of tramadol may also induce seizure. PMID:26495407
Jung, Hong Soo; Seo, Kwon Hui; Kang, Jae Hyuk; Jeong, Jin-Young; Kim, Yong-Shin; Han, Na-Re
2018-04-01
Adjuvant perineural dexmedetomidine can be used to prolong the analgesic effect of interscalene brachial plexus block (ISB). We investigated the optimal dose of dexmedetomidine in ISB for postoperative analgesia in patients undergoing arthroscopic shoulder surgery. One hundred patients scheduled for elective shoulder arthroscopic surgery were enrolled in this randomized, double-blind study. Ultrasound-guided ISB was performed before general anesthesia using 22 mL of ropivacaine 0.5% combined with 1, 1.5, or 2 μg/kg of dexmedetomidine (group D1, D2, and D3, respectively) or with normal saline as a control (group R, n = 25 per group). The primary outcome was the duration of analgesia (DOA), numeric pain rating scale (NRS), and consumption of additional analgesics during 36 h after ISB. Secondary outcome included durations of motor and sensory block (DOM and DOS), hemodynamic variables and sedation and dyspnea scores. Ninety-seven patients completed the study. The DOS, DOM, and DOA were significantly longer in the dexmedetomidine groups than in group R. The DOA was significantly longer in group D3 than in groups D1 (P = .026) and D2 (P = .039). The DOA was 808.13 ± 179.97, 1032.60 ± 288.14, 1042.04 ± 188.13, and 1223.96 ± 238.06 min in groups R, D1, D2, and D3, respectively. The NRS score was significantly higher in group R than in the dexmedetomidine groups 12 h after ISB (P < .001) and significantly lower in group D3 than in the other groups 18 h after ISB (P = .02). The incidence of hypotension was higher in groups D2 and D3 than in group R during surgery (P = .008 and P = .011, respectively). There were no significant differences in consumption of rescue analgesics, sedation, and dyspnea scores between the study groups. Perineural dexmedetomidine 2 μg/kg could be the optimal dose in ISB for arthroscopic shoulder surgery in that it provides an adequate DOA. However, this dose was associated with increased risk of hypotension.
NASA Astrophysics Data System (ADS)
Monica, Z.; Sękala, A.; Gwiazda, A.; Banaś, W.
2016-08-01
Nowadays a key issue is to reduce the energy consumption of road vehicles. In particular solution one could find different strategies of energy optimization. The most popular but not sophisticated is so called eco-driving. In this strategy emphasized is particular behavior of drivers. In more sophisticated solution behavior of drivers is supported by control system measuring driving parameters and suggesting proper operation of the driver. The other strategy is concerned with application of different engineering solutions that aid optimization the process of energy consumption. Such systems take into consideration different parameters measured in real time and next take proper action according to procedures loaded to the control computer of a vehicle. The third strategy bases on optimization of the designed vehicle taking into account especially main sub-systems of a technical mean. In this approach the optimal level of energy consumption by a vehicle is obtained by synergetic results of individual optimization of particular constructional sub-systems of a vehicle. It is possible to distinguish three main sub-systems: the structural one the drive one and the control one. In the case of the structural sub-system optimization of the energy consumption level is related with the optimization or the weight parameter and optimization the aerodynamic parameter. The result is optimized body of a vehicle. Regarding the drive sub-system the optimization of the energy consumption level is related with the fuel or power consumption using the previously elaborated physical models. Finally the optimization of the control sub-system consists in determining optimal control parameters.
Taxes on tobacco, alcohol and sugar sweetened beverages: Linkages and lessons learned.
Blecher, Evan
2015-07-01
Increased consumption of sugar-sweetened beverages (SSBs) has been linked to increases in obesity in both high-income and low- and middle-income countries. Tobacco and alcohol taxes have proven to be effective tools to reduce tobacco and alcohol use. Many public health advocates propose using similar taxes to reduce consumption of SSBs. South Africa is a middle-income country that is considered a leader in the area of tobacco tax policy. A case study of tobacco and alcohol taxes is used to better understand optimal tax structures for SSBs. The case study tracks aggregate data over time on taxes, prices, consumption, tax revenues, and marketing expenditures at the brand level. Tobacco and alcohol taxes are shown to be effective in reducing the demand for tobacco. Additionally, taxes on the dose of alcohol rather than the volume of the beverage may incentivize producers to reduce the volume of alcohol in beverages through the supply side. While specific taxes based on the volume of beverages are likely to reduce the demand for SSBs, policy makers should also consider taxes on alcohol and SSBs that tax the dose of the alcohol and calories in order to create supply-side incentives for producers to lower alcohol and calorie levels in existing products or promote products with lower levels of alcohol and calories. Copyright © 2015 Elsevier Ltd. All rights reserved.
Push the flash floating gate memories toward the future low energy application
NASA Astrophysics Data System (ADS)
Della Marca, V.; Just, G.; Regnier, A.; Ogier, J.-L.; Simola, R.; Niel, S.; Postel-Pellerin, J.; Lalande, F.; Masoero, L.; Molas, G.
2013-01-01
In this paper the energy consumption of flash floating gate cell, during a channel hot electron operation, is investigated. We characterize the device using different ramp and box pulses on control gate, to find the best solution to have low energy consumption and good cell performances. We use a new dynamic method to measure the drain current absorption in order to evaluate the impact of different bias conditions, and to study the cell behavior. The programming window and the energy consumption are considered as fundamental parameters. Using this dynamic technique, three zones of work are found; it is possible to optimize the drain voltage during the programming operation to minimize the energy consumption. Moreover, the cell's performances are improved using the CHISEL effect, with a reverse body bias. After the study concerning the programming pulses adjusting, we show the results obtained by increasing the channel doping dose parameter. Considering a channel hot electron programming operation, it is important to focus our attention on the bitline leakage consumption contribution. We measured it for the unselected bitline cells, and we show the effects of the lightly doped drain implantation energy on the leakage current. In this way the impact of gate induced drain leakage in band-to-band tunneling regime decreases, improving the cell's performances in a memory array.
Optimized Dose Distribution of Gammamed Plus Vaginal Cylinders
DOE Office of Scientific and Technical Information (OSTI.GOV)
Supe, Sanjay S.; Bijina, T.K.; Varatharaj, C.
2009-04-01
Endometrial carcinoma is the most common malignancy arising in the female genital tract. Intracavitary vaginal cuff irradiation may be given alone or with external beam irradiation in patients determined to be at risk for locoregional recurrence. Vaginal cylinders are often used to deliver a brachytherapy dose to the vaginal apex and upper vagina or the entire vaginal surface in the management of postoperative endometrial cancer or cervical cancer. The dose distributions of HDR vaginal cylinders must be evaluated carefully, so that clinical experiences with LDR techniques can be used in guiding optimal use of HDR techniques. The aim of thismore » study was to optimize dose distribution for Gammamed plus vaginal cylinders. Placement of dose optimization points was evaluated for its effect on optimized dose distributions. Two different dose optimization point models were used in this study, namely non-apex (dose optimization points only on periphery of cylinder) and apex (dose optimization points on periphery and along the curvature including the apex points). Thirteen dwell positions were used for the HDR dosimetry to obtain a 6-cm active length. Thus 13 optimization points were available at the periphery of the cylinder. The coordinates of the points along the curvature depended on the cylinder diameters and were chosen for each cylinder so that four points were distributed evenly in the curvature portion of the cylinder. Diameter of vaginal cylinders varied from 2.0 to 4.0 cm. Iterative optimization routine was utilized for all optimizations. The effects of various optimization routines (iterative, geometric, equal times) was studied for the 3.0-cm diameter vaginal cylinder. The effect of source travel step size on the optimized dose distributions for vaginal cylinders was also evaluated. All optimizations in this study were carried for dose of 6 Gy at dose optimization points. For both non-apex and apex models of vaginal cylinders, doses for apex point and three dome points were higher for the apex model compared with the non-apex model. Mean doses to the optimization points for both the cylinder models and all the cylinder diameters were 6 Gy, matching with the prescription dose of 6 Gy. Iterative optimization routine resulted in the highest dose to apex point and dome points. The mean dose for optimization point was 6.01 Gy for iterative optimization and was much higher than 5.74 Gy for geometric and equal times routines. Step size of 1 cm gave the highest dose to the apex point. This step size was superior in terms of mean dose to optimization points. Selection of dose optimization points for the derivation of optimized dose distributions for vaginal cylinders affects the dose distributions.« less
Calculations of dose distributions using a neural network model
NASA Astrophysics Data System (ADS)
Mathieu, R.; Martin, E.; Gschwind, R.; Makovicka, L.; Contassot-Vivier, S.; Bahi, J.
2005-03-01
The main goal of external beam radiotherapy is the treatment of tumours, while sparing, as much as possible, surrounding healthy tissues. In order to master and optimize the dose distribution within the patient, dosimetric planning has to be carried out. Thus, for determining the most accurate dose distribution during treatment planning, a compromise must be found between the precision and the speed of calculation. Current techniques, using analytic methods, models and databases, are rapid but lack precision. Enhanced precision can be achieved by using calculation codes based, for example, on Monte Carlo methods. However, in spite of all efforts to optimize speed (methods and computer improvements), Monte Carlo based methods remain painfully slow. A newer way to handle all of these problems is to use a new approach in dosimetric calculation by employing neural networks. Neural networks (Wu and Zhu 2000 Phys. Med. Biol. 45 913-22) provide the advantages of those various approaches while avoiding their main inconveniences, i.e., time-consumption calculations. This permits us to obtain quick and accurate results during clinical treatment planning. Currently, results obtained for a single depth-dose calculation using a Monte Carlo based code (such as BEAM (Rogers et al 2003 NRCC Report PIRS-0509(A) rev G)) require hours of computing. By contrast, the practical use of neural networks (Mathieu et al 2003 Proceedings Journées Scientifiques Francophones, SFRP) provides almost instant results and quite low errors (less than 2%) for a two-dimensional dosimetric map.
Calculations of dose distributions using a neural network model.
Mathieu, R; Martin, E; Gschwind, R; Makovicka, L; Contassot-Vivier, S; Bahi, J
2005-03-07
The main goal of external beam radiotherapy is the treatment of tumours, while sparing, as much as possible, surrounding healthy tissues. In order to master and optimize the dose distribution within the patient, dosimetric planning has to be carried out. Thus, for determining the most accurate dose distribution during treatment planning, a compromise must be found between the precision and the speed of calculation. Current techniques, using analytic methods, models and databases, are rapid but lack precision. Enhanced precision can be achieved by using calculation codes based, for example, on Monte Carlo methods. However, in spite of all efforts to optimize speed (methods and computer improvements), Monte Carlo based methods remain painfully slow. A newer way to handle all of these problems is to use a new approach in dosimetric calculation by employing neural networks. Neural networks (Wu and Zhu 2000 Phys. Med. Biol. 45 913-22) provide the advantages of those various approaches while avoiding their main inconveniences, i.e., time-consumption calculations. This permits us to obtain quick and accurate results during clinical treatment planning. Currently, results obtained for a single depth-dose calculation using a Monte Carlo based code (such as BEAM (Rogers et al 2003 NRCC Report PIRS-0509(A) rev G)) require hours of computing. By contrast, the practical use of neural networks (Mathieu et al 2003 Proceedings Journees Scientifiques Francophones, SFRP) provides almost instant results and quite low errors (less than 2%) for a two-dimensional dosimetric map.
Roh, Kum-Hwan; Kim, Ji Yeoun; Shin, Yong Hyun
2017-01-01
In this paper, we investigate the optimal consumption and portfolio selection problem with negative wealth constraints for an economic agent who has a quadratic utility function of consumption and receives a constant labor income. Due to the property of the quadratic utility function, we separate our problem into two cases and derive the closed-form solutions for each case. We also illustrate some numerical implications of the optimal consumption and portfolio.
Crane, Tracy E.; Kubota, Chieri; West, Julie L.; Kroggel, Mark A.; Wertheim, Betsy C.; Thomson, Cynthia A.
2011-01-01
The optimal amount of vegetable consumption required to reduce chronic disease risk is widely debated. Intervention trials evaluating biological activity of vegetables at various doses are limited. We conducted a 3-dose, crossover feeding trial to test the hypothesis that vegetable intake is associated in a dose-dependent manner with increased plasma carotenoids and subsequently reduced oxidative stress and inflammation in 49 overweight, postmenopausal women. Participants were assigned in random order to 2 (130 g), 5 (287 g), and 10 (614 g) daily servings of fresh, greenhouse-grown vegetables for 3-wk intervals with a 4-wk washout period between treatments. Plasma total carotenoids significantly increased from 1.63 to 2.07 μmol/L with a dose of 2 vegetable servings, from 1.49 to 2.84 μmol/L with a dose of 5 vegetable servings, and from 1.40 to 4.42 μmol/L with a dose of 10 vegetable servings (pre-post paired ttests, all P < 0.001). The change during each feeding period increased with each dose level (P < 0.001). Urine concentrations of 8-isoprostane F2α, hexanoyl lysine, and serum high sensitivity C-reactive protein were not affected by any administered vegetable dose. In this variable-dose vegetable study, a dose-response for plasma carotenoids was demonstrated without significant change in oxidative stress and inflammation in overweight, postmenopausal women. PMID:21865569
DOE Office of Scientific and Technical Information (OSTI.GOV)
Anderson, D.M.; Bates, D.J.; Marsh, T.L.
This report details the methods used and the results of the study on the estimated historic levels of food consumption by individuals in the Hanford Environmental Dose Reconstruction (HEDR) study area from 1945--1957. This period includes the time of highest releases from Hanford and is the period for which data are being collected in the Hanford Thyroid Disease Study. These estimates provide the food-consumption inputs for the HEDR database of individual diets. This database will be an input file in the Hanford Environmental Dose Reconstruction Integrated Code (HEDRIC) computer model that will be used to calculate the radiation dose. Themore » report focuses on fresh milk, eggs, lettuce, and spinach. These foods were chosen because they have been found to be significant contributors to radiation dose based on the Technical Steering Panel dose decision level.« less
Estimation of 1945 to 1957 food consumption. Hanford Environmental Dose Reconstruction Project
DOE Office of Scientific and Technical Information (OSTI.GOV)
Anderson, D.M.; Bates, D.J.; Marsh, T.L.
This report details the methods used and the results of the study on the estimated historic levels of food consumption by individuals in the Hanford Environmental Dose Reconstruction (HEDR) study area from 1945--1957. This period includes the time of highest releases from Hanford and is the period for which data are being collected in the Hanford Thyroid Disease Study. These estimates provide the food-consumption inputs for the HEDR database of individual diets. This database will be an input file in the Hanford Environmental Dose Reconstruction Integrated Code (HEDRIC) computer model that will be used to calculate the radiation dose. Themore » report focuses on fresh milk, eggs, lettuce, and spinach. These foods were chosen because they have been found to be significant contributors to radiation dose based on the Technical Steering Panel dose decision level.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ali, I; Algan, O; Ahmad, S
Purpose: To model patient motion and produce four-dimensional (4D) optimized dose distributions that consider motion-artifacts in the dose calculation during the treatment planning process. Methods: An algorithm for dose calculation is developed where patient motion is considered in dose calculation at the stage of the treatment planning. First, optimal dose distributions are calculated for the stationary target volume where the dose distributions are optimized considering intensity-modulated radiation therapy (IMRT). Second, a convolution-kernel is produced from the best-fitting curve which matches the motion trajectory of the patient. Third, the motion kernel is deconvolved with the initial dose distribution optimized for themore » stationary target to produce a dose distribution that is optimized in four-dimensions. This algorithm is tested with measured doses using a mobile phantom that moves with controlled motion patterns. Results: A motion-optimized dose distribution is obtained from the initial dose distribution of the stationary target by deconvolution with the motion-kernel of the mobile target. This motion-optimized dose distribution is equivalent to that optimized for the stationary target using IMRT. The motion-optimized and measured dose distributions are tested with the gamma index with a passing rate of >95% considering 3% dose-difference and 3mm distance-to-agreement. If the dose delivery per beam takes place over several respiratory cycles, then the spread-out of the dose distributions is only dependent on the motion amplitude and not affected by motion frequency and phase. This algorithm is limited to motion amplitudes that are smaller than the length of the target along the direction of motion. Conclusion: An algorithm is developed to optimize dose in 4D. Besides IMRT that provides optimal dose coverage for a stationary target, it extends dose optimization to 4D considering target motion. This algorithm provides alternative to motion management techniques such as beam-gating or breath-holding and has potential applications in adaptive radiation therapy.« less
Piao, Wenhua; Kim, Changwon; Cho, Sunja; Kim, Hyosoo; Kim, Minsoo; Kim, Yejin
2016-12-01
In wastewater treatment plants (WWTPs), the portion of operating costs related to electric power consumption is increasing. If the electric power consumption decreased, however, it would be difficult to comply with the effluent water quality requirements. A protocol was proposed to minimize the environmental impacts as well as to optimize the electric power consumption under the conditions needed to meet the effluent water quality standards in this study. This protocol was comprised of six phases of procedure and was tested using operating data from S-WWTP to prove its applicability. The 11 major operating variables were categorized into three groups using principal component analysis and K-mean cluster analysis. Life cycle assessment (LCA) was conducted for each group to deduce the optimal operating conditions for each operating state. Then, employing mathematical modeling, six improvement plans to reduce electric power consumption were deduced. The electric power consumptions for suggested plans were estimated using an artificial neural network. This was followed by a second round of LCA conducted on the plans. As a result, a set of optimized improvement plans were derived for each group that were able to optimize the electric power consumption and life cycle environmental impact, at the same time. Based on these test results, the WWTP operating management protocol presented in this study is deemed able to suggest optimal operating conditions under which power consumption can be optimized with minimal life cycle environmental impact, while allowing the plant to meet water quality requirements.
Inconsistent Investment and Consumption Problems
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kronborg, Morten Tolver, E-mail: mtk@atp.dk; Steffensen, Mogens, E-mail: mogens@math.ku.dk
In a traditional Black–Scholes market we develop a verification theorem for a general class of investment and consumption problems where the standard dynamic programming principle does not hold. The theorem is an extension of the standard Hamilton–Jacobi–Bellman equation in the form of a system of non-linear differential equations. We derive the optimal investment and consumption strategy for a mean-variance investor without pre-commitment endowed with labor income. In the case of constant risk aversion it turns out that the optimal amount of money to invest in stocks is independent of wealth. The optimal consumption strategy is given as a deterministic bang-bangmore » strategy. In order to have a more realistic model we allow the risk aversion to be time and state dependent. Of special interest is the case were the risk aversion is inversely proportional to present wealth plus the financial value of future labor income net of consumption. Using the verification theorem we give a detailed analysis of this problem. It turns out that the optimal amount of money to invest in stocks is given by a linear function of wealth plus the financial value of future labor income net of consumption. The optimal consumption strategy is again given as a deterministic bang-bang strategy. We also calculate, for a general time and state dependent risk aversion function, the optimal investment and consumption strategy for a mean-standard deviation investor without pre-commitment. In that case, it turns out that it is optimal to take no risk at all.« less
Aircraft Trajectory Optimization and Contrails Avoidance in the Presence of Winds
NASA Technical Reports Server (NTRS)
Ng, Hok K.; Chen, Neil Y.
2010-01-01
There are indications that persistent contrails can lead to adverse climate change, although the complete effect on climate forcing is still uncertain. A flight trajectory optimization algorithm with fuel and contrails models, which develops alternative flight paths, provides policy makers the necessary data to make tradeoffs between persistent contrails mitigation and aircraft fuel consumption. This study develops an algorithm that calculates wind-optimal trajectories for cruising aircraft while avoiding the regions of airspace prone to persistent contrails formation. The optimal trajectories are developed by solving a non-linear optimal control problem with path constraints. The regions of airspace favorable to persistent contrails formation are modeled as penalty areas that aircraft should avoid and are adjustable. The tradeoff between persistent contrails formation and additional fuel consumption is investigated, with and without altitude optimization, for 12 city-pairs in the continental United States. Without altitude optimization, the reduction in contrail travel times is gradual with increase in total fuel consumption. When altitude is optimized, a two percent increase in total fuel consumption can reduce the total travel times through contrail regions by more than six times. Allowing further increase in fuel consumption does not seem to result in proportionate decrease in contrail travel times.
Optimal Energy Consumption Analysis of Natural Gas Pipeline
Liu, Enbin; Li, Changjun; Yang, Yi
2014-01-01
There are many compressor stations along long-distance natural gas pipelines. Natural gas can be transported using different boot programs and import pressures, combined with temperature control parameters. Moreover, different transport methods have correspondingly different energy consumptions. At present, the operating parameters of many pipelines are determined empirically by dispatchers, resulting in high energy consumption. This practice does not abide by energy reduction policies. Therefore, based on a full understanding of the actual needs of pipeline companies, we introduce production unit consumption indicators to establish an objective function for achieving the goal of lowering energy consumption. By using a dynamic programming method for solving the model and preparing calculation software, we can ensure that the solution process is quick and efficient. Using established optimization methods, we analyzed the energy savings for the XQ gas pipeline. By optimizing the boot program, the import station pressure, and the temperature parameters, we achieved the optimal energy consumption. By comparison with the measured energy consumption, the pipeline now has the potential to reduce energy consumption by 11 to 16 percent. PMID:24955410
Fabritius, Maria Louise; Wetterslev, Jørn; Mathiesen, Ole; Dahl, Jørgen B
2017-01-01
Background During the last 15 years, gabapentin has become an established component of postoperative pain treatment. Gabapentin has been employed in a wide range of doses, but little is known about the optimal dose, providing the best balance between benefit and harm. This systematic review with meta-analyses aimed to explore the beneficial and harmful effects of various doses of gabapentin administered to surgical patients. Materials and methods Data in this paper were derived from an original review, and the subgroup analyses were predefined in an International Prospective Register of Systematic Reviews published protocol: PROSPERO (ID: CRD42013006538). The methods followed Cochrane guidelines. The Cochrane Library’s CENTRAL, PubMed, EMBASE, Science Citation Index Expanded, Google Scholar, and FDA database were searched for relevant trials. Randomized clinical trials comparing gabapentin versus placebo were included. Four different dose intervals were investigated: 0–350, 351–700, 701–1050, and >1050 mg. Primary co-outcomes were 24-hour morphine consumption and serious adverse events (SAEs), with emphasis put on trials with low risk of bias. Results One hundred and twenty-two randomized clinical trials, with 8466 patients, were included. Sixteen were overall low risk of bias. No consistent increase in morphine-sparing effect was observed with increasing doses of gabapentin from the trials with low risk of bias. Analyzing all trials, the smallest and the highest dose subgroups demonstrated numerically the most prominent reduction in morphine consumption. Twenty-seven trials reported 72 SAEs, of which 83% were reported in the >1050 mg subgroup. No systematic increase in SAEs was observed with increasing doses of gabapentin. Conclusion Data were sparse, and the small number of trials with low risk of bias is a major limitation for firm conclusions. Taking these limitations into account, we were not able to demonstrate a clear relationship between the dosage of gabapentin and opioid-sparing or harmful effects. These subgroup analyses are exploratory and hypothesis-generating for future trialists. PMID:29138592
Biel, Sara; Mesa, Maria-Dolores; de la Torre, Rafael; Espejo, Juan-Antonio; Fernández-Navarro, Jose-Ramón; Fitó, Montserrat; Sánchez-Rodriguez, Estefanía; Rosa, Carmen; Marchal, Rosa; Alche, Juan de Dios; Expósito, Manuela; Brenes, Manuel; Gandul, Beatriz; Calleja, Miguel Angel; Covas, María-Isabel
2016-10-22
Virgin olive oil, a recognized healthy food, cannot be consumed in great quantities. We aim to assess in humans whether an optimized virgin olive oil with high phenolic content (OVOO, 429 mg/Kg) and a functional one (FOO), both rich in phenolic compounds (429 mg/Kg) and triterpenic acids (389 mg/kg), could provide health benefits additional to those supplied a by a standard virgin olive oil (VOO). A randomized, double-blind, crossover, controlled study will be conducted. Healthy volunteers (aged 20 to 50) will be randomized into one of three groups of daily raw olive oil consumption: VOO, OVOO, and FOO (30 mL/d). Olive oils will be administered over 3-week periods preceded by 2-week washout ones. The main outcomes will be markers of lipid and DNA oxidation, inflammation, and vascular damage. A bioavailability and dose-response study will be nested within this sustained- consumption one. It will be made up of 18 volunteers and be performed at two stages after a single dose of each olive oil. Endothelial function and nitric oxide will be assessed at baseline and at 4 h and 6 h after olive oil single dose ingestion. For the first time the NUTRAOLEUM Study will provide first level evidence on the health benefits in vivo in humans of olive oil triterpenes (oleanolic and maslinic acid) in addition to their bioavailability and disposition. The Trial has been registered in ClinicalTrials.gov ID: NCT02520739 .
Estimation of 1945 to 1957 food consumption
DOE Office of Scientific and Technical Information (OSTI.GOV)
Anderson, D.M.; Bates, D.J.; Marsh, T.L.
This report details the methods used and the results of the study on the estimated historic levels of food consumption by individuals in the Hanford Environmental Dose Reconstruction (HEDR) study area from 1945--1957. This period includes the time of highest releases from Hanford and is the period for which data are being collected in the Hanford Thyroid Disease Study. These estimates provide the food-consumption inputs for the HEDR database of individual diets. This database will be an input file in the Hanford Environmental Dose Reconstruction Integrated Code (HEDRIC) computer model that will be used to calculate the radiation dose. Themore » report focuses on fresh milk, eggs, lettuce, and spinach. These foods were chosen because they have been found to be significant contributors to radiation dose based on the Technical Steering Panel dose decision level.« less
Influence of experimental hyperthyroidism on skeletal muscle metabolism in the rat.
van Hardeveld, C; Kassenaar, A A
1977-05-01
In this study hind-limb perfusion was used to investigate the influence of thyroid hormones on some metabolic parameters in the skeletal muscle of the rat. Daily injection of 20 microng L-thyroxine (T4) per 100 g b. w. for a week caused a 25% increase in oxygen consumption. Further enlargement of the T4 dose had little additive effect. In the dose range 20--80 microng T4/100g b.w., no important changes occurred in lactate production or glucose consumption. Only at the highest T4 dose did the glucose consumption increase significantly. The most profound effect of T4 was on lipolysis. A daily dose of 20 microng T4/100 g b. w. gave a doubling of glycerol production rate, the maximum occuring at a dose of 40 microng T4/100 g b. w. Inactivation of the nervous system was without influence on the T4-induced increase in oxygen consumption. However, the T4-induced elevation of lipolysis disappeared after abolition of the nervous activity. This raises the possibility that the T4 effect on lipolysis in skeletal muscle is a potentiation of catecholamine effects. The T4-induced oxygen consumption increase might be dependent not on the lipolytic process but rather on other energy-consuming cell processes.
Liu, Xueying; Du, Xiaoyuan; Han, Guanying; Gao, Wenyuan
2017-01-01
Background The epidemiological evidence for a dose-response relationship between tea consumption and risk of cognitive disorders is sparse. The aim of the study was to summarize the evidence for the association of tea consumption with risk of cognitive disorders and assess the dose-response relationship. Methods We searched electronic databases of Pubmed, Embase, and Cochrane Library (from 1965 to Jan 19, 2017) for eligible studies that published in the international journals. A random-effects model was used to pool the most adjusted odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Results Seventeen studies involving 48,435 participants were included in our study. The meta-analysis showed that a higher tea consumption was associated with a significant reduction in the risk of cognitive disorders (OR=0.73, 95% CI: 0.65-0.82). When considering the specific types of tea consumption, the significantly inverse association is only found in green tea consumption (OR=0.64, 95% CI: 0.53-0.77) but not in black/oolong tea consumption (OR=0.75, 95% CI: 0.55-1.01). Dose-response meta-analysis indicated that tea consumption is linearly associated with a reduced risk of cognitive disorders. An increment of 100 ml/day, 300 ml/day, and 500 ml/day of tea consumption was associated with a 6% (OR=0.94, 95% CI: 0.92-0.96), 19% (OR=0.81, 95% CI: 0.74-0.88), and 29% (OR=0.71, 95% CI: 0.62-0.82) lower risk of cognitive disorders. Conclusions Tea consumption is inversely and linearly related to the risk of cognitive disorders. More studies are needed to further confirm our findings. PMID:28496007
Liu, Xueying; Du, Xiaoyuan; Han, Guanying; Gao, Wenyuan
2017-06-27
The epidemiological evidence for a dose-response relationship between tea consumption and risk of cognitive disorders is sparse. The aim of the study was to summarize the evidence for the association of tea consumption with risk of cognitive disorders and assess the dose-response relationship. We searched electronic databases of Pubmed, Embase, and Cochrane Library (from 1965 to Jan 19, 2017) for eligible studies that published in the international journals. A random-effects model was used to pool the most adjusted odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Seventeen studies involving 48,435 participants were included in our study. The meta-analysis showed that a higher tea consumption was associated with a significant reduction in the risk of cognitive disorders (OR=0.73, 95% CI: 0.65-0.82). When considering the specific types of tea consumption, the significantly inverse association is only found in green tea consumption (OR=0.64, 95% CI: 0.53-0.77) but not in black/oolong tea consumption (OR=0.75, 95% CI: 0.55-1.01). Dose-response meta-analysis indicated that tea consumption is linearly associated with a reduced risk of cognitive disorders. An increment of 100 ml/day, 300 ml/day, and 500 ml/day of tea consumption was associated with a 6% (OR=0.94, 95% CI: 0.92-0.96), 19% (OR=0.81, 95% CI: 0.74-0.88), and 29% (OR=0.71, 95% CI: 0.62-0.82) lower risk of cognitive disorders. Tea consumption is inversely and linearly related to the risk of cognitive disorders. More studies are needed to further confirm our findings.
Schellack, Natalie; Benjamin, Deon; Brink, Adrian; Duse, Adriano; Faure, Kim; Goff, Debra; Mendelson, Marc; Meyer, Johanna; Miot, Jacqui; Perovic, Olga; Pople, Troy; Suleman, Fatima; van Vuuren, Moritz; Essack, Sabiha
2017-11-01
The Global Action Plan on antimicrobial resistance calls for the use of antimicrobial medicines in human and animal health to be optimized, in tandem with a strengthening of the knowledge and evidence base through surveillance and research. However, there is a paucity of consumption data for African countries such as South Africa. Determining antimicrobial consumption data in low-resource settings remains a challenge. This article describes alternative mechanisms of assessing antimicrobial consumption data, such as the use of Intercontinental Marketing Services (IMS) data and contract data arising from tenders (an open Request for Proposal, RFP), as opposed to the international norms of daily defined doses per 100 patient-days or per 1000 population. Despite their limitations, these serve as indicators of antimicrobial exposure at the population level and represent an alternative method for ascertaining antimicrobial consumption in human health. Furthermore, South Africa has the largest antiretroviral treatment programme globally and carries a high burden of tuberculosis. This prompted the inclusion of antiretroviral and anti-tuberculosis antibiotic consumption data. Knowledge of antimicrobial utilization is imperative for meaningful future interventions. Baseline antimicrobial utilization data could guide future research initiatives that could provide a better understanding of the different measures of antibiotic use and the level of antibiotic resistance. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Is Dosing of Therapeutic Immunoglobulins Optimal? A Review of a Three-Decade Long Debate in Europe
Kerr, Jacqueline; Quinti, Isabella; Eibl, Martha; Chapel, Helen; Späth, Peter J.; Sewell, W. A. Carrock; Salama, Abdulgabar; van Schaik, Ivo N.; Kuijpers, Taco W.; Peter, Hans-Hartmut
2014-01-01
The consumption of immunoglobulins (Ig) is increasing due to better recognition of antibody deficiencies, an aging population, and new indications. This review aims to examine the various dosing regimens and research developments in the established and in some of the relevant off-label indications in Europe. The background to the current regulatory settings in Europe is provided as a backdrop for the latest developments in primary and secondary immunodeficiencies and in immunomodulatory indications. In these heterogeneous areas, clinical trials encompassing different routes of administration, varying intervals, and infusion rates are paving the way toward more individualized therapy regimens. In primary antibody deficiencies, adjustments in dosing and intervals will depend on the clinical presentation, effective IgG trough levels and IgG metabolism. Ideally, individual pharmacokinetic profiles in conjunction with the clinical phenotype could lead to highly tailored treatment. In practice, incremental dosage increases are necessary to titrate the optimal dose for more severely ill patients. Higher intravenous doses in these patients also have beneficial immunomodulatory effects beyond mere IgG replacement. Better understanding of the pharmacokinetics of Ig therapy is leading to a move away from simplistic “per kg” dosing. Defective antibody production is common in many secondary immunodeficiencies irrespective of whether the causative factor was lymphoid malignancies (established indications), certain autoimmune disorders, immunosuppressive agents, or biologics. This antibody failure, as shown by test immunization, may be amenable to treatment with replacement Ig therapy. In certain immunomodulatory settings [e.g., idiopathic thrombocytopenic purpura (ITP)], selection of patients for Ig therapy may be enhanced by relevant biomarkers in order to exclude non-responders and thus obtain higher response rates. In this review, the developments in dosing of therapeutic immunoglobulins have been limited to high and some medium priority indications such as ITP, Kawasaki’ disease, Guillain–Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, myasthenia gravis, multifocal motor neuropathy, fetal alloimmune thrombocytopenia, fetal hemolytic anemia, and dermatological diseases. PMID:25566244
Ivermectin reduces alcohol intake and preference in mice
Yardley, Megan; Wyatt, Letisha; Khoja, Sheraz; Asatryan, Liana; Ramaker, Marcia J.; Finn, Deborah A.; Alkana, Ronald L.; Huynh, Nhat; Louie, Stan G.; Petasis, Nicos A.; Bortolato, Marco; Davies, Daryl L.
2012-01-01
The high rate of therapeutic failure in the management of alcohol use disorders (AUDs) underscores the urgent need for novel and effective strategies that can deter ethanol consumption. Recent findings from our group showed that ivermectin (IVM), a broad-spectrum anthelmintic with high tolerability and optimal safety profile in humans and animals, antagonized ethanol-mediated inhibition of P2X4 receptors (P2X4Rs) expressed in Xenopus oocytes. This finding prompted us to hypothesize that IVM may reduce alcohol consumption; thus, in the present study we investigated the effects of this agent on several models of alcohol self-administration in male and female C57BL/6 mice. Overall, IVM (1.25–10 mg/kg, intraperitoneal) significantly reduced 24-h alcohol consumption and intermittent limited access (4-h) binge drinking, and operant alcohol self-administration (1-h). The effects on alcohol intake were dose-dependent with the significant reduction in intake at 9 h after administration corresponding to peak IVM concentrations (Cmax) in the brain. IVM also produced a significant reduction in 24-h saccharin consumption, but did not alter operant sucrose self-administration. Taken together, the findings indicate that IVM reduces alcohol intake across several different models of self-administration and suggest that IVM may be useful in the treatment of AUDs. PMID:22465817
Moore, Catherine F; Protzuk, Omar A; Johnson, Bankole A; Lynch, Wendy J
2014-01-01
Combined medication approaches, by targeting multiple neurotransmitter systems involved in alcohol use disorders (AUDs), may be more efficacious than single-medication approaches. We examined, in animal models of consumption and reinforcement, the combined effects of naltrexone (an opioid antagonist) and topiramate (a GABA/glutamate modulator), two medications that have shown promise for treating AUDs, hypothesizing that their combination would be more efficacious than either alone. The effects of naltrexone and topiramate on ethanol consumption were examined in alcohol preferring (P) rats (N=10) and in rats from their background strain (Wistar, N=9) using conditions that induce high levels of consumption (24-h, 3-bottle, free-choice procedure). Low doses of each medication (1mg/kg, naltrexone; 10mg/kg, topiramate) were selected in an attempt to maximize their combined efficacy while minimizing potential side-effects. Their effects on ethanol reinforcement were assessed under a progressive-ratio schedule in additional groups of (N=22) P rats. A moderate dose of topiramate (20mg/kg) was also included to verify topiramate's efficacy on its own. In P rats, but not in Wistar rats, the combination effectively and persistently reduced consumption; whereas, neither dose alone was effective. The combination and naltrexone alone were equally effective at reducing ethanol reinforcement; however, with the combination, but not naltrexone alone, this effect was selective for ethanol. All treatments produced a similar decrease in home-cage food consumption. The 20mg/kg dose of topiramate also effectively reduced ethanol consumption and reinforcement. With greater efficacy and fewer side-effects, the combination shows promise as a treatment for AUDs. Copyright © 2013 Elsevier Inc. All rights reserved.
Moore, Catherine F; Protzuk, Omar A; Johnson, Bankole A; Lynch, Wendy J
2013-01-01
Rationale Combined medication approaches, by targeting multiple neurotransmitter systems involved in alcohol use disorders (AUDs), may be more efficacious than single-medication approaches. Objectives We examined, in animals models of consumption and reinforcement, the combined effects of naltrexone (an opioid antagonist) and topiramate (a GABA/glutamate modulator), two medications that have shown promise for treating AUDs, hypothesizing that their combination would be more efficacious than either alone. Methods The effects of naltrexone and topiramate on ethanol consumption were examined in alcohol preferring (P) rats (N=10) and in rats from their background strain (Wistar, N=9) using conditions that induce high levels of consumption (24-hr, 3-bottle, free-choice procedure). Low doses of each medication (1 mg/kg, naltrexone; 10 mg/kg, topiramate) were selected in an attempt to maximize their combined efficacy while minimizing potential side-effects. Their effects on ethanol reinforcement were assessed under a progressive-ratio schedule in additional groups of (N=22) P rats. A moderate dose of topiramate (20 mg/kg) was also included to verify topiramate’s efficacy on its own. Results In P rats, but not Wistar rats, the combination effectively and persistently reduced consumption; whereas, neither dose alone was effective. The combination and naltrexone alone were equally effective at reducing ethanol reinforcement; however, with the combination, but not naltrexone alone, this effect was selective for ethanol. All treatments produced a similar decrease in home-cage food consumption. The 20 mg/kg dose of topiramate also effectively reduced ethanol consumption and reinforcement. Conclusions With greater efficacy and fewer side-effects, the combination shows promise as a treatment for AUDs. PMID:24252444
Dose to mass for evaluation and optimization of lung cancer radiation therapy.
Tyler Watkins, William; Moore, Joseph A; Hugo, Geoffrey D; Siebers, Jeffrey V
2017-11-01
To evaluate potential organ at risk dose-sparing by using dose-mass-histogram (DMH) objective functions compared with dose-volume-histogram (DVH) objective functions. Treatment plans were retrospectively optimized for 10 locally advanced non-small cell lung cancer patients based on DVH and DMH objectives. DMH-objectives were the same as DVH objectives, but with mass replacing volume. Plans were normalized to dose to 95% of the PTV volume (PTV-D95v) or mass (PTV-D95m). For a given optimized dose, DVH and DMH were intercompared to ascertain dose-to-volume vs. dose-to-mass differences. Additionally, the optimized doses were intercompared using DVH and DMH metrics to ascertain differences in optimized plans. Mean dose to volume, D v ‾, mean dose to mass, D M ‾, and fluence maps were intercompared. For a given dose distribution, DVH and DMH differ by >5% in heterogeneous structures. In homogeneous structures including heart and spinal cord, DVH and DMH are nearly equivalent. At fixed PTV-D95v, DMH-optimization did not significantly reduce dose to OARs but reduced PTV-D v ‾ by 0.20±0.2Gy (p=0.02) and PTV-D M ‾ by 0.23±0.3Gy (p=0.02). Plans normalized to PTV-D95m also result in minor PTV dose reductions and esophageal dose sparing (D v ‾ reduced 0.45±0.5Gy, p=0.02 and D M ‾ reduced 0.44±0.5Gy, p=0.02) compared to DVH-optimized plans. Optimized fluence map comparisons indicate that DMH optimization reduces dose in the periphery of lung PTVs. DVH- and DMH-dose indices differ by >5% in lung and lung target volumes for fixed dose distributions, but optimizing DMH did not reduce dose to OARs. The primary difference observed in DVH- and DMH-optimized plans were variations in fluence to the periphery of lung target PTVs, where low density lung surrounds tumor. Copyright © 2017 Elsevier B.V. All rights reserved.
Siebers, Jeffrey V
2008-04-04
Monte Carlo (MC) is rarely used for IMRT plan optimization outside of research centres due to the extensive computational resources or long computation times required to complete the process. Time can be reduced by degrading the statistical precision of the MC dose calculation used within the optimization loop. However, this eventually introduces optimization convergence errors (OCEs). This study determines the statistical noise levels tolerated during MC-IMRT optimization under the condition that the optimized plan has OCEs <100 cGy (1.5% of the prescription dose) for MC-optimized IMRT treatment plans.Seven-field prostate IMRT treatment plans for 10 prostate patients are used in this study. Pre-optimization is performed for deliverable beams with a pencil-beam (PB) dose algorithm. Further deliverable-based optimization proceeds using: (1) MC-based optimization, where dose is recomputed with MC after each intensity update or (2) a once-corrected (OC) MC-hybrid optimization, where a MC dose computation defines beam-by-beam dose correction matrices that are used during a PB-based optimization. Optimizations are performed with nominal per beam MC statistical precisions of 2, 5, 8, 10, 15, and 20%. Following optimizer convergence, beams are re-computed with MC using 2% per beam nominal statistical precision and the 2 PTV and 10 OAR dose indices used in the optimization objective function are tallied. For both the MC-optimization and OC-optimization methods, statistical equivalence tests found that OCEs are less than 1.5% of the prescription dose for plans optimized with nominal statistical uncertainties of up to 10% per beam. The achieved statistical uncertainty in the patient for the 10% per beam simulations from the combination of the 7 beams is ~3% with respect to maximum dose for voxels with D>0.5D(max). The MC dose computation time for the OC-optimization is only 6.2 minutes on a single 3 Ghz processor with results clinically equivalent to high precision MC computations.
Qi, Hui; Li, Shixue
2014-04-01
A dose-response meta-analysis was carried out between Parkinson's disease (PD) risk, and coffee, tea and caffeine consumption. A comprehensive search was carried out to identify eligible studies. The fixed or random effect model was used based on heterogeneity test. The dose-response relationship was assessed by restricted cubic spline. A total of 13 articles involving 901 764 participants for coffee, eight articles involving 344 895 participants for tea and seven articles involving 492 724 participants for caffeine were included. A non-linear relationship was found between coffee consumption and PD risk overall, and the strength of protection reached the maximum at approximately 3 cups/day (smoking-adjusted relative risk: 0.72, 95% confidence interval 0.65-0.81). A linear relationship was found between tea and caffeine consumption, and PD risk overall, and the smoking-adjusted risk of PD decreased by 26% and 17% for every two cups/day and 200 mg/day increments, respectively. The association of coffee and tea consumption with PD risk was stronger for men than that for women, and the association of caffeine consumption with PD risk was stronger for ever users of hormones than that for never users of hormones among postmenopausal women. The aforementioned associations were weaker for USA relative to Europe or Asia. A linear dose-relationship for decreased PD risk with tea and caffeine consumption was found, whereas the strength of protection reached a maximum at approximately 3 cups/day for coffee consumption overall. Further studies are required to confirm the findings. © 2013 Japan Geriatrics Society.
A rational eating model of binges, diets and obesity.
Dragone, Davide
2009-07-01
This paper addresses the rapid diffusion of obesity and the existence of different individual patterns of food consumption between non-dieters and chronic dieters. I propose a rational eating model where a forward-looking agent optimizes the intertemporal satisfaction from eating, taking into account the cost of changing consumption habits and the negative health consequences of having a non-optimal body weight. Consistent with the evidence, I show that the intertemporal maximization problem leads to a condition of overweightness, and that heterogeneity in the individual relevance of habits in consumption can determine the observed differences in the individual intertemporal patterns of food consumption and body weight. Sufficient conditions for determining when the convergence to the steady state implies oscillations or is monotonic are given. In the former case, the agent optimally alternates diets and binges until the steady state is reached, in the latter a regular intertemporal pattern of food consumption is optimal.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Francesco Ganda; Jasmina Vujic; Ehud Greenspan
2010-12-01
This work assesses the feasibility of using a small, safe, and inexpensive keff 0.98 subcritical fission assembly [subcritical neutron multiplier (SCM)] to amplify the treatment neutron beam intensity attainable from a compact deuterium-deuterium (D-D) fusion neutron source delivering [approximately]1012 n/s. The objective is to reduce the treatment time for deep-seated brain tumors to [approximately]1 h. The paper describes the optimal SCM design and two optimal beam-shaping assemblies (BSAs) - one designed to maximize the dose rate and the other designed to maximize the total dose that can be delivered to a deep-seated tumor. The neutron beam intensity amplification achieved withmore » the optimized SCM and BSA results in an increase in the treatment dose rate by a factor of 18: from 0.56 Gy/h without the SCM to 10.1 Gy/h. The entire SCM is encased in an aluminum structure. The total amount of 20% enriched uranium required for the SCM is 8.5 kg, and the cost (not including fabrication) is estimated to be less than $60,000. The SCM power level is estimated at 400 W when driven by a 1012 n/s D-D neutron source. This translates into consumption of only [approximately]0.6% of the initially loaded 235U atoms during 50 years of continuous operation and implies that the SCM could operate continuously for the entire lifetime of the facility without refueling. Cooling the SCM does not pose a challenge; it may be accomplished by natural circulation as the maximum heat flux is only 0.034 W/cm2.« less
Wigal, Sharon B; Childress, Ann; Berry, Sally A; Belden, Heidi W; Chappell, Phillip; Wajsbrot, Dalia B; Nagraj, Praneeta; Abbas, Richat; Palumbo, Donna
2018-06-01
To examine methylphenidate extended-release chewable tablets (MPH ERCT) dose patterns, attention-deficit/hyperactivity disorder (ADHD) symptom scores, and safety during the 6-week, open-label (OL) dose-optimization period of a phase 3, laboratory classroom study. Boys and girls (6-12 years) diagnosed with ADHD were enrolled. MPH ERCT was initiated at 20 mg/day; participants were titrated in 10-20 mg/day increments weekly based on efficacy and tolerability (maximum dose, 60 mg/day). Dose-optimization period efficacy assessments included the ADHD Rating Scale (ADHD-RS-IV), analyzed by week in a post hoc analysis using a mixed-effects model for repeated measures with final optimized dose (20, 30/40, or 50/60 mg), visit, final optimized dose and visit interaction, and baseline score as terms. Adverse events (AEs) and concomitant medications were collected throughout the study. Mean MPH ERCT daily dose increased weekly from 29.4 mg/day after the first dose adjustment at week 1 (n = 90) to 42.8 mg/day after the final adjustment at week 5 (n = 86). Final optimized MPH ERCT dose ranged from 20 to 60 mg/day. Mean final optimized MPH ERCT dose ranged from 40.0 mg/day in 6-8 year-old participants to 44.8 mg/day for 11-12 year-old participants. There was a progressive decrease in mean (standard deviation) ADHD-RS-IV total score from 40.1 (8.72) at baseline to 12.4 (7.88) at OL week 5, with similar improvement patterns for hyperactivity/impulsivity and inattentiveness subscale scores. Participants optimized to MPH ERCT 50/60 mg/day had a significantly higher mean (standard error) ADHD-RS-IV score at baseline compared with participants optimized to MPH ERCT 20 mg/day (42.4 [1.34] vs. 35.1 [2.55]; p = 0.013). Treatment-emergent AEs were reported by 65/90 (72.2%) participants in the dose-optimization period. Dose-optimization period results describing relationships between change in ADHD symptom scores and final optimized MPH ERCT dose will be valuable for clinicians optimizing MPH ERCT dose.
Dose-mass inverse optimization for minimally moving thoracic lesions
NASA Astrophysics Data System (ADS)
Mihaylov, I. B.; Moros, E. G.
2015-05-01
In the past decade, several different radiotherapy treatment plan evaluation and optimization schemes have been proposed as viable approaches, aiming for dose escalation or an increase of healthy tissue sparing. In particular, it has been argued that dose-mass plan evaluation and treatment plan optimization might be viable alternatives to the standard of care, which is realized through dose-volume evaluation and optimization. The purpose of this investigation is to apply dose-mass optimization to a cohort of lung cancer patients and compare the achievable healthy tissue sparing to that one achievable through dose-volume optimization. Fourteen non-small cell lung cancer (NSCLC) patient plans were studied retrospectively. The range of tumor motion was less than 0.5 cm and motion management in the treatment planning process was not considered. For each case, dose-volume (DV)-based and dose-mass (DM)-based optimization was performed. Nine-field step-and-shoot IMRT was used, with all of the optimization parameters kept the same between DV and DM optimizations. Commonly used dosimetric indices (DIs) such as dose to 1% the spinal cord volume, dose to 50% of the esophageal volume, and doses to 20 and 30% of healthy lung volumes were used for cross-comparison. Similarly, mass-based indices (MIs), such as doses to 20 and 30% of healthy lung masses, 1% of spinal cord mass, and 33% of heart mass, were also tallied. Statistical equivalence tests were performed to quantify the findings for the entire patient cohort. Both DV and DM plans for each case were normalized such that 95% of the planning target volume received the prescribed dose. DM optimization resulted in more organs at risk (OAR) sparing than DV optimization. The average sparing of cord, heart, and esophagus was 23, 4, and 6%, respectively. For the majority of the DIs, DM optimization resulted in lower lung doses. On average, the doses to 20 and 30% of healthy lung were lower by approximately 3 and 4%, whereas lung volumes receiving 2000 and 3000 cGy were lower by 3 and 2%, respectively. The behavior of MIs was very similar. The statistical analyses of the results again indicated better healthy anatomical structure sparing with DM optimization. The presented findings indicate that dose-mass-based optimization results in statistically significant OAR sparing as compared to dose-volume-based optimization for NSCLC. However, the sparing is case-dependent and it is not observed for all tallied dosimetric endpoints.
Basu-Roy, Somapriya; Kar, Sanjay Kumar; Das, Sounik; Lahiri, Annesha
2017-01-01
Purpose This study is intended to compare dose-volume parameters evaluated using different forward planning- optimization techniques, involving two applicator systems in intracavitary brachytherapy for cervical cancer. It looks for the best applicator-optimization combination to fulfill recommended dose-volume objectives in different high-dose-rate (HDR) fractionation schedules. Material and methods We used tandem-ring and Fletcher-style tandem-ovoid applicator in same patients in two fractions of brachytherapy. Six plans were generated for each patient utilizing 3 forward optimization techniques for each applicator used: equal dwell weight/times (‘no optimization’), ‘manual dwell weight/times’, and ‘graphical’. Plans were normalized to left point A and dose of 8 Gy was prescribed. Dose volume and dose point parameters were compared. Results Without graphical optimization, maximum width and thickness of volume enclosed by 100% isodose line, dose to 90%, and 100% of clinical target volume (CTV); minimum, maximum, median, and average dose to both rectum and bladder are significantly higher with Fletcher applicator. Even if it is done, dose to both points B, minimum dose to CTV, and treatment time; dose to 2 cc (D2cc) rectum and rectal point etc.; D2cc, minimum, maximum, median, and average dose to sigmoid colon; D2cc of bladder remain significantly higher with this applicator. Dose to bladder point is similar (p > 0.05) between two applicators, after all optimization techniques. Conclusions Fletcher applicator generates higher dose to both CTV and organs at risk (2 cc volumes) after all optimization techniques. Dose restriction to rectum is possible using graphical optimization only during selected HDR fractionation schedules. Bladder always receives dose higher than recommended, and 2 cc sigmoid colon always gets permissible dose. Contrarily, graphical optimization with ring applicators fulfills all dose volume objectives in all HDR fractionations practiced. PMID:29204164
Contribution of breastfeeding to vitamin A nutrition of infants: a simulation model.
Ross, Jay S.; Harvey, Philip W. J.
2003-01-01
OBJECTIVE: To provide information on the potential contribution to vitamin A nutrition in infants of strategies for improving maternal vitamin A status and increasing the consumption of breast milk. METHODS: The contribution of breastfeeding to the vitamin A nutrition of children in eight age groups between 0 and 24 months was simulated under four sets of conditions involving two levels of breast milk consumption with or without maternal vitamin A supplementation. FINDINGS: During the first 6 months, optimal breastfeeding on its own (compared with withholding colostrum and then partially breastfeeding after the first week) was as effective as postpartum maternal supplementation alone, retinol intakes being increased by 59 micrograms per day and 68 micrograms per day, respectively. Combined in synergy, these strategies increase retinol intake by 144 micrograms per day, or 36% of the recommended intake. After 6 months, partial breastfeeding continued to provide a significant proportion of the recommended intakes: 42% from 6-12 months and 61% during the second year. CONCLUSION: Maternal supplementation with a high dose of vitamin A at the time of delivery and the promotion of optimal breastfeeding practices are highly effective strategies for improving vitamin A nutrition in infants and should be strengthened as key components of comprehensive child survival programmes. PMID:12751415
Fuel consumption optimization for smart hybrid electric vehicle during a car-following process
NASA Astrophysics Data System (ADS)
Li, Liang; Wang, Xiangyu; Song, Jian
2017-03-01
Hybrid electric vehicles (HEVs) provide large potential to save energy and reduce emission, and smart vehicles bring out great convenience and safety for drivers. By combining these two technologies, vehicles may achieve excellent performances in terms of dynamic, economy, environmental friendliness, safety, and comfort. Hence, a smart hybrid electric vehicle (s-HEV) is selected as a platform in this paper to study a car-following process with optimizing the fuel consumption. The whole process is a multi-objective optimal problem, whose optimal solution is not just adding an energy management strategy (EMS) to an adaptive cruise control (ACC), but a deep fusion of these two methods. The problem has more restricted conditions, optimal objectives, and system states, which may result in larger computing burden. Therefore, a novel fuel consumption optimization algorithm based on model predictive control (MPC) is proposed and some search skills are adopted in receding horizon optimization to reduce computing burden. Simulations are carried out and the results indicate that the fuel consumption of proposed method is lower than that of the ACC+EMS method on the condition of ensuring car-following performances.
Gutwinski, Stefan; Schreiter, Stefanie; Priller, Josef; Henssler, Jonathan; Wiers, Corinde E; Heinz, Andreas
2017-09-26
Regular alcohol consumption affects cognitive performance and the development of dementia. So far, findings are contradicting, which might be explained in part by dose-related effects. For this narrative review, we undertook a literature search for surveys investigating the impact of alcohol consumption on cognitive performance and the development of dementia. The majority of studies observed a U-shaped relationship between regular alcohol consumption and cognitive function: frequent heavy consumption of alcohol alters brain functions and decreases cognitive performance; regular light and moderate consumption may have protective impact. In many studies, total abstainers show an inferior cognitive performance than people with moderate or light consumption. Nevertheless, policy implications are difficult to draw for at least 2 reasons: (1) the possible risks associated with alcohol consumption and (2) the potential confounders in the group of non-consumers and heavy consumers. © Georg Thieme Verlag KG Stuttgart · New York.
USDA-ARS?s Scientific Manuscript database
ABSTRACT Background: Enhanced n-3 intake benefit CVD risk reduction. Increasing consumption at a population level will be better addressed by dietary modification than through supplementation. However, limited data are available on the effect of increasing doses of fish intake on circulating level...
USDA-ARS?s Scientific Manuscript database
Toxoplasma gondii is a protozoan parasite that is responsible for approximately 24% of deaths attributed to foodborne pathogens in the United States.A substantial portion of human T. gondii infections may be acquired through the consumption of meats. The dose-response relationship for human exposure...
Micek, Agnieszka; Godos, Justyna; Lafranconi, Alessandra; Marranzano, Marina; Pajak, Andrzej
2018-06-01
To determine the association between total, caffeinated and decaffeinated coffee consumption and melanoma risk a dose-response meta-analysis on prospective cohort studies were performed. Eligible studies were identified searching PubMed and EMBASE databases from the earliest available online indexing year to March 2017. The dose-response relationship was assessed by random-effects meta-analysis and the shape of the exposure-outcome curve was modelled linearly and using restricted cubic splines. A total of seven studies eligible for meta-analysis were identified that comprised 1,418,779 participants and 9211 melanoma cases. A linear dose-response meta-analysis showed a significant association between total coffee consumption and melanoma risk. An increase in coffee consumption of one cup per day was associated with a 3% reduction in melanoma risk (RR 0.97; 95% CI 0.95-0.99). Our findings suggest that coffee intake may be inversely associated with incidence of melanoma. Nevertheless, further studies exploring also the role of confounding factors are needed to explain the heterogeneity among studies.
Li, Yongbao; Tian, Zhen; Shi, Feng; Song, Ting; Wu, Zhaoxia; Liu, Yaqiang; Jiang, Steve; Jia, Xun
2015-04-07
Intensity-modulated radiation treatment (IMRT) plan optimization needs beamlet dose distributions. Pencil-beam or superposition/convolution type algorithms are typically used because of their high computational speed. However, inaccurate beamlet dose distributions may mislead the optimization process and hinder the resulting plan quality. To solve this problem, the Monte Carlo (MC) simulation method has been used to compute all beamlet doses prior to the optimization step. The conventional approach samples the same number of particles from each beamlet. Yet this is not the optimal use of MC in this problem. In fact, there are beamlets that have very small intensities after solving the plan optimization problem. For those beamlets, it may be possible to use fewer particles in dose calculations to increase efficiency. Based on this idea, we have developed a new MC-based IMRT plan optimization framework that iteratively performs MC dose calculation and plan optimization. At each dose calculation step, the particle numbers for beamlets were adjusted based on the beamlet intensities obtained through solving the plan optimization problem in the last iteration step. We modified a GPU-based MC dose engine to allow simultaneous computations of a large number of beamlet doses. To test the accuracy of our modified dose engine, we compared the dose from a broad beam and the summed beamlet doses in this beam in an inhomogeneous phantom. Agreement within 1% for the maximum difference and 0.55% for the average difference was observed. We then validated the proposed MC-based optimization schemes in one lung IMRT case. It was found that the conventional scheme required 10(6) particles from each beamlet to achieve an optimization result that was 3% difference in fluence map and 1% difference in dose from the ground truth. In contrast, the proposed scheme achieved the same level of accuracy with on average 1.2 × 10(5) particles per beamlet. Correspondingly, the computation time including both MC dose calculations and plan optimizations was reduced by a factor of 4.4, from 494 to 113 s, using only one GPU card.
Optimal Consumption When Consumption Takes Time
ERIC Educational Resources Information Center
Miller, Norman C.
2009-01-01
A classic article by Gary Becker (1965) showed that when it takes time to consume, the first order conditions for optimal consumption require the marginal rate of substitution between any two goods to equal their relative full costs. These include the direct money price and the money value of the time needed to consume each good. This important…
Krizman, Ivona; Senta, Ivan; Ahel, Marijan; Terzic, Senka
2016-10-01
A comprehensive study of spatial and temporal consumption patterns of the selected illicit drugs (heroin, cocaine, amphetamine, MDMA, methamphetamine, cannabis) and therapeutic opioids (codeine, methadone) has been performed in six Croatian cities by applying wastewater-based epidemiology. The investigated cities (Bjelovar, Vinkovci, Varazdin, Karlovac, Zadar and Zagreb) varied widely in the population size (27,000-688,000 inhabitants) as well as in the number of registered drug consumers included in compulsory and voluntary medical treatment and rehabilitation programs (30-513 persons/100,000 inhabitants of age 15-64). The most consumed illicit drugs were cannabis (10-70doses/day/1000 inhabitants), heroin (<0.2-10doses/day/1000 inhabitants) and cocaine (0.2-8.7doses/day/1000 inhabitants), while the consumption of amphetamine-type drugs was much lower (<0.01-4.4doses/day/1000 inhabitants). Enhanced consumption of illegal drugs was generally associated with larger urban centers (Zagreb and Zadar) however comparatively high consumption rate of cocaine, MDMA and methadone was determined in some smaller cities as well. The overall average dose number of 3 major illegal stimulants (cocaine, MDMA, amphetamine) was rather similar to the number of corresponding heroin doses, which is in disagreement with a comparatively much higher proportion of heroin users in the total number of registered drug users in Croatia. Furthermore, the illicit drug consumption pattern in the large continental city (Zagreb) was characterized by a significant enhancement of the consumption of all stimulants during the weekend, which could not be confirmed neither for the coastal city of Zadar nor for the remaining small continental cities. On the other hand, the city of Zadar exhibited a significant increase of stimulant drug usage during summer vacation period, as a result of pronounced seasonal changes of the population composition and lifestyle in coastal tourist centers. The obtained results represent a valuable complementary data source for the optimisation and implementation of strategies to combat drug abuse in Croatia. Copyright © 2016. Published by Elsevier B.V.
Cognitive radio adaptation for power consumption minimization using biogeography-based optimization
NASA Astrophysics Data System (ADS)
Qi, Pei-Han; Zheng, Shi-Lian; Yang, Xiao-Niu; Zhao, Zhi-Jin
2016-12-01
Adaptation is one of the key capabilities of cognitive radio, which focuses on how to adjust the radio parameters to optimize the system performance based on the knowledge of the radio environment and its capability and characteristics. In this paper, we consider the cognitive radio adaptation problem for power consumption minimization. The problem is formulated as a constrained power consumption minimization problem, and the biogeography-based optimization (BBO) is introduced to solve this optimization problem. A novel habitat suitability index (HSI) evaluation mechanism is proposed, in which both the power consumption minimization objective and the quality of services (QoS) constraints are taken into account. The results show that under different QoS requirement settings corresponding to different types of services, the algorithm can minimize power consumption while still maintaining the QoS requirements. Comparison with particle swarm optimization (PSO) and cat swarm optimization (CSO) reveals that BBO works better, especially at the early stage of the search, which means that the BBO is a better choice for real-time applications. Project supported by the National Natural Science Foundation of China (Grant No. 61501356), the Fundamental Research Funds of the Ministry of Education, China (Grant No. JB160101), and the Postdoctoral Fund of Shaanxi Province, China.
Developmental toxicity study of D-tagatose in rats.
Kruger, C L; Whittaker, M H; Frankos, V H; Schroeder, R E
1999-04-01
D-tagatose is a low-calorie sweetener that tastes like sucrose. The developmental toxicity of D-tagatose was investigated in Crl:CD(SD)BR rats administered D-tagatose at three dose levels (4000, 12,000, and 20,000 mg/kg body wt/day) via gastric intubation on days 6-15 of gestation. No compound-related toxicity was seen among any of the maternal groups. No treatment-related clinical effects were seen in the maternal animals at the 4000 mg/kg/day dose level. At the mid- and high-dose levels, most maternal animals had unformed or watery stools; this effect was most prominent early in the treatment period (Gestation Days 6-8). This effect was attributed to the osmotic effect of the large amount of D-tagatose given to the animals at these doses. Since D-tagatose is not digested or absorbed to a large extent, most of the sugar passes into the colon where it absorbs water and is fermented by colonic bacteria. Mean weight gain for the low- and mid-dose animals was comparable to the control; however, the high-dose group experienced a mean weight loss over the Gestation Day 6-9 interval. Over the entire treatment interval, however, mean weight gain for the high-dose animals was comparable to control. The decreased weight gain in the high-dose animals during the Gestation Day 6-9 interval was considered to be a direct result of laxation. In addition to the effect of laxation on body weight, reduced food consumption also contributed to the decreased weight gain. In the low-dose animals, no effect on food consumption was seen; however, both mid- and high-dose animals had food consumption values that were statistically significantly lower than the control. Food consumption was lowest during the Gestation Day 6-9 interval, the period when laxation was most prominent. Food consumption rebounded and was statistically significantly higher than the control for the mid- and high-dose animals during the posttreatment interval. Maternal liver weight for the low-dose animals was comparable to the control. However, a statistically significant increase in mean maternal liver weight was noted for the mid-and high-dose animals. Based on a lack of any corresponding histopathology, the increased liver weights were not considered toxicologically significant. There were no adverse effects on reproductive performance noted in any treatment group. No adverse treatment-related fetal effects on fetal weight, sex distribution, liver weight, or external, skeletal, or visceral malformations were noted at any dose level. Copyright 1999 Academic Press.
Giżyńska, Marta K.; Kukołowicz, Paweł F.; Kordowski, Paweł
2014-01-01
Aim The aim of this work is to present a method of beam weight and wedge angle optimization for patients with prostate cancer. Background 3D-CRT is usually realized with forward planning based on a trial and error method. Several authors have published a few methods of beam weight optimization applicable to the 3D-CRT. Still, none on these methods is in common use. Materials and methods Optimization is based on the assumption that the best plan is achieved if dose gradient at ICRU point is equal to zero. Our optimization algorithm requires beam quality index, depth of maximum dose, profiles of wedged fields and maximum dose to femoral heads. The method was tested for 10 patients with prostate cancer, treated with the 3-field technique. Optimized plans were compared with plans prepared by 12 experienced planners. Dose standard deviation in target volume, and minimum and maximum doses were analyzed. Results The quality of plans obtained with the proposed optimization algorithms was comparable to that prepared by experienced planners. Mean difference in target dose standard deviation was 0.1% in favor of the plans prepared by planners for optimization of beam weights and wedge angles. Introducing a correction factor for patient body outline for dose gradient at ICRU point improved dose distribution homogeneity. On average, a 0.1% lower standard deviation was achieved with the optimization algorithm. No significant difference in mean dose–volume histogram for the rectum was observed. Conclusions Optimization shortens very much time planning. The average planning time was 5 min and less than a minute for forward and computer optimization, respectively. PMID:25337411
Pokharel, Shyam; Rana, Suresh; Blikenstaff, Joseph; Sadeghi, Amir; Prestidge, Bradley
2013-07-08
The purpose of this study is to investigate the effectiveness of the HIPO planning and optimization algorithm for real-time prostate HDR brachytherapy. This study consists of 20 patients who underwent ultrasound-based real-time HDR brachytherapy of the prostate using the treatment planning system called Oncentra Prostate (SWIFT version 3.0). The treatment plans for all patients were optimized using inverse dose-volume histogram-based optimization followed by graphical optimization (GRO) in real time. The GRO is manual manipulation of isodose lines slice by slice. The quality of the plan heavily depends on planner expertise and experience. The data for all patients were retrieved later, and treatment plans were created and optimized using HIPO algorithm with the same set of dose constraints, number of catheters, and set of contours as in the real-time optimization algorithm. The HIPO algorithm is a hybrid because it combines both stochastic and deterministic algorithms. The stochastic algorithm, called simulated annealing, searches the optimal catheter distributions for a given set of dose objectives. The deterministic algorithm, called dose-volume histogram-based optimization (DVHO), optimizes three-dimensional dose distribution quickly by moving straight downhill once it is in the advantageous region of the search space given by the stochastic algorithm. The PTV receiving 100% of the prescription dose (V100) was 97.56% and 95.38% with GRO and HIPO, respectively. The mean dose (D(mean)) and minimum dose to 10% volume (D10) for the urethra, rectum, and bladder were all statistically lower with HIPO compared to GRO using the student pair t-test at 5% significance level. HIPO can provide treatment plans with comparable target coverage to that of GRO with a reduction in dose to the critical structures.
[Gradation in the level of vitamin consumption: possible risk of excessive consumption].
Kodentsova, V M
2014-01-01
The ratio between the levels of consumption of certain vitamins and minerals [recommended daily allowance for labelling purposes < maximum supplement levels < tolerable upper intake level (UL) < safe level (limit) of consumption < or = therapeutic dose has been characterized. Vitamin A and beta-carotene maximum supplement levels coincides with UL, and recommended daily allowance for these micronutrients coincides with the maximal level of consumption through dietary supplements and/or multivitamins. Except for vitamin A and beta-carotene recommended daily allowance for other vitamins adopted in Russia are considerably lower than the upper safe level of consumption. For vitamin A and beta-carotene there is a potential risk for excess consumption. According to the literature data (meta-analysis) prolonged intake of high doses of antioxidant vitamins (above the RDA) both alone and in combination with two other vitamins or vitamin C [> 800 microg (R.E.) of vitamin A, > 9.6 mg of beta-carotene, > 15 mg (T.E.) of vitamin E] do not possess preventive effects and may be harmful with unwanted consequences to health, especially in well-nourished populations, persons having risk of lung cancer (smokers, workers exposed to asbestos), in certain conditions (in the atmosphere with high oxygen content, hyperoxia, oxygen therapy). Proposed mechanisms of such action may be due to the manifestation of prooxidant action when taken in high doses, shifting balance with other important natural antioxidants, their displacement (substitution), interference with the natural defense mechanisms. Athletes are the population group that requires attention as used antioxidant vitamins A, C, E, both individually and in combination in extremely high doses. In summary, it should be noted that intake of physiological doses which are equivalent to the needs of the human organism, as well as diet inclusion of fortified foods not only pose no threat to health, but will bring undoubted benefits, filling the existing lack of vitamins in the ration.
Cost and fuel consumption per nautical mile for two engine jet transports using OPTIM and TRAGEN
NASA Technical Reports Server (NTRS)
Wiggs, J. F.
1982-01-01
The cost and fuel consumption per nautical mile for two engine jet transports are computed using OPTIM and TRAGEN. The savings in fuel and direct operating costs per nautical mile for each of the different types of optimal trajectories over a standard profile are shown.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cao, W; Zaghian, M; Lim, G
2015-06-15
Purpose: The current practice of considering the relative biological effectiveness (RBE) of protons in intensity modulated proton therapy (IMPT) planning is to use a generic RBE value of 1.1. However, RBE is indeed a variable depending on the dose per fraction, the linear energy transfer, tissue parameters, etc. In this study, we investigate the impact of using variable RBE based optimization (vRBE-OPT) on IMPT dose distributions compared by conventional fixed RBE based optimization (fRBE-OPT). Methods: Proton plans of three head and neck cancer patients were included for our study. In order to calculate variable RBE, tissue specific parameters were obtainedmore » from the literature and dose averaged LET values were calculated by Monte Carlo simulations. Biological effects were calculated using the linear quadratic model and they were utilized in the variable RBE based optimization. We used a Polak-Ribiere conjugate gradient algorithm to solve the model. In fixed RBE based optimization, we used conventional physical dose optimization to optimize doses weighted by 1.1. IMPT plans for each patient were optimized by both methods (vRBE-OPT and fRBE-OPT). Both variable and fixed RBE weighted dose distributions were calculated for both methods and compared by dosimetric measures. Results: The variable RBE weighted dose distributions were more homogenous within the targets, compared with the fixed RBE weighted dose distributions for the plans created by vRBE-OPT. We observed that there were noticeable deviations between variable and fixed RBE weighted dose distributions if the plan were optimized by fRBE-OPT. For organs at risk sparing, dose distributions from both methods were comparable. Conclusion: Biological dose based optimization rather than conventional physical dose based optimization in IMPT planning may bring benefit in improved tumor control when evaluating biologically equivalent dose, without sacrificing OAR sparing, for head and neck cancer patients. The research is supported in part by National Institutes of Health Grant No. 2U19CA021239-35.« less
Kirkham, Kyle Robert; Jacot-Guillarmod, Alain; Albrecht, Eric
2018-01-01
Perineural dexamethasone has gained popularity in regional anesthesia to prolong analgesia duration. However, uncertainty remains regarding the optimal perineural dose. Clarification of this characteristic is of significant importance as the administration of dexamethasone may lead to dose-dependent complications. The objective of this meta-analysis was to define the optimal perineural dexamethasone dose to prolong analgesia after brachial plexus blockade for adult patients undergoing upper limb surgery. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines and searched databases including MEDLINE, PubMed, and EMBASE until January 2017, without language restriction. Only trials comparing perineural dexamethasone and local anesthetics with local anesthetics alone for brachial plexus blocks were included in the present meta-analysis. The Cochrane Collaboration's Risk of Bias Tool was used to assess the methodological quality of each trial and meta-analyses were performed following a random effects model. The primary outcome was duration of analgesia for each type of local anesthetic (short-/intermediate-acting and long-acting local anesthetics). A meta-regression followed by a subgroup analysis were performed to assess the impact of different perineural dexamethasone doses on duration of analgesia; for the latter analysis, trials were grouped in low (1-4 mg) and moderate (5-10 mg) dexamethasone doses. Secondary outcomes included the rate of neurologic complication and resting pain scores and morphine consumption within the first 24 hours. Thirty-three controlled trials, including 2138 patients, were identified. The meta-regression revealed a ceiling effect with a perineural dexamethasone dose of 4 mg when combined with short-/intermediate-acting (8 trials; 366 participants) or long-acting local anesthetics (23 trials; 1869 participants). This finding was confirmed by subgroup analyses comparing low and moderate dexamethasone doses. With short-/intermediate-acting local anesthetics, the mean difference (95% confidence interval) of analgesia duration with low and moderate doses was 277 (234-322) minutes and 229 (161-297) minutes, respectively. With long-acting local anesthetics, the mean differences with low and moderate doses were 505 (342-669) minutes and 509 (443-575) minutes. Perineural dexamethasone did not increase the rate of neurologic complications (risk ratio [95% confidence interval], 1.40 [0.54-3.63]). The Grades of Recommendation, Assessment, Development, and Evaluation quality of evidence for the primary and secondary outcomes were very low, due mainly to limitations, inconsistency, indirectness, and publication bias. There is currently very low quality evidence that 4 mg of perineural dexamethasone represents a ceiling dose that prolongs analgesia duration by a mean period of 6 and 8 hours when combined with short-/intermediate- or long-acting local anesthetics, respectively. Additional data are needed to explore the threshold for this effect, particularly with doses below 4 mg. The risk of neurologic complications is probably not increased (very low evidence).
Turhan, K S Cakar; Akmese, R; Ozkan, F; Okten, F F
2015-04-01
In the current prospective, randomized study, we aimed to compare the effects of low dose selective spinal anesthesia with 5 mg of hyperbaric bupivacaine and single-shot femoral nerve block combination with conventional dose selective spinal anesthesia in terms of intraoperative anesthesia characteristics, block recovery characteristics, and postoperative analgesic consumption. After obtaining institutional Ethics Committee approval, 52 ASA I-II patients aged 25-65, undergoing arthroscopic meniscus repair were randomly assigned to Group S (conventional dose selective spinal anesthesia with 10 mg bupivacaine) and Group FS (low-dose selective spinal anesthesia with 5mg bupivacaine +single-shot femoral block with 0.25% bupivacaine). Primary endpoints were time to reach T12 sensory block level, L2 regression, and complete motor block regression. Secondary endpoints were maximum sensory block level (MSBL); time to reach MSBL, time to first urination, time to first analgesic consumption and pain severity at the time of first mobilization. Demographic characteristics were similar in both groups (p > 0.05). MSBL and time to reach T12 sensory level were similar in both groups (p > 0.05). Time to reach L2 regression, complete motor block regression, and time to first micturition were significantly shorter; time to first analgesic consumption was significantly longer; and total analgesic consumption and severity of pain at time of first mobilization were significantly lower in Group FS (p < 0.05). The findings of the current study suggest that addition of single-shot femoral block to low dose spinal anesthesia could be an alternative to conventional dose spinal anesthesia in outpatient arthroscopic meniscus repair. NCT02322372.
Darr, Christa R; Varner, Dickson D; Teague, Sheila; Cortopassi, Gino A; Datta, Sandipan; Meyers, Stuart A
2016-08-01
Stallion sperm rely primarily on oxidative phosphorylation for production of ATP used in sperm motility and metabolism. The objective of the study was to identify which substrates included in Biggers, Whitten, and Whittingham (BWW) media are key to optimal mitochondrial function through measurements of sperm motility parameters, mitochondrial oxygen consumption, and cellular reactive oxygen species (ROS) production. It was expected that mitochondrial substrates, pyruvate and lactate, would support sperm motility and mitochondrial function better than the glycolytic substrate, glucose, due to direct utilization within the mitochondria. Measurements were performed after incubation in modified BWW media with varying concentrations of lactate, pyruvate, and glucose. The effects of media and duration of incubation on sperm motility, ROS production, and oxygen consumption were determined using a linear mixed-effects model. Duplicate ejaculates from four stallions were used in three separate experiments to determine the effects of substrate availability and concentration on sperm motility and mitochondrial function and the relationship of oxygen consumption with cellular ROS production. The present results indicate that lactate and pyruvate are the most important sources of energy for stallion sperm motility and velocity, and elicit a dose-dependent response. Additionally, lactate and pyruvate are ideal for maximal mitochondrial function, as sperm in these media operate at a very high level of their bioenergetic capability due to the high rate of energy metabolism. Moreover, we found that addition of glucose to the media is not necessary for short-term storage of equine sperm, and may even result in reduction of mitochondrial function. Finally, we have confirmed that ROS production can be the result of mitochondrial dysfunction as well as intense mitochondrial activity. © 2016 by the Society for the Study of Reproduction, Inc.
Welsch, C W; DeHoog, J V; O'Connor, D H
1988-04-15
The effect of caffeine and/or coffee consumption (via the drinking water) during the initiation phase and promotion phase of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary gland tumorigenesis in female Sprague-Dawley rats fed a commercial laboratory animal chow was examined. In the initiation studies, DMBA was administered once at 53-55 days of age; caffeine (100-860 mg/liter of drinking water) and/or coffee (moderate or high dose, sole source of drinking water) treatments were for 32 consecutive days, commencing 29 days prior to DMBA treatment and terminating 3 days after DMBA treatment. In the promotion studies, DMBA was administered once at 54-55 days of age; caffeine and/or coffee treatments were daily from 57-58 days of age to termination of experiments (12-21 weeks after carcinogen treatment). In the initiation studies, either moderate (100-400 mg) or high (860 mg) dose levels of caffeine or moderate to high dose levels of caffeinated coffee significantly (P less than 0.05) reduced mammary carcinoma multiplicity (number of tumors/rat). Consumption of high or moderate dose levels of decaffeinated coffee did not significantly alter mammary carcinoma multiplicity. The addition of caffeine to the moderate dose level of decaffeinated coffee resulted in a significant (P less than 0.05) reduction in mammary carcinoma multiplicity. In the promotion studies, prolonged consumption of moderated dose levels of caffeine or moderate or high dose levels of caffeinated coffee or decaffeinated coffee did not significantly effect mammary carcinoma multiplicity. In the early stages of promotion, however, a significant (p less than 0.05) stimulatory effect of caffeine on mammary carcinoma multiplicity was observed; an effect that was temperate and transitory. In both the initiation and promotion studies caffeine and/or coffee consumption did not significantly affect the incidence of mammary carcinomas (percentage of rats bearing mammary carcinomas) or the mean latency period of mammary tumor appearance. These results provide evidence that caffeine and/or caffeinated coffee consumption can significantly influence mammary carcinoma multiplicity in female rats treated with DMBA, an effect that is dependent upon the dose level, duration, and time-span of caffeine administration.
Radiological risk from consuming fish and wildlife to Native Americans on the Hanford Site (USA).
Delistraty, Damon; Van Verst, Scott; Rochette, Elizabeth A
2010-02-01
Historical operations at the Hanford Site (Washington State, USA) have released a wide array of non-radionuclide and radionuclide contaminants into the environment. As a result of stakeholder concerns, Native American exposure scenarios have been integrated into Hanford risk assessments. Because its contribution to radiological risk to Native Americans is culturally and geographically specific but quantitatively uncertain, a fish and wildlife ingestion pathway was examined in this study. Adult consumption rates were derived from 20 Native American scenarios (based on 12 studies) at Hanford, and tissue concentrations of key radionuclides in fish, game birds, and game mammals were compiled from the Hanford Environmental Information System (HEIS) database for a recent time interval (1995-2007) during the post-operational period. It was assumed that skeletal muscle comprised 90% of intake, while other tissues accounted for the remainder. Acknowledging data gaps, median concentrations of eight radionuclides (i.e., Co-60, Cs-137, Sr-90, Tc-99, U-234, U-238, Pu-238, and Pu-239/240) in skeletal muscle and other tissues were below 0.01 and 1 pCi/g wet wt, respectively. These radionuclide concentrations were not significantly different (Bonferroni P>0.05) on and off the Hanford Site. Despite no observed difference between onsite and offsite tissue concentrations, radiation dose and risk were calculated for the fish and wildlife ingestion pathway using onsite data. With median consumption rates and radionuclide tissue concentrations, skeletal muscle provided 42% of the dose, while other tissues (primarily bone and carcass) accounted for 58%. In terms of biota, fish ingestion was the largest contributor to dose (64%). Among radionuclides, Sr-90 was dominant, accounting for 47% of the dose. At median intake and radionuclide levels, estimated annual dose (0.36 mrem/yr) was below a dose limit of 15 mrem/yr recommended by the United States Environmental Protection Agency (USEPA), as well as below a dose limit of 100 mrem/yr proposed by the International Commission on Radiation Protection (ICRP). Similarly, lifetime cancer risk (1.7E-5), calculated with median inputs, was below risk levels corresponding to these dose limits. However, our dose and risk estimates apply to only one pathway within a multidimensional exposure scenario for Native Americans. On the other hand, radiation dose and risk corresponding to onsite tissue concentrations were not significantly different from those corresponding to offsite (background) concentrations. Recognizing uncertainties in exposure and toxicity assessments, our results may facilitate informed decision making and optimize resource allocation within a risk assessment framework at the Hanford Site. (c) 2009 Elsevier Inc. All rights reserved.
Radiological risk from consuming fish and wildlife to Native Americans on the Hanford Site (USA)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Delistraty, Damon, E-mail: DDEL461@ecy.wa.gov; Verst, Scott Van; Rochette, Elizabeth A.
Historical operations at the Hanford Site (Washington State, USA) have released a wide array of non-radionuclide and radionuclide contaminants into the environment. As a result of stakeholder concerns, Native American exposure scenarios have been integrated into Hanford risk assessments. Because its contribution to radiological risk to Native Americans is culturally and geographically specific but quantitatively uncertain, a fish and wildlife ingestion pathway was examined in this study. Adult consumption rates were derived from 20 Native American scenarios (based on 12 studies) at Hanford, and tissue concentrations of key radionuclides in fish, game birds, and game mammals were compiled from themore » Hanford Environmental Information System (HEIS) database for a recent time interval (1995-2007) during the post-operational period. It was assumed that skeletal muscle comprised 90% of intake, while other tissues accounted for the remainder. Acknowledging data gaps, median concentrations of eight radionuclides (i.e., Co-60, Cs-137, Sr-90, Tc-99, U-234, U-238, Pu-238, and Pu-239/240) in skeletal muscle and other tissues were below 0.01 and 1 pCi/g wet wt, respectively. These radionuclide concentrations were not significantly different (Bonferroni P>0.05) on and off the Hanford Site. Despite no observed difference between onsite and offsite tissue concentrations, radiation dose and risk were calculated for the fish and wildlife ingestion pathway using onsite data. With median consumption rates and radionuclide tissue concentrations, skeletal muscle provided 42% of the dose, while other tissues (primarily bone and carcass) accounted for 58%. In terms of biota, fish ingestion was the largest contributor to dose (64%). Among radionuclides, Sr-90 was dominant, accounting for 47% of the dose. At median intake and radionuclide levels, estimated annual dose (0.36 mrem/yr) was below a dose limit of 15 mrem/yr recommended by the United States Environmental Protection Agency (USEPA), as well as below a dose limit of 100 mrem/yr proposed by the International Commission on Radiation Protection (ICRP). Similarly, lifetime cancer risk (1.7E-5), calculated with median inputs, was below risk levels corresponding to these dose limits. However, our dose and risk estimates apply to only one pathway within a multidimensional exposure scenario for Native Americans. On the other hand, radiation dose and risk corresponding to onsite tissue concentrations were not significantly different from those corresponding to offsite (background) concentrations. Recognizing uncertainties in exposure and toxicity assessments, our results may facilitate informed decision making and optimize resource allocation within a risk assessment framework at the Hanford Site.« less
Gacek, Maria
2014-03-01
The aim of this study was to analyze selected individual determinants of consumption of soy products and legumes by menopausal women. The analyzed individual characteristics included the level of general self-efficacy, optimism, and satisfaction with life. The study, using a questionnaire for the assessment of food product consumption frequency, and psychological tests (GSES, LOT-R, SWLS), was conducted in a group of 320 women aged between 45 and 55 years. Spearman's coefficient of rank correlation and the Kruskal-Wallis test with the Dunn test for multiple comparisons were used for statistical analysis (p < 0.05). The analyzed 45-55-year-old women consumed legume seeds several times a month on average, while the frequency of soy/soy product consumption was lower than once a month. Statistical analysis revealed that the frequency of soy product consumption increased with the level of self-efficacy, optimism and satisfaction with life (p < 0.01). Also the increased frequency of legume seed consumption was associated with higher level of optimism and satisfaction with life (p < 0.01). Intergroup comparisons of the average consumption frequency of these products confirmed that legume seeds were significantly more frequently chosen by women characterized by high rather than low levels of optimism (3.36 vs. 2.62, p < 0.001) and satisfaction with life (3.36 vs. 2.65, p < 0.01). Also soy products were preferred significantly more often by women with higher levels of optimism (2.00 vs. 1.38, p < 0.05) and satisfaction with life (2.02 vs. 1.39, p < 0.05). The consumption of legume seeds, and especially soy products, was revealed to be very low among perimenopausal women, and varied depending on the analyzed individual traits, with a tendency to more frequent ingestion by individuals with higher levels of self-efficacy, optimism, and satisfaction with life.
Wang, Yuhao; Li, Xin; Xu, Kai; Ren, Fengbo; Yu, Hao
2017-04-01
Compressive sensing is widely used in biomedical applications, and the sampling matrix plays a critical role on both quality and power consumption of signal acquisition. It projects a high-dimensional vector of data into a low-dimensional subspace by matrix-vector multiplication. An optimal sampling matrix can ensure accurate data reconstruction and/or high compression ratio. Most existing optimization methods can only produce real-valued embedding matrices that result in large energy consumption during data acquisition. In this paper, we propose an efficient method that finds an optimal Boolean sampling matrix in order to reduce the energy consumption. Compared to random Boolean embedding, our data-driven Boolean sampling matrix can improve the image recovery quality by 9 dB. Moreover, in terms of sampling hardware complexity, it reduces the energy consumption by 4.6× and the silicon area by 1.9× over the data-driven real-valued embedding.
Linear energy transfer incorporated intensity modulated proton therapy optimization
NASA Astrophysics Data System (ADS)
Cao, Wenhua; Khabazian, Azin; Yepes, Pablo P.; Lim, Gino; Poenisch, Falk; Grosshans, David R.; Mohan, Radhe
2018-01-01
The purpose of this study was to investigate the feasibility of incorporating linear energy transfer (LET) into the optimization of intensity modulated proton therapy (IMPT) plans. Because increased LET correlates with increased biological effectiveness of protons, high LETs in target volumes and low LETs in critical structures and normal tissues are preferred in an IMPT plan. However, if not explicitly incorporated into the optimization criteria, different IMPT plans may yield similar physical dose distributions but greatly different LET, specifically dose-averaged LET, distributions. Conventionally, the IMPT optimization criteria (or cost function) only includes dose-based objectives in which the relative biological effectiveness (RBE) is assumed to have a constant value of 1.1. In this study, we added LET-based objectives for maximizing LET in target volumes and minimizing LET in critical structures and normal tissues. Due to the fractional programming nature of the resulting model, we used a variable reformulation approach so that the optimization process is computationally equivalent to conventional IMPT optimization. In this study, five brain tumor patients who had been treated with proton therapy at our institution were selected. Two plans were created for each patient based on the proposed LET-incorporated optimization (LETOpt) and the conventional dose-based optimization (DoseOpt). The optimized plans were compared in terms of both dose (assuming a constant RBE of 1.1 as adopted in clinical practice) and LET. Both optimization approaches were able to generate comparable dose distributions. The LET-incorporated optimization achieved not only pronounced reduction of LET values in critical organs, such as brainstem and optic chiasm, but also increased LET in target volumes, compared to the conventional dose-based optimization. However, on occasion, there was a need to tradeoff the acceptability of dose and LET distributions. Our conclusion is that the inclusion of LET-dependent criteria in the IMPT optimization could lead to similar dose distributions as the conventional optimization but superior LET distributions in target volumes and normal tissues. This may have substantial advantages in improving tumor control and reducing normal tissue toxicities.
Meng, Qing-chun; Rong, Xiao-xia; Zhang, Yi-min; Wan, Xiao-le; Liu, Yuan-yuan; Wang, Yu-zhi
2016-01-01
CO2 emission influences not only global climate change but also international economic and political situations. Thus, reducing the emission of CO2, a major greenhouse gas, has become a major issue in China and around the world as regards preserving the environmental ecology. Energy consumption from coal, oil, and natural gas is primarily responsible for the production of greenhouse gases and air pollutants such as SO2 and NOX, which are the main air pollutants in China. In this study, a mathematical multi-objective optimization method was adopted to analyze the collaborative emission reduction of three kinds of gases on the basis of their common restraints in different ways of energy consumption to develop an economic, clean, and efficient scheme for energy distribution. The first part introduces the background research, the collaborative emission reduction for three kinds of gases, the multi-objective optimization, the main mathematical modeling, and the optimization method. The second part discusses the four mathematical tools utilized in this study, which include the Granger causality test to analyze the causality between air quality and pollutant emission, a function analysis to determine the quantitative relation between energy consumption and pollutant emission, a multi-objective optimization to set up the collaborative optimization model that considers energy consumption, and an optimality condition analysis for the multi-objective optimization model to design the optimal-pole algorithm and obtain an efficient collaborative reduction scheme. In the empirical analysis, the data of pollutant emission and final consumption of energies of Tianjin in 1996-2012 was employed to verify the effectiveness of the model and analyze the efficient solution and the corresponding dominant set. In the last part, several suggestions for collaborative reduction are recommended and the drawn conclusions are stated.
Zhang, Yi-min; Wan, Xiao-le; Liu, Yuan-yuan; Wang, Yu-zhi
2016-01-01
CO2 emission influences not only global climate change but also international economic and political situations. Thus, reducing the emission of CO2, a major greenhouse gas, has become a major issue in China and around the world as regards preserving the environmental ecology. Energy consumption from coal, oil, and natural gas is primarily responsible for the production of greenhouse gases and air pollutants such as SO2 and NOX, which are the main air pollutants in China. In this study, a mathematical multi-objective optimization method was adopted to analyze the collaborative emission reduction of three kinds of gases on the basis of their common restraints in different ways of energy consumption to develop an economic, clean, and efficient scheme for energy distribution. The first part introduces the background research, the collaborative emission reduction for three kinds of gases, the multi-objective optimization, the main mathematical modeling, and the optimization method. The second part discusses the four mathematical tools utilized in this study, which include the Granger causality test to analyze the causality between air quality and pollutant emission, a function analysis to determine the quantitative relation between energy consumption and pollutant emission, a multi-objective optimization to set up the collaborative optimization model that considers energy consumption, and an optimality condition analysis for the multi-objective optimization model to design the optimal-pole algorithm and obtain an efficient collaborative reduction scheme. In the empirical analysis, the data of pollutant emission and final consumption of energies of Tianjin in 1996–2012 was employed to verify the effectiveness of the model and analyze the efficient solution and the corresponding dominant set. In the last part, several suggestions for collaborative reduction are recommended and the drawn conclusions are stated. PMID:27010658
Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials
Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L.; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori
2016-01-01
Purpose The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. Patients and Methods We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. Results A total of 13,008 toxicities were captured: 46% of patients’ first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m2, the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. Conclusions When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. PMID:26926682
Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials.
Lee, Shing M; Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori
2016-04-20
The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. A total of 13,008 toxicities were captured: 46% of patients' first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m(2), the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. © 2016 by American Society of Clinical Oncology.
Huss, Michael; Duhan, Praveen; Gandhi, Preetam; Chen, Chien-Wei; Spannhuth, Carsten; Kumar, Vinod
2017-01-01
Attention-deficit/hyperactivity disorder (ADHD) is a chronic psychiatric disorder characterized by hyperactivity and/or inattention and is often associated with a substantial impact on psychosocial functioning. Methylphenidate (MPH), a central nervous system stimulant, is commonly used for pharmacological treatment of adults and children with ADHD. Current practice guidelines recommend optimizing MPH dosage to individual patient needs; however, the clinical benefits of individual dose optimization compared with fixed-dose regimens remain unclear. Here we review the available literature on MPH dose optimization from clinical trials and real-world experience on ADHD management. In addition, we report safety and efficacy data from the largest MPH modified-release long-acting Phase III clinical trial conducted to examine benefits of dose optimization in adults with ADHD. Overall, MPH is an effective ADHD treatment with a good safety profile; data suggest that dose optimization may enhance the safety and efficacy of treatment. Further research is required to establish the extent to which short-term clinical benefits of MPH dose optimization translate into improved long-term outcomes for patients with ADHD. PMID:28740389
Huss, Michael; Duhan, Praveen; Gandhi, Preetam; Chen, Chien-Wei; Spannhuth, Carsten; Kumar, Vinod
2017-01-01
Attention-deficit/hyperactivity disorder (ADHD) is a chronic psychiatric disorder characterized by hyperactivity and/or inattention and is often associated with a substantial impact on psychosocial functioning. Methylphenidate (MPH), a central nervous system stimulant, is commonly used for pharmacological treatment of adults and children with ADHD. Current practice guidelines recommend optimizing MPH dosage to individual patient needs; however, the clinical benefits of individual dose optimization compared with fixed-dose regimens remain unclear. Here we review the available literature on MPH dose optimization from clinical trials and real-world experience on ADHD management. In addition, we report safety and efficacy data from the largest MPH modified-release long-acting Phase III clinical trial conducted to examine benefits of dose optimization in adults with ADHD. Overall, MPH is an effective ADHD treatment with a good safety profile; data suggest that dose optimization may enhance the safety and efficacy of treatment. Further research is required to establish the extent to which short-term clinical benefits of MPH dose optimization translate into improved long-term outcomes for patients with ADHD.
Kitzmann, JP; O’Gorman, D; Kin, T; Gruessner, AC; Senior, P; Imes, S; Gruessner, RW; Shapiro, AMJ; Papas, KK
2014-01-01
Human islet allotransplant (ITx) for the treatment of type 1 diabetes is in phase III clinical registration trials in the US and standard of care in several other countries. Current islet product release criteria include viability based on cell membrane integrity stains, glucose stimulated insulin release (GSIR), and islet equivalent (IE) dose based on counts. However, only a fraction of patients transplanted with islets that meet or exceed these release criteria become insulin independent following one transplant. Measurements of islet oxygen consumption rate (OCR) have been reported as highly predictive of transplant outcome in many models. In this paper we report on the assessment of clinical islet allograft preparations using islet oxygen consumption rate (OCR) dose (or viable IE dose) and current product release assays in a series of 13 first transplant recipients. The predictive capability of each assay was examined and successful graft function was defined as 100% insulin independence within 45 days post-transplant. Results showed that OCR dose was most predictive of CTO. IE dose was also highly predictive, while GSIR and membrane integrity stains were not. In conclusion, OCR dose can predict CTO with high specificity and sensitivity and is a useful tool for evaluating islet preparations prior to clinical ITx. PMID:25131089
Spatial frequency performance limitations of radiation dose optimization and beam positioning
NASA Astrophysics Data System (ADS)
Stewart, James M. P.; Stapleton, Shawn; Chaudary, Naz; Lindsay, Patricia E.; Jaffray, David A.
2018-06-01
The flexibility and sophistication of modern radiotherapy treatment planning and delivery methods have advanced techniques to improve the therapeutic ratio. Contemporary dose optimization and calculation algorithms facilitate radiotherapy plans which closely conform the three-dimensional dose distribution to the target, with beam shaping devices and image guided field targeting ensuring the fidelity and accuracy of treatment delivery. Ultimately, dose distribution conformity is limited by the maximum deliverable dose gradient; shallow dose gradients challenge techniques to deliver a tumoricidal radiation dose while minimizing dose to surrounding tissue. In this work, this ‘dose delivery resolution’ observation is rigorously formalized for a general dose delivery model based on the superposition of dose kernel primitives. It is proven that the spatial resolution of a delivered dose is bounded by the spatial frequency content of the underlying dose kernel, which in turn defines a lower bound in the minimization of a dose optimization objective function. In addition, it is shown that this optimization is penalized by a dose deposition strategy which enforces a constant relative phase (or constant spacing) between individual radiation beams. These results are further refined to provide a direct, analytic method to estimate the dose distribution arising from the minimization of such an optimization function. The efficacy of the overall framework is demonstrated on an image guided small animal microirradiator for a set of two-dimensional hypoxia guided dose prescriptions.
Gaujoux-Viala, Cécile; Rincheval, Nathalie; Dougados, Maxime; Combe, Bernard; Fautrel, Bruno
2017-12-01
Although methotrexate (MTX) is the consensual first-line disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA), substantial heterogeneity remains with its prescription and dosage, which are often not optimal. To evaluate the symptomatic and structural impact of optimal MTX dose in patients with early RA in daily clinical practice over 2 years. Patients included in the early arthritis ESPOIR cohort who fulfilled the ACR-EULAR (American College of Rheumatology/European League against Rheumatism) criteria for RA and received MTX as a first DMARD were assessed. Optimal MTX dose was defined as ≥10 mg/week during the first 3 months, with escalation to ≥20 mg/week or 0.3 mg/kg/week at 6 months without Disease Activity Score in 28 joints remission. Symptomatic and structural efficacy with and without optimal MTX dose was assessed by generalised logistic regression with adjustment for appropriate variables. Within the first year of follow-up, 314 patients (53%) with RA received MTX as a first DMARD (mean dose 12.2±3.8 mg/week). Only 26.4% (n=76) had optimal MTX dose. After adjustment, optimal versus non-optimal MTX dose was more efficient in achieving ACR-EULAR remission at 1 year (OR 4.28 (95% CI 1.86 to 9.86)) and normal functioning (Health Assessment Questionnaire ≤0.5; OR at 1 year 4.36 (95% CI 2.03 to 9.39)), with no effect on radiological progression. Results were similar during the second year. Optimal MTX dose is more efficacious than non-optimal dose for remission and function in early arthritis in daily practice, with no impact on radiological progression over 2 years. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Berretta, Massimiliano; Micek, Agnieszka; Lafranconi, Alessandra; Rossetti, Sabrina; Di Francia, Raffaele; De Paoli, Paolo; Rossi, Paola; Facchini, Gaetano
2018-04-17
Coffee consumption has been associated with numerous cancers, but evidence on ovarian cancer risk is controversial. Therefore, we performed a meta-analysis on prospective cohort studies in order to review the evidence on coffee consumption and risk of ovarian cancer. Studies were identified through searching the PubMed and MEDLINE databases up to March 2017. Risk estimates were retrieved from the studies, and dose-response analysis was modelled by using restricted cubic splines. Additionally, a stratified analysis by menopausal status was performed. A total of 8 studies were eligible for the dose-response meta-analysis. Studies included in the analysis comprised 787,076 participants and 3,541 ovarian cancer cases. The results showed that coffee intake was not associated with ovarian cancer risk (RR = 1.06, 95% CI: 0.89, 1.26). Stratified and subgroup analysis showed consisted results. This comprehensive meta-analysis did not find evidence of an association between the consumption of coffee and risk of ovarian cancer.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Park, J; Research Institute of Biomedical Engineering, The Catholic University of Korea, Seoul; Park, H
Purpose: Dosimetric effect and discrepancy according to the rectum definition methods and dose perturbation by air cavity in an endo-rectal balloon (ERB) were verified using rectal-wall (Rwall) dose maps considering systematic errors in dose optimization and calculation accuracy in intensity-modulated radiation treatment (IMRT) for prostate cancer patients. Methods: When the inflated ERB having average diameter of 4.5 cm and air volume of 100 cc is used for patient, Rwall doses were predicted by pencil-beam convolution (PBC), anisotropic analytic algorithm (AAA), and AcurosXB (AXB) with material assignment function. The errors of dose optimization and calculation by separating air cavity from themore » whole rectum (Rwhole) were verified with measured rectal doses. The Rwall doses affected by the dose perturbation of air cavity were evaluated using a featured rectal phantom allowing insert of rolled-up gafchromic films and glass rod detectors placed along the rectum perimeter. Inner and outer Rwall doses were verified with reconstructed predicted rectal wall dose maps. Dose errors and extent at dose levels were evaluated with estimated rectal toxicity. Results: While AXB showed insignificant difference of target dose coverage, Rwall doses underestimated by up to 20% in dose optimization for the Rwhole than Rwall at all dose range except for the maximum dose. As dose optimization for Rwall was applied, the Rwall doses presented dose error less than 3% between dose calculation algorithm except for overestimation of maximum rectal dose up to 5% in PBC. Dose optimization for Rwhole caused dose difference of Rwall especially at intermediate doses. Conclusion: Dose optimization for Rwall could be suggested for more accurate prediction of rectal wall dose prediction and dose perturbation effect by air cavity in IMRT for prostate cancer. This research was supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (MSIP) (Grant No. 200900420)« less
System and method of vehicle operating condition management
Sujan, Vivek A.; Vajapeyazula, Phani; Follen, Kenneth; Wu, An; Moffett, Barty L.
2015-10-20
A vehicle operating condition profile can be determined over a given route while also considering imposed constraints such as deviation from time targets, deviation from maximum governed speed limits, etc. Given current vehicle speed, engine state and transmission state, the present disclosure optimally manages the engine map and transmission to provide a recommended vehicle operating condition that optimizes fuel consumption in transitioning from one vehicle state to a target state. Exemplary embodiments provide for offline and online optimizations relative to fuel consumption. The benefit is increased freight efficiency in transporting cargo from source to destination by minimizing fuel consumption and maintaining drivability.
Huss, Michael; Ginsberg, Ylva; Arngrim, Torben; Philipsen, Alexandra; Carter, Katherine; Chen, Chien-Wei; Gandhi, Preetam; Kumar, Vinod
2014-09-01
In the management of attention-deficit hyperactivity disorder (ADHD) in adults it is important to recognize that individual patients respond to a wide range of methylphenidate doses. Studies with methylphenidate modified release long acting (MPH-LA) in children have reported the need for treatment optimization for improved outcomes. We report the results from a post hoc analysis of a 5-week dose optimization phase from a large randomized, placebo-controlled, multicenter 40-week study (9-week double-blind dose confirmation phase, 5-week open-label dose optimization phase, and 26-week double-blind maintenance of effect phase). Patients entering the open-label dose optimization phase initiated treatment with MPH-LA 20 mg/day; up/down titrated to their optimal dose (at which there was balance between control of symptoms and side effects) of 40, 60, or 80 mg/day in increments of 20 mg/week by week 12 or 13. Safety was assessed by monitoring the adverse events (AEs) and serious AEs. Efficacy was assessed by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, Attention-Deficit Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) and Sheehan Disability Scale (SDS) total scores. At the end of the dose confirmation phase, similar numbers of patients were treated optimally with each of the 40, 60, and 80 mg/day doses (152, 177, and 160, respectively) for MPH-LA. Mean improvement from baseline in the dose confirmation phase in total scores of DSM-IV ADHD RS and SDS were 23.5 ± 9.90 and 9.7 ± 7.36, respectively. Dose optimization with MPH-LA (40, 60, or 80 mg/day) improved treatment outcomes and was well-tolerated in adult ADHD patients.
Optimal design of clinical trials with biologics using dose-time-response models.
Lange, Markus R; Schmidli, Heinz
2014-12-30
Biologics, in particular monoclonal antibodies, are important therapies in serious diseases such as cancer, psoriasis, multiple sclerosis, or rheumatoid arthritis. While most conventional drugs are given daily, the effect of monoclonal antibodies often lasts for months, and hence, these biologics require less frequent dosing. A good understanding of the time-changing effect of the biologic for different doses is needed to determine both an adequate dose and an appropriate time-interval between doses. Clinical trials provide data to estimate the dose-time-response relationship with semi-mechanistic nonlinear regression models. We investigate how to best choose the doses and corresponding sample size allocations in such clinical trials, so that the nonlinear dose-time-response model can be precisely estimated. We consider both local and conservative Bayesian D-optimality criteria for the design of clinical trials with biologics. For determining the optimal designs, computer-intensive numerical methods are needed, and we focus here on the particle swarm optimization algorithm. This metaheuristic optimizer has been successfully used in various areas but has only recently been applied in the optimal design context. The equivalence theorem is used to verify the optimality of the designs. The methodology is illustrated based on results from a clinical study in patients with gout, treated by a monoclonal antibody. Copyright © 2014 John Wiley & Sons, Ltd.
Xue, Xiu-Juan; Gao, Qing; Qiao, Jian-Hong; Zhang, Jie; Xu, Cui-Ping; Liu, Ju
2014-01-01
This meta-analysis was to summarize the published studies about the association between red/processed meat consumption and the risk of lung cancer. 5 databases were systematically reviewed, and random-effect model was used to pool the study results and to assess dose-response relationships. Results shown that six cohort studies and twenty eight case-control studies were included in this meat-analysis. The pooled Risk Radios (RR) for total red meat and processed meat were 1.44 (95% CI, 1.29-1.61) and 1.23 (95% CI, 1.10-1.37), respectively. Dose-response analysis revealed that for every increment of 120 grams red meat per day the risk of lung cancer increases 35% and for every increment of 50 grams red meat per day the risk of lung cancer increases 20%. The present dose-response meta-analysis suggested that both red and processed meat consumption showed a positive effect on lung cancer risk. PMID:25035778
Li, Mingjie; Zhou, Ping; Wang, Hong; ...
2017-09-19
As one of the most important unit in the papermaking industry, the high consistency (HC) refining system is confronted with challenges such as improving pulp quality, energy saving, and emissions reduction in its operation processes. Here in this correspondence, an optimal operation of HC refining system is presented using nonlinear multiobjective model predictive control strategies that aim at set-point tracking objective of pulp quality, economic objective, and specific energy (SE) consumption objective, respectively. First, a set of input and output data at different times are employed to construct the subprocess model of the state process model for the HC refiningmore » system, and then the Wiener-type model can be obtained through combining the mechanism model of Canadian Standard Freeness and the state process model that determines their structures based on Akaike information criterion. Second, the multiobjective optimization strategy that optimizes both the set-point tracking objective of pulp quality and SE consumption is proposed simultaneously, which uses NSGA-II approach to obtain the Pareto optimal set. Furthermore, targeting at the set-point tracking objective of pulp quality, economic objective, and SE consumption objective, the sequential quadratic programming method is utilized to produce the optimal predictive controllers. In conclusion, the simulation results demonstrate that the proposed methods can make the HC refining system provide a better performance of set-point tracking of pulp quality when these predictive controllers are employed. In addition, while the optimal predictive controllers orienting with comprehensive economic objective and SE consumption objective, it has been shown that they have significantly reduced the energy consumption.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Mingjie; Zhou, Ping; Wang, Hong
As one of the most important unit in the papermaking industry, the high consistency (HC) refining system is confronted with challenges such as improving pulp quality, energy saving, and emissions reduction in its operation processes. Here in this correspondence, an optimal operation of HC refining system is presented using nonlinear multiobjective model predictive control strategies that aim at set-point tracking objective of pulp quality, economic objective, and specific energy (SE) consumption objective, respectively. First, a set of input and output data at different times are employed to construct the subprocess model of the state process model for the HC refiningmore » system, and then the Wiener-type model can be obtained through combining the mechanism model of Canadian Standard Freeness and the state process model that determines their structures based on Akaike information criterion. Second, the multiobjective optimization strategy that optimizes both the set-point tracking objective of pulp quality and SE consumption is proposed simultaneously, which uses NSGA-II approach to obtain the Pareto optimal set. Furthermore, targeting at the set-point tracking objective of pulp quality, economic objective, and SE consumption objective, the sequential quadratic programming method is utilized to produce the optimal predictive controllers. In conclusion, the simulation results demonstrate that the proposed methods can make the HC refining system provide a better performance of set-point tracking of pulp quality when these predictive controllers are employed. In addition, while the optimal predictive controllers orienting with comprehensive economic objective and SE consumption objective, it has been shown that they have significantly reduced the energy consumption.« less
Gwynn, Justin P; Nalbandyan, Anna; Rudolfsen, Geir
2013-02-01
This paper discusses activity concentrations of (210)Po, (210)Pb, (40)K and (137)Cs in edible wild berries and mushrooms collected from Øvre Dividalen national park, Northern Norway and derives committed effective ingestion doses to man based on high consumption rates of these wild foods. Edible wild berries and mushrooms accumulated similar levels of (210)Pb, but mushrooms accumulated higher levels of (210)Po and (40)K than berries. There appears to be a clear difference in the ability of Leccinum spp. of fungi to accumulate (210)Po and/or translocate (210)Po to mushrooms compared to Russula spp. of fungi. Activity concentrations of (137)Cs in edible wild berries and mushrooms from Øvre Dividalen national park reflected the lower levels of fallout of this radionuclide in Northern Norway compared to more central areas following the Chernobyl accident. For mushrooms, ingestion doses are dominated by (210)Po, while for berries, (40)K is typically the main contributor to dose. Based on high consumption rates, ingestion doses arising from the combination of (210)Po, (210)Pb and (40)K were up to 0.05 mSv/a for berries and 0.50 mSv/a for mushrooms. Consumption of such wild foods may result in a significant contribution to total annual doses when consumed in large quantities, particularly when selecting mushrooms species that accumulate high activity concentrations of (210)Po. Copyright © 2012 Elsevier Ltd. All rights reserved.
Hyun, Seung Won; Wong, Weng Kee
2016-01-01
We construct an optimal design to simultaneously estimate three common interesting features in a dose-finding trial with possibly different emphasis on each feature. These features are (1) the shape of the dose-response curve, (2) the median effective dose and (3) the minimum effective dose level. A main difficulty of this task is that an optimal design for a single objective may not perform well for other objectives. There are optimal designs for dual objectives in the literature but we were unable to find optimal designs for 3 or more objectives to date with a concrete application. A reason for this is that the approach for finding a dual-objective optimal design does not work well for a 3 or more multiple-objective design problem. We propose a method for finding multiple-objective optimal designs that estimate the three features with user-specified higher efficiencies for the more important objectives. We use the flexible 4-parameter logistic model to illustrate the methodology but our approach is applicable to find multiple-objective optimal designs for other types of objectives and models. We also investigate robustness properties of multiple-objective optimal designs to mis-specification in the nominal parameter values and to a variation in the optimality criterion. We also provide computer code for generating tailor made multiple-objective optimal designs. PMID:26565557
Hyun, Seung Won; Wong, Weng Kee
2015-11-01
We construct an optimal design to simultaneously estimate three common interesting features in a dose-finding trial with possibly different emphasis on each feature. These features are (1) the shape of the dose-response curve, (2) the median effective dose and (3) the minimum effective dose level. A main difficulty of this task is that an optimal design for a single objective may not perform well for other objectives. There are optimal designs for dual objectives in the literature but we were unable to find optimal designs for 3 or more objectives to date with a concrete application. A reason for this is that the approach for finding a dual-objective optimal design does not work well for a 3 or more multiple-objective design problem. We propose a method for finding multiple-objective optimal designs that estimate the three features with user-specified higher efficiencies for the more important objectives. We use the flexible 4-parameter logistic model to illustrate the methodology but our approach is applicable to find multiple-objective optimal designs for other types of objectives and models. We also investigate robustness properties of multiple-objective optimal designs to mis-specification in the nominal parameter values and to a variation in the optimality criterion. We also provide computer code for generating tailor made multiple-objective optimal designs.
Chew, Boon; Mathison, Bridget; Kimble, Lindsey; McKay, Diane; Kaspar, Kerrie; Khoo, Christina; Chen, C-Y Oliver; Blumberg, Jeffrey
2018-02-23
We studied the health benefits of low calorie cranberry beverage consumption on glucoregulation, oxidative damage, inflammation, and lipid metabolism in overweight but otherwise healthy humans. 78 overweight or obese men and women (30-70 years; BMI 27-35 kg/m 2 ) with abdominal adiposity (waist: hip > 0.8 for women and > 0.9 for men; waist: height ≥ 0.5) consumed 450 mL placebo or low calorie, high polyphenol cranberry extract beverage (CEB) daily for 8 week in a randomized, double-blind, placebo-controlled, parallel design trial. Blood and urine samples were collected after overnight fast at baseline and after 8 weeks of daily beverage consumption. Blood and urine samples were also collected during 3 oral glucose tolerance test (OGTT) challenges: (1) pre-intervention without the test beverages, (2) following a single dose of placebo or CEB at baseline (week 0), and (3) following a single dose of placebo or CEB at 8 week. Compared to placebo, a single CEB dose at baseline lowered endothelin-1 and elevated nitric oxide and the reduced:oxidized glutathione ratio (P < 0.05). Interferon-γ was elevated (P < 0.05) after a single CEB dose at baseline; however, after 8 week of CEB intervention, fasting C-reactive protein was lower (P < 0.05). CEB consumption for 8 week also reduced serum insulin and increased HDL cholesterol compared to placebo (P < 0.05). An acute dose of low calorie, high polyphenol cranberry beverage improved antioxidant status, while 8 week daily consumption reduced cardiovascular disease risk factors by improving glucoregulation, downregulating inflammatory biomarkers, and increasing HDL cholesterol.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Grelewicz, Z; Wiersma, R
Purpose: Real-time fluoroscopy may allow for improved patient positioning and tumor tracking, particularly in the treatment of lung tumors. In order to mitigate the effects of the imaging dose, previous studies have demonstrated the effect of including both imaging dose and imaging constraints into the inverse treatment planning object function. That method of combined MV+kV optimization may Result in plans with treatment beams chosen to allow for more gentle imaging beam-on times. Direct-aperture optimization (DAO) is also known to produce treatment plans with fluence maps more conducive to lower beam-on times. Therefore, in this work we demonstrate the feasibility ofmore » a combination of DAO and MV+kV optimization for further optimized real-time kV imaging. Methods: Therapeutic and imaging beams were modeled in the EGSnrc Monte Carlo environment, and applied to a patient model for a previously treated lung patient to provide dose influence matrices from DOSXYZnrc. An MV + kV IMRT DAO treatment planning system was developed to compare DAO treatment plans with and without MV+kV optimization. The objective function was optimized using simulated annealing. In order to allow for comparisons between different cases of the stochastically optimized plans, the optimization was repeated twenty times. Results: Across twenty optimizations, combined MV+kV IMRT resulted in an average of 12.8% reduction in peak skin dose. Both non-optimized and MV+kV optimized imaging beams delivered, on average, mean dose of approximately 1 cGy per fraction to the target, with peak doses to target of approximately 6 cGy per fraction. Conclusion: When using DAO, MV+kV optimization is shown to Result in improvements to plan quality in terms of skin dose, when compared to the case of MV optimization with non-optimized kV imaging. The combination of DAO and MV+kV optimization may allow for real-time imaging without excessive imaging dose. Financial support for the work has been provided in part by NIH Grant T32 EB002103, ACS RSG-13-313-01-CCE, and NIH S10 RR021039 and P30 CA14599 grants. The contents of this submission do not necessarily represent the official views of any of the supporting organizations.« less
Baclofen blocks yohimbine-induced increases in ethanol-reinforced responding in rats.
Williams, Keith L; Nickel, Melissa M; Bielak, Justin T
2016-05-01
Chronic or repeated stress increases alcohol consumption. The GABA-B agonist baclofen decreases alcohol consumption and may be most effective for individuals with comorbid anxiety/stress disorders. The present study sought to determine if baclofen blocks stress-induced increases in ethanol self-administration as modeled by repeated yohimbine injections in rats. Rats were trained to respond for 15% w/v ethanol in operant chambers using a method that applies neither water deprivation nor saccharin/sucrose fading. Following training, the rats received 6 injections of 1.25mg/kg yohimbine were given immediately prior to the operant sessions during a 2-week time period. Subsequently, some rats were pair-matched to receive either 1.25mg/kg yohimbine or saline in the presence of 0.3, 1, and 3mg/kg baclofen prior to sessions. Acquisition of ethanol self-administration was poor. Pretreatment with yohimbine consistently increased responding across repeated injections. Yohimbine's effect on ethanol intake unexpectedly diverged from the effect on responding as the rats failed to consume all reinforcers earned. Smaller doses of baclofen paired with saline injections had no effect on ethanol responding; only 3mg/kg baclofen reduced ethanol self-administration. The smallest baclofen dose of 0.3mg/kg failed to block the yohimbine-induced increase in self-administration. The large baclofen dose of 3mg/kg continued to suppress ethanol self-administration when given with yohimbine. Baclofen 1mg/kg blocked the effect of yohimbine even though it had no effect when given in the absence of yohimbine. Exposure to high ethanol concentrations may induce self-administration only in certain conditions. The dissociation between responding and intake suggests that repeated yohimbine injections may initiate other behavioral or physiological mechanisms that confound its effects as a pharmacological stressor. Furthermore, an optimal baclofen dose range may specifically protect against stress-induced alcohol self-administration, highlighting a specific contribution of GABA-B receptors and a potential therapeutic efficacy of GABA-B agonists at a non-sedating dose. Copyright © 2016 Elsevier Inc. All rights reserved.
Yao, Rui; Templeton, Alistair K; Liao, Yixiang; Turian, Julius V; Kiel, Krystyna D; Chu, James C H
2014-01-01
To validate an in-house optimization program that uses adaptive simulated annealing (ASA) and gradient descent (GD) algorithms and investigate features of physical dose and generalized equivalent uniform dose (gEUD)-based objective functions in high-dose-rate (HDR) brachytherapy for cervical cancer. Eight Syed/Neblett template-based cervical cancer HDR interstitial brachytherapy cases were used for this study. Brachytherapy treatment plans were first generated using inverse planning simulated annealing (IPSA). Using the same dwell positions designated in IPSA, plans were then optimized with both physical dose and gEUD-based objective functions, using both ASA and GD algorithms. Comparisons were made between plans both qualitatively and based on dose-volume parameters, evaluating each optimization method and objective function. A hybrid objective function was also designed and implemented in the in-house program. The ASA plans are higher on bladder V75% and D2cc (p=0.034) and lower on rectum V75% and D2cc (p=0.034) than the IPSA plans. The ASA and GD plans are not significantly different. The gEUD-based plans have higher homogeneity index (p=0.034), lower overdose index (p=0.005), and lower rectum gEUD and normal tissue complication probability (p=0.005) than the physical dose-based plans. The hybrid function can produce a plan with dosimetric parameters between the physical dose-based and gEUD-based plans. The optimized plans with the same objective value and dose-volume histogram could have different dose distributions. Our optimization program based on ASA and GD algorithms is flexible on objective functions, optimization parameters, and can generate optimized plans comparable with IPSA. Copyright © 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.
Crippa, Alessio; Discacciati, Andrea; Larsson, Susanna C; Wolk, Alicja; Orsini, Nicola
2014-10-15
Several studies have analyzed the relationship between coffee consumption and mortality, but the shape of the association remains unclear. We conducted a dose-response meta-analysis of prospective studies to examine the dose-response associations between coffee consumption and mortality from all causes, cardiovascular disease (CVD), and all cancers. Pertinent studies, published between 1966 and 2013, were identified by searching PubMed and by reviewing the reference lists of the selected articles. Prospective studies in which investigators reported relative risks of mortality from all causes, CVD, and all cancers for 3 or more categories of coffee consumption were eligible. Results from individual studies were pooled using a random-effects model. Twenty-one prospective studies, with 121,915 deaths and 997,464 participants, met the inclusion criteria. There was strong evidence of nonlinear associations between coffee consumption and mortality for all causes and CVD (P for nonlinearity < 0.001). The largest risk reductions were observed for 4 cups/day for all-cause mortality (16%, 95% confidence interval: 13, 18) and 3 cups/day for CVD mortality (21%, 95% confidence interval: 16, 26). Coffee consumption was not associated with cancer mortality. Findings from this meta-analysis indicate that coffee consumption is inversely associated with all-cause and CVD mortality. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gao, Y; Liu, B; Kalra, M
Purpose: X-rays from CT scans can increase cancer risk to patients. Lifetime Attributable Risk of Cancer Incidence for adult patients has been investigated and shown to decrease as patient age. However, a new risk model shows an increasing risk trend for several radiosensitive organs for middle age patients. This study investigates the feasibility of a general method for optimizing tube current modulation (TCM) functions to minimize risk by reducing radiation dose to radiosensitive organs of patients. Methods: Organ-based TCM has been investigated in literature for eye lens dose and breast dose. Adopting the concept in organ-based TCM, this study seeksmore » to find an optimized tube current for minimal total risk to breasts and lungs by reducing dose to these organs. The contributions of each CT view to organ dose are determined through simulations of CT scan view-by-view using a GPU-based fast Monte Carlo code, ARCHER. A Linear Programming problem is established for tube current optimization, with Monte Carlo results as weighting factors at each view. A pre-determined dose is used as upper dose boundary, and tube current of each view is optimized to minimize the total risk. Results: An optimized tube current is found to minimize the total risk of lungs and breasts: compared to fixed current, the risk is reduced by 13%, with breast dose reduced by 38% and lung dose reduced by 7%. The average tube current is maintained during optimization to maintain image quality. In addition, dose to other organs in chest region is slightly affected, with relative change in dose smaller than 10%. Conclusion: Optimized tube current plans can be generated to minimize cancer risk to lungs and breasts while maintaining image quality. In the future, various risk models and greater number of projections per rotation will be simulated on phantoms of different gender and age. National Institutes of Health R01EB015478.« less
Svensson, Elin M; Yngman, Gunnar; Denti, Paolo; McIlleron, Helen; Kjellsson, Maria C; Karlsson, Mats O
2018-05-01
Fixed-dose combination formulations where several drugs are included in one tablet are important for the implementation of many long-term multidrug therapies. The selection of optimal dose ratios and tablet content of a fixed-dose combination and the design of individualized dosing regimens is a complex task, requiring multiple simultaneous considerations. In this work, a methodology for the rational design of a fixed-dose combination was developed and applied to the case of a three-drug pediatric anti-tuberculosis formulation individualized on body weight. The optimization methodology synthesizes information about the intended use population, the pharmacokinetic properties of the drugs, therapeutic targets, and practical constraints. A utility function is included to penalize deviations from the targets; a sequential estimation procedure was developed for stable estimation of break-points for individualized dosing. The suggested optimized pediatric anti-tuberculosis fixed-dose combination was compared with the recently launched World Health Organization-endorsed formulation. The optimized fixed-dose combination included 15, 36, and 16% higher amounts of rifampicin, isoniazid, and pyrazinamide, respectively. The optimized fixed-dose combination is expected to result in overall less deviation from the therapeutic targets based on adult exposure and substantially fewer children with underexposure (below half the target). The development of this design tool can aid the implementation of evidence-based formulations, integrating available knowledge and practical considerations, to optimize drug exposures and thereby treatment outcomes.
CORRECTING ENERGY EXPENDITURES FOR FATIGUE AND EXCESS POST-EXERCISE OXYGEN CONSUMPTION
The EPA's human exposure and dose models often require a quantification of oxygen consumption for a simulated individual. Oxygen consumption is dependent on the individual's current level of physical activity (PA), which is determined from activity diaries selected from the Conso...
Data on cost-optimal Nearly Zero Energy Buildings (NZEBs) across Europe.
D'Agostino, Delia; Parker, Danny
2018-04-01
This data article refers to the research paper A model for the cost-optimal design of Nearly Zero Energy Buildings (NZEBs) in representative climates across Europe [1]. The reported data deal with the design optimization of a residential building prototype located in representative European locations. The study focus on the research of cost-optimal choices and efficiency measures in new buildings depending on the climate. The data linked within this article relate to the modelled building energy consumption, renewable production, potential energy savings, and costs. Data allow to visualize energy consumption before and after the optimization, selected efficiency measures, costs and renewable production. The reduction of electricity and natural gas consumption towards the NZEB target can be visualized together with incremental and cumulative costs in each location. Further data is available about building geometry, costs, CO 2 emissions, envelope, materials, lighting, appliances and systems.
MO-G-18A-01: Radiation Dose Reducing Strategies in CT, Fluoroscopy and Radiography
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mahesh, M; Gingold, E; Jones, A
2014-06-15
Advances in medical x-ray imaging have provided significant benefits to patient care. According to NCRP 160, there are more than 400 million x-ray procedures performed annually in the United States alone that contributes to nearly half of all the radiation exposure to the US population. Similar growth trends in medical x-ray imaging are observed worldwide. Apparent increase in number of medical x-ray imaging procedures, new protocols and the associated radiation dose and risk has drawn considerable attention. This has led to a number of technological innovations such as tube current modulation, iterative reconstruction algorithms, dose alerts, dose displays, flat panelmore » digital detectors, high efficient digital detectors, storage phosphor radiography, variable filters, etc. that are enabling users to acquire medical x-ray images at a much lower radiation dose. Along with these, there are number of radiation dose optimization strategies that users can adapt to effectively lower radiation dose in medical x-ray procedures. The main objectives of this SAM course are to provide information and how to implement the various radiation dose optimization strategies in CT, Fluoroscopy and Radiography. Learning Objectives: To update impact of technological advances on dose optimization in medical imaging. To identify radiation optimization strategies in computed tomography. To describe strategies for configuring fluoroscopic equipment that yields optimal images at reasonable radiation dose. To assess ways to configure digital radiography systems and recommend ways to improve image quality at optimal dose.« less
Power Consumption Optimization in Tooth Gears Processing
NASA Astrophysics Data System (ADS)
Kanatnikov, N.; Harlamov, G.; Kanatnikova, P.; Pashmentova, A.
2018-01-01
The paper reviews the issue of optimization of technological process of tooth gears production of the power consumption criteria. The authors dwell on the indices used for cutting process estimation by the consumed energy criteria and their applicability in the analysis of the toothed wheel production process. The inventors proposed a method for optimization of power consumptions based on the spatial modeling of cutting pattern. The article is aimed at solving the problem of effective source management in order to achieve economical and ecological effect during the mechanical processing of toothed gears. The research was supported by Russian Science Foundation (project No. 17-79-10316).
Grosso, Giuseppe; Micek, Agnieszka; Godos, Justyna; Pajak, Andrzej; Sciacca, Salvatore; Bes-Rastrollo, Maira; Galvano, Fabio; Martinez-Gonzalez, Miguel A
2017-08-17
To perform a dose-response meta-analysis of prospective cohort studies investigating the association between long-term coffee intake and risk of hypertension. An online systematic search of studies published up to November 2016 was performed. Linear and non-linear dose-response meta-analyses were conducted; potential evidence of heterogeneity, publication bias, and confounding effect of selected variables were investigated through sensitivity and meta-regression analyses. Seven cohorts including 205,349 individuals and 44,120 cases of hypertension were included. In the non-linear analysis, there was a 9% significant decreased risk of hypertension per seven cups of coffee a day, while, in the linear dose-response association, there was a 1% decreased risk of hypertension for each additional cup of coffee per day. Among subgroups, there were significant inverse associations for females, caffeinated coffee, and studies conducted in the US with longer follow-up. Analysis of potential confounders revealed that smoking-related variables weakened the strength of association between coffee consumption and risk of hypertension. Increased coffee consumption is associated with a modest decrease in risk of hypertension in prospective cohort studies. Smoking status is a potential effect modifier on the association between coffee consumption and risk of hypertension.
Effect of bromocriptine on acute ethanol tolerance in UChB rats.
Tampier, L; Prado, C; Quintanilla, M E; Mardones, J
1999-07-01
It has been suggested that a higher capacity to develop acute tolerance during a single dose of ethanol may promote higher ethanol consumption in alcohol-preferring rodents. Several studies have shown that the dopaminergic system may be involved in voluntary ethanol consumption. In the present paper we studied the effect of bromocriptine, a dopaminergic agonist drug, that is known to reduce voluntary consumption of ethanol, on acute tolerance in high (UChB) ethanol consumer rats. Acute tolerance was evaluated in bromocriptine and saline-treated rats by motor impairment induced by a subnarcotic dose of ethanol of 2.3 g/kg IP using a modified tilting plane test. Results showed a highly significant positive correlation between acute tolerance and the voluntary ethanol consumption by the rat. Bromocriptine treatment decreased ethanol consumption and also decreased acute tolerance development. This adds further support to the postulate that the acquisition of acute tolerance to ethanol may promote increased alcohol consumption. Moreover, these results also suggest that dopaminergic receptors involved in ethanol voluntary consumption may also be in acute tolerance development.
Grosso, Giuseppe; Micek, Agnieszka; Castellano, Sabrina; Pajak, Andzrej; Galvano, Fabio
2016-01-01
The aim of the study was to systematically review and analyze results from observational studies on coffee, caffeine, and tea consumption and association or risk of depression. Embase and PubMed databases were searched from inception to June 2015 for observational studies reporting the odds ratios or relative risks (RRs) and 95% confidence intervals (CI) of depression by coffee/tea/caffeine consumption. Random effects models, subgroup analyses, and dose-response analyses were performed. Twelve studies with 23 datasets were included in the meta-analysis, accounting for a total of 346 913 individuals and 8146 cases of depression. Compared to individuals with lower coffee consumption, those with higher intakes had pooled RR of depression of 0.76 (95% CI: 0.64, 0.91). Dose-response effect suggests a nonlinear J-shaped relation between coffee consumption and risk of depression with a peak of protective effect for 400 mL/day. A borderline nonsignificant association between tea consumption and risk of depression was found (RR 0.70, 95% CI: 0.48, 1.01), while significant results were found only for analysis of prospective studies regarding caffeine consumption (RR = 0.84, 95% CI: 0.75, 0.93). This study suggests a protective effect of coffee and, partially, of tea and caffeine on risk of depression. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Credibility of Uncertainty Analyses for 131-I Pathway Assessments
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hoffman, F O.; Anspaugh, L. R.; Apostoaei, A. I.
2004-05-01
We would like to make your readers aware of numerous concerns we have with respect to the paper by A. A. Simpkins and D. M. Hamby on Uncertainty in transport factors used to calculate historic dose from 131I releases at the Savannah River Site. The paper by Simpkins and Hamby concludes by saying their uncertainty analysis would add credibility to current dose reconstruction efforts of public exposures to historic releases of 131I from the operations at the Savannah River Site, yet we have found their paper to be afflicted with numerous errors in assumptions and methodology, which in turn leadmore » to grossly misleading conclusions. Perhaps the most egregious errors are their conclusions, which state that: a. the vegetable pathway, not the ingestion of fresh milk, was the main contributor to thyroid dose for exposure to 131I (even though dietary intake of vegetables was less in the past than at present), and b. the probability distribution assigned to the fraction of iodine released in the elemental form (Uniform 0, 0.6) is responsible for 64.6% of the total uncertainty in thyroid dose, given a unit release of 131I to the atmosphere. The assumptions used in the paper by Simpkins and Hamby lead to a large overestimate of the contamination of vegetables by airborne 131I. The interception by leafy and non-leafy vegetables of freshly deposited 131I is known to be highly dependent on the growth form of the crop and the standing crop biomass of leafy material. Unrealistic assumptions are made for losses of 131I from food processing, preparation, and storage prior to human consumption. These assumptions tend to bias their conclusions toward an overestimate of the amount of 131I retained by vegetation prior to consumption. For example, the generic assumption of a 6-d hold-up time is used for the loss from radioactive decay for the time period from harvest to human consumption of fruits, vegetables, and grains. We anticipate hold-up times of many weeks, if not months, between harvest and consumption for most grains and non-leafy forms of vegetation. The combined assumptions made by Simpkins and Hamby about the fraction of fresh deposition intercepted by vegetation, and the rather short hold-up time for most vegetables consumed, probably caused the authors to conclude that the consumption of 131I-contaminated vegetables was more important to dose than was the consumption of fresh sources of milk. This conclusion is surprising, given that the consumption rate assumed for whole milk was rather large and that the value of the milk transfer coefficient was also higher and more uncertain than most distributions reported in the literature. In our experience, the parameters contributing most to the uncertainty in dose for the 131I air-deposition-vegetation-milk-human-thyroid pathway are the deposition velocity for elemental iodine, the mass interception factor for pasture vegetation, the milk transfer coefficient, and the thyroid dose conversion factor. In none of our previous investigations has the consumption of fruits, vegetables, and grains been the dominant contributor to the thyroid dose (or the uncertainty in dose) when the individual also was engaged in the consumption of even moderate quantities of fresh milk. The results of the relative contribution of uncertain input parameters to the overall uncertainty in exposure are counterintuitive. We suspect that calculational errors may have occurred in their application of the software that was used to estimate the relative sensitivity for each uncertain input variable. Their claim that the milk transfer coefficient contributed only 4% to the total uncertainty in the aggregated transfer from release to dose, and that the uncertainty in the vegetation interception fraction contributed only 3.3%, despite relatively large uncertainties assigned to both of these variables, violates our sense of face validity.« less
Carvalho, Vitor Oliveira; Guimarães, Guilherme Veiga; Bocchi, Edimar Alcides
2008-01-01
BACKGROUND The relationship between the percentage of oxygen consumption reserve and percentage of heart rate reserve in heart failure patients either on non-optimized or off beta-blocker therapy is known to be unreliable. The aim of this study was to evaluate the relationship between the percentage of oxygen consumption reserve and percentage of heart rate reserve in heart failure patients receiving optimized and non-optimized beta-blocker treatment during a treadmill cardiopulmonary exercise test. METHODS A total of 27 sedentary heart failure patients (86% male, 50±12 years) on optimized beta-blocker therapy with a left ventricle ejection fraction of 33±8% and 35 sedentary non-optimized heart failure patients (75% male, 47±10 years) with a left ventricle ejection fraction of 30±10% underwent the treadmill cardiopulmonary exercise test (Naughton protocol). Resting and peak effort values of both the percentage of oxygen consumption reserve and percentage of heart rate reserve were, by definition, 0 and 100, respectively. RESULTS The heart rate slope for the non-optimized group was derived from the points 0.949±0.088 (0 intercept) and 1.055±0.128 (1 intercept), p<0.0001. The heart rate slope for the optimized group was derived from the points 1.026±0.108 (0 intercept) and 1.012±0.108 (1 intercept), p=0.47. Regression linear plots for the heart rate slope for each patient in the non-optimized and optimized groups revealed a slope of 0.986 (almost perfect) for the optimized group, but the regression analysis for the non-optimized group was 0.030 (far from perfect, which occurs at 1). CONCLUSION The relationship between the percentage of oxygen consumption reserve and percentage of heart rate reserve in patients on optimized beta-blocker therapy was reliable, but this relationship was unreliable in non-optimized heart failure patients. PMID:19060991
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chi, Y; Li, Y; Tian, Z
2015-06-15
Purpose: Pencil-beam or superposition-convolution type dose calculation algorithms are routinely used in inverse plan optimization for intensity modulated radiation therapy (IMRT). However, due to their limited accuracy in some challenging cases, e.g. lung, the resulting dose may lose its optimality after being recomputed using an accurate algorithm, e.g. Monte Carlo (MC). It is the objective of this study to evaluate the feasibility and advantages of a new method to include MC in the treatment planning process. Methods: We developed a scheme to iteratively perform MC-based beamlet dose calculations and plan optimization. In the MC stage, a GPU-based dose engine wasmore » used and the particle number sampled from a beamlet was proportional to its optimized fluence from the previous step. We tested this scheme in four lung cancer IMRT cases. For each case, the original plan dose, plan dose re-computed by MC, and dose optimized by our scheme were obtained. Clinically relevant dosimetric quantities in these three plans were compared. Results: Although the original plan achieved a satisfactory PDV dose coverage, after re-computing doses using MC method, it was found that the PTV D95% were reduced by 4.60%–6.67%. After re-optimizing these cases with our scheme, the PTV coverage was improved to the same level as in the original plan, while the critical OAR coverages were maintained to clinically acceptable levels. Regarding the computation time, it took on average 144 sec per case using only one GPU card, including both MC-based beamlet dose calculation and treatment plan optimization. Conclusion: The achieved dosimetric gains and high computational efficiency indicate the feasibility and advantages of the proposed MC-based IMRT optimization method. Comprehensive validations in more patient cases are in progress.« less
SU-E-T-503: IMRT Optimization Using Monte Carlo Dose Engine: The Effect of Statistical Uncertainty.
Tian, Z; Jia, X; Graves, Y; Uribe-Sanchez, A; Jiang, S
2012-06-01
With the development of ultra-fast GPU-based Monte Carlo (MC) dose engine, it becomes clinically realistic to compute the dose-deposition coefficients (DDC) for IMRT optimization using MC simulation. However, it is still time-consuming if we want to compute DDC with small statistical uncertainty. This work studies the effects of the statistical error in DDC matrix on IMRT optimization. The MC-computed DDC matrices are simulated here by adding statistical uncertainties at a desired level to the ones generated with a finite-size pencil beam algorithm. A statistical uncertainty model for MC dose calculation is employed. We adopt a penalty-based quadratic optimization model and gradient descent method to optimize fluence map and then recalculate the corresponding actual dose distribution using the noise-free DDC matrix. The impacts of DDC noise are assessed in terms of the deviation of the resulted dose distributions. We have also used a stochastic perturbation theory to theoretically estimate the statistical errors of dose distributions on a simplified optimization model. A head-and-neck case is used to investigate the perturbation to IMRT plan due to MC's statistical uncertainty. The relative errors of the final dose distributions of the optimized IMRT are found to be much smaller than those in the DDC matrix, which is consistent with our theoretical estimation. When history number is decreased from 108 to 106, the dose-volume-histograms are still very similar to the error-free DVHs while the error in DDC is about 3.8%. The results illustrate that the statistical errors in the DDC matrix have a relatively small effect on IMRT optimization in dose domain. This indicates we can use relatively small number of histories to obtain the DDC matrix with MC simulation within a reasonable amount of time, without considerably compromising the accuracy of the optimized treatment plan. This work is supported by Varian Medical Systems through a Master Research Agreement. © 2012 American Association of Physicists in Medicine.
Human exposure and dose models often require a quantification of oxygen consumption for a simulated individual. Oxygen consumption is dependent on the modeled Individual's physical activity level as described in an activity diary. Activity level is quantified via standardized val...
4D Optimization of Scanned Ion Beam Tracking Therapy for Moving Tumors
Eley, John Gordon; Newhauser, Wayne David; Lüchtenborg, Robert; Graeff, Christian; Bert, Christoph
2014-01-01
Motion mitigation strategies are needed to fully realize the theoretical advantages of scanned ion beam therapy for patients with moving tumors. The purpose of this study was to determine whether a new four-dimensional (4D) optimization approach for scanned-ion-beam tracking could reduce dose to avoidance volumes near a moving target while maintaining target dose coverage, compared to an existing 3D-optimized beam tracking approach. We tested these approaches computationally using a simple 4D geometrical phantom and a complex anatomic phantom, that is, a 4D computed tomogram of the thorax of a lung cancer patient. We also validated our findings using measurements of carbon-ion beams with a motorized film phantom. Relative to 3D-optimized beam tracking, 4D-optimized beam tracking reduced the maximum predicted dose to avoidance volumes by 53% in the simple phantom and by 13% in the thorax phantom. 4D-optimized beam tracking provided similar target dose homogeneity in the simple phantom (standard deviation of target dose was 0.4% versus 0.3%) and dramatically superior homogeneity in the thorax phantom (D5-D95 was 1.9% versus 38.7%). Measurements demonstrated that delivery of 4D-optimized beam tracking was technically feasible and confirmed a 42% decrease in maximum film exposure in the avoidance region compared with 3D-optimized beam tracking. In conclusion, we found that 4D-optimized beam tracking can reduce the maximum dose to avoidance volumes near a moving target while maintaining target dose coverage, compared with 3D-optimized beam tracking. PMID:24889215
4D optimization of scanned ion beam tracking therapy for moving tumors
NASA Astrophysics Data System (ADS)
Eley, John Gordon; Newhauser, Wayne David; Lüchtenborg, Robert; Graeff, Christian; Bert, Christoph
2014-07-01
Motion mitigation strategies are needed to fully realize the theoretical advantages of scanned ion beam therapy for patients with moving tumors. The purpose of this study was to determine whether a new four-dimensional (4D) optimization approach for scanned-ion-beam tracking could reduce dose to avoidance volumes near a moving target while maintaining target dose coverage, compared to an existing 3D-optimized beam tracking approach. We tested these approaches computationally using a simple 4D geometrical phantom and a complex anatomic phantom, that is, a 4D computed tomogram of the thorax of a lung cancer patient. We also validated our findings using measurements of carbon-ion beams with a motorized film phantom. Relative to 3D-optimized beam tracking, 4D-optimized beam tracking reduced the maximum predicted dose to avoidance volumes by 53% in the simple phantom and by 13% in the thorax phantom. 4D-optimized beam tracking provided similar target dose homogeneity in the simple phantom (standard deviation of target dose was 0.4% versus 0.3%) and dramatically superior homogeneity in the thorax phantom (D5-D95 was 1.9% versus 38.7%). Measurements demonstrated that delivery of 4D-optimized beam tracking was technically feasible and confirmed a 42% decrease in maximum film exposure in the avoidance region compared with 3D-optimized beam tracking. In conclusion, we found that 4D-optimized beam tracking can reduce the maximum dose to avoidance volumes near a moving target while maintaining target dose coverage, compared with 3D-optimized beam tracking.
Hard beta and gamma emissions of 124I. Impact on occupational dose in PET/CT.
Kemerink, G J; Franssen, R; Visser, M G W; Urbach, C J A; Halders, S G E A; Frantzen, M J; Brans, B; Teule, G J J; Mottaghy, F M
2011-01-01
The hard beta and gamma radiation of 124I can cause high doses to PET/CT workers. In this study we tried to quantify this occupational exposure and to optimize radioprotection. Thin MCP-Ns thermoluminescent dosimeters suitable for measuring beta and gamma radiation were used for extremity dosimetry, active personal dosimeters for whole-body dosimetry. Extremity doses were determined during dispensing of 124I and oral administration of the activity to the patient, the body dose during all phases of the PET/CT procedure. In addition, dose rates of vials and syringes as used in clinical practice were measured. The procedure for dispensing 124I was optimized using newly developed shielding. Skin dose rates up to 100 mSv/min were measured when in contact with the manufacturer's vial containing 370 MBq of 124I. For an unshielded 5 ml syringe the positron skin dose was about seven times the gamma dose. Before optimization of the preparation of 124I, using an already reasonably safe technique, the highest mean skin dose caused by handling 370 MBq was 1.9 mSv (max. 4.4 mSv). After optimization the skin dose was below 0.2 mSv. The highly energetic positrons emitted by 124I can cause high skin doses if radioprotection is poor. Under optimized conditions occupational doses are acceptable. Education of workers is of paramount importance.
Optimization of equivalent uniform dose using the L-curve criterion.
Chvetsov, Alexei V; Dempsey, James F; Palta, Jatinder R
2007-10-07
Optimization of equivalent uniform dose (EUD) in inverse planning for intensity-modulated radiation therapy (IMRT) prevents variation in radiobiological effect between different radiotherapy treatment plans, which is due to variation in the pattern of dose nonuniformity. For instance, the survival fraction of clonogens would be consistent with the prescription when the optimized EUD is equal to the prescribed EUD. One of the problems in the practical implementation of this approach is that the spatial dose distribution in EUD-based inverse planning would be underdetermined because an unlimited number of nonuniform dose distributions can be computed for a prescribed value of EUD. Together with ill-posedness of the underlying integral equation, this may significantly increase the dose nonuniformity. To optimize EUD and keep dose nonuniformity within reasonable limits, we implemented into an EUD-based objective function an additional criterion which ensures the smoothness of beam intensity functions. This approach is similar to the variational regularization technique which was previously studied for the dose-based least-squares optimization. We show that the variational regularization together with the L-curve criterion for the regularization parameter can significantly reduce dose nonuniformity in EUD-based inverse planning.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wan Chan Tseung, H; Ma, J; Ma, D
2015-06-15
Purpose: To demonstrate the feasibility of fast Monte Carlo (MC) based biological planning for the treatment of thyroid tumors in spot-scanning proton therapy. Methods: Recently, we developed a fast and accurate GPU-based MC simulation of proton transport that was benchmarked against Geant4.9.6 and used as the dose calculation engine in a clinically-applicable GPU-accelerated IMPT optimizer. Besides dose, it can simultaneously score the dose-averaged LET (LETd), which makes fast biological dose (BD) estimates possible. To convert from LETd to BD, we used a linear relation based on cellular irradiation data. Given a thyroid patient with a 93cc tumor volume, we createdmore » a 2-field IMPT plan in Eclipse (Varian Medical Systems). This plan was re-calculated with our MC to obtain the BD distribution. A second 5-field plan was made with our in-house optimizer, using pre-generated MC dose and LETd maps. Constraints were placed to maintain the target dose to within 25% of the prescription, while maximizing the BD. The plan optimization and calculation of dose and LETd maps were performed on a GPU cluster. The conventional IMPT and biologically-optimized plans were compared. Results: The mean target physical and biological doses from our biologically-optimized plan were, respectively, 5% and 14% higher than those from the MC re-calculation of the IMPT plan. Dose sparing to critical structures in our plan was also improved. The biological optimization, including the initial dose and LETd map calculations, can be completed in a clinically viable time (∼30 minutes) on a cluster of 25 GPUs. Conclusion: Taking advantage of GPU acceleration, we created a MC-based, biologically optimized treatment plan for a thyroid patient. Compared to a standard IMPT plan, a 5% increase in the target’s physical dose resulted in ∼3 times as much increase in the BD. Biological planning was thus effective in escalating the target BD.« less
Eilat-Adar, Sigal; Lipovetzky, Nestor; Goldbourt, Uri; Henkin, Yaakov
2004-08-01
Evidence from epidemiological and randomized controlled trials shows beneficial effects of omega-3 (n-3) fatty acids from fish and plant sources on cardiovascular disease (CVD), especially in patients with preexisting CVD. The optimal dose of n-3 is not yet determined, but prospective secondary prevention studies suggest that the addition of 0.5-1.8 grams/day of marine-derived eicosapentaenoic acid and docosahexaenoic acid, or plant derived alpha-linolenic acid at a dose of 1.5-3 grams/day significantly reduce subsequent cardiac events and mortality. These data have led the American Heart Association Dietary Guidelines committee to recommend to the general population the consumption of at least two servings of fatty fish per week, in addition to vegetable oils high in alpha-linolenic acid. The risk of adverse effects and toxicity from contaminants at this dose is low. The amount of daily n-3 fatty acids recommended for patients with coronary heart disease is 1 gram/day. In patients who cannot consume this dose of n-3 fatty acids through diet alone, addition of n-3 supplements should be considered. Higher doses of contaminant-free n-3 supplements, 2-4 grams/day, can be used in the treatment of hypertriglyceridemia. Data on the content of n-3 fatty acids and contaminants in Israeli bred fish is limited. Thus, caution should be exercised when applying these recommendations to the Israeli fish market.
NASA Astrophysics Data System (ADS)
Kunz, A.; Pihet, P.; Arend, E.; Menzel, H. G.
1990-12-01
A portable area monitor for the measurement of dose-equivalent quantities in practical radiation-protection work has been developed. The detector applied is a low-pressure proportional counter (TEPC) used in microdosimetry. The complex analysis system required has been optimized with regard to low power consumption and small size to achieve a real operational survey meter. The newly designed electronic includes complete analog, digital and microprocessor boards. It presents the characteristic of fast pulse-height processing over a large (5 decades) dynamic range. Three original circuits have been specifically developed, consisting of: (1) a miniaturized adjustable high-voltage power supply with low ripple and high stability; (2) a double spectroscopy amplifier with constant gain ratio and common pole-zero stage; and (3) an analog-to-digital converter with quasi-logarithmic characteristics based on a flash converter using fast comparators associated in parallel. With the incorporated single-board computer, the maximal total power consumption is 5 W, enabling 40 hours operation time with batteries. With minor adaptations the equipment is proposed as a low-cost solution for various measuring problems in environmental studies.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jannik, G. T.; Dixon, K. L.
This report presents the environmental dose assessment methods and the estimated potential doses to the offsite public from 2015 Savannah River Site (SRS) atmospheric and liquid radioactive releases. Also documented are potential doses from special-case exposure scenarios - such as the consumption of deer meat, fish, and goat milk.
Savun-Hekimoğlu, Başak; Ince, Nilsun H
2017-11-01
The study is about the degradation of a widely used pharmaceutical and personal care product-salicylic acid by sonocatalysis, and the experimental design of the reaction system. The first part of the study consists of sonication (572kHz) in the presence of zero-valent iron (ZVI) with or without H 2 O 2 to select and optimize the operational parameters as frequency, time, initial solute concentration, dose of reagents and pH. The second part consists of the use of response surface methodology and multiple regression to develop an experimental design modeland to assess the individual and interactive effects of pH, power (P o ), ZVI dose and H 2 O 2 . The results showed that the optimal conditions predicted by the model without defining any restrictions are: pH=2.0, P o =120W, ZVI=24mgL -1 , which provide total salicyclic acid and 48% TOC decay. However, the prediction implies intensive consumption of energy and reagents, and must therefore be modified by restricting the value of TOC decay to a lower value and that of pH to a higher one. Cross-validation tests showed that the prediction accuracy of the model was considerably high with 5.0-9.4% deviation from the experimental data. Copyright © 2017 Elsevier B.V. All rights reserved.
Savun-Hekimoğlu, Başak; Ince, Nilsun H
2018-01-01
The study is about the degradation of a widely used pharmaceutical and personal care product-salicylic acid by sonocatalysis, and the experimental design of the reaction system. The first part of the study consists of sonication (572kHz) in the presence of zero-valent iron (ZVI) with or without H 2 O 2 to select and optimize the operational parameters as frequency, time, initial solute concentration, dose of reagents and pH. The second part consists of the use of response surface methodology and multiple regression to develop an experimental design modeland to assess the individual and interactive effects of pH, power (P o ), ZVI dose and H 2 O 2 . The results showed that the optimal conditions predicted by the model without defining any restrictions are: pH=2.0, P o =120W, ZVI=24mgL -1 , which provide total salicyclic acid and 48% TOC decay. However, the prediction implies intensive consumption of energy and reagents, and must therefore be modified by restricting the value of TOC decay to a lower value and that of pH to a higher one. Cross-validation tests showed that the prediction accuracy of the model was considerably high with 5.0-9.4% deviation from the experimental data. Copyright © 2017. Published by Elsevier B.V.
Wiczkowski, Wieslaw; Romaszko, Ewa; Piskula, Mariusz K
2010-12-08
The aim of this study was to investigate the bioavailability of anthocyanins from chokeberry juice with a dietary-relevant dose of anthocyanins. Thirteen healthy volunteers consumed chokeberry juice providing 0.8 mg of anthocyanins/kg of body weight. Before and after juice consumption, blood and urine were collected. Concentration of anthocyanins was measured with HPLC-PDA-MS-ESI. Cyanidin-3-galactoside comprised 66% of total chokeberry anthocyanins. Eight cyanidin derivatives were found in blood and urine after juice consumption. The maximum plasma anthocyanin concentration of 32.7 ± 2.9 nmol/L was reached at 1.3 ± 0.1 h after juice consumption. The anthocyanins' urine excretion rate (62.9 ± 5.0 nmol/h) was the highest within the first 2 h. In total, 0.25 ± 0.02% of the ingested anthocyanins was excreted by the renal route during 24 h, mainly as metabolites of cyanidin. According to these observations, after consumption of a dietary-relevant dose of anthocyanins as natural chokeberry juice, anthocyanins and their metabolites were present in plasma and urine of volunteers.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bender, Edward T.
Purpose: To develop a robust method for deriving dose-painting prescription functions using spatial information about the risk for disease recurrence. Methods: Spatial distributions of radiobiological model parameters are derived from distributions of recurrence risk after uniform irradiation. These model parameters are then used to derive optimal dose-painting prescription functions given a constant mean biologically effective dose. Results: An estimate for the optimal dose distribution can be derived based on spatial information about recurrence risk. Dose painting based on imaging markers that are moderately or poorly correlated with recurrence risk are predicted to potentially result in inferior disease control when comparedmore » the same mean biologically effective dose delivered uniformly. A robust optimization approach may partially mitigate this issue. Conclusions: The methods described here can be used to derive an estimate for a robust, patient-specific prescription function for use in dose painting. Two approximate scaling relationships were observed: First, the optimal choice for the maximum dose differential when using either a linear or two-compartment prescription function is proportional to R, where R is the Pearson correlation coefficient between a given imaging marker and recurrence risk after uniform irradiation. Second, the predicted maximum possible gain in tumor control probability for any robust optimization technique is nearly proportional to the square of R.« less
Egner, Patricia A.; Chen, Jian Guo; Wang, Jin Bing; Wu, Yan; Sun, Yan; Lu, Jian Hua; Zhu, Jian; Zhang, Yong Hui; Chen, Yong Sheng; Friesen, Marlin D.; Jacobson, Lisa P.; Muñoz, Alvaro; Ng, Derek; Qian, Geng Sun; Zhu, Yuan Rong; Chen, Tao Yang; Botting, Nigel P.; Zhang, Qingzhi; Fahey, Jed W.; Talalay, Paul; Groopman, John D; Kensler, Thomas W.
2011-01-01
One of several challenges in design of clinical chemoprevention trials is the selection of the dose, formulation and dose schedule of the intervention agent. Therefore, a cross-over clinical trial was undertaken to compare the bioavailability and tolerability of sulforaphane from two of broccoli sprout-derived beverages: one glucoraphanin-rich (GRR) and the other sulforaphane-rich (SFR). Sulforaphane was generated from glucoraphanin contained in GRR by gut microflora or formed by treatment of GRR with myrosinase from daikon (Raphanus sativus) sprouts to provide SFR. Fifty healthy, eligible participants were requested to refrain from crucifer consumption and randomized into two treatment arms. The study design was as follows: 5-day run-in period, 7-day administration of beverages, 5-day washout period, and 7-day administration of the opposite intervention. Isotope dilution mass spectrometry was used to measure levels of glucoraphanin, sulforaphane and sulforaphane thiol conjugates in urine samples collected daily throughout the study. Bioavailability, as measured by urinary excretion of sulforaphane and its metabolites (in approximately 12 hour collections after dosing), was substantially greater with the SFR (mean = 70%) than with GRR (mean = 5%) beverages. Interindividual variability in excretion was considerably lower with SFR than GRR beverage. Elimination rates were considerably slower with GRR allowing for achievement of steady state dosing as opposed to bolus dosing with SFR. Optimal dosing formulations in future studies should consider blends of sulforaphane and glucoraphanin as SFR and GRR mixtures to achieve peak concentrations for activation of some targets and prolonged inhibition of others implicated in the protective actions of sulforaphane. PMID:21372038
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Heng, E-mail: hengli@mdanderson.org; Zhu, X. Ronald; Zhang, Xiaodong
Purpose: To develop and validate a novel delivery strategy for reducing the respiratory motion–induced dose uncertainty of spot-scanning proton therapy. Methods and Materials: The spot delivery sequence was optimized to reduce dose uncertainty. The effectiveness of the delivery sequence optimization was evaluated using measurements and patient simulation. One hundred ninety-one 2-dimensional measurements using different delivery sequences of a single-layer uniform pattern were obtained with a detector array on a 1-dimensional moving platform. Intensity modulated proton therapy plans were generated for 10 lung cancer patients, and dose uncertainties for different delivery sequences were evaluated by simulation. Results: Without delivery sequence optimization,more » the maximum absolute dose error can be up to 97.2% in a single measurement, whereas the optimized delivery sequence results in a maximum absolute dose error of ≤11.8%. In patient simulation, the optimized delivery sequence reduces the mean of fractional maximum absolute dose error compared with the regular delivery sequence by 3.3% to 10.6% (32.5-68.0% relative reduction) for different patients. Conclusions: Optimizing the delivery sequence can reduce dose uncertainty due to respiratory motion in spot-scanning proton therapy, assuming the 4-dimensional CT is a true representation of the patients' breathing patterns.« less
Robust optimization in lung treatment plans accounting for geometric uncertainty.
Zhang, Xin; Rong, Yi; Morrill, Steven; Fang, Jian; Narayanasamy, Ganesh; Galhardo, Edvaldo; Maraboyina, Sanjay; Croft, Christopher; Xia, Fen; Penagaricano, Jose
2018-05-01
Robust optimization generates scenario-based plans by a minimax optimization method to find optimal scenario for the trade-off between target coverage robustness and organ-at-risk (OAR) sparing. In this study, 20 lung cancer patients with tumors located at various anatomical regions within the lungs were selected and robust optimization photon treatment plans including intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) plans were generated. The plan robustness was analyzed using perturbed doses with setup error boundary of ±3 mm in anterior/posterior (AP), ±3 mm in left/right (LR), and ±5 mm in inferior/superior (IS) directions from isocenter. Perturbed doses for D 99 , D 98 , and D 95 were computed from six shifted isocenter plans to evaluate plan robustness. Dosimetric study was performed to compare the internal target volume-based robust optimization plans (ITV-IMRT and ITV-VMAT) and conventional PTV margin-based plans (PTV-IMRT and PTV-VMAT). The dosimetric comparison parameters were: ITV target mean dose (D mean ), R 95 (D 95 /D prescription ), Paddick's conformity index (CI), homogeneity index (HI), monitor unit (MU), and OAR doses including lung (D mean , V 20 Gy and V 15 Gy ), chest wall, heart, esophagus, and maximum cord doses. A comparison of optimization results showed the robust optimization plan had better ITV dose coverage, better CI, worse HI, and lower OAR doses than conventional PTV margin-based plans. Plan robustness evaluation showed that the perturbed doses of D 99 , D 98 , and D 95 were all satisfied at least 99% of the ITV to received 95% of prescription doses. It was also observed that PTV margin-based plans had higher MU than robust optimization plans. The results also showed robust optimization can generate plans that offer increased OAR sparing, especially for normal lungs and OARs near or abutting the target. Weak correlation was found between normal lung dose and target size, and no other correlation was observed in this study. © 2018 University of Arkansas for Medical Sciences. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.
Effects of caffeine on mood and performance: a study of realistic consumption.
Brice, Carolyn F; Smith, Andrew P
2002-11-01
There is a vast literature on the behavioural effects of caffeine. Many of the studies have involved single administration of a large dose of caffeine that is not representative of the way in which caffeine is usually ingested. Further information is required, therefore, on the behavioural effects of realistic patterns of consumption. The present study aimed to determine whether a realistic drinking regime (multiple small doses - 4 x 65 mg over a 5-h period) produced the same effects as a single large dose (200 mg). The smaller doses were selected so that the amount of caffeine present in the body after 5 h would be equivalent to that found with the single dose. A double-blind, placebo-controlled, within-subjects experiment was, therefore, carried out. The participants ( n=24) attended for four sessions. Each session started with a baseline measurement of mood and performance at 0930 hours. On two of the sessions, coffee was then consumed at 1000, 1100, 1200 and 1300 hours. In one of these sessions 65 mg caffeine was added to the de-caffeinated coffee. In the other two sessions, the participants consumed coffee at 1300 hours and 200 mg caffeine was added in one of the sessions. The volunteers completed the battery of tests again at 1500 hours. The results showed that in both consumption regimes caffeine led to increased alertness and anxiety and improved performance on simple and choice reactive tasks, a cognitive vigilance task, a task requiring sustained response and a dual task involving tracking and target detection. These results suggest that previous findings from studies using a large single dose may be applicable to normal patterns of caffeine consumption.
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
Cai, Hongliang; Sun, Lei; Miao, John; Krishman, Suma; Lebel, Francois; Barrett, John A
2017-05-01
Major obstacles to developing effective immunotherapy are the ability of tumors to escape the immune system and the toxicity associated with systemic administration. To overcome these challenges, a gene delivery platform technology, RheoSwitch Therapeutic System (RTS), has been developed to enable the regulated expression of a target gene, Ad-RTS-IL-12, administered intratumorally, where IL-12 expression is controlled via the administration of an oral activator ligand, veledimex. Pharmacokinetics in healthy human subjects indicated that veledimex plasma exposure increased with increasing dose after single- and multiple-dose administration in Labrasol slurry and F-22 capsule formulations. No apparent formulation or sex-related difference in veledimex pharmacokinetics (PK) was observed. Minimal or no plasma accumulation of veledimex was observed after once-daily oral administration for 14 days. Veledimex steady state in plasma was reached after 5 daily doses. Food consumption prior to veledimex administration prolonged and enhanced absorption with no impact on the elimination rate and extent of metabolism of veledimex, resulting in significantly increased systemic exposure to veledimex and its 2 major circulating metabolites. Overall, veledimex was well tolerated and exhibited a PK profile supportive of once-daily dosing. For enhanced efficacy, veledimex should be taken under fed conditions to ensure optimal absorption and sufficient systemic exposure. © 2016, The American College of Clinical Pharmacology.
Godos, Justyna; Micek, Agnieszka; Marranzano, Marina; Salomone, Federico; Rio, Daniele Del; Ray, Sumantra
2017-08-28
A meta-analysis was conducted to summarize the evidence from prospective cohort and case-control studies regarding the association between coffee intake and biliary tract cancer (BTC) and liver cancer risk. Eligible studies were identified by searches of PubMed and EMBASE databases from the earliest available online indexing year to March 2017. The dose-response relationship was assessed by a restricted cubic spline model and multivariate random-effect meta-regression. A stratified and subgroup analysis by smoking status and hepatitis was performed to identify potential confounding factors. We identified five studies on BTC risk and 13 on liver cancer risk eligible for meta-analysis. A linear dose-response meta-analysis did not show a significant association between coffee consumption and BTC risk. However, there was evidence of inverse correlation between coffee consumption and liver cancer risk. The association was consistent throughout the various potential confounding factors explored including smoking status, hepatitis, etc. Increasing coffee consumption by one cup per day was associated with a 15% reduction in liver cancer risk (RR 0.85; 95% CI 0.82 to 0.88). The findings suggest that increased coffee consumption is associated with decreased risk of liver cancer, but not BTC.
Ahmad, Nur Syamsina; Abdul Aziz, Azlina; Kong, Kin Weng; Hamid, Mohamad Shariff A; Cheong, Jadeera Phaik Geok; Hamzah, Sareena Hanim
2017-12-01
Tualang honey (TH) contains antioxidants such as ascorbic acid, phenolic acids, and flavonoids that may be protective against oxidative stress of exercise. The aim of this study was to examine the postprandial antioxidant activity and oxidative stress after ingestion of high and low dosages of TH in female athletes. Twenty female athletes (aged 21.3 [2.1] years; body weight [BW] 54.1 [5.7] kg) were randomly assigned into two groups and consumed either 1.5 g/kg BW TH (high honey; HH; n = 10) or 0.75 g/kg BW TH (low honey; LH; n = 10). Blood sample was collected at fasting and at 0.5, 1, 2, and 3 h after TH consumption. Plasma was analyzed for total phenolic content (TPC), antioxidant activity (ferric reducing antioxidant power [FRAP]), and oxidative stress biomarkers (malondialdehyde [MDA] and reactive oxygen species [ROS]). The 3-h area under the curve (AUC) for MDA was significantly lower in the LH group compared with HH group, suggesting less oxidative stress in the LH group. However, the AUCs for TPC, FRAP, and ROS were not affected by the dosages. The concentrations of TPC and FRAP increased from baseline to 2 and 1 h after TH consumption, respectively, and concentrations returned toward baseline at 3 h in both LH and HH groups. MDA concentration significantly decreased (p < 0.05) from baseline to 2 h and significantly increased from 2 to 3 h in the HH group. Meanwhile, ROS levels increased significantly from 0.5 to 3 h in the HH group. The LH group showed similar trends as the HH group for MDA and ROS; however, this was not significant. The consumption of high and low doses of TH demonstrated a comparable response in increasing antioxidant activity and suppressing oxidative stress in female athletes. The time-course effect of TH that provides optimal antioxidant activity and oxidative stress protection was between 1 and 2 h after its consumption.
DOE Office of Scientific and Technical Information (OSTI.GOV)
McGeachy, P; Villarreal-Barajas, JE; Khan, R
2015-06-15
Purpose: The dosimetric outcome of optimized treatment plans obtained by modulating the photon beamlet energy and fluence on a small cohort of four Head and Neck (H and N) patients was investigated. This novel optimization technique is denoted XMRT for modulated photon radiotherapy. The dosimetric plans from XMRT for H and N treatment were compared to conventional, 6 MV intensity modulated radiotherapy (IMRT) optimization plans. Methods: An arrangement of two non-coplanar and five coplanar beams was used for all four H and N patients. Both XMRT and IMRT were subject to the same optimization algorithm, with XMRT optimization allowing bothmore » 6 and 18 MV beamlets while IMRT was restricted to 6 MV only. The optimization algorithm was based on a linear programming approach with partial-volume constraints implemented via the conditional value-at-risk method. H and N constraints were based off of those mentioned in the Radiation Therapy Oncology Group 1016 protocol. XMRT and IMRT solutions were assessed using metrics suggested by International Commission on Radiation Units and Measurements report 83. The Gurobi solver was used in conjunction with the CVX package to solve each optimization problem. Dose calculations and analysis were done in CERR using Monte Carlo dose calculation with VMC{sub ++}. Results: Both XMRT and IMRT solutions met all clinical criteria. Trade-offs were observed between improved dose uniformity to the primary target volume (PTV1) and increased dose to some of the surrounding healthy organs for XMRT compared to IMRT. On average, IMRT improved dose to the contralateral parotid gland and spinal cord while XMRT improved dose to the brainstem and mandible. Conclusion: Bi-energy XMRT optimization for H and N patients provides benefits in terms of improved dose uniformity to the primary target and reduced dose to some healthy structures, at the expense of increased dose to other healthy structures when compared with IMRT.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stewart, J; Lindsay, P; University of Toronto, Toronto
Purpose: Recent progress in small animal radiotherapy systems has provided the foundation for delivering the heterogeneous, millimeter scale dose distributions demanded by preclinical radiobiology investigations. Despite advances in preclinical dose planning, delivery of highly heterogeneous dose distributions is constrained by the fixed collimation systems and large x-ray focal spot common in small animal radiotherapy systems. This work proposes a dual focal spot dose optimization and delivery method with a large x-ray focal spot used to deliver homogeneous dose regions and a small focal spot to paint spatially heterogeneous dose regions. Methods: Two-dimensional dose kernels were measured for a 1 mmmore » circular collimator with radiochromic film at 10 mm depth in a solid water phantom for the small and large x-ray focal spots on a recently developed small animal microirradiator. These kernels were used in an optimization framework which segmented a desired dose distribution into low- and high-spatial frequency regions for delivery by the large and small focal spot, respectively. For each region, the method determined an optimal set of stage positions and beam-on times. The method was demonstrated by optimizing a bullseye pattern consisting of 0.75 mm radius circular target and 0.5 and 1.0 mm wide rings alternating between 0 and 2 Gy. Results: Compared to a large focal spot technique, the dual focal spot technique improved the optimized dose distribution: 69.2% of the optimized dose was within 0.5 Gy of the intended dose for the large focal spot, compared to 80.6% for the dual focal spot method. The dual focal spot design required 14.0 minutes of optimization, and will require 178.3 minutes for automated delivery. Conclusion: The dual focal spot optimization and delivery framework is a novel option for delivering conformal and heterogeneous dose distributions at the preclinical level and provides a new experimental option for unique radiobiological investigations. Funding Support: this work is supported by funding the National Sciences and Engineering Research Council of Canada, and a Mitacs-accelerate fellowship. Conflict of Interest: Dr. Lindsay and Dr. Jaffray are listed as inventors of the small animal microirradiator described herein. This system has been licensed for commercial development.« less
Impact of a phenytoin loading dose program in the emergency department.
Brancaccio, Adam; Giuliano, Christopher; McNorton, Kelly; Delgado, George
2014-11-01
The use of a combined physician-and pharmacist-directed phenytoin loading dose program in an emergency department (ED) was evaluated. This single-center, observational, preimplementation-postimplementation study evaluated adult patients who received a phenytoin loading dose in the ED. The primary outcome compared the proportion of optimal phenytoin loading doses in the preimplementation and postimplementation groups. The postimplementation group was further stratified into pharmacist- and prescriber-dosing groups. Other outcomes evaluated included the numbers of appropriate serum phenytoin concentrations measured, adverse drug reactions (ADRs), and recurrence of seizures within 24 hours of loading dose administration in the preimplementation and postimplementation groups. There was no difference in the proportion of optimal phenytoin loading doses between the preimplementation and postimplementation groups (50% versus 62%, respectively; p=0.19). When stratified by individual groups, the rate of optimal phenytoin loading doses increased by 64% in the postimplementation pharmacist group (50% versus 82%, p=0.007), while the rate in the prescriber-dosing group remained relatively unchanged (50% versus 49%, p=0.91). The number of appropriate serum phenytoin concentrations significantly improved in the postimplementation versus preimplementation group (65% versus 40%, p=0.025). Rates of ADRs and recurrence of seizures did not differ across the study groups. No change in the percentage of optimal phenytoin loading doses in the ED was observed after implementation of a combined pharmacist- and physician- dosing program. When stratified into pharmacist or prescriber dosing, the pharmacist-led dosing program significantly improved the proportion of patients who received optimal phenytoin loading doses. Copyright © 2014 by the American Society of Health-System Pharmacists, Inc. All rights reserved.
Wen, Z G; Jiang, Y; Tang, J; Xie, M; Yang, P L; Hou, S S
2016-09-01
In order to avoid excess feed consumption during the force-feeding period in foie gras production, a dose-response experiment with seven feed consumption levels (450, 540, 630, 720, 810, 900, 990 g/day per bird) was conducted to evaluate the effects of feed consumption levels on growth performance and carcass composition of male Mule ducks from 91 to 102 days of age. One-day-old Mule ducklings (sterile and artificial hybrid of male Albatre Muscovy duck and female Pekin duck were fed a two-phase commercial diets for ad libitum intake from hatching to 91 days of age, followed by graded feeding levels of a corn diet by force-feeding from 91 to 102 days of age. Fifty-six 91-day-old male Mule ducks with similar BW were randomly assigned to seven treatments, with eight birds per treatment. Birds were housed in individual pens. At 102 days of age, final BW was measured and BW gain and feed conversion ratio of ducks from each treatment were calculated from day 91 to 102, and then all ducks were slaughtered to evaluate the yields of skin with subcutaneous fat, abdominal fat, breast meat (including pectoralis major and pectoralis minor), leg meat (including thigh and drum stick), and liver. Significant differences in BW gain, total liver weight and liver relative weight were observed among the treatments (P<0.001). According to the broken-line regression analysis, the optimal feed consumption levels of male Mule ducks from 91 to 102 days of age for maximum BW gain, total liver weight and liver relative weight were 217, 227 and 216 g feed/kg BW0.75·per day, respectively.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Papp, D; Unkelbach, J
2014-06-01
Purpose: Non-uniform fractionation, i.e. delivering distinct dose distributions in two subsequent fractions, can potentially improve outcomes by increasing biological dose to the target without increasing dose to healthy tissues. This is possible if both fractions deliver a similar dose to normal tissues (exploit the fractionation effect) but high single fraction doses to subvolumes of the target (hypofractionation). Optimization of such treatment plans can be formulated using biological equivalent dose (BED), but leads to intractable nonconvex optimization problems. We introduce a novel optimization approach to address this challenge. Methods: We first optimize a reference IMPT plan using standard techniques that deliversmore » a homogeneous target dose in both fractions. The method then divides the pencil beams into two sets, which are assigned to either fraction one or fraction two. The total intensity of each pencil beam, and therefore the physical dose, remains unchanged compared to the reference plan. The objectives are to maximize the mean BED in the target and to minimize the mean BED in normal tissues, which is a quadratic function of the pencil beam weights. The optimal reassignment of pencil beams to one of the two fractions is formulated as a binary quadratic optimization problem. A near-optimal solution to this problem can be obtained by convex relaxation and randomized rounding. Results: The method is demonstrated for a large arteriovenous malformation (AVM) case treated in two fractions. The algorithm yields a treatment plan, which delivers a high dose to parts of the AVM in one of the fractions, but similar doses in both fractions to the normal brain tissue adjacent to the AVM. Using the approach, the mean BED in the target was increased by approximately 10% compared to what would have been possible with a uniform reference plan for the same normal tissue mean BED.« less
Obtaining the Optimal Dose in Alcohol Dependence Studies
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
Premji, Zulfiqarali G; Abdulla, Salim; Ogutu, Bernhards; Ndong, Alice; Falade, Catherine O; Sagara, Issaka; Mulure, Nathan; Nwaiwu, Obiyo; Kokwaro, Gilbert
2008-01-01
A fixed-dose combination of artemether-lumefantrine (AL, Coartem®) has shown high efficacy, good tolerability and cost-effectiveness in adults and children with uncomplicated malaria caused by Plasmodium falciparum. Lumefantrine bioavailability is enhanced by food, particularly fat. As the fat content of sub-Saharan African meals is approximately a third that of Western countries, it raises the question of whether fat consumption by African patients is sufficient for good efficacy. Data from healthy volunteers have indicated that drinking 36 mL soya milk (containing only 1.2 g of fat) results in 90% of the lumefantrine absorption obtained with 500 mL milk (16 g fat). African diets are typically based on a carbohydrate staple (starchy root vegetables, fruit [plantain] or cereals) supplemented by soups, relishes and sauces derived from vegetables, pulses, nuts or fish. The most important sources of dietary fat in African countries are oil crops (e.g. peanuts, soya beans) and cooking oils as red palm, peanut, coconut and sesame oils. Total fat intake in the majority of subSaharan countries is estimated to be in the range 30–60 g/person/day across the whole population (average 43 g/person/day). Breast-feeding of infants up to two years of age is standard, with one study estimating a fat intake of 15–30 g fat/day from breast milk up to the age of 18 months. Weaning foods typically contain low levels of fat, and the transition from breast milk to complete weaning is associated with a marked reduction in dietary fat. Nevertheless, fat intake >10 g/day has been reported in young children post-weaning. A randomized trial in Uganda reported no difference in the efficacy of AL between patients receiving supervised meals with a fixed fat content (~23 g fat) or taking AL unsupervised, suggesting that fat intake at home was sufficient for optimal efficacy. Moreover, randomized trials in African children aged 5–59 months have shown similar high cure rates to those observed in older populations, indicating that food consumption is adequate post-weaning. In conclusion, it appears that only a very small amount of dietary fat is necessary to ensure optimal efficacy with AL and that the fat content of standard meals or breast milk in sub-Saharan Africa is adequate. PMID:19032767
Yilmaz, A Erdem; Boncukcuoğlu, Recep; Kocakerim, M Muhtar
2007-06-01
In this study, it was investigated parameters affecting energy consumption in boron removal from boron containing wastewaters prepared synthetically, via electrocoagulation method. The solution pH, initial boron concentration, dose of supporting electrolyte, current density and temperature of solution were selected as experimental parameters affecting energy consumption. The obtained experimental results showed that boron removal efficiency reached up to 99% under optimum conditions, in which solution pH was 8.0, current density 6.0 mA/cm(2), initial boron concentration 100mg/L and solution temperature 293 K. The current density was an important parameter affecting energy consumption too. High current density applied to electrocoagulation cell increased energy consumption. Increasing solution temperature caused to decrease energy consumption that high temperature decreased potential applied under constant current density. That increasing initial boron concentration and dose of supporting electrolyte caused to increase specific conductivity of solution decreased energy consumption. As a result, it was seen that energy consumption for boron removal via electrocoagulation method could be minimized at optimum conditions. An empirical model was predicted by statistically. Experimentally obtained values were fitted with values predicted from empirical model being as following; [formula in text]. Unfortunately, the conditions obtained for optimum boron removal were not the conditions obtained for minimum energy consumption. It was determined that support electrolyte must be used for increase boron removal and decrease electrical energy consumption.
SU-E-T-422: Fast Analytical Beamlet Optimization for Volumetric Intensity-Modulated Arc Therapy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chan, Kenny S K; Lee, Louis K Y; Xing, L
2015-06-15
Purpose: To implement a fast optimization algorithm on CPU/GPU heterogeneous computing platform and to obtain an optimal fluence for a given target dose distribution from the pre-calculated beamlets in an analytical approach. Methods: The 2D target dose distribution was modeled as an n-dimensional vector and estimated by a linear combination of independent basis vectors. The basis set was composed of the pre-calculated beamlet dose distributions at every 6 degrees of gantry angle and the cost function was set as the magnitude square of the vector difference between the target and the estimated dose distribution. The optimal weighting of the basis,more » which corresponds to the optimal fluence, was obtained analytically by the least square method. Those basis vectors with a positive weighting were selected for entering into the next level of optimization. Totally, 7 levels of optimization were implemented in the study.Ten head-and-neck and ten prostate carcinoma cases were selected for the study and mapped to a round water phantom with a diameter of 20cm. The Matlab computation was performed in a heterogeneous programming environment with Intel i7 CPU and NVIDIA Geforce 840M GPU. Results: In all selected cases, the estimated dose distribution was in a good agreement with the given target dose distribution and their correlation coefficients were found to be in the range of 0.9992 to 0.9997. Their root-mean-square error was monotonically decreasing and converging after 7 cycles of optimization. The computation took only about 10 seconds and the optimal fluence maps at each gantry angle throughout an arc were quickly obtained. Conclusion: An analytical approach is derived for finding the optimal fluence for a given target dose distribution and a fast optimization algorithm implemented on the CPU/GPU heterogeneous computing environment greatly reduces the optimization time.« less
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 gEUD-based inverse planning technique for HDR prostate brachytherapy: Feasibility study
DOE Office of Scientific and Technical Information (OSTI.GOV)
Giantsoudi, D.; Department of Radiation Oncology, Francis H. Burr Proton Therapy Center, Boston, Massachusetts 02114; Baltas, D.
2013-04-15
Purpose: The purpose of this work was to study the feasibility of a new inverse planning technique based on the generalized equivalent uniform dose for image-guided high dose rate (HDR) prostate cancer brachytherapy in comparison to conventional dose-volume based optimization. Methods: The quality of 12 clinical HDR brachytherapy implants for prostate utilizing HIPO (Hybrid Inverse Planning Optimization) is compared with alternative plans, which were produced through inverse planning using the generalized equivalent uniform dose (gEUD). All the common dose-volume indices for the prostate and the organs at risk were considered together with radiobiological measures. The clinical effectiveness of the differentmore » dose distributions was investigated by comparing dose volume histogram and gEUD evaluators. Results: Our results demonstrate the feasibility of gEUD-based inverse planning in HDR brachytherapy implants for prostate. A statistically significant decrease in D{sub 10} or/and final gEUD values for the organs at risk (urethra, bladder, and rectum) was found while improving dose homogeneity or dose conformity of the target volume. Conclusions: Following the promising results of gEUD-based optimization in intensity modulated radiation therapy treatment optimization, as reported in the literature, the implementation of a similar model in HDR brachytherapy treatment plan optimization is suggested by this study. The potential of improved sparing of organs at risk was shown for various gEUD-based optimization parameter protocols, which indicates the ability of this method to adapt to the user's preferences.« less
Kinetic modeling and energy efficiency of UV/H₂O₂ treatment of iodinated trihalomethanes.
Xiao, Yongjun; Zhang, Lifeng; Yue, Junqi; Webster, Richard D; Lim, Teik-Thye
2015-05-15
Photodegradation of I-THMs including CHCl2I and CHI3 by the UV/H2O2 system was investigated in this study. CHCl2I and CHI3 react rapidly with hydroxyl radical (OH) produced by the UV/H2O2 system, with second-order rate constants of 8.0 × 10(9) and 8.9 × 10(9) M(-1) s(-1), respectively. A fraction of CHCl2I could be completely mineralized within 15 min and the remaining fraction was mainly converted to formic acid (HCO2H). Cl(-) and I(-) were identified as the predominant end-products. No ClO3(-) was observed during the photodegradation process, while IO3(-) was detected but at less than 2% of the total liberated iodine species at the end of the reaction. The effects of pH, H2O2 dose, and matrix species such as humic acid (HA), HCO3(-), SO4(2-), Cl(-), NO3(-) on the photodegradation kinetics were evaluated. The steady-state kinetic model has been proven to successfully predict the destruction of CHCl2I and CHI3 by UV/H2O2 in different water matrices. On this basis, the kinetic model combined with electrical energy per order (EE/O) concept was applied to evaluate the efficiency of the photodegradation process and to optimize the H2O2 dose for different scenarios. The optimal H2O2 doses in deionized (DI) water, model natural water, and surface water are estimated at 5, 12, and 16 mg L(-1), respectively, which correspond to the lowest total energy consumption (EE/Ototal) of 0.2, 0.31, and 0.45 kWhm(-3)order(-1). Copyright © 2015 Elsevier Ltd. All rights reserved.
Lupfer, Gwen; Murphy, Eric S; Merculieff, Zoe; Radcliffe, Kori; Duddleston, Khrystyne N
2015-06-01
Ethanol consumption and sensitivity in many species are influenced by the frequency with which ethanol is encountered in their niches. In Experiment 1, dwarf hamsters (Phodopus campbelli) with ad libitum access to food and water consumed high amounts of unsweetened alcohol solutions. Their consumption of 15%, but not 30%, ethanol was reduced when they were fed a high-fat diet; a high carbohydrate diet did not affect ethanol consumption. In Experiment 2, intraperitoneal injections of ethanol caused significant dose-related motor impairment. Much larger doses administered orally, however, had no effect. In Experiment 3, ryegrass seeds, a common food source for wild dwarf hamsters, supported ethanol fermentation. Results of these experiments suggest that dwarf hamsters may have adapted to consume foods in which ethanol production naturally occurs. Copyright © 2015 Elsevier B.V. All rights reserved.
Failure-probability driven dose painting
DOE Office of Scientific and Technical Information (OSTI.GOV)
Vogelius, Ivan R.; Håkansson, Katrin; Due, Anne K.
Purpose: To demonstrate a data-driven dose-painting strategy based on the spatial distribution of recurrences in previously treated patients. The result is a quantitative way to define a dose prescription function, optimizing the predicted local control at constant treatment intensity. A dose planning study using the optimized dose prescription in 20 patients is performed.Methods: Patients treated at our center have five tumor subvolumes from the center of the tumor (PET positive volume) and out delineated. The spatial distribution of 48 failures in patients with complete clinical response after (chemo)radiation is used to derive a model for tumor control probability (TCP). Themore » total TCP is fixed to the clinically observed 70% actuarial TCP at five years. Additionally, the authors match the distribution of failures between the five subvolumes to the observed distribution. The steepness of the dose–response is extracted from the literature and the authors assume 30% and 20% risk of subclinical involvement in the elective volumes. The result is a five-compartment dose response model matching the observed distribution of failures. The model is used to optimize the distribution of dose in individual patients, while keeping the treatment intensity constant and the maximum prescribed dose below 85 Gy.Results: The vast majority of failures occur centrally despite the small volumes of the central regions. Thus, optimizing the dose prescription yields higher doses to the central target volumes and lower doses to the elective volumes. The dose planning study shows that the modified prescription is clinically feasible. The optimized TCP is 89% (range: 82%–91%) as compared to the observed TCP of 70%.Conclusions: The observed distribution of locoregional failures was used to derive an objective, data-driven dose prescription function. The optimized dose is predicted to result in a substantial increase in local control without increasing the predicted risk of toxicity.« less
Faster Self-paced Rate of Drinking for Alcohol Mixed with Energy Drinks versus Alcohol Alone
Marczinski, Cecile A.; Fillmore, Mark T.; Maloney, Sarah F.; Stamates, Amy L.
2016-01-01
The consumption of alcohol mixed with energy drinks (AmED) has been associated with higher rates of binge drinking and impaired driving when compared to alcohol alone. However, it remains unclear why the risks of use of AmED are heightened compared to alcohol alone even when the doses of alcohol consumed are similar. Therefore, the purpose of this laboratory study was to investigate if the rate of self-paced beverage consumption was faster for a dose of AmED versus alcohol alone using a double-blind, within-subjects, placebo-controlled study design. Participants (n = 16) of equal gender who were social drinkers attended 4 separate test sessions that involved consumption of alcohol (1.97 ml/kg vodka) and energy drinks, alone and in combination. On each test day, the dose assigned was divided into 10 cups. Participants were informed that they would have a two hour period to consume the 10 drinks. After the self-paced drinking period, participants completed a cued go/no-go reaction time task and subjective ratings of stimulation and sedation. The results indicated that participants consumed the AmED dose significantly faster (by approximately 16 minutes) than the alcohol dose. For the performance task, participants’ mean reaction times were slower in the alcohol conditions and faster in the energy drink conditions. In conclusion, alcohol consumers should be made aware that rapid drinking might occur for AmED beverages thus heightening alcohol-related safety risks. The fast rate of drinking may be related to the generalized speeding of responses following energy drink consumption. PMID:27819431
Schlenker, E H; Eikanger, J
1997-06-01
The purposes of these studies were: 1) to determine the effects of various doses of propranolol, a nonspecific beta-adrenergic antagonist, on ventilation, oxygen consumption, and body temperature in hamsters, and 2) to test the hypothesis that in hamsters the stimulatory effects of naloxone, an opioid receptor antagonist, on ventilation and oxygen consumption occur, at least in part, through the release of catecholamines that act via beta-adrenergic receptors. Propranolol, a non-specific beta adrenergic receptor antagonist, at a 20 mg/kg depressed body temperature, oxygen consumption, tidal volume, and ventilation relative to saline. The lower dose of 10 mg/kg had only transitory effects on tidal volume at 60 min and ventilation at 30 min post-injection-Naloxone (1 mg/kg) relative to saline stimulated ventilation and oxygen consumption. These effects were blocked by propranolol pretreatment. The results of these experiments demonstrate that in the hamster, 1) body temperature, oxygen consumption, and ventilation appear to be modulated by beta-adrenergic receptors, and 2) the stimulatory effects of naloxone on oxygen consumption and ventilation may occur through the interaction of endogenous opioids and beta-adrenergic receptor systems.
Optimal design of a magnetorheological damper used in smart prosthetic knees
NASA Astrophysics Data System (ADS)
Gao, Fei; Liu, Yan-Nan; Liao, Wei-Hsin
2017-03-01
In this paper, a magnetorheological (MR) damper is optimally designed for use in smart prosthetic knees. The objective of optimization is to minimize the total energy consumption during one gait cycle and weight of the MR damper. Firstly, a smart prosthetic knee employing a DC motor, MR damper and springs is developed based on the kinetics characteristics of human knee during walking. Then the function of the MR damper is analyzed. In the initial stance phase and swing phase, the MR damper is powered off (off-state). While during the late stance phase, the MR damper is powered on to work as a clutch (on-state). Based on the MR damper model as well as the prosthetic knee model, the instantaneous energy consumption of the MR damper is derived in the two working states. Then by integrating in one gait cycle, the total energy consumption is obtained. Particle swarm optimization algorithm is used to optimize the geometric dimensions of MR damper. Finally, a prototype of the optimized MR damper is fabricated and tested with comparison to simulation.
Imatoh, T; Tanihara, S; Miyazaki, M; Momose, Y; Uryu, Y; Une, H
2011-06-01
Coffee is among the most widely consumed beverages in the world. Numerous epidemiological studies have reported a significant inverse association between coffee consumption and risk of type 2 diabetes mellitus, but the underlying mechanisms are still not fully understood. Therefore, we conducted an epidemiological study to clarify the relationship between coffee consumption and adiponectin levels in Japanese males. We also evaluated whether green tea consumption affected adiponectin levels. We carried out a cross-sectional study. The subjects were 665 male employees in Japan. Coffee consumption was assessed, using a self-administered questionnaire, as the number of times per week and cups per day respondents drank, and subjects were grouped into four levels (non, 1-5 times/week, 1-2 cups/day and ≥3 cups/day). The means of adiponectin levels were positively associated with coffee consumption. A dose-response relationship was found between coffee consumption and circulating adiponectin levels. The relationship remained significant after adjustment for potential confounding factors (P for trend <0.05). However, green tea consumption was not significantly associated with adiponectin levels (P for trend = 0.90). We not only revealed that habitual coffee consumption is associated with higher adiponectin levels in Japanese males but also found a dose-dependent association between coffee consumption and adiponectin levels. Therefore, our study suggested that coffee components might play an important role in the elevation of adiponectin level.
Mustard, Julie A; Wright, Geraldine A; Edgar, Elaina A; Mazade, Reece E.; Wu, Chen; Lillvis, Joshua L
2008-01-01
Invertebrates are valuable models for increasing our understanding of the effects of ethanol on the nervous system, but most studies on invertebrates and ethanol have focused on the effects of ethanol on locomotor behavior. In this work we investigate the influence of an acute dose of ethanol on appetitive olfactory learning in the honey bee (Apis mellifera), a model system for learning and memory. Adult worker honey bees were fed a range of doses (2.5, 5, 10 or 25%) of ethanol and then conditioned to associate an odor with a sucrose reward using either a simple or differential conditioning paradigm. Consumption of ethanol before conditioning significantly reduced both the rate of acquisition and the asymptotic strength of the association. Honey bees also exhibited a dose dependent reduction in arousal/attention during conditioning. Consumption of ethanol after conditioning did not affect recall 24 h later. The observed deficits in acquisition were not due to the affect of ethanol on gustatory sensitivity or motor function. However, honey bees given higher doses of ethanol had difficulty discriminating amongst different odors suggesting that ethanol consumption influences olfactory processing. Taken together, these results demonstrate that an acute dose of ethanol affects appetitive learning and olfactory perception in the honey bee. PMID:18723103
Tamhankar, Ashok J; Karnik, Shreyasee S; Stålsby Lundborg, Cecilia
2018-04-23
Antibiotic resistance, a consequence of antibiotic use, is a threat to health, with severe consequences for resource constrained settings. If determinants for human antibiotic use in India, a lower middle income country, with one of the highest antibiotic consumption in the world could be understood, interventions could be developed, having implications for similar settings. Year wise data for India, for potential determinants and antibiotic consumption, was sourced from publicly available databases for the years 2000-2010. Data was analyzed using Partial Least Squares regression and correlation between determinants and antibiotic consumption was evaluated, formulating 'Predictors' and 'Prediction models'. The 'prediction model' with the statistically most significant predictors (root mean square errors of prediction for train set-377.0 and test set-297.0) formulated from a combination of Health infrastructure + Surface transport infrastructure (HISTI), predicted antibiotic consumption within 95% confidence interval and estimated an antibiotic consumption of 11.6 standard units/person (14.37 billion standard units totally; standard units = number of doses sold in the country; a dose being a pill, capsule, or ampoule) for India for 2014. The HISTI model may become useful in predicting antibiotic consumption for countries/regions having circumstances and data similar to India, but without resources to measure actual data of antibiotic consumption.
Li, Ruiying; Ma, Wenting; Huang, Ning; Kang, Rui
2017-01-01
A sophisticated method for node deployment can efficiently reduce the energy consumption of a Wireless Sensor Network (WSN) and prolong the corresponding network lifetime. Pioneers have proposed many node deployment based lifetime optimization methods for WSNs, however, the retransmission mechanism and the discrete power control strategy, which are widely used in practice and have large effect on the network energy consumption, are often neglected and assumed as a continuous one, respectively, in the previous studies. In this paper, both retransmission and discrete power control are considered together, and a more realistic energy-consumption-based network lifetime model for linear WSNs is provided. Using this model, we then propose a generic deployment-based optimization model that maximizes network lifetime under coverage, connectivity and transmission rate success constraints. The more accurate lifetime evaluation conduces to a longer optimal network lifetime in the realistic situation. To illustrate the effectiveness of our method, both one-tiered and two-tiered uniformly and non-uniformly distributed linear WSNs are optimized in our case studies, and the comparisons between our optimal results and those based on relatively inaccurate lifetime evaluation show the advantage of our method when investigating WSN lifetime optimization problems.
Universal field matching in craniospinal irradiation by a background-dose gradient-optimized method.
Traneus, Erik; Bizzocchi, Nicola; Fellin, Francesco; Rombi, Barbara; Farace, Paolo
2018-01-01
The gradient-optimized methods are overcoming the traditional feathering methods to plan field junctions in craniospinal irradiation. In this note, a new gradient-optimized technique, based on the use of a background dose, is described. Treatment planning was performed by RayStation (RaySearch Laboratories, Stockholm, Sweden) on the CT scans of a pediatric patient. Both proton (by pencil beam scanning) and photon (by volumetric modulated arc therapy) treatments were planned with three isocenters. An 'in silico' ideal background dose was created first to cover the upper-spinal target and to produce a perfect dose gradient along the upper and lower junction regions. Using it as background, the cranial and the lower-spinal beams were planned by inverse optimization to obtain dose coverage of their relevant targets and of the junction volumes. Finally, the upper-spinal beam was inversely planned after removal of the background dose and with the previously optimized beams switched on. In both proton and photon plans, the optimized cranial and the lower-spinal beams produced a perfect linear gradient in the junction regions, complementary to that produced by the optimized upper-spinal beam. The final dose distributions showed a homogeneous coverage of the targets. Our simple technique allowed to obtain high-quality gradients in the junction region. Such technique universally works for photons as well as protons and could be applicable to the TPSs that allow to manage a background dose. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.
NASA Astrophysics Data System (ADS)
Tang, Dunbing; Dai, Min
2015-09-01
The traditional production planning and scheduling problems consider performance indicators like time, cost and quality as optimization objectives in manufacturing processes. However, environmentally-friendly factors like energy consumption of production have not been completely taken into consideration. Against this background, this paper addresses an approach to modify a given schedule generated by a production planning and scheduling system in a job shop floor, where machine tools can work at different cutting speeds. It can adjust the cutting speeds of the operations while keeping the original assignment and processing sequence of operations of each job fixed in order to obtain energy savings. First, the proposed approach, based on a mixed integer programming mathematical model, changes the total idle time of the given schedule to minimize energy consumption in the job shop floor while accepting the optimal solution of the scheduling objective, makespan. Then, a genetic-simulated annealing algorithm is used to explore the optimal solution due to the fact that the problem is strongly NP-hard. Finally, the effectiveness of the approach is performed smalland large-size instances, respectively. The experimental results show that the approach can save 5%-10% of the average energy consumption while accepting the optimal solution of the makespan in small-size instances. In addition, the average maximum energy saving ratio can reach to 13%. And it can save approximately 1%-4% of the average energy consumption and approximately 2.4% of the average maximum energy while accepting the near-optimal solution of the makespan in large-size instances. The proposed research provides an interesting point to explore an energy-aware schedule optimization for a traditional production planning and scheduling problem.
Miura, Hideharu; Ozawa, Shuichi; Nagata, Yasushi
2017-09-01
This study investigated position dependence in planning target volume (PTV)-based and robust optimization plans using full-arc and partial-arc volumetric modulated arc therapy (VMAT). The gantry angles at the periphery, intermediate, and center CTV positions were 181°-180° (full-arc VMAT) and 181°-360° (partial-arc VMAT). A PTV-based optimization plan was defined by 5 mm margin expansion of the CTV to a PTV volume, on which the dose constraints were applied. The robust optimization plan consisted of a directly optimized dose to the CTV under a maximum-uncertainties setup of 5 mm. The prescription dose was normalized to the CTV D 99% (the minimum relative dose that covers 99% of the volume of the CTV) as an original plan. The isocenter was rigidly shifted at 1 mm intervals in the anterior-posterior (A-P), superior-inferior (S-I), and right-left (R-L) directions from the original position to the maximum-uncertainties setup of 5 mm in the original plan, yielding recalculated dose distributions. It was found that for the intermediate and center positions, the uncertainties in the D 99% doses to the CTV for all directions did not significantly differ when comparing the PTV-based and robust optimization plans (P > 0.05). For the periphery position, uncertainties in the D 99% doses to the CTV in the R-L direction for the robust optimization plan were found to be lower than those in the PTV-based optimization plan (P < 0.05). Our study demonstrated that a robust optimization plan's efficacy using partial-arc VMAT depends on the periphery CTV position. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.
Seasonal regulation of condensed tannin consumption by free-ranging goats in a semi-arid savanna
Heitkӧnig, Ignas M. A.; Scogings, Peter F.; Hattas, Dawood; Dziba, Luthando E.; Prins, Herbert H. T.; de Boer, Willem F.
2018-01-01
Although condensed tannins (CTs) are known to reduce forage intake by mammalian herbivores in controlled experiments, few studies have tested these effects in the field. Thus the role of CTs on foraging ecology of free-ranging herbivores is inadequately understood. To investigate the effects of CTs under natural savanna conditions, we pre-dosed groups of goats with polyethylene glycol (PEG, a CT-neutralising chemical), CT powder or water before observing their foraging behaviour. While accounting for the effects of season and time of the day, we tested the hypothesis that herbivores forage in ways that reduce the intake rate (g DM per minute) of CTs. We expected pre-dosing goats with CTs to reduce CT intake rates by (1) consuming diets low in CTs, (2) reducing bite rates, (3) increasing the number of foraging bouts, or (4) reducing the length of foraging bouts. Lastly, (5) expected CT to have no influence the number of dietary forage species. In both wet and dry seasons, pre-dosing goats with CTs resulted in lower CT consumption rates compared to PEG goats which seemed relieved from the stress associated with CT consumption. During dry season, the number of dietary forage species was similar across treatments, although goats that were dosed with PEG significantly increased this number in the wet season. Dosing goats with PEG increased the number and length of browsing bouts compared to goats from the other treatments. Pre-loading goats with PEG also tended to increase bite rates on browse forages, which contributed to increased consumption rates of CTs. Based on the behavioural adjustments made by goats in this study and within the constraints imposed by chemical complexity in savanna systems, we concluded that herbivores under natural conditions foraged in ways that minimised CTs consumption. More research should further elucidate the mechanism through which CTs regulated feeding behaviour. PMID:29293513
The meaning of death: some simulations of a model of healthy and unhealthy consumption.
Forster, M
2001-07-01
Simulations of a model of healthy and unhealthy consumption are used to investigate the impact of various terminal conditions on life-span, pathways of health-related consumption and health. A model in which life-span and the 'death' stock of health are fixed is compared to versions in which (i) the 'death' stock of health is freely chosen; (ii) life-span is freely chosen; (iii) both the 'death' stock of health and life-span are freely chosen. The choice of terminal conditions has a striking impact on optimal plans. Results are discussed with reference to the existing demand for health literature and illustrate the application of iterative processes to determine optimal life-span, the role played by the marginal value of health capital in determining optimal plans, and the importance of checking the second-order conditions for the optimal choice of life-span.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Y; UT Southwestern Medical Center, Dallas, TX; Tian, Z
2015-06-15
Purpose: Intensity-modulated proton therapy (IMPT) is increasingly used in proton therapy. For IMPT optimization, Monte Carlo (MC) is desired for spots dose calculations because of its high accuracy, especially in cases with a high level of heterogeneity. It is also preferred in biological optimization problems due to the capability of computing quantities related to biological effects. However, MC simulation is typically too slow to be used for this purpose. Although GPU-based MC engines have become available, the achieved efficiency is still not ideal. The purpose of this work is to develop a new optimization scheme to include GPU-based MC intomore » IMPT. Methods: A conventional approach using MC in IMPT simply calls the MC dose engine repeatedly for each spot dose calculations. However, this is not the optimal approach, because of the unnecessary computations on some spots that turned out to have very small weights after solving the optimization problem. GPU-memory writing conflict occurring at a small beam size also reduces computational efficiency. To solve these problems, we developed a new framework that iteratively performs MC dose calculations and plan optimizations. At each dose calculation step, the particles were sampled from different spots altogether with Metropolis algorithm, such that the particle number is proportional to the latest optimized spot intensity. Simultaneously transporting particles from multiple spots also mitigated the memory writing conflict problem. Results: We have validated the proposed MC-based optimization schemes in one prostate case. The total computation time of our method was ∼5–6 min on one NVIDIA GPU card, including both spot dose calculation and plan optimization, whereas a conventional method naively using the same GPU-based MC engine were ∼3 times slower. Conclusion: A fast GPU-based MC dose calculation method along with a novel optimization workflow is developed. The high efficiency makes it attractive for clinical usages.« less
SU-F-T-428: An Optimization-Based Commissioning Tool for Finite Size Pencil Beam Dose Calculations
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Y; Tian, Z; Song, T
Purpose: Finite size pencil beam (FSPB) algorithms are commonly used to pre-calculate the beamlet dose distribution for IMRT treatment planning. FSPB commissioning, which usually requires fine tuning of the FSPB kernel parameters, is crucial to the dose calculation accuracy and hence the plan quality. Yet due to the large number of beamlets, FSPB commissioning could be very tedious. This abstract reports an optimization-based FSPB commissioning tool we have developed in MatLab to facilitate the commissioning. Methods: A FSPB dose kernel generally contains two types of parameters: the profile parameters determining the dose kernel shape, and a 2D scaling factors accountingmore » for the longitudinal and off-axis corrections. The former were fitted using the penumbra of a reference broad beam’s dose profile with Levenberg-Marquardt algorithm. Since the dose distribution of a broad beam is simply a linear superposition of the dose kernel of each beamlet calculated with the fitted profile parameters and scaled using the scaling factors, these factors could be determined by solving an optimization problem which minimizes the discrepancies between the calculated dose of broad beams and the reference dose. Results: We have commissioned a FSPB algorithm for three linac photon beams (6MV, 15MV and 6MVFFF). Dose of four field sizes (6*6cm2, 10*10cm2, 15*15cm2 and 20*20cm2) were calculated and compared with the reference dose exported from Eclipse TPS system. For depth dose curves, the differences are less than 1% of maximum dose after maximum dose depth for most cases. For lateral dose profiles, the differences are less than 2% of central dose at inner-beam regions. The differences of the output factors are within 1% for all the three beams. Conclusion: We have developed an optimization-based commissioning tool for FSPB algorithms to facilitate the commissioning, providing sufficient accuracy of beamlet dose calculation for IMRT optimization.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sugano, Yasutaka; Mizuta, Masahiro; Takao, Seishin
Purpose: Radiotherapy of solid tumors has been performed with various fractionation regimens such as multi- and hypofractionations. However, the ability to optimize the fractionation regimen considering the physical dose distribution remains insufficient. This study aims to optimize the fractionation regimen, in which the authors propose a graphical method for selecting the optimal number of fractions (n) and dose per fraction (d) based on dose–volume histograms for tumor and normal tissues of organs around the tumor. Methods: Modified linear-quadratic models were employed to estimate the radiation effects on the tumor and an organ at risk (OAR), where the repopulation of themore » tumor cells and the linearity of the dose-response curve in the high dose range of the surviving fraction were considered. The minimization problem for the damage effect on the OAR was solved under the constraint that the radiation effect on the tumor is fixed by a graphical method. Here, the damage effect on the OAR was estimated based on the dose–volume histogram. Results: It was found that the optimization of fractionation scheme incorporating the dose–volume histogram is possible by employing appropriate cell surviving models. The graphical method considering the repopulation of tumor cells and a rectilinear response in the high dose range enables them to derive the optimal number of fractions and dose per fraction. For example, in the treatment of prostate cancer, the optimal fractionation was suggested to lie in the range of 8–32 fractions with a daily dose of 2.2–6.3 Gy. Conclusions: It is possible to optimize the number of fractions and dose per fraction based on the physical dose distribution (i.e., dose–volume histogram) by the graphical method considering the effects on tumor and OARs around the tumor. This method may stipulate a new guideline to optimize the fractionation regimen for physics-guided fractionation.« less
Kulasekere, Ravi; Moran, Jean M.; Fraass, Benedick A.; Roberson, Peter L.
2006-01-01
A single calibration film method was evaluated for use with intensity‐modulated radiation therapy film quality assurance measurements. The single‐film method has the potential advantages of exposure simplicity, less media consumption, and improved processor quality control. Potential disadvantages include cross contamination of film exposure, implementation effort to document delivered dose, and added complication of film response analysis. Film response differences were measured between standard and single‐film calibration methods. Additional measurements were performed to help trace causes for the observed discrepancies. Kodak X‐OmatV (XV) film was found to have greater response variability than extended dose range (EDR) film. We found it advisable for XV film to relate the film response calibration for the single‐film method to a user‐defined optimal calibration geometry. Using a single calibration film exposed at the time of experiment, the total uncertainty of film response was estimated to be <2% (1%) for XV (EDR) film at 50 (100) cGy and higher, respectively. PACS numbers: 87.53.‐j, 87.53.Dq PMID:17533325
DOE Office of Scientific and Technical Information (OSTI.GOV)
Beghian, L.; Melnick, J.
1986-11-01
Irradiation of live bivalve molluscs is a promising new technique to reduce the public health threats of viral and bacterial pathogens in the consumption of raw shellfish. In studies conducted within the past year, live hardshelled clams and oysters were innoculated with Simian Rotavirus SA-11, Poliovirus I, and Hepatitis-A virus and treated with gamma ray ionizing radiation from University of Lowell/DOE 800,000 Curie /sup 60/Co source over a dose range of 0.5--10 kiloGray (50--1000 kilorad) to determine the effectiveness of the process in eliminating viral activity and thus easing the potential viral health threats associated with uncooked bivalves. Two viralmore » strains, SA-11 and Poliovirus I, were employed as models to perfect laboratory technique and to estimate the most appropriate range of dose exposures necessary for optimal inactivation of the infectious pathogen, Hepatitis A. Post-irradiation survivorship of the oysters and quahogs was assessed over a range of exposures, and showed an exceptionally high degree of radioresistance for these molluscan species. 7 refs., 7 figs., 14 tabs.« less
Delta receptor antagonism, ethanol taste reactivity, and ethanol consumption in outbred male rats.
Higley, Amanda E; Kiefer, Stephen W
2006-11-01
Naltrexone, a nonspecific opioid antagonist, produces significant changes in ethanol responsivity in rats by rendering the taste of ethanol aversive as well as producing a decrease in voluntary ethanol consumption. The present study investigated the effect of naltrindole, a specific antagonist of delta opioid receptors, on ethanol taste reactivity and ethanol consumption in outbred rats. In the first experiment, rats received acute treatment of naltrexone, naltrindole, or saline followed by the measurement of ethanol consumption in a short-term access period. The second experiment involved the same treatments and investigated ethanol palatability (using the taste-reactivity test) as well as ethanol consumption. Results indicated that treatment with 3 mg/kg naltrexone significantly affected palatability (rendered ethanol more aversive, Experiment 2) and decreased voluntary ethanol consumption (Experiments 1 and 2). The effects of naltrindole were inconsistent. In Experiment 1, 8 mg/kg naltrindole significantly decreased voluntary ethanol consumption but this was not replicated in Experiment 2. The 8 mg/kg dose produced a significant increase in aversive responding (Experiment 2) but did not affect ingestive responding. Lower doses of naltrindole (2 and 4 mg/kg) were ineffective in altering rats' taste-reactivity response to and consumption of ethanol. While these data suggest that delta receptors are involved in rats' taste-reactivity response to ethanol and rats' ethanol consumption, it is likely that multiple opioid receptors mediate both behavioral responses.
Emergency strategy optimization for the environmental control system in manned spacecraft
NASA Astrophysics Data System (ADS)
Li, Guoxiang; Pang, Liping; Liu, Meng; Fang, Yufeng; Zhang, Helin
2018-02-01
It is very important for a manned environmental control system (ECS) to be able to reconfigure its operation strategy in emergency conditions. In this article, a multi-objective optimization is established to design the optimal emergency strategy for an ECS in an insufficient power supply condition. The maximum ECS lifetime and the minimum power consumption are chosen as the optimization objectives. Some adjustable key variables are chosen as the optimization variables, which finally represent the reconfigured emergency strategy. The non-dominated sorting genetic algorithm-II is adopted to solve this multi-objective optimization problem. Optimization processes are conducted at four different carbon dioxide partial pressure control levels. The study results show that the Pareto-optimal frontiers obtained from this multi-objective optimization can represent the relationship between the lifetime and the power consumption of the ECS. Hence, the preferred emergency operation strategy can be recommended for situations when there is suddenly insufficient power.
NASA Astrophysics Data System (ADS)
Deufel, Christopher L.; Furutani, Keith M.
2014-02-01
As dose optimization for high dose rate brachytherapy becomes more complex, it becomes increasingly important to have a means of verifying that optimization results are reasonable. A method is presented for using a simple optimization as quality assurance for the more complex optimization algorithms typically found in commercial brachytherapy treatment planning systems. Quality assurance tests may be performed during commissioning, at regular intervals, and/or on a patient specific basis. A simple optimization method is provided that optimizes conformal target coverage using an exact, variance-based, algebraic approach. Metrics such as dose volume histogram, conformality index, and total reference air kerma agree closely between simple and complex optimizations for breast, cervix, prostate, and planar applicators. The simple optimization is shown to be a sensitive measure for identifying failures in a commercial treatment planning system that are possibly due to operator error or weaknesses in planning system optimization algorithms. Results from the simple optimization are surprisingly similar to the results from a more complex, commercial optimization for several clinical applications. This suggests that there are only modest gains to be made from making brachytherapy optimization more complex. The improvements expected from sophisticated linear optimizations, such as PARETO methods, will largely be in making systems more user friendly and efficient, rather than in finding dramatically better source strength distributions.
Povinec, Pavel P.; Hirose, Katsumi
2015-01-01
Variations of Fukushima-derived radionuclides (90Sr, 134Cs and 137Cs) in seawater and biota offshore Fukushima and in the NW Pacific Ocean were investigated and radiation doses to the Japanese and world population from ingestion of seafood contaminated by Fukushima radionuclides were estimated and compared with those from other sources of anthropogenic and natural radionuclides. The total effective dose commitment from ingestion of radionuclides in fish, shellfish and seaweed caught in coastal waters off Fukushima was estimated to be 0.6 ± 0.4 mSv/y. The individual effective dose commitment from consumption of radioactive-contaminated fish caught in the open Pacific Ocean was estimated to be 0.07 ± 0.05 mSv/y. These doses are comparable or much lower than doses delivered from the consumption of natural 210Po in fish and in shellfish (0.7 mSv/y). The estimated individual doses have been below the levels when any health damage of the Japanese and world population could be expected. PMID:25761420
Povinec, Pavel P; Hirose, Katsumi
2015-03-12
Variations of Fukushima-derived radionuclides ((90)Sr, (134)Cs and (137)Cs) in seawater and biota offshore Fukushima and in the NW Pacific Ocean were investigated and radiation doses to the Japanese and world population from ingestion of seafood contaminated by Fukushima radionuclides were estimated and compared with those from other sources of anthropogenic and natural radionuclides. The total effective dose commitment from ingestion of radionuclides in fish, shellfish and seaweed caught in coastal waters off Fukushima was estimated to be 0.6 ± 0.4 mSv/y. The individual effective dose commitment from consumption of radioactive-contaminated fish caught in the open Pacific Ocean was estimated to be 0.07 ± 0.05 mSv/y. These doses are comparable or much lower than doses delivered from the consumption of natural (210)Po in fish and in shellfish (0.7 mSv/y). The estimated individual doses have been below the levels when any health damage of the Japanese and world population could be expected.
Maze, Ian S; Wright, Geraldine A; Mustard, Julie A
2006-01-01
Ethanol consumption produces characteristic behavioral states in animals that include sedation, disorientation, and disruption of motor function. Using individual honey bees, we assessed the effects of ethanol ingestion on motor function via continuous observations of their behavior. Consumption of 1 M sucrose solutions containing a range of ethanol doses led to hemolymph ethanol levels of approximately 40-100 mM. Using ethanol doses in this range, we observed time and dose-dependent effects of ethanol on the percent of time our subjects spent walking, stopped, or upside down, and on the duration and frequency of bouts of behavior. The effects on grooming and flying behavior were more complex. Behavioral recovery from ethanol treatment was both time and ethanol dose dependent, occurring between 12 and 24 h post-ingestion for low doses and at 24-48 h for higher doses. Furthermore, the amount of ethanol measured in honey bee hemolymph appeared to correlate with recovery. We predict that the honey bee will prove to be an excellent model system for studying the influence of ethanol on the neural mechanisms underlying behavior.
Klockars, Anica; Brunton, Chloe; Li, Lu; Levine, Allen S; Olszewski, Pawel K
2017-07-01
Despite its limited ability to cross the blood-brain barrier, peripherally administered oxytocin (OT) acutely decreases food intake, most likely via the brainstem and hypothalamic mechanisms. Studies performed to date have focused mainly on the effects of subcutaneous or intraperitoneal OT on the consumption of only solid calorie-dense diets (either standard or high-fat), whereas it is unknown whether, similarly to central OT, peripherally administered peptide reduces intake of calorie-dilute and non-caloric palatable solutions. In this project, we established that 0.1μg/kg intravenous (IV) OT is the lowest anorexigenic dose, decreasing deprivation-induced standard chow intake by ca. 40% in rats and its effect does not stem from aversion. We then used this dose in paradigms in which effects of centrally acting OT ligands on consumption of palatable solutions had been previously reported. We found that IV OT did not change episodic intake of individually presented palatable solutions containing 10% sucrose, 0.1% saccharin, combined 10% sucrose-0.1% saccharin or 4.1%. Intralipid and it failed to affect daily scheduled consumption of a sucrose solution in non-deprived rats. In a two-bottle choice test, IV OT did not shift animals' preference from sucrose to Intralipid. Finally, OT injected IV prior to the simultaneous presentation chow and a sucrose solution in food-deprived rats significantly decreased chow intake, whereas sugar water consumption remained unchanged. We conclude that IV OT reduces deprivation-induced chow intake without causing aversion, but the dose effective in decreasing energy-driven consumption of high-calorie food fails to affect consumption of palatable calorie-dilute solutions. Copyright © 2017 Elsevier Inc. All rights reserved.
Weaver, Connie M.
2013-01-01
Potassium was identified as a shortfall nutrient by the Dietary Guidelines for Americans 2010 Advisory Committee. The committee concluded that there was a moderate body of evidence of the association between potassium intake and blood pressure reduction in adults, which in turn influences the risk of stroke and coronary heart disease. Evidence is also accumulating of the protective effect of adequate dietary potassium on age-related bone loss and reduction of kidney stones. These benefits depend on organic anions associated with potassium as occurs in foods such as fruits and vegetables, in contrast to similar blood pressure-lowering benefits of potassium chloride. Benefits to blood pressure and bone health may occur at levels below current recommendations for potassium intake, especially from diet, but dose-response trials are needed to confirm this. Nevertheless, intakes considerably above current levels are needed for optimal health, and studies evaluating small increases in fruit and vegetable intake on bone and heart outcomes for short periods have had disappointing results. In modern societies, Western diets have led to a decrease in potassium intake with reduced consumption of fruits and vegetables with a concomitant increase in sodium consumption through increased consumption of processed foods. Consumption of white vegetables is associated with decreased risk of stroke, possibly related to their high potassium content. Potatoes are the highest source of dietary potassium, but the addition of salt should be limited. Low potassium-to-sodium intake ratios are more strongly related to cardiovascular disease risk than either nutrient alone. This relationship deserves further attention for multiple target tissue endpoints. PMID:23674806
Yuan, Sheng; Li, Xia; Jin, Yalei; Lu, Jinping
2017-07-02
Although epidemiological studies have examined the role of chocolate in preventing cardiometabolic disease, the results remain inconsistent. Herein, we conducted a meta-analysis of prospective studies to determine the association between chocolate intake and risk of coronary heart disease (CHD), stroke, and diabetes. A systematical search in PubMed and Embase through March 2017, together with reference scrutiny of relevant literatures, was performed to identify eligible studies. Relative risks (RRs) and 95% confidence intervals (CIs) were pooled using random effect models. Fourteen prospective studies of primary prevention with 508,705 participants were finally included, with follow-up durations ranging from 5 to 16 years. The summary RRs for the highest versus lowest chocolate consumption were 0.90 (95% CI: 0.82-0.97; n = 6) for CHD, 0.84 (95% CI: 0.78-0.90; n = 7) for stroke, and 0.82 (95% CI: 0.70-0.96; n = 5) for diabetes. Dose-response meta-analysis suggested a nonlinear association of chocolate consumption with all outcomes. For both CHD and stroke, there was little additional risk reduction when consuming chocolate ≥3 servings/week (one serving was defined as 30 g of chocolate). For diabetes, the peak protective effect of chocolate emerged at 2 servings/week (RR: 0.75, 95% CI: 0.63-0.89), with no benefit observed when increasing consumption above 6 servings/week. In conclusion, chocolate intake is associated with decreased risks of CHD, stroke, and diabetes. Consuming chocolate in moderation (≤6 servings/week) may be optimal for preventing these disorders.
Zheng, Xiaoming
2017-12-01
The purpose of this work was to examine the effects of relationship functions between diagnostic image quality and radiation dose on the governing equations for image acquisition parameter variations in X-ray imaging. Various equations were derived for the optimal selection of peak kilovoltage (kVp) and exposure parameter (milliAmpere second, mAs) in computed tomography (CT), computed radiography (CR), and direct digital radiography. Logistic, logarithmic, and linear functions were employed to establish the relationship between radiation dose and diagnostic image quality. The radiation dose to the patient, as a function of image acquisition parameters (kVp, mAs) and patient size (d), was used in radiation dose and image quality optimization. Both logistic and logarithmic functions resulted in the same governing equation for optimal selection of image acquisition parameters using a dose efficiency index. For image quality as a linear function of radiation dose, the same governing equation was derived from the linear relationship. The general equations should be used in guiding clinical X-ray imaging through optimal selection of image acquisition parameters. The radiation dose to the patient could be reduced from current levels in medical X-ray imaging.
Digital radiography: optimization of image quality and dose using multi-frequency software.
Precht, H; Gerke, O; Rosendahl, K; Tingberg, A; Waaler, D
2012-09-01
New developments in processing of digital radiographs (DR), including multi-frequency processing (MFP), allow optimization of image quality and radiation dose. This is particularly promising in children as they are believed to be more sensitive to ionizing radiation than adults. To examine whether the use of MFP software reduces the radiation dose without compromising quality at DR of the femur in 5-year-old-equivalent anthropomorphic and technical phantoms. A total of 110 images of an anthropomorphic phantom were imaged on a DR system (Canon DR with CXDI-50 C detector and MLT[S] software) and analyzed by three pediatric radiologists using Visual Grading Analysis. In addition, 3,500 images taken of a technical contrast-detail phantom (CDRAD 2.0) provide an objective image-quality assessment. Optimal image-quality was maintained at a dose reduction of 61% with MLT(S) optimized images. Even for images of diagnostic quality, MLT(S) provided a dose reduction of 88% as compared to the reference image. Software impact on image quality was found significant for dose (mAs), dynamic range dark region and frequency band. By optimizing image processing parameters, a significant dose reduction is possible without significant loss of image quality.
A comprehensive formulation for volumetric modulated arc therapy planning
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nguyen, Dan; Lyu, Qihui; Ruan, Dan
2016-07-15
Purpose: Volumetric modulated arc therapy (VMAT) is a widely employed radiation therapy technique, showing comparable dosimetry to static beam intensity modulated radiation therapy (IMRT) with reduced monitor units and treatment time. However, the current VMAT optimization has various greedy heuristics employed for an empirical solution, which jeopardizes plan consistency and quality. The authors introduce a novel direct aperture optimization method for VMAT to overcome these limitations. Methods: The comprehensive VMAT (comVMAT) planning was formulated as an optimization problem with an L2-norm fidelity term to penalize the difference between the optimized dose and the prescribed dose, as well as an anisotropicmore » total variation term to promote piecewise continuity in the fluence maps, preparing it for direct aperture optimization. A level set function was used to describe the aperture shapes and the difference between aperture shapes at adjacent angles was penalized to control MLC motion range. A proximal-class optimization solver was adopted to solve the large scale optimization problem, and an alternating optimization strategy was implemented to solve the fluence intensity and aperture shapes simultaneously. Single arc comVMAT plans, utilizing 180 beams with 2° angular resolution, were generated for a glioblastoma multiforme case, a lung (LNG) case, and two head and neck cases—one with three PTVs (H&N{sub 3PTV}) and one with foue PTVs (H&N{sub 4PTV})—to test the efficacy. The plans were optimized using an alternating optimization strategy. The plans were compared against the clinical VMAT (clnVMAT) plans utilizing two overlapping coplanar arcs for treatment. Results: The optimization of the comVMAT plans had converged within 600 iterations of the block minimization algorithm. comVMAT plans were able to consistently reduce the dose to all organs-at-risk (OARs) as compared to the clnVMAT plans. On average, comVMAT plans reduced the max and mean OAR dose by 6.59% and 7.45%, respectively, of the prescription dose. Reductions in max dose and mean dose were as high as 14.5 Gy in the LNG case and 15.3 Gy in the H&N{sub 3PTV} case. PTV coverages measured by D95, D98, and D99 were within 0.25% of the prescription dose. By comprehensively optimizing all beams, the comVMAT optimizer gained the freedom to allow some selected beams to deliver higher intensities, yielding a dose distribution that resembles a static beam IMRT plan with beam orientation optimization. Conclusions: The novel nongreedy VMAT approach simultaneously optimizes all beams in an arc and then directly generates deliverable apertures. The single arc VMAT approach thus fully utilizes the digital Linac’s capability in dose rate and gantry rotation speed modulation. In practice, the new single VMAT algorithm generates plans superior to existing VMAT algorithms utilizing two arcs.« less
Favazza, Christopher P; Ferrero, Andrea; Yu, Lifeng; Leng, Shuai; McMillan, Kyle L; McCollough, Cynthia H
2017-07-01
The use of iterative reconstruction (IR) algorithms in CT generally decreases image noise and enables dose reduction. However, the amount of dose reduction possible using IR without sacrificing diagnostic performance is difficult to assess with conventional image quality metrics. Through this investigation, achievable dose reduction using a commercially available IR algorithm without loss of low contrast spatial resolution was determined with a channelized Hotelling observer (CHO) model and used to optimize a clinical abdomen/pelvis exam protocol. A phantom containing 21 low contrast disks-three different contrast levels and seven different diameters-was imaged at different dose levels. Images were created with filtered backprojection (FBP) and IR. The CHO was tasked with detecting the low contrast disks. CHO performance indicated dose could be reduced by 22% to 25% without compromising low contrast detectability (as compared to full-dose FBP images) whereas 50% or more dose reduction significantly reduced detection performance. Importantly, default settings for the scanner and protocol investigated reduced dose by upward of 75%. Subsequently, CHO-based protocol changes to the default protocol yielded images of higher quality and doses more consistent with values from a larger, dose-optimized scanner fleet. CHO assessment provided objective data to successfully optimize a clinical CT acquisition protocol.
Acute Caffeine Consumption Enhances the Executive Control of Visual Attention in Habitual Consumers
ERIC Educational Resources Information Center
Brunye, Tad T.; Mahoney, Caroline R.; Lieberman, Harris R.; Giles, Grace E.; Taylor, Holly A.
2010-01-01
Recent work suggests that a dose of 200-400mg caffeine can enhance both vigilance and the executive control of visual attention in individuals with low caffeine consumption profiles. The present study seeks to determine whether individuals with relatively high caffeine consumption profiles would show similar advantages. To this end, we examined…
Application of low-mixing energy input for the coagulation process.
Vadasarukkai, Yamuna S; Gagnon, Graham A
2015-11-01
Rapid-mixing tanks with mechanical mixers are a common design used in treatment plants. Yet, the role of such rapid-mixing systems on the effectiveness of the coagulation performance is unclear. This study looked at optimizing the direct energy used in the coagulation process for removal of natural dissolved organic matter (DOM). The role of coagulation mixing intensity (G-value) on total organic carbon (TOC) and turbidity removal was examined for the water types with high organic content, with a specific ultraviolet absorbance (SUVA) of at least 2-2.5 units of m(-1) of absorbance per mg/L. A standard jar test using ferric sulfate coagulant was performed to optimize the chemical condition in coagulation for removal of dissolved organics as well as particles. The jar test analysis at an acidic pH (4.5 ± 0.3) required an iron dose <0.3 mM to arrive at an optimal coagulant concentration and resulted in above 75% of TOC removal. The influence of coagulation mixing on TOC and turbidity removal was evaluated at G varying from 0 to 1500 s(-1) at the optimized coagulant dose and pH conditions for enhanced coagulation. In this study, a combined effective removal of TOC and turbidity was achieved at a low-mixing intensity range of 110 s(-1) < G < 450 s(-1). Coagulation operated at G greater than 450 s(-1) showed negligible improvement in TOC removal. Minimizing energy consumption in enhanced coagulation is feasible at the proposed mixing intensity range (i.e., 110 s(-1) < G < 450 s(-1)), without sacrificing the effectiveness of DOM removal by coagulation. These findings represent an opportunity for energy savings for the water industry without sacrificing quality. Copyright © 2015 Elsevier Ltd. All rights reserved.
Lan, Yihua; Li, Cunhua; Ren, Haozheng; Zhang, Yong; Min, Zhifang
2012-10-21
A new heuristic algorithm based on the so-called geometric distance sorting technique is proposed for solving the fluence map optimization with dose-volume constraints which is one of the most essential tasks for inverse planning in IMRT. The framework of the proposed method is basically an iterative process which begins with a simple linear constrained quadratic optimization model without considering any dose-volume constraints, and then the dose constraints for the voxels violating the dose-volume constraints are gradually added into the quadratic optimization model step by step until all the dose-volume constraints are satisfied. In each iteration step, an interior point method is adopted to solve each new linear constrained quadratic programming. For choosing the proper candidate voxels for the current dose constraint adding, a so-called geometric distance defined in the transformed standard quadratic form of the fluence map optimization model was used to guide the selection of the voxels. The new geometric distance sorting technique can mostly reduce the unexpected increase of the objective function value caused inevitably by the constraint adding. It can be regarded as an upgrading to the traditional dose sorting technique. The geometry explanation for the proposed method is also given and a proposition is proved to support our heuristic idea. In addition, a smart constraint adding/deleting strategy is designed to ensure a stable iteration convergence. The new algorithm is tested on four cases including head-neck, a prostate, a lung and an oropharyngeal, and compared with the algorithm based on the traditional dose sorting technique. Experimental results showed that the proposed method is more suitable for guiding the selection of new constraints than the traditional dose sorting method, especially for the cases whose target regions are in non-convex shapes. It is a more efficient optimization technique to some extent for choosing constraints than the dose sorting method. By integrating a smart constraint adding/deleting scheme within the iteration framework, the new technique builds up an improved algorithm for solving the fluence map optimization with dose-volume constraints.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lin, X; Sun, T; Liu, T
2014-06-01
Purpose: To evaluate the dosimetric characteristics of intensity-modulated radiotherapy (IMRT) treatment plan with beam angle optimization. Methods: Ten post-operation patients with cervical cancer were included in this analysis. Two IMRT plans using seven beams were designed in each patient. A standard coplanar equi-space beam angles were used in the first plan (plan 1), whereas the selection of beam angle was optimized by beam angle optimization algorithm in Varian Eclipse treatment planning system for the same number of beams in the second plan (plan 2). Two plans were designed for each patient with the same dose-volume constraints and prescription dose. Allmore » plans were normalized to the mean dose to PTV. The dose distribution in the target, the dose to the organs at risk and total MU were compared. Results: For conformity and homogeneity in PTV, no statistically differences were observed in the two plans. For the mean dose in bladder, plan 2 were significantly lower than plan 1(p<0.05). No statistically significant differences were observed between two plans for the mean doses in rectum, left and right femur heads. Compared with plan1, the average monitor units reduced 16% in plan 2. Conclusion: The IMRT plan based on beam angle optimization for cervical cancer could reduce the dose delivered to bladder and also reduce MU. Therefore there were some dosimetric advantages in the IMRT plan with beam angle optimization for cervical cancer.« less
Wu, L; Sun, D; He, Y
2016-10-01
The role of dietary factors on chronic diseases seems essential in the potentially adverse or preventive effects. However, no evidence of dose-response meta-analysis of prospective cohort studies has verified the association between the intake of fruit and/or vegetables and the risk of developing hypertension. The PubMed and Embase were searched for prospective cohort studies. A generic inverse-variance method with random effects model was used to calculate the pooled relative risks (RRs) and 95% confidence intervals (CIs). Generalized least squares trend estimation model was used to calculate the study-specific slopes for the dose-response analyses. Seven articles comprised nine cohorts involving 185 676 participants were assessed. The highest intake of fruit or vegetables separately, and total fruit and vegetables were inversely associated with the incident risk of hypertension compared with the lowest level, and the pooled RRs and 95% CIs were 0.87 (0.79, 0.95), 0.88 (0.79, 0.99) and 0.90 (0.84, 0.98), respectively. We also found an inverse dose-response relation between the risk of developing hypertension and fruit intake, and total fruit and vegetables consumption. The incident risk of hypertension was decreased by 1.9% for each serving per day of fruit consumption, and decreased by 1.2% for each serving per day of total fruit and vegetables consumption. Our results support the recommendation to increase the consumption of fruit and vegetables with respect to preventing the risk of developing hypertension. However, further large prospective studies and long-term high-quality randomized controlled trials are still needed to confirm the observed association.
Chocolate Consumption and Risk of Heart Failure: A Meta-Analysis of Prospective Studies.
Gong, Fei; Yao, Shuyuan; Wan, Jing; Gan, Xuedong
2017-04-20
Epidemiological studies have shown inconsistent findings on the association between chocolate consumption and risk of heart failure (HF). We, therefore, performed a meta-analysis of prospective studies to determine the role of chocolate intake in the prevention of HF. We searched databases of PubMed, Web of Science, and Scopus through December 2016 and scrutinized the reference lists of relevant literatures to identify eligible studies. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were aggregated using random effect models. The dose-response relationship between chocolate consumption and incident HF was also assessed. This meta-analysis is registered with PROSPERO, number CRD42017054230. Five prospective studies with 106,109 participants were finally included. Compared to no consumption of chocolate, the pooled HRs (95% CIs) of HF were 0.86 (0.82-0.91) for low-to-moderate consumption (<7 servings/week) and 0.94 (0.80-1.09) for high consumption (≥7 servings/week). In dose-response meta-analysis, we detected a curve linear relationship between chocolate consumption and risk of HF ( p for nonlinearity = 0.005). Compared with non-consumption, the HRs (95% CIs) of HF across chocolate consumption levels were 0.92 (0.88-0.97), 0.86 (0.78-0.94), 0.93 (0.85-1.03), and 1.07 (0.92-1.23) for 1, 3, 7, and 10 servings/week, respectively. In conclusion, chocolate consumption in moderation may be associated with a decreased risk of HF.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Heinzelman, K M; Mansfield, W G
This document evaluates the expected radiation dose due to the consumption of several specific food classes (dairy, meat, produce, etc.) contaminated with specific radionuclides, and relates concentration levels in food to the detection abilities of typical aboratory analysis/measurement methods. The attached charts present the limiting organ dose as a function of the radionuclide concentration in a particular food class, and allow the user to compare these concentrations and doses to typical analytical detection apabilities. The expected radiation dose depends on several factors: the age of the individual; the radionuclide present in the food; the concentration of the radionuclide in themore » food; and the amount of food consumed. Food consumption rates for individuals of various ges were taken from the 1998 United States Food and Drug Administration (FDA) document, Accidental Radioactive Contamination of HUman Food and Animal Feeds: Recommendations for State and Local Agencies. In that document, the FDA defines the erived Intervention Level (DIL), which is the concentration of a particular radionuclide in food that if consumed could result in an individual receiving a radiation dose exceeding the Protection Action Guide (PAG) thresholds for intervention. This document also resents odified, food class specific DIL, which is calculated using a somewhat modified version of the FDA's procedure. This document begins with an overview of the FDA's DIL calculation, followed by a description of the food class specific DIL calculations, and finally charts of the radiation dose per radioactivity concentration for several food class/radionuclide combinations.« less
Energy consumption of agitators in activated sludge tanks - actual state and optimization potential.
Füreder, K; Svardal, K; Frey, W; Kroiss, H; Krampe, J
2018-02-01
Depending on design capacity, agitators consume about 5 to 20% of the total energy consumption of a wastewater treatment plant. Based on inhabitant-specific energy consumption (kWh PE 120 -1 a -1 ; PE 120 is population equivalent, assuming 120 g chemical oxygen demand per PE per day), power density (W m -3 ) and volume-specific energy consumption (Wh m -3 d -1 ) as evaluation indicators, this paper provides a sound contribution to understanding energy consumption and energy optimization potentials of agitators. Basically, there are two ways to optimize agitator operation: the reduction of the power density and the reduction of the daily operating time. Energy saving options range from continuous mixing with low power densities of 1 W m -3 to mixing by means of short, intense energy pulses (impulse aeration, impulse stirring). However, the following correlation applies: the shorter the duration of energy input, the higher the power density on the respective volume-specific energy consumption isoline. Under favourable conditions with respect to tank volume, tank geometry, aeration and agitator position, mixing energy can be reduced to 24 Wh m -3 d -1 and below. Additionally, it could be verified that power density of agitators stands in inverse relation to tank volume.
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.
Guidelines for exposure assessment in health risk studies following a nuclear reactor accident.
Bouville, André; Linet, Martha S; Hatch, Maureen; Mabuchi, Kiyohiko; Simon, Steven L
2014-01-01
Worldwide concerns regarding health effects after the Chernobyl and Fukushima nuclear power plant accidents indicate a clear need to identify short- and long-term health impacts that might result from accidents in the future. Fundamental to addressing this problem are reliable and accurate radiation dose estimates for the affected populations. The available guidance for activities following nuclear accidents is limited with regard to strategies for dose assessment in health risk studies. Here we propose a comprehensive systematic approach to estimating radiation doses for the evaluation of health risks resulting from a nuclear power plant accident, reflected in a set of seven guidelines. Four major nuclear reactor accidents have occurred during the history of nuclear power production. The circumstances leading to these accidents were varied, as were the magnitude of the releases of radioactive materials, the pathways by which persons were exposed, the data collected afterward, and the lifestyle factors and dietary consumption that played an important role in the associated radiation exposure of the affected populations. Accidents involving nuclear reactors may occur in the future under a variety of conditions. The guidelines we recommend here are intended to facilitate obtaining reliable dose estimations for a range of different exposure conditions. We recognize that full implementation of the proposed approach may not always be feasible because of other priorities during the nuclear accident emergency and because of limited resources in manpower and equipment. The proposed approach can serve as a basis to optimize the value of radiation dose reconstruction following a nuclear reactor accident.
Radiological impact of 2016 operations at the Savannah River Site
DOE Office of Scientific and Technical Information (OSTI.GOV)
Minter, K. L.; Jannik, G. T.; Dixon, K. M.
This report presents the environmental dose assessment methods and the estimated potential doses to the offsite public from 2016 Savannah River Site (SRS) air and liquid radioactive releases. Also documented are potential doses from special-case exposure scenarios, such as the consumption of wildlife or goat milk.
Multiple anatomy optimization of accumulated dose
DOE Office of Scientific and Technical Information (OSTI.GOV)
Watkins, W. Tyler, E-mail: watkinswt@virginia.edu; Siebers, Jeffrey V.; Moore, Joseph A.
Purpose: To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. Methods: MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dosemore » variations were also investigated. Results: By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. Conclusions: MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated.« less
Turner, James D; Henshaw, Daryl S; Weller, Robert S; Jaffe, J Douglas; Edwards, Christopher J; Reynolds, J Wells; Russell, Gregory B; Dobson, Sean W
2018-05-08
To determine whether perineural dexamethasone prolongs peripheral nerve blockade (PNB) when measured objectively; and to determine if a 1 mg and 4 mg dose provide equivalent PNB prolongation compared to PNB without dexamethasone. Multiple studies have reported that perineural dexamethasone added to local anesthetics (LA) can prolong PNB. However, these studies have relied on subjective end-points to quantify PNB duration. The optimal dose remains unknown. We hypothesized that 1 mg of perineural dexamethasone would be equivalent in prolonging an adductor canal block (ACB) when compared to 4 mg of dexamethasone, and that both doses would be superior to an ACB performed without dexamethasone. This was a prospective, randomized, double-blind, placebo-controlled equivalency trial involving 85 patients undergoing a unicompartmental knee arthroplasty. All patients received an ACB with 20 ml of 0.25% bupivacaine with 1:400,000 epinephrine. Twelve patients had 0 mg of dexamethasone (placebo) added to the LA mixture; 36 patients had 1 mg of dexamethasone in the LA; and 37 patients had 4 mg of dexamethasone in the LA. The primary outcome was block duration determined by serial neurologic pinprick examinations. Secondary outcomes included time to first analgesic, serial pain scores, and cumulative opioid consumption. The 1 mg (31.8 ± 10.5 h) and 4 mg (37.9 ± 10 h) groups were not equivalent, TOST [Mean difference (95% CI); 6.1 (-10.5, -2.3)]. Also, the 4 mg group was superior to the 1 mg group (p-value = 0.035), and the placebo group (29.7 ± 6.8 h, p-value = 0.011). There were no differences in opioid consumption or time to analgesic request; however, some pain scores were significantly lower in the dexamethasone groups when compared to placebo. Dexamethasone 4 mg, but not 1 mg, prolonged the duration of an ACB when measured by serial neurologic pinprick exams. NCT02462148. Copyright © 2018 Elsevier Inc. All rights reserved.
Muscimol microinjected in the arcuate nucleus affects metabolism, body temperature & ventilation.
Schlenker, Evelyn H
2016-06-15
Effects of microinjection of 2 doses of γ-aminobutyric acid (GABA)A receptor agonist, muscimol (M), into the hypothalamic arcuate nucleus on oxygen consumption and control of ventilation over time and body temperature (BT) at the end of the experiment were compared in adult male and female rats. Relative to cerebrospinal fluid (CSF, 0 nmol), BT was decreased only in male rats with both doses of M, while in female rats, the 5 nmol dose depressed oxygen consumption. Ventilation was depressed by 5 nmol M in male and 10 nmol M in female rats by decreasing tidal volume. M did not affect the ventilatory response of male or female rats to hypoxia, whereas in females 5 and 10 nmol M and in males 10 nmol M depressed the ventilatory response to hypercapnia. Thus, in rats GABAA receptors in the arcuate nucleus modulate BT, oxygen consumption, and ventilation in air and in response to hypercapnia in a sexually dimorphic manner. Copyright © 2016 Elsevier B.V. All rights reserved.
Davison, Kade; Howe, Peter R C
2015-11-18
The metabolic syndrome is a pathological state whereby cardiovascular and metabolic dysfunction coexist and typically progress in a mutual feed-forward manner to further dysfunction and ultimately disease. The health and function of the vascular endothelium is integral in this phenomenon and thus represents a logical target for intervention. Consumption of foods high in cocoa flavanols has demonstrated a capacity to markedly improve endothelial function and key markers of the metabolic syndrome including blood pressure and insulin sensitivity. The typically high energy content of foods containing sufficient doses of cocoa flavanols has caused some reservations around its therapeutic use, but this is dependent upon the particulars of the food matrix used. Further to this, the food matrix appears to influence the dose response curve of cocoa flavanols, particularly on blood pressure, with dark chocolate appearing to be 8 times more effective in systolic blood pressure reduction than a cocoa powder drink for the equivalent dose of flavanol. Cocoa flavanol consumption conclusively demonstrates a positive impact on cardiometabolic function; however, more research is needed to understand how best to consume it to maximize the benefit while avoiding excessive fat and sugar consumption.
Novoseltsev, V N; Arking, R; Novoseltseva, J A; Yashin, A I
2002-06-01
The general purpose of the paper is to test evolutionary optimality theories with experimental data on reproduction, energy consumption, and longevity in a particular Drosophila genotype. We describe the resource allocation in Drosophila females in terms of the oxygen consumption rates devoted to reproduction and to maintenance. The maximum ratio of the component spent on reproduction to the total rate of oxygen consumption, which can be realized by the female reproductive machinery, is called metabolic reproductive efficiency (MRE). We regard MRE as an evolutionary constraint. We demonstrate that MRE may be evaluated for a particular Drosophila phenotype given the fecundity pattern, the age-related pattern of oxygen consumption rate, and the longevity. We use a homeostatic model of aging to simulate a life history of a representative female fly, which describes the control strain in the long-term experiments with the Wayne State Drosophila genotype. We evaluate the theoretically optimal trade-offs in this genotype. Then we apply the Van Noordwijk-de Jong resource acquisition and allocation model, Kirkwood's disposable soma theory. and the Partridge-Barton optimality approach to test if the experimentally observed trade-offs may be regarded as close to the theoretically optimal ones. We demonstrate that the two approaches by Partridge-Barton and Kirkwood allow a positive answer to the question, whereas the Van Noordwijk-de Jong approach may be used to illustrate the optimality. We discuss the prospects of applying the proposed technique to various Drosophila experiments, in particular those including manipulations affecting fecundity.
An optimization method of VON mapping for energy efficiency and routing in elastic optical networks
NASA Astrophysics Data System (ADS)
Liu, Huanlin; Xiong, Cuilian; Chen, Yong; Li, Changping; Chen, Derun
2018-03-01
To improve resources utilization efficiency, network virtualization in elastic optical networks has been developed by sharing the same physical network for difference users and applications. In the process of virtual nodes mapping, longer paths between physical nodes will consume more spectrum resources and energy. To address the problem, we propose a virtual optical network mapping algorithm called genetic multi-objective optimize virtual optical network mapping algorithm (GM-OVONM-AL), which jointly optimizes the energy consumption and spectrum resources consumption in the process of virtual optical network mapping. Firstly, a vector function is proposed to balance the energy consumption and spectrum resources by optimizing population classification and crowding distance sorting. Then, an adaptive crossover operator based on hierarchical comparison is proposed to improve search ability and convergence speed. In addition, the principle of the survival of the fittest is introduced to select better individual according to the relationship of domination rank. Compared with the spectrum consecutiveness-opaque virtual optical network mapping-algorithm and baseline-opaque virtual optical network mapping algorithm, simulation results show the proposed GM-OVONM-AL can achieve the lowest bandwidth blocking probability and save the energy consumption.
NASA Astrophysics Data System (ADS)
Shi, Luyang; Liu, Jing; Zhang, Huibo
2017-11-01
The object of this article is to investigate the influence of thermal performance of envelopes in shallow-buried buildings on energy consumption for different climate zones of China. For the purpose of this study, an effective building energy simulation tool (DeST) developed by Tsinghua University was chosen to model the heat transfer in underground buildings. Based on the simulative results, energy consumption for heating and cooling for the whole year was obtained. The results showed that the relationship between energy consumption and U-value of envelopes for underground buildings is different compared with above-ground buildings: improving thermal performance of exterior walls cannot reduce energy consumption, on the contrary, may result in more energy cost. Besides, it is can be derived that optimized U-values of underground building envelopes vary with climate zones of China in this study. For severe cold climate zone, the optimized U-value of underground building envelopes is 0.8W/(m2·K); for cold climate zone, the optimized U-value is 1.5W/(m2·K); for warm climate zone, the U-value is 2.0W/(m2·K).
Zaghian, Maryam; Cao, Wenhua; Liu, Wei; Kardar, Laleh; Randeniya, Sharmalee; Mohan, Radhe; Lim, Gino
2017-03-01
Robust optimization of intensity-modulated proton therapy (IMPT) takes uncertainties into account during spot weight optimization and leads to dose distributions that are resilient to uncertainties. Previous studies demonstrated benefits of linear programming (LP) for IMPT in terms of delivery efficiency by considerably reducing the number of spots required for the same quality of plans. However, a reduction in the number of spots may lead to loss of robustness. The purpose of this study was to evaluate and compare the performance in terms of plan quality and robustness of two robust optimization approaches using LP and nonlinear programming (NLP) models. The so-called "worst case dose" and "minmax" robust optimization approaches and conventional planning target volume (PTV)-based optimization approach were applied to designing IMPT plans for five patients: two with prostate cancer, one with skull-based cancer, and two with head and neck cancer. For each approach, both LP and NLP models were used. Thus, for each case, six sets of IMPT plans were generated and assessed: LP-PTV-based, NLP-PTV-based, LP-worst case dose, NLP-worst case dose, LP-minmax, and NLP-minmax. The four robust optimization methods behaved differently from patient to patient, and no method emerged as superior to the others in terms of nominal plan quality and robustness against uncertainties. The plans generated using LP-based robust optimization were more robust regarding patient setup and range uncertainties than were those generated using NLP-based robust optimization for the prostate cancer patients. However, the robustness of plans generated using NLP-based methods was superior for the skull-based and head and neck cancer patients. Overall, LP-based methods were suitable for the less challenging cancer cases in which all uncertainty scenarios were able to satisfy tight dose constraints, while NLP performed better in more difficult cases in which most uncertainty scenarios were hard to meet tight dose limits. For robust optimization, the worst case dose approach was less sensitive to uncertainties than was the minmax approach for the prostate and skull-based cancer patients, whereas the minmax approach was superior for the head and neck cancer patients. The robustness of the IMPT plans was remarkably better after robust optimization than after PTV-based optimization, and the NLP-PTV-based optimization outperformed the LP-PTV-based optimization regarding robustness of clinical target volume coverage. In addition, plans generated using LP-based methods had notably fewer scanning spots than did those generated using NLP-based methods. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.
Optimization of fuel-cell tram operation based on two dimension dynamic programming
NASA Astrophysics Data System (ADS)
Zhang, Wenbin; Lu, Xuecheng; Zhao, Jingsong; Li, Jianqiu
2018-02-01
This paper proposes an optimal control strategy based on the two-dimension dynamic programming (2DDP) algorithm targeting at minimizing operation energy consumption for a fuel-cell tram. The energy consumption model with the tram dynamics is firstly deduced. Optimal control problem are analyzed and the 2DDP strategy is applied to solve the problem. The optimal tram speed profiles are obtained for each interstation which consist of three stages: accelerate to the set speed with the maximum traction power, dynamically adjust to maintain a uniform speed and decelerate to zero speed with the maximum braking power at a suitable timing. The optimal control curves of all the interstations are connected with the parking time to form the optimal control method of the whole line. The optimized speed profiles are also simplified for drivers to follow.
Faster self-paced rate of drinking for alcohol mixed with energy drinks versus alcohol alone.
Marczinski, Cecile A; Fillmore, Mark T; Maloney, Sarah F; Stamates, Amy L
2017-03-01
The consumption of alcohol mixed with energy drinks (AmED) has been associated with higher rates of binge drinking and impaired driving when compared with alcohol alone. However, it remains unclear why the risks of use of AmED are heightened compared with alcohol alone even when the doses of alcohol consumed are similar. Therefore, the purpose of this laboratory study was to investigate if the rate of self-paced beverage consumption was faster for a dose of AmED versus alcohol alone using a double-blind, within-subjects, placebo-controlled study design. Participants (n = 16) of equal gender who were social drinkers attended 4 separate test sessions that involved consumption of alcohol (1.97 ml/kg vodka) and energy drinks, alone and in combination. On each test day, the dose assigned was divided into 10 cups. Participants were informed that they would have a 2-h period to consume the 10 drinks. After the self-paced drinking period, participants completed a cued go/no-go reaction time (RT) task and subjective ratings of stimulation and sedation. The results indicated that participants consumed the AmED dose significantly faster (by ∼16 min) than the alcohol dose. For the performance task, participants' mean RTs were slower in the alcohol conditions and faster in the energy-drink conditions. In conclusion, alcohol consumers should be made aware that rapid drinking might occur for AmED beverages, thus heightening alcohol-related safety risks. The fast rate of drinking may be related to the generalized speeding of responses after energy-drink consumption. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Anthony, Winston E; Palmer-Young, Evan C; Leonard, Anne S; Irwin, Rebecca E; Adler, Lynn S
2015-01-01
The impact of consuming biologically active compounds is often dose-dependent, where small quantities can be medicinal while larger doses are toxic. The consumption of plant secondary compounds can be toxic to herbivores in large doses, but can also improve survival in parasitized herbivores. In addition, recent studies have found that consuming nectar secondary compounds may decrease parasite loads in pollinators. However, the effect of compound dose on bee survival and parasite loads has not been assessed. To determine how secondary compound consumption affects survival and pathogen load in Bombus impatiens, we manipulated the presence of a common gut parasite, Crithidia bombi, and dietary concentration of anabasine, a nectar alkaloid produced by Nicotiana spp. using four concentrations naturally observed in floral nectar. We hypothesized that increased consumption of secondary compounds at concentrations found in nature would decrease survival of uninfected bees, but improve survival and ameliorate parasite loads in infected bees. We found medicinal effects of anabasine in infected bees; the high-anabasine diet decreased parasite loads and increased the probability of clearing the infection entirely. However, survival time was not affected by any level of anabasine concentration, or by interactive effects of anabasine concentration and infection. Crithidia infection reduced survival time by more than two days, but this effect was not significant. Our results support a medicinal role for anabasine at the highest concentration; moreover, we found no evidence for a survival-related cost of anabasine consumption across the concentration range found in nectar. Our results suggest that consuming anabasine at the higher levels of the natural range could reduce or clear pathogen loads without incurring costs for healthy bees.
NASA Technical Reports Server (NTRS)
Soloway, Donald I.; Alberts, Thomas E.
1989-01-01
It is often proposed that the redundancy in choosing a force distribution for multiple arms grasping a single object should be handled by minimizing a quadratic performance index. The performance index may be formulated in terms of joint torques or in terms of the Cartesian space force/torque applied to the body by the grippers. The former seeks to minimize power consumption while the latter minimizes body stresses. Because the cost functions are related to each other by a joint angle dependent transformation on the weight matrix, it might be argued that either method tends to reduce power consumption, but clearly the joint space minimization is optimal. A comparison of these two options is presented with consideration given to computational cost and power consumption. Simulation results using a two arm robot system are presented to show the savings realized by employing the joint space optimization. These savings are offset by additional complexity, computation time and in some cases processor power consumption.
Evaluation of the subchronic toxicity of kefir by oral administration in Wistar rats.
Diniz Rosa, Damiana; Gouveia Peluzio, Maria do Carmo; Pérez Bueno, Tania; Vega Cañizares, Ernesto; Sánchez Miranda, Lilian; Mancebo Dorbignyi, Betty; Chong Dubí, Dainé; Espinosa Castaño, Ivette; Marcin Grzes Kowiak, Lukasz; Fortes Ferreira, Célia Lucia de Luces
2014-06-01
Kefir is obtained by fermentation of milk with complex microbial populations present in kefir grains. Several health-promoting benefits have been attributed to kefir consumption. The objective of this work was to conduct a subchronic toxicity study, offering the rats normal or high-doses of kefir and evaluating growth, hematology and blood chemistry, as well as assessing bacterial translocation and the integrity of the intestinal mucosa of animals. Wistar rats were randomly divided into three groups (n = 6/group): control group received 0.7 mL of water, kefir group received 0.7 mL/day of kefir, (normodose), and Hkefir group received 3.5 mL/day of kefir (fivefold higher dose). Feeding was carried out by gavage. The animals were housed in individual cages and maintained under standard conditions for 4 weeks. The normodose and high-dose of kefir supplementation did not harm the animals since growth, hematology and blood chemistry in rats, as well as the potential pathogenicity in tissues were within normal limits, demonstrating that consumption of normodose and highdose of kefir are safe. In addition, administration of the normodose of kefir reduced cholesterol levels and improved the intestinal mucosa of the rats. These results demonstrate that the consumption of kefir is safe. Importantly, while damages are not seen for the high-dose, the normodose consumption is recommended due to the pronounced beneficial effects, as safety is concerned. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.
SCCT guidelines on radiation dose and dose-optimization strategies in cardiovascular CT
Halliburton, Sandra S.; Abbara, Suhny; Chen, Marcus Y.; Gentry, Ralph; Mahesh, Mahadevappa; Raff, Gilbert L.; Shaw, Leslee J.; Hausleiter, Jörg
2012-01-01
Over the last few years, computed tomography (CT) has developed into a standard clinical test for a variety of cardiovascular conditions. The emergence of cardiovascular CT during a period of dramatic increase in radiation exposure to the population from medical procedures and heightened concern about the subsequent potential cancer risk has led to intense scrutiny of the radiation burden of this new technique. This has hastened the development and implementation of dose reduction tools and prompted closer monitoring of patient dose. In an effort to aid the cardiovascular CT community in incorporating patient-centered radiation dose optimization and monitoring strategies into standard practice, the Society of Cardiovascular Computed Tomography has produced a guideline document to review available data and provide recommendations regarding interpretation of radiation dose indices and predictors of risk, appropriate use of scanner acquisition modes and settings, development of algorithms for dose optimization, and establishment of procedures for dose monitoring. PMID:21723512
Series Hybrid Electric Vehicle Power System Optimization Based on Genetic Algorithm
NASA Astrophysics Data System (ADS)
Zhu, Tianjun; Li, Bin; Zong, Changfu; Wu, Yang
2017-09-01
Hybrid electric vehicles (HEV), compared with conventional vehicles, have complex structures and more component parameters. If variables optimization designs are carried on all these parameters, it will increase the difficulty and the convergence of algorithm program, so this paper chooses the parameters which has a major influence on the vehicle fuel consumption to make it all work at maximum efficiency. First, HEV powertrain components modelling are built. Second, taking a tandem hybrid structure as an example, genetic algorithm is used in this paper to optimize fuel consumption and emissions. Simulation results in ADVISOR verify the feasibility of the proposed genetic optimization algorithm.
Philibert, Robert; Dogan, Meesha; Noel, Amanda; Miller, Shelly; Krukow, Brianna; Papworth, Emma; Cowley, Joseph; Long, Jeffrey D; Beach, Steven R H; Black, Donald W
2018-01-01
The tobacco use disorders are the largest preventable cause of morbidity and mortality in the world. A substantial barrier to the development of better intervention and screening measures is the lack of clinically employable biomarkers to detect the existence and extent of tobacco consumption. In prior work, we and others have shown that array based assessment of DNA methylation status at cg05575921 is a sensitive and quantitative method for assessing cigarette consumption. Unfortunately, in general, arrays are not practical clinical tools. Herein, we detail the prediction performance metrics and dose dependency of a clinically implementable droplet digital PCR (ddPCR) assay for cigarette consumption in adults. First, we demonstrate that measurements of cg05575921 as determined by Illumina array and ddPCR are highly correlated ( R 2 = 0.98, n = 92). Second, using clinical data and biomaterial from 177 subjects ranging from 18 to 78 years of age, we show that the Receiver Operating Characteristic (ROC) area under the curve (AUC) for classifying smoking status using methylation status at cg05575921 is 0.99. Finally, we conduct modeling analyses of cigarette consumption over discrete time periods to show that methylation status is best correlated with mean cigarette consumption over the past year ( R 2 = 0.5) and that demethylation at cg05575921 is dose dependent with a demethylation (delta beta) of 1% being equivalent to 1.2 cigarettes per day. But we do not find a relationship between Fagerstrom score and DNA methylation. We conclude that ddPCR assessment of cg05575921 methylation is an accurate method for assessing the presence and extent of cigarette consumption in adult subjects. We suggest that skillful clinical implementation of this approach alone or in combination with other assessment methods could lead to substantial reduction of cigarette consumption related morbidity and mortality.
Philibert, Robert; Dogan, Meesha; Noel, Amanda; Miller, Shelly; Krukow, Brianna; Papworth, Emma; Cowley, Joseph; Long, Jeffrey D.; Beach, Steven R. H.; Black, Donald W.
2018-01-01
The tobacco use disorders are the largest preventable cause of morbidity and mortality in the world. A substantial barrier to the development of better intervention and screening measures is the lack of clinically employable biomarkers to detect the existence and extent of tobacco consumption. In prior work, we and others have shown that array based assessment of DNA methylation status at cg05575921 is a sensitive and quantitative method for assessing cigarette consumption. Unfortunately, in general, arrays are not practical clinical tools. Herein, we detail the prediction performance metrics and dose dependency of a clinically implementable droplet digital PCR (ddPCR) assay for cigarette consumption in adults. First, we demonstrate that measurements of cg05575921 as determined by Illumina array and ddPCR are highly correlated (R2 = 0.98, n = 92). Second, using clinical data and biomaterial from 177 subjects ranging from 18 to 78 years of age, we show that the Receiver Operating Characteristic (ROC) area under the curve (AUC) for classifying smoking status using methylation status at cg05575921 is 0.99. Finally, we conduct modeling analyses of cigarette consumption over discrete time periods to show that methylation status is best correlated with mean cigarette consumption over the past year (R2 = 0.5) and that demethylation at cg05575921 is dose dependent with a demethylation (delta beta) of 1% being equivalent to 1.2 cigarettes per day. But we do not find a relationship between Fagerstrom score and DNA methylation. We conclude that ddPCR assessment of cg05575921 methylation is an accurate method for assessing the presence and extent of cigarette consumption in adult subjects. We suggest that skillful clinical implementation of this approach alone or in combination with other assessment methods could lead to substantial reduction of cigarette consumption related morbidity and mortality. PMID:29740475
Coffee and caffeine consumption and depression: A meta-analysis of observational studies.
Wang, Longfei; Shen, Xiaoli; Wu, Yili; Zhang, Dongfeng
2016-03-01
The results from observation studies on the relationship between coffee intake and risk of depression and the relationship between caffeine consumption and depression remain controversial. We conducted a meta-analysis with a dose-response analysis to quantitatively summarize the evidence about the association between coffee and caffeine intakes and risk of depression. Relevant articles were identified by researching PubMed, Web of Science, China National Knowledge Infrastructure and WANFANG DATA in English or Chinese from 1 January 1980 to 1 May 2015. Case-control, cohort or cross-sectional studies evaluating coffee or caffeine consumption and depression were included. A random-effects model was used to combine study-specific relative risk and 95% confidence interval. Dose-response relationship was assessed by restricted cubic spline functions. Data were obtained from 11 observation articles; 330,677 participants from seven studies in seven articles were included in the coffee-depression analysis, while 38,223 participants from eight studies in seven articles were involved in the caffeine-depression analysis. Compared with the lowest level consumption, the pooled relative risk (95% confidence interval) for coffee-depression and caffeine-depression was 0.757 [0.624, 0.917] and 0.721 [0.522, 0.997], respectively. For dose-response analysis, evidence of a linear association was found between coffee consumption and depression, and the risk of depression decreased by 8% (relative risk = 0.92, 95% confidence interval = [0.87, 0.97], p = 0.002) for each cup/day increment in coffee intake; a nonlinear association was found between caffeine consumption and depression, the risk of depression decreased faster and the association became significant when the caffeine consumption was above 68 mg/day and below 509 mg/day. Coffee and caffeine consumption were significantly associated with decreased risk of depression. © The Royal Australian and New Zealand College of Psychiatrists 2015.
Oxytocin Reduces Ethanol Self-Administration in Mice
King, Courtney E.; Griffin, William C.; Luderman, Lauryn N.; Kates, Malcolm M.; McGinty, Jacqueline F.; Becker, Howard C.
2017-01-01
Background Excessive ethanol consumption remains an important health concern and effective treatments are lacking. The central oxytocin system has emerged as a potentially important therapeutic target for alcohol and drug addiction. These studies tested the hypothesis that oxytocin reduces ethanol consumption. Methods Male C57BL/6J mice were given access to ethanol (20% v/v) using a model of binge-like drinking (“drinking-in-the-dark”) that also included the use of lickometer circuits to evaluate the temporal pattern of intake as well as 2-bottle choice drinking in the home cage. In addition, ethanol (12% v/v) and sucrose (5% w/v) self-administration on fixed- and progressive- ratio schedules were also evaluated. A wide range of systemically administered oxytocin doses were tested (0 to 10 mg/kg) in these models. Results Oxytocin (0, 0.3, 1, 3 or 10mg/kg) dose-dependently reduced ethanol consumption (maximal 45% reducton) in the binge drinking model, with lower effective doses having minimal effects on general locomotor activity. Oxytocin’s effect was blocked by pretreatment with an oxytocin receptor antagonist and the pattern of contacts (licks) at the ethanol bottle suggested a reduction in motivation to drink ethanol. Oxytocin decreased 2-bottle choice drinking without altering general fluid intake. Oxytocin also reduced operant responding for ethanol and sucrose in a dose-related manner. However, oxytocin decreased responding and motivation (breakpoint values) for ethanol at doses that did not alter responding for sucrose. Discussion These results indicate that oxytocin reduces ethanol consumption in different models of self-administration. The effects are not likely due to a general sedative effect of the neuropeptide. Further, oxytocin reduces motivation for ethanol at doses that do not alter responding for a natural reward (sucrose). While some evidence supports a role for oxytocin receptors in mediating these effects, additional studies are needed to further elucidate underlying mechanisms. Neverthess, these results support the therapeutic potential of oxytocin as a treatment for alcohol use disorder. PMID:28212464
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gorissen, BL; Giantsoudi, D; Unkelbach, J
Purpose: Cell survival experiments suggest that the relative biological effectiveness (RBE) of proton beams depends on linear energy transfer (LET), leading to higher RBE near the end of range. With intensity-modulated proton therapy (IMPT), multiple treatment plans that differ in the dose contribution per field may yield a similar physical dose distribution, but the RBE-weighted dose distribution may be disparate. RBE models currently do not have the required predictive power to be included in an optimization model due to the variations in experimental data. We propose an LET-based planning method that guides IMPT optimization models towards plans with reduced RBE-weightedmore » dose in surrounding organs at risk (OARs) compared to inverse planning based on physical dose alone. Methods: Optimization models for physical dose are extended with a term for dose times LET (doseLET). Monte Carlo code is used to generate the physical dose and doseLET distribution of each individual pencil beam. The method is demonstrated for an atypical meningioma patient where the target volume abuts the brainstem and partially overlaps with the optic nerve. Results: A reference plan optimized based on physical dose alone yields high doseLET values in parts of the brainstem and optic nerve. Minimizing doseLET in these critical structures as an additional planning goal reduces the risk of high RBE-weighted dose. The resulting treatment plan avoids the distal fall-off of the Bragg peaks for shaping the dose distribution in front of critical stuctures. The maximum dose in the OARs evaluated with RBE models from literature is reduced by 8–14\\% with our method compared to conventional planning. Conclusion: LET-based inverse planning for IMPT offers the ability to reduce the RBE-weighted dose in OARs without sacrificing target dose. This project was in part supported by NCI - U19 CA 21239.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shi, F; Tian, Z; Jia, X
Purpose: In treatment plan optimization for Intensity Modulated Radiation Therapy (IMRT), after a plan is initially developed by a dosimetrist, the attending physician evaluates its quality and often would like to improve it. As opposed to having the dosimetrist implement the improvements, it is desirable to have the physician directly and efficiently modify the plan for a more streamlined and effective workflow. In this project, we developed an interactive optimization system for physicians to conveniently and efficiently fine-tune iso-dose curves. Methods: An interactive interface is developed under C++/Qt. The physician first examines iso-dose lines. S/he then picks an iso-dose curvemore » to be improved and drags it to a more desired configuration using a computer mouse or touchpad. Once the mouse is released, a voxel-based optimization engine is launched. The weighting factors corresponding to voxels between the iso-dose lines before and after the dragging are modified. The underlying algorithm then takes these factors as input to re-optimize the plan in near real-time on a GPU platform, yielding a new plan best matching the physician's desire. The re-optimized DVHs and iso-dose curves are then updated for the next iteration of modifications. This process is repeated until a physician satisfactory plan is achieved. Results: We have tested this system for a series of IMRT plans. Results indicate that our system provides the physicians an intuitive and efficient tool to edit the iso-dose curves according to their preference. The input information is used to guide plan re-optimization, which is achieved in near real-time using our GPU-based optimization engine. Typically, a satisfactory plan can be developed by a physician in a few minutes using this tool. Conclusion: With our system, physicians are able to manipulate iso-dose curves according to their preferences. Preliminary results demonstrate the feasibility and effectiveness of this tool.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Y
2016-06-15
Purpose: To test the impact of the use of apex optimization points for new vaginal cylinder (VC) applicators. Methods: New “ClickFit” single channel VC applicators (Varian) that have a different top thicknesses but the same diameters as the old VC applicators (2.3 cm diameter, 2.6 cm, 3.0 cm, and 3.5 cm) were compared using phantom studies. Old VC applicator plans without apex optimization points were also compared to the plans with the optimization points. The apex doses were monitored at 5 mm depth doses (8 points) where a prescription dose (Rx) of 6Gy was prescribed. VC surface doses (8 points)more » were also analyzed. Results: The new VC applicator plans without apex optimization points presented significantly lower 5mm depth doses than Rx (on average −31 ± 7%, p <0.00001) due to their thicker VC tops (3.4 ± 1.1 mm thicker with the range of 1.2 to 4.4 mm) than the old VC applicators. Old VC applicator plans also showed a statistically significant reduction (p <0.00001) due to Ir-192 source anisotropic effect at the apex region but the % reduction over Rx was only −7 ± 9%. However, by adding apex optimization points to the new VC applicator plans, the plans improved 5 mm depth doses (−7 ± 9% over Rx) that were not statistically different from old VC plans (p = 0.923), along with apex VC surface doses (−22 ± 10% over old VC versus −46 ± 7% without using apex optimization points). Conclusion: The use of apex optimization points are important in order to avoid significant additional cold doses (−24 ± 2%) at the prescription depth (5 mm) of apex, especially for the new VC applicators that have thicker tops.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gomez-Cardona, D; Li, K; Lubner, M G
Purpose: The introduction of the highly nonlinear MBIR algorithm to clinical CT systems has made CNR an invalid metric for kV optimization. The purpose of this work was to develop a task-based framework to unify kV and mAs optimization for both FBP- and MBIR-based CT systems. Methods: The kV-mAs optimization was formulated as a constrained minimization problem: to select kV and mAs to minimize dose under the constraint of maintaining the detection performance as clinically prescribed. To experimentally solve this optimization problem, exhaustive measurements of detectability index (d’) for a hepatic lesion detection task were performed at 15 different mAmore » levels and 4 kV levels using an anthropomorphic phantom. The measured d’ values were used to generate an iso-detectability map; similarly, dose levels recorded at different kV-mAs combinations were used to generate an iso-dose map. The iso-detectability map was overlaid on top of the iso-dose map so that for a prescribed detectability level d’, the optimal kV-mA can be determined from the crossing between the d’ contour and the dose contour that corresponds to the minimum dose. Results: Taking d’=16 as an example: the kV-mAs combinations on the measured iso-d’ line of MBIR are 80–150 (3.8), 100–140 (6.6), 120–150 (11.3), and 140–160 (17.2), where values in the parentheses are measured dose values. As a Result, the optimal kV was 80 and optimal mA was 150. In comparison, the optimal kV and mA for FBP were 100 and 500, which corresponded to a dose level of 24 mGy. Results of in vivo animal experiments were consistent with the phantom results. Conclusion: A new method to optimize kV and mAs selection has been developed. This method is applicable to both linear and nonlinear CT systems such as those using MBIR. Additional dose savings can be achieved by combining MBIR with this method. This work was partially supported by an NIH grant R01CA169331 and GE Healthcare. K. Li, D. Gomez-Cardona, M. G. Lubner: Nothing to disclose. P. J. Pickhardt: Co-founder, VirtuoCTC, LLC Stockholder, Cellectar Biosciences, Inc. G.-H. Chen: Research funded, GE Healthcare; Research funded, Siemens AX.« less
Tang, Haijing; Wang, Siye; Zhang, Yanjun
2013-01-01
Clustering has become a common trend in very long instruction words (VLIW) architecture to solve the problem of area, energy consumption, and design complexity. Register-file-connected clustered (RFCC) VLIW architecture uses the mechanism of global register file to accomplish the inter-cluster data communications, thus eliminating the performance and energy consumption penalty caused by explicit inter-cluster data move operations in traditional bus-connected clustered (BCC) VLIW architecture. However, the limit number of access ports to the global register file has become an issue which must be well addressed; otherwise the performance and energy consumption would be harmed. In this paper, we presented compiler optimization techniques for an RFCC VLIW architecture called Lily, which is designed for encryption systems. These techniques aim at optimizing performance and energy consumption for Lily architecture, through appropriate manipulation of the code generation process to maintain a better management of the accesses to the global register file. All the techniques have been implemented and evaluated. The result shows that our techniques can significantly reduce the penalty of performance and energy consumption due to access port limitation of global register file. PMID:23970841
DOE Office of Scientific and Technical Information (OSTI.GOV)
Liu, X; Belcher, AH; Grelewicz, Z
Purpose: Real-time kV fluoroscopic tumor tracking has the benefit of direct tumor position monitoring. However, there is clinical concern over the excess kV imaging dose cost to the patient when imaging in continuous fluoroscopic mode. This work addresses this specific issue by proposing a combined MV+kV direct-aperture optimization (DAO) approach to integrate the kV imaging beam into a treatment planning such that the kV radiation is considered as a contributor to the overall dose delivery. Methods: The combined MV+kV DAO approach includes three algorithms. First, a projected Quasi-Newton algorithm (L-BFGS) is used to find optimized fluence with MV+kV dose formore » the best possible dose distribution. Then, Engel’s algorithm is applied to optimize the total number of monitor units and heuristically optimize the number of apertures. Finally, an aperture shape optimization (ASO) algorithm is applied to locally optimize the leaf positions of MLC. Results: Compared to conventional DAO MV plans with continuous kV fluoroscopic tracking, combined MV+kV DAO plan leads to a reduction in the total number of MV monitor units due to inclusion of kV dose as part of the PTV, and was also found to reduce the mean and maximum doses on the organs at risk (OAR). Compared to conventional DAO MV plan without kV tracking, the OAR dose in the combined MV+kV DAO plan was only slightly higher. DVH curves show that combined MV+kV DAO plan provided about the same PTV coverage as that in the conventional DAO plans without kV imaging. Conclusion: We report a combined MV+kV DAO approach that allows real time kV imager tumor tracking with only a trivial increasing on the OAR doses while providing the same coverage to PTV. The approach is suitable for clinic implementation.« less
System and method of cylinder deactivation for optimal engine torque-speed map operation
Sujan, Vivek A; Frazier, Timothy R; Follen, Kenneth; Moon, Suk-Min
2014-11-11
This disclosure provides a system and method for determining cylinder deactivation in a vehicle engine to optimize fuel consumption while providing the desired or demanded power. In one aspect, data indicative of terrain variation is utilized in determining a vehicle target operating state. An optimal active cylinder distribution and corresponding fueling is determined from a recommendation from a supervisory agent monitoring the operating state of the vehicle of a subset of the total number of cylinders, and a determination as to which number of cylinders provides the optimal fuel consumption. Once the optimal cylinder number is determined, a transmission gear shift recommendation is provided in view of the determined active cylinder distribution and target operating state.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Unkelbach, Jan, E-mail: junkelbach@mgh.harvard.edu; Botas, Pablo; Faculty of Physics, Ruprecht-Karls-Universität Heidelberg, Heidelberg
Purpose: We describe a treatment plan optimization method for intensity modulated proton therapy (IMPT) that avoids high values of linear energy transfer (LET) in critical structures located within or near the target volume while limiting degradation of the best possible physical dose distribution. Methods and Materials: To allow fast optimization based on dose and LET, a GPU-based Monte Carlo code was extended to provide dose-averaged LET in addition to dose for all pencil beams. After optimizing an initial IMPT plan based on physical dose, a prioritized optimization scheme is used to modify the LET distribution while constraining the physical dosemore » objectives to values close to the initial plan. The LET optimization step is performed based on objective functions evaluated for the product of LET and physical dose (LET×D). To first approximation, LET×D represents a measure of the additional biological dose that is caused by high LET. Results: The method is effective for treatments where serial critical structures with maximum dose constraints are located within or near the target. We report on 5 patients with intracranial tumors (high-grade meningiomas, base-of-skull chordomas, ependymomas) in whom the target volume overlaps with the brainstem and optic structures. In all cases, high LET×D in critical structures could be avoided while minimally compromising physical dose planning objectives. Conclusion: LET-based reoptimization of IMPT plans represents a pragmatic approach to bridge the gap between purely physical dose-based and relative biological effectiveness (RBE)-based planning. The method makes IMPT treatments safer by mitigating a potentially increased risk of side effects resulting from elevated RBE of proton beams near the end of range.« less
Maricelli, Joseph W; Bishaw, Yemeserach M; Wang, Bo; Du, Min; Rodgers, Buel D
2018-03-01
Striated muscle wasting occurs with a variety of disease indications, contributing to mortality and compromising life quality. Recent studies indicate that the recombinant adeno-associated virus (serotype 6) Smad7 gene therapeutic, AVGN7, enhances skeletal and cardiac muscle mass and prevents cancer-induced wasting of both tissues. This is accomplished by attenuating ActRIIb intracellular signaling and, as a result, the physiological actions of myostatin and other ActRIIb ligands. AVGN7 also enhances isolated skeletal muscle twitch force, but is unknown to improve systemic muscle function similarly, especially exercise capacity. A 2-month-long dose-escalation study was therefore conducted using 5 × 10 11 , 1 × 10 12 , and 5 × 10 12 vg/mouse and different tests of systemic muscle function. Body mass, skeletal muscle mass, heart mass, and forelimb grip strength were all increased in a dose-dependent manner, as was the fiber cross-sectional area of tibialis anterior muscles. Maximal oxygen consumption (VO 2 max), a measure of metabolic rate, was similarly enhanced during forced treadmill running, and although the total distance traveled was only elevated by the highest dose, all doses reduced the energy expenditure rate compared to control mice injected with an empty vector. Such improvements in VO 2 max are consistent with physiological cardiac hypertrophy, which is highly beneficial and a normal adaptive response to exercise. This was particularly evident at the lowest dose tested, which had minimal significant effects on skeletal muscle mass and/or function, but increased heart weight and exercise capacity. These results together suggest that AVGN7 enhances striated muscle mass and systemic muscle function. They also define minimally effective and optimal doses for future preclinical trials and toxicology studies and in turn will aid in establishing dose ranges for clinical trials.
Li, Ke; Gomez-Cardona, Daniel; Hsieh, Jiang; Lubner, Meghan G.; Pickhardt, Perry J.; Chen, Guang-Hong
2015-01-01
Purpose: For a given imaging task and patient size, the optimal selection of x-ray tube potential (kV) and tube current-rotation time product (mAs) is pivotal in achieving the maximal radiation dose reduction while maintaining the needed diagnostic performance. Although contrast-to-noise (CNR)-based strategies can be used to optimize kV/mAs for computed tomography (CT) imaging systems employing the linear filtered backprojection (FBP) reconstruction method, a more general framework needs to be developed for systems using the nonlinear statistical model-based iterative reconstruction (MBIR) method. The purpose of this paper is to present such a unified framework for the optimization of kV/mAs selection for both FBP- and MBIR-based CT systems. Methods: The optimal selection of kV and mAs was formulated as a constrained optimization problem to minimize the objective function, Dose(kV,mAs), under the constraint that the achievable detectability index d′(kV,mAs) is not lower than the prescribed value of d℞′ for a given imaging task. Since it is difficult to analytically model the dependence of d′ on kV and mAs for the highly nonlinear MBIR method, this constrained optimization problem is solved with comprehensive measurements of Dose(kV,mAs) and d′(kV,mAs) at a variety of kV–mAs combinations, after which the overlay of the dose contours and d′ contours is used to graphically determine the optimal kV–mAs combination to achieve the lowest dose while maintaining the needed detectability for the given imaging task. As an example, d′ for a 17 mm hypoattenuating liver lesion detection task was experimentally measured with an anthropomorphic abdominal phantom at four tube potentials (80, 100, 120, and 140 kV) and fifteen mA levels (25 and 50–700) with a sampling interval of 50 mA at a fixed rotation time of 0.5 s, which corresponded to a dose (CTDIvol) range of [0.6, 70] mGy. Using the proposed method, the optimal kV and mA that minimized dose for the prescribed detectability level of d℞′=16 were determined. As another example, the optimal kV and mA for an 8 mm hyperattenuating liver lesion detection task were also measured using the developed framework. Both an in vivo animal and human subject study were used as demonstrations of how the developed framework can be applied to the clinical work flow. Results: For the first task, the optimal kV and mAs were measured to be 100 and 500, respectively, for FBP, which corresponded to a dose level of 24 mGy. In comparison, the optimal kV and mAs for MBIR were 80 and 150, respectively, which corresponded to a dose level of 4 mGy. The topographies of the iso-d′ map and the iso-CNR map were the same for FBP; thus, the use of d′- and CNR-based optimization methods generated the same results for FBP. However, the topographies of the iso-d′ and iso-CNR map were significantly different in MBIR; the CNR-based method overestimated the performance of MBIR, predicting an overly aggressive dose reduction factor. For the second task, the developed framework generated the following optimization results: for FBP, kV = 140, mA = 350, dose = 37.5 mGy; for MBIR, kV = 120, mA = 250, dose = 18.8 mGy. Again, the CNR-based method overestimated the performance of MBIR. Results of the preliminary in vivo studies were consistent with those of the phantom experiments. Conclusions: A unified and task-driven kV/mAs optimization framework has been developed in this work. The framework is applicable to both linear and nonlinear CT systems such as those using the MBIR method. As expected, the developed framework can be reduced to the conventional CNR-based kV/mAs optimization frameworks if the system is linear. For MBIR-based nonlinear CT systems, however, the developed task-based kV/mAs optimization framework is needed to achieve the maximal dose reduction while maintaining the desired diagnostic performance. PMID:26328971
García-Esquinas, Esther; Rahi, Berna; Peres, Karine; Colpo, Marco; Dartigues, Jean-François; Bandinelli, Stefania; Feart, Catherine; Rodríguez-Artalejo, Fernando
2016-07-01
Consuming fruit and vegetables (FVs) may protect against frailty, but to our knowledge no study has yet assessed their prospective dose-response relation. We sought to examine the dose-response association between FV consumption and the risk of frailty in older adults. Data were taken from 3 independent cohorts of community-dwelling older adults: the Seniors-ENRICA (Study on Nutrition and Cardiovascular Risk Factors in Spain) cohort (n = 1872), Three-City (3C) Bordeaux cohort (n = 581), and integrated multidisciplinary approach cohort (n = 473). Baseline food consumption was assessed with a validated computerized diet history (Seniors-ENRICA) or with a food-frequency questionnaire (3C Bordeaux and AMI). In all cohorts, incident frailty was assessed with the use of the Fried criteria. Results across cohorts were pooled with the use of a random-effects model. During a mean 2.5-y follow-up, 300 incident frailty cases occurred. Fully adjusted models showed that the pooled ORs (95% CIs) of incident frailty comparing participants who consumed 1, 2, or ≥3 portions of fruit/d to those with no consumption were, respectively, 0.59 (0.27, 0.90), 0.58 (0.29, 0.86), and 0.48 (0.20, 0.75), with a P-trend of 0.04. The corresponding values for vegetables were 0.69 (0.42, 0.97), 0.56 (0.35, 0.77), and 0.52 (0.13, 0.92), with a P-trend < 0.01. When FVs were analyzed together, the pooled ORs (95% CIs) of incident frailty were 0.41 (0.21, 0.60), 0.47 (0.25, 0.68), 0.36 (0.18, 0.53), and 0.31 (0.13, 0.48), with a P-trend < 0.01 for participants who consumed 2, 3, 4, or ≥5 portions/d, respectively, compared with those who consumed ≤1 portion/d. An inverse dose-response relation was also found between the baseline consumption of fruit and risk of exhaustion, low physical activity, and slow walking speed, whereas the consumption of vegetables was associated with a decreased risk of exhaustion and unintentional weight loss. Among community-dwelling older adults, FV consumption was associated with a lower short-term risk of frailty in a dose-response manner, and the strongest association was obtained with 3 portions of fruit/d and 2 portions of vegetables/d. © 2016 American Society for Nutrition.
Fruits and vegetables consumption and risk of stroke: a meta-analysis of prospective cohort studies.
Hu, Dan; Huang, Junqian; Wang, Yuchun; Zhang, Dongfeng; Qu, Yan
2014-06-01
We conducted a meta-analysis to summarize evidence from prospective cohort studies about the association of fruits and vegetables consumption with the risk of stroke. Pertinent studies were identified by a search of Embase and PubMed databases to January 2014. Study-specific relative risks with 95% confidence intervals were pooled using a random-effects model. Dose-response relationship was assessed by restricted cubic spline. Twenty prospective cohort studies were included, involving 16 981 stroke events among 760 629 participants. The multivariable relative risk (95% confidence intervals) of stroke for the highest versus lowest category of total fruits and vegetables consumption was 0.79 (0.75-0.84), and the effect was 0.77 (0.71-0.84) for fruits consumption and 0.86 (0.79-0.93) for vegetables consumption. Subgroup and meta-regression showed that the inverse association of total fruits and vegetables consumption with the risk of stroke was consistent in subgroup analysis. Citrus fruits, apples/pears, and leafy vegetables might contribute to the protection. The linear dose-response relationship showed that the risk of stroke decreased by 32% (0.68 [0.56-0.82]) and 11% (0.89 [0.81-0.98]) for every 200 g per day increment in fruits consumption (P for nonlinearity=0.77) and vegetables consumption (P for nonlinearity=0.62), respectively. Fruits and vegetables consumption are inversely associated with the risk of stroke. © 2014 American Heart Association, Inc.
Whey protein: The “whey” forward for treatment of type 2 diabetes?
Mignone, Linda E; Wu, Tongzhi; Horowitz, Michael; Rayner, Christopher K
2015-01-01
A cost-effective nutritional approach to improve postprandial glycaemia is attractive considering the rising burden of diabetes throughout the world. Whey protein, a by-product of the cheese-making process, can be used to manipulate gut function in order to slow gastric emptying and stimulate incretin hormone secretion, thereby attenuating postprandial glycaemic excursions. The function of the gastrointestinal tract plays a pivotal role in glucose homeostasis, particularly during the postprandial period, and this review will discuss the mechanisms by which whey protein slows gastric emptying and stimulates release of gut peptides, including the incretins. Whey protein is also a rich source of amino acids, and these can directly stimulate beta cells to secrete insulin, which contributes to the reduction in postprandial glycaemia. Appetite is suppressed with consumption of whey, due to its effects on the gut-brain axis and the hypothalamus. These properties of whey protein suggest its potential in the management of type 2 diabetes. However, the optimal dose and timing of whey protein ingestion are yet to be defined, and studies are required to examine the long-term benefits of whey consumption for overall glycaemic control. PMID:26516411
NASA Astrophysics Data System (ADS)
Kant Garg, Girish; Garg, Suman; Sangwan, K. S.
2018-04-01
The manufacturing sector consumes huge energy demand and the machine tools used in this sector have very less energy efficiency. Selection of the optimum machining parameters for machine tools is significant for energy saving and for reduction of environmental emission. In this work an empirical model is developed to minimize the power consumption using response surface methodology. The experiments are performed on a lathe machine tool during the turning of AISI 6061 Aluminum with coated tungsten inserts. The relationship between the power consumption and machining parameters is adequately modeled. This model is used for formulation of minimum power consumption criterion as a function of optimal machining parameters using desirability function approach. The influence of machining parameters on the energy consumption has been found using the analysis of variance. The validation of the developed empirical model is proved using the confirmation experiments. The results indicate that the developed model is effective and has potential to be adopted by the industry for minimum power consumption of machine tools.
Postprandial effects of wine consumption on lipids and oxidative stress biomarkers.
Covas, M I; Konstantinidou, V; Mysytaki, E; Fitó, M; Weinbrenner, T; De La Torre, R; Farré-Albadalejo, M; Lamuela-Raventós, R
2003-01-01
Postprandial lipemia has been recognized as a risk factor for atherosclerosis development. Consuming meals with suitable sources of antioxidants such as red wine reduces postprandial oxidative stress. However, information about the postprandial effects of wine ingestion outside meals on lipids and on in vivo low-density lipoprotein (LDL) oxidation in humans is scarce. The aim of this study was to investigate postprandial changes in lipids and in vivo LDL oxidation after moderate (250 ml) red wine ingestion, before and after sustained wine consumption of 250 ml/day for 4 days. After 4 days of sustained wine consumption a decrease in the LDL/high-density lipoprotein cholesterol ratio was observed after wine ingestion (p = 0.026). On day 4, a decrease in oxidized LDL levels and an increase in the antioxidant enzyme glutathione peroxidase activity (p = 0.025) were observed after wine ingestion. Our results show that consumption of red wine at moderate doses outside meals does not promote oxidative stress. Daily consumption of moderate doses of red wine can improve postprandial lipid profile and oxidative status when wine is ingested outside meals.
Analysis and Optimization of Building Energy Consumption
NASA Astrophysics Data System (ADS)
Chuah, Jun Wei
Energy is one of the most important resources required by modern human society. In 2010, energy expenditures represented 10% of global gross domestic product (GDP). By 2035, global energy consumption is expected to increase by more than 50% from current levels. The increased pace of global energy consumption leads to significant environmental and socioeconomic issues: (i) carbon emissions, from the burning of fossil fuels for energy, contribute to global warming, and (ii) increased energy expenditures lead to reduced standard of living. Efficient use of energy, through energy conservation measures, is an important step toward mitigating these effects. Residential and commercial buildings represent a prime target for energy conservation, comprising 21% of global energy consumption and 40% of the total energy consumption in the United States. This thesis describes techniques for the analysis and optimization of building energy consumption. The thesis focuses on building retrofits and building energy simulation as key areas in building energy optimization and analysis. The thesis first discusses and evaluates building-level renewable energy generation as a solution toward building energy optimization. The thesis next describes a novel heating system, called localized heating. Under localized heating, building occupants are heated individually by directed radiant heaters, resulting in a considerably reduced heated space and significant heating energy savings. To support localized heating, a minimally-intrusive indoor occupant positioning system is described. The thesis then discusses occupant-level sensing (OLS) as the next frontier in building energy optimization. OLS captures the exact environmental conditions faced by each building occupant, using sensors that are carried by all building occupants. The information provided by OLS enables fine-grained optimization for unprecedented levels of energy efficiency and occupant comfort. The thesis also describes a retrofit-oriented building energy simulator, ROBESim, that natively supports building retrofits. ROBESim extends existing building energy simulators by providing a platform for the analysis of novel retrofits, in addition to simulating existing retrofits. Using ROBESim, retrofits can be automatically applied to buildings, obviating the need for users to manually update building characteristics for comparisons between different building retrofits. ROBESim also includes several ease-of-use enhancements to support users of all experience levels.
NASA Astrophysics Data System (ADS)
Zhu, Zhenzhou; Guan, Qingyan; Guo, Ying; He, Jingren; Liu, Gang; Li, Shuyi; Barba, Francisco J.; Jaffrin, Michel Y.
2016-01-01
Response surface methodology was used to optimize experimental conditions for ultrasound-assisted extraction of valuable components (anthocyanins and phenolics) from purple sweet potatoes using water as a solvent. The Box-Behnken design was used for optimizing extraction responses of anthocyanin extraction yield, phenolic extraction yield, and specific energy consumption. Conditions to obtain maximal anthocyanin extraction yield, maximal phenolic extraction yield, and minimal specific energy consumption were different; an overall desirability function was used to search for overall optimal conditions: extraction temperature of 68ºC, ultrasonic treatment time of 52 min, and a liquid/solid ratio of 20. The optimized anthocyanin extraction yield, phenolic extraction yield, and specific energy consumption were 4.91 mg 100 g-1 fresh weight, 3.24 mg g-1 fresh weight, and 2.07 kWh g-1, respectively, with a desirability of 0.99. This study indicates that ultrasound-assisted extraction should contribute to a green process for valorization of purple sweet potatoes.
Liu, W; Mohan, R
2012-06-01
Proton dose distributions, IMPT in particular, are highly sensitive to setup and range uncertainties. We report a novel method, based on per-voxel standard deviation (SD) of dose distributions, to evaluate the robustness of proton plans and to robustly optimize IMPT plans to render them less sensitive to uncertainties. For each optimization iteration, nine dose distributions are computed - the nominal one, and one each for ± setup uncertainties along x, y and z axes and for ± range uncertainty. SD of dose in each voxel is used to create SD-volume histogram (SVH) for each structure. SVH may be considered a quantitative representation of the robustness of the dose distribution. For optimization, the desired robustness may be specified in terms of an SD-volume (SV) constraint on the CTV and incorporated as a term in the objective function. Results of optimization with and without this constraint were compared in terms of plan optimality and robustness using the so called'worst case' dose distributions; which are obtained by assigning the lowest among the nine doses to each voxel in the clinical target volume (CTV) and the highest to normal tissue voxels outside the CTV. The SVH curve and the area under it for each structure were used as quantitative measures of robustness. Penalty parameter of SV constraint may be varied to control the tradeoff between robustness and plan optimality. We applied these methods to one case each of H&N and lung. In both cases, we found that imposing SV constraint improved plan robustness but at the cost of normal tissue sparing. SVH-based optimization and evaluation is an effective tool for robustness evaluation and robust optimization of IMPT plans. Studies need to be conducted to test the methods for larger cohorts of patients and for other sites. This research is supported by National Cancer Institute (NCI) grant P01CA021239, the University Cancer Foundation via the Institutional Research Grant program at the University of Texas MD Anderson Cancer Center, and MD Anderson’s cancer center support grant CA016672. © 2012 American Association of Physicists in Medicine.
Program optimizations: The interplay between power, performance, and energy
Leon, Edgar A.; Karlin, Ian; Grant, Ryan E.; ...
2016-05-16
Practical considerations for future supercomputer designs will impose limits on both instantaneous power consumption and total energy consumption. Working within these constraints while providing the maximum possible performance, application developers will need to optimize their code for speed alongside power and energy concerns. This paper analyzes the effectiveness of several code optimizations including loop fusion, data structure transformations, and global allocations. A per component measurement and analysis of different architectures is performed, enabling the examination of code optimizations on different compute subsystems. Using an explicit hydrodynamics proxy application from the U.S. Department of Energy, LULESH, we show how code optimizationsmore » impact different computational phases of the simulation. This provides insight for simulation developers into the best optimizations to use during particular simulation compute phases when optimizing code for future supercomputing platforms. Here, we examine and contrast both x86 and Blue Gene architectures with respect to these optimizations.« less
Robust optimization methods for cardiac sparing in tangential breast IMRT
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mahmoudzadeh, Houra, E-mail: houra@mie.utoronto.ca; Lee, Jenny; Chan, Timothy C. Y.
Purpose: In left-sided tangential breast intensity modulated radiation therapy (IMRT), the heart may enter the radiation field and receive excessive radiation while the patient is breathing. The patient’s breathing pattern is often irregular and unpredictable. We verify the clinical applicability of a heart-sparing robust optimization approach for breast IMRT. We compare robust optimized plans with clinical plans at free-breathing and clinical plans at deep inspiration breath-hold (DIBH) using active breathing control (ABC). Methods: Eight patients were included in the study with each patient simulated using 4D-CT. The 4D-CT image acquisition generated ten breathing phase datasets. An average scan was constructedmore » using all the phase datasets. Two of the eight patients were also imaged at breath-hold using ABC. The 4D-CT datasets were used to calculate the accumulated dose for robust optimized and clinical plans based on deformable registration. We generated a set of simulated breathing probability mass functions, which represent the fraction of time patients spend in different breathing phases. The robust optimization method was applied to each patient using a set of dose-influence matrices extracted from the 4D-CT data and a model of the breathing motion uncertainty. The goal of the optimization models was to minimize the dose to the heart while ensuring dose constraints on the target were achieved under breathing motion uncertainty. Results: Robust optimized plans were improved or equivalent to the clinical plans in terms of heart sparing for all patients studied. The robust method reduced the accumulated heart dose (D10cc) by up to 801 cGy compared to the clinical method while also improving the coverage of the accumulated whole breast target volume. On average, the robust method reduced the heart dose (D10cc) by 364 cGy and improved the optBreast dose (D99%) by 477 cGy. In addition, the robust method had smaller deviations from the planned dose to the accumulated dose. The deviation of the accumulated dose from the planned dose for the optBreast (D99%) was 12 cGy for robust versus 445 cGy for clinical. The deviation for the heart (D10cc) was 41 cGy for robust and 320 cGy for clinical. Conclusions: The robust optimization approach can reduce heart dose compared to the clinical method at free-breathing and can potentially reduce the need for breath-hold techniques.« less
Lee, Hyunchan; Jang, Minji; Kim, Woonhee; Noh, Jihyun
2017-08-01
Tobacco smoking occurs in a wide array of social circumstances. Social support for quitting is generally used to stop smoking, while peer interactions may be a crucial factor in triggering tobacco use among adolescents. To determine the role of social factors on nicotine dependence, we compared single- and pair-housed rats subjected to voluntary oral nicotine consumption tests. Six-week-old adolescent rats were subjected to experimental procedures and assigned to one of the following groups: a male single group, a male pair group with a sibling, a female single group, and a female pair group with a sibling. To measure voluntary nicotine intake, we adopted a two-bottle free-choice paradigm for each two days using 25 μg/ml and 100 μg/ml nicotine solution. There were no differences in change in body weight or food intake between the two groups of either sex. Pair-housed female rats showed a reduction in nicotine consumption and preference for both low- and high-dose nicotine solution, while pair-housed male rats showed only reduced consumption and preference for high-dose nicotine solution, but not low-dose solution, as compared to single-housed male rats. Nicotine consumption is sex-dependently controlled by the social circumstances of rats. This study broadens our perspectives on the role of social interactions as a therapeutic strategy to treat nicotine addiction-related behaviors depending on sex.
Algorithms for the optimization of RBE-weighted dose in particle therapy.
Horcicka, M; Meyer, C; Buschbacher, A; Durante, M; Krämer, M
2013-01-21
We report on various algorithms used for the nonlinear optimization of RBE-weighted dose in particle therapy. Concerning the dose calculation carbon ions are considered and biological effects are calculated by the Local Effect Model. Taking biological effects fully into account requires iterative methods to solve the optimization problem. We implemented several additional algorithms into GSI's treatment planning system TRiP98, like the BFGS-algorithm and the method of conjugated gradients, in order to investigate their computational performance. We modified textbook iteration procedures to improve the convergence speed. The performance of the algorithms is presented by convergence in terms of iterations and computation time. We found that the Fletcher-Reeves variant of the method of conjugated gradients is the algorithm with the best computational performance. With this algorithm we could speed up computation times by a factor of 4 compared to the method of steepest descent, which was used before. With our new methods it is possible to optimize complex treatment plans in a few minutes leading to good dose distributions. At the end we discuss future goals concerning dose optimization issues in particle therapy which might benefit from fast optimization solvers.
Algorithms for the optimization of RBE-weighted dose in particle therapy
NASA Astrophysics Data System (ADS)
Horcicka, M.; Meyer, C.; Buschbacher, A.; Durante, M.; Krämer, M.
2013-01-01
We report on various algorithms used for the nonlinear optimization of RBE-weighted dose in particle therapy. Concerning the dose calculation carbon ions are considered and biological effects are calculated by the Local Effect Model. Taking biological effects fully into account requires iterative methods to solve the optimization problem. We implemented several additional algorithms into GSI's treatment planning system TRiP98, like the BFGS-algorithm and the method of conjugated gradients, in order to investigate their computational performance. We modified textbook iteration procedures to improve the convergence speed. The performance of the algorithms is presented by convergence in terms of iterations and computation time. We found that the Fletcher-Reeves variant of the method of conjugated gradients is the algorithm with the best computational performance. With this algorithm we could speed up computation times by a factor of 4 compared to the method of steepest descent, which was used before. With our new methods it is possible to optimize complex treatment plans in a few minutes leading to good dose distributions. At the end we discuss future goals concerning dose optimization issues in particle therapy which might benefit from fast optimization solvers.
Thompson, Zoe; Kolb, Erik M; Garland, Theodore
2018-01-01
To explore reward substitution in the context of voluntary exercise, female mice from four replicate high-runner (HR) lines (bred for wheel running) and four non-selected control (C) lines were given simultaneous access to wheels and palatable solutions as competing rewards (two doses of saccharin [0.1, 0.2% w/v]; two doses of common artificial sweetener blends containing saccharin [Sweet 'N Low ® : 0.1, 0.2% w/v], aspartame [Equal ® : 0.04, 0.08% w/v], or sucralose [Splenda ® : 0.08, 0.16% w/v]; or two doses of sucrose [3.5, 10.5% w/v]). Wheel running and fluid consumption were measured daily, with each dose (including plain water) lasting two days and two "washout" days between solutions. In a separate set of mice, the experiment was repeated without wheel access. The artificial sweeteners had no statistical effect on wheel running. However, based on proportional responses, both doses of sucrose significantly elevated wheel running in C but not HR mice. In contrast, the high dose of sucrose suppressed home-cage activity for both linetypes. Both sucrose and the artificial blends generally increased fluid consumption in a dose-dependent manner. When they had access to wheels, HR had a significantly smaller increase in consumption of artificial sweetener blends when compared with C mice, but not when housed without wheels. Overall, these results provide further evidence that the reward system of HR mice has evolved, and specifically suggest that HR mice have a reduced incentive salience for some artificial sweetener blends, likely attributable to the stronger competing reward of wheel running that has evolved in these lines. Copyright © 2017 Elsevier B.V. All rights reserved.
Raatz, Susan K.; Rosenberger, Thad A.; Johnson, LuAnn K.; Wolters, William W.; Burr, Gary S; Picklo, Matthew J.
2013-01-01
Enhanced omega-3 fatty acid (n-3) intake benefits cardiovascular disease (CVD) risk reduction. Increasing consumption at a population level may be better addressed by diet than through supplementation. However, limited data are available on the effect of the dose response to fish intake on plasma levels of n-3 fatty acids. To compare the effects of different doses of farmed Atlantic salmon on plasma phospholipid fatty acid (PLFA) proportions and CVD risk biomarkers (glucose, insulin, HOMAIR, hsCRP, and IL-6) in healthy subjects we performed a randomized 3-period cross-over designed trial (4 wk treatment, 4-8 wk washout) to compare the effects of twice/wk consumption of farmed Atlantic salmon at doses of 90, 180, and 270 g in 19 apparently healthy men and women with a mean age of aged 40-65 years and a BMI between 25-34.9 kg/m2. All study visits were conducted at the USDA, ARS Grand Forks Human Nutrition Research Center. EPA and total n-3 were increased (p<0.05) by all treatments in a dose response manner, with total n-3 of 8.03 ± 0.26 and 9.21 ± 0.26 % for 180 and 270 g doses, respectively. Linoleic acid did not change in response to treatment while arachidonic acid (P<0.05) and total omega-6 fatty acids (n-6) decreased dose dependently (<0.0001). The addition of farmed Atlantic salmon to the diet twice/wk for 4 wk at portions of 180g and 270g modifies PLFA proportions of n-3 and n-6 in a level associated with decreased risk for CVD. PMID:23351633
Maze, Ian S.; Wright, Geraldine A.; Mustard, Julie A.
2006-01-01
Ethanol consumption produces characteristic behavioral states in animals that include sedation, disorientation, and disruption of motor function. Using individual honey bees, we assessed the effects of ethanol ingestion on motor function via continuous observations of their behavior. Consumption of 1 M sucrose solutions containing a range of ethanol doses lead to hemolymph ethanol levels of approximately 40 to 100 mM. Using ethanol doses in this range, we observed time and dose-dependent effects of ethanol on the percent of time our subjects spent walking, stopped, or upside down, and on the duration and frequency of bouts of behavior. The effects on grooming and flying behavior were more complex. Behavioral recovery from ethanol treatment was both time and ethanol dose dependent, occurring between 12 and 24 hr post-ingestion for low doses and at 24 to 48 hours for higher doses. Furthermore, the amount of ethanol measured in honey bee hemolymph appeared to correlate with recovery. We predict that the honey bee will prove to be an excellent model system for studying the influence of ethanol on the neural mechanisms underlying behavior. PMID:17070538
Design Optimization of a Hybrid Electric Vehicle Powertrain
NASA Astrophysics Data System (ADS)
Mangun, Firdause; Idres, Moumen; Abdullah, Kassim
2017-03-01
This paper presents an optimization work on hybrid electric vehicle (HEV) powertrain using Genetic Algorithm (GA) method. It focused on optimization of the parameters of powertrain components including supercapacitors to obtain maximum fuel economy. Vehicle modelling is based on Quasi-Static-Simulation (QSS) backward-facing approach. A combined city (FTP-75)-highway (HWFET) drive cycle is utilized for the design process. Seeking global optimum solution, GA was executed with different initial settings to obtain sets of optimal parameters. Starting from a benchmark HEV, optimization results in a smaller engine (2 l instead of 3 l) and a larger battery (15.66 kWh instead of 2.01 kWh). This leads to a reduction of 38.3% in fuel consumption and 30.5% in equivalent fuel consumption. Optimized parameters are also compared with actual values for HEV in the market.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lee, E; Yuan, F; Templeton, A
Purpose: The ultimate goal of radiotherapy treatment planning is to find a treatment that will yield a high tumor-control-probability(TCP) with an acceptable normal-tissue-complication probability(NTCP). Yet most treatment planning today is not based upon optimization of TCPs and NTCPs, but rather upon meeting physical dose and volume constraints defined by the planner. We design treatment plans that optimize TCP directly and contrast them with the clinical dose-based plans. PET image is incorporated to evaluate gain in TCP for dose escalation. Methods: We build a nonlinear mixed integer programming optimization model that maximizes TCP directly while satisfying the dose requirements on themore » targeted organ and healthy tissues. The solution strategy first fits the TCP function with a piecewise-linear approximation, then solves the problem that maximizes the piecewise linear approximation of TCP, and finally performs a local neighborhood search to improve the TCP value. To gauge the feasibility, characteristics, and potential benefit of PET-image guided dose escalation, initial validation consists of fifteen cervical cancer HDR patient cases. These patients have all received prior 45Gy of external radiation dose. For both escalated strategies, we consider 35Gy PTV-dose, and two variations (37Gy-boost to BTV vs 40Gy-boost) to PET-image-pockets. Results: TCP for standard clinical plans range from 59.4% - 63.6%. TCP for dose-based PET-guided escalated-dose-plan ranges from 63.8%–98.6% for all patients; whereas TCP-optimized plans achieves over 91% for all patients. There is marginal difference in TCP among those with 37Gy-boosted vs 40Gy-boosted. There is no increase in rectum and bladder dose among all plans. Conclusion: Optimizing TCP directly results in highly conformed treatment plans. The TCP-optimized plan is individualized based on the biological PET-image of the patients. The TCP-optimization framework is generalizable and has been applied successfully to other external-beam delivery modalities. A clinical trial is on-going to gauge the clinical significance. Partially supported by the National Science Foundation.« less
MO-DE-204-02: Optimization of the Patient CT Dose in Europe
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tsapaki, V.
2016-06-15
The main topic of the session is to show how dose optimization is being implemented in various regions of the world, including Europe, Australia, North America and other regions. A multi-national study conducted under International Atomic Energy Agency (IAEA) across more than 50 less resourced countries gave insight into patient radiation doses and safety practices in CT, mammography, radiography and interventional procedures, both for children and adults. An important outcome was the capability development on dose assessment and management. An overview of recent European projects related to CT radiation dose and optimization both to adults and children will be presented.more » Existing data on DRLs together with a European methodology proposed on establishing and using DRLs for paediatric radiodiagnostic imaging and interventional radiology practices will be shown. Compared with much of Europe at least, many Australian imaging practices are relatively new to the task of diagnostic imaging dose optimisation. In 2008 the Australian Government prescribed a requirement to periodically compare patient radiation doses with diagnostic reference levels (DRLs), where DRLs have been established. Until recently, Australia had only established DRLs for computed tomography (CT). Regardless, both professional society and individual efforts to improved data collection and develop optimisation strategies across a range of modalities continues. Progress in this field, principally with respect to CT and interventional fluoroscopy will be presented. In the US, dose reduction and optimization efforts for computed tomography have been promoted and mandated by several organizations and accrediting entities. This presentation will cover the general motivation, implementation, and implications of such efforts. Learning Objectives: Understand importance of the dose optimization in Diagnostic Radiology. See how this goal is achieved in different regions of the World. Learn about the global trend in the dose optimization and future prospectives. M. Rehani, The work was a part of the work of IAEA where I was an employee and IAEA is a United Nations organization.« less
Dose optimization of total or partial skin electron irradiation by thermoluminescent dosimetry.
Schüttrumpf, Lars; Neumaier, Klement; Maihoefer, Cornelius; Niyazi, Maximilian; Ganswindt, Ute; Li, Minglun; Lang, Peter; Reiner, Michael; Belka, Claus; Corradini, Stefanie
2018-05-01
Due to the complex surface of the human body, total or partial skin irradiation using large electron fields is challenging. The aim of the present study was to quantify the magnitude of dose optimization required after the application of standard fields. Total skin electron irradiation (TSEI) was applied using the Stanford technique with six dual-fields. Patients presenting with localized lesions were treated with partial skin electron irradiation (PSEI) using large electron fields, which were individually adapted. In order to verify and validate the dose distribution, in vivo dosimetry with thermoluminescent dosimeters (TLD) was performed during the first treatment fraction to detect potential dose heterogeneity and to allow for an individual dose optimization with adjustment of the monitor units (MU). Between 1984 and 2017, a total of 58 patients were treated: 31 patients received TSEI using 12 treatment fields, while 27 patients underwent PSEI and were treated with 4-8 treatment fields. After evaluation of the dosimetric results, an individual dose optimization was necessary in 21 patients. Of these, 7 patients received TSEI (7/31). Monitor units (MU) needed to be corrected by a mean value of 117 MU (±105, range 18-290) uniformly for all 12 treatment fields, corresponding to a mean relative change of 12% of the prescribed MU. In comparison, the other 14 patients received PSEI (14/27) and the mean adjustment of monitor units was 282 MU (±144, range 59-500) to single or multiple fields, corresponding to a mean relative change of 22% of the prescribed MU. A second dose optimization to obtain a satisfying dose at the prescription point was need in 5 patients. Thermoluminescent dosimetry allows an individual dose optimization in TSEI and PSEI to enable a reliable adjustment of the MUs to obtain the prescription dose. Especially in PSEI in vivo dosimetry is of fundamental importance.
Torque-based optimal acceleration control for electric vehicle
NASA Astrophysics Data System (ADS)
Lu, Dongbin; Ouyang, Minggao
2014-03-01
The existing research of the acceleration control mainly focuses on an optimization of the velocity trajectory with respect to a criterion formulation that weights acceleration time and fuel consumption. The minimum-fuel acceleration problem in conventional vehicle has been solved by Pontryagin's maximum principle and dynamic programming algorithm, respectively. The acceleration control with minimum energy consumption for battery electric vehicle(EV) has not been reported. In this paper, the permanent magnet synchronous motor(PMSM) is controlled by the field oriented control(FOC) method and the electric drive system for the EV(including the PMSM, the inverter and the battery) is modeled to favor over a detailed consumption map. The analytical algorithm is proposed to analyze the optimal acceleration control and the optimal torque versus speed curve in the acceleration process is obtained. Considering the acceleration time, a penalty function is introduced to realize a fast vehicle speed tracking. The optimal acceleration control is also addressed with dynamic programming(DP). This method can solve the optimal acceleration problem with precise time constraint, but it consumes a large amount of computation time. The EV used in simulation and experiment is a four-wheel hub motor drive electric vehicle. The simulation and experimental results show that the required battery energy has little difference between the acceleration control solved by analytical algorithm and that solved by DP, and is greatly reduced comparing with the constant pedal opening acceleration. The proposed analytical and DP algorithms can minimize the energy consumption in EV's acceleration process and the analytical algorithm is easy to be implemented in real-time control.
Hanford Environmental Dose Reconstruction Project
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cannon, S.D.; Finch, S.M.
1992-10-01
The objective of the Hanford Environmental Dose Reconstruction (HEDR) Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The independent Technical Steering Panel (TSP) provides technical direction. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed from release to impact on humans (dose estimates):Source Terms, Environmental Transport, Environmental Monitoring Data, Demography, Food Consumption, and Agriculture, and Environmental Pathways and Dose Estimates.
Systematic review with meta-analysis: coffee consumption and the risk of gallstone disease.
Zhang, Y-P; Li, W-Q; Sun, Y-L; Zhu, R-T; Wang, W-J
2015-09-01
Epidemiologic evidence on coffee consumption reducing the risk of gallstone disease has been contradictory. To perform a meta-analysis of observational studies, to investigate an association and dose-response of coffee consumption with gallstone disease. We used PubMed and EMBASE databases to identify all published studies before June 2015. A random-effects model was used to compute a pooled relative risk (RR) and corresponding 95% confidence intervals (CIs). One case-control study and five prospective cohort studies (with seven cohorts) involving 227,749 participants and 11,477 gallstone disease cases were included. Coffee consumption was significantly associated with a reduced risk of gallstone disease (RR, 0.83; 95% CI, 0.76 to 0.89; I(2) = 35.9%), based on prospective studies; specifically, we observed an inverse relation in females, but not in males. The case-control study did not reveal any association between coffee and gallstone disease (OR, 0.99; 95% CI, 0.64 to 1.53). In a dose-response analysis, the RR of gallstone disease was 0.95 (95% CI, 0.91 to 1.00; P = 0.049) per 1 cup/day of coffee consumption. A significant nonlinear dose-response association was also identified (P for nonlinearity = 0.0106). For people who drank 2, 4 and 6 cups of coffee per day, the estimated RRs of gallstone disease were 0.89 (95% CI, 0.79 to 0.99), 0.81 (95% CI, 0.72 to 0.92) and 0.75 (95% CI, 0.64 to 0.88), respectively, compared with the lowest level drinkers. This study suggests that coffee consumption is related to a significantly decreased risk of gallstone disease. © 2015 John Wiley & Sons Ltd.
Rafati, Ali; Noorafshan, Ali; Jahangir, Mahboubeh; Hosseini, Leila; Karbalay-Doust, Saied
2018-01-01
Aspartame is an artificial sweetener used in about 6000 sugar-free products. Aspartame consumption could be associated with various neurological disorders. This study aimed to evaluate the effect of aspartame onmedial Prefrontal Cortex (mPFC) as well as neuroprotective effects of vitamin E. The rats were divided into seven groups, including distilled water, corn oil, vitamin E (100mg/kg/day), and low (acceptable daily dose) and high doses of aspartame (40 and 200mg/kg/day) respectively, with or without vitamin E consumption, for 8 weeks. Behavioral tests were recorded and the brain was prepared for stereological assessments. Novel objects test and eight-arm radial maze showed impairmentoflong- and short-termmemoriesin aspartame groups. Besides, mPFC volume, infralimbic volume, neurons number, glial cells number, dendrites length per neuron,and number of spines per dendrite length were decreased by 7-61% in the rats treated with aspartame. However, neurons' number, glial cells number, and rats' performance in eight-arm radial mazes were improved by concomitant consumption of vitamin E and aspartame. Yet, the mPFC volume and infralimbic cortex were protected only in the rats receiving the low dose of aspartame+vitamin E. On the other hand, dendrites length, spines number,and novel object recognition were not protected by treatment with vitamin E+aspartame. The acceptable daily dose or higher doses of aspartame could induce memory impairments and cortical cells loss in mPFC. However, vitamin E could ameliorate some of these changes. Copyright © 2017 Elsevier GmbH. All rights reserved.
Alcohol consumption impairs stimulus- and error-related processing during a Go/No-Go Task.
Easdon, Craig; Izenberg, Aaron; Armilio, Maria L; Yu, He; Alain, Claude
2005-12-01
Alcohol consumption has been shown to increase the number of errors in tasks that require a high degree of cognitive control, such as a go/no-go task. The alcohol-related decline in performance may be related to difficulties in maintaining attention on the task at hand and/or deficits in inhibiting a prepotent response. To test these two accounts, we investigated the effects of alcohol on stimulus- and response-locked evoked potentials recorded during a go/no-go task that involved the withholding of key presses to rare targets. All participants performed the task prior to drinking and were then assigned randomly to either a control, low-dose, or moderate-dose treatment. Both doses of alcohol increased the number of errors relative to alcohol-free performance. Success in withholding a prepotent response was associated with an early-enhanced stimulus-locked negativity at inferior parietal sites, which was delayed when participants failed to inhibit the motor command. Moreover, low and moderate doses of alcohol reduced N170 and P3 amplitudes during go, no-go, and error trials. In comparison with the correct responses, errors generated large response-locked negative (Ne) and positive (Pe) waves at central sites. Both doses of alcohol reduced the Ne amplitude whereas the Pe amplitude decreased only after moderate doses of alcohol. These results are consistent with the interpretation that behavioral disinhibition following alcohol consumption involved alcohol-induced deficits in maintaining and allocating attention thereby affecting the processing of incoming stimuli and the recognition that an errant response has been made.
The Impact of Monte Carlo Dose Calculations on Intensity-Modulated Radiation Therapy
NASA Astrophysics Data System (ADS)
Siebers, J. V.; Keall, P. J.; Mohan, R.
The effect of dose calculation accuracy for IMRT was studied by comparing different dose calculation algorithms. A head and neck IMRT plan was optimized using a superposition dose calculation algorithm. Dose was re-computed for the optimized plan using both Monte Carlo and pencil beam dose calculation algorithms to generate patient and phantom dose distributions. Tumor control probabilities (TCP) and normal tissue complication probabilities (NTCP) were computed to estimate the plan outcome. For the treatment plan studied, Monte Carlo best reproduces phantom dose measurements, the TCP was slightly lower than the superposition and pencil beam results, and the NTCP values differed little.
Adaptive radiation therapy of prostate cancer
NASA Astrophysics Data System (ADS)
Wen, Ning
ART is a close-loop feedback algorithm which evaluates the organ deformation and motion right before the treatment and takes into account dose delivery variation daily to compensate for the difference between planned and delivered dose. It also has potential to allow further dose escalation and margin reduction to improve the clinical outcome. This retrospective study evaluated ART for prostate cancer treatment and radiobiological consequences. An IRB approved protocol has been used to evaluate actual dose delivery of patients with prostate cancer undergoing treatment with daily CBCT. The dose from CBCT was measured in phantom using TLD and ion chamber techniques in the pelvic scan setting. There were two major findings from the measurements of CBCT dose: (1) the lateral dose distribution was not symmetrical, with Lt Lat being ˜40% higher than Rt Lat and (2) AP skin dose varies with patient size, ranging 3.2--6.1 cGy for patient's AP separation of 20--33 cm (the larger the separation, the less the skin dose) but lateral skin doses depend little on separations. Dose was recalculated on each CBCT set under the same treatment plan. DIR was performed between SIM-CT and evaluated for each CT sets. Dose was reconstructed and accumulated to reflect the actual dose delivered to the patient. Then the adaptive plans were compared to the original plan to evaluate tumor control and normal tissue complication using radiobiological model. Different PTV margins were also studied to access margin reduction techniques. If the actual dose delivered to the PTV deviated significantly from the prescription dose for the given fractions or the OAR received higher dose than expected, the treatment plan would be re-optimized based on the previously delivered dose. The optimal schedule was compared based on the balance of PTV dose coverage and inhomogeneity, OAR dose constraints and labor involved. DIR was validated using fiducial marker position, visual comparison and UE. The mean and standard deviation of markers after rigid registration in L-R direction was 0 and 1 mm. But the mean was 2--4 mm in the A-P and S-I direction and standard deviation was about 2 mm. After DIR, the mean in all three directions became 0 and standard deviation was within sub millimeter. UE images were generated for each CT set and carefully reviewed in the prostate region. DIR provided accurate transformation matrix to be used for dose reconstruction. The delivered dose was evaluated with radiobiological models. TCP for the CTV was calculated to evaluate tumor control in different margin settings. TCP calculated from the reconstructed dose agreed within 5% of the value in the plan for all patients with three different margins. EUD and NTCP were calculated to evaluate reaction of rectum to radiation. Similar biological evaluation was performed for bladder. EUD of actual dose was 3%--9% higher than that of planned dose of patient 1--3, 11%--20% higher of patient 4--5. Smaller margins could not reduce late GU toxicity effectively since bladder complication was directly related to Dmax which was at the same magnitude in the bladder no matter which margin was applied. Re-optimization was performed at the 10th, 20th , 30th, and 40th fraction to evaluate the effectiveness to limit OAR dose while maintaining the target coverage. Reconstructed dose was added to dose from remaining fractions after optimization to show the total dose patient would receive. It showed that if the plan was re-optimized at 10th or 20th fraction, total dose to rectum and bladder were very similar to planned dose with minor deviations. If the plan was re-optimized at the 30th fraction, since there was a large deviation between reconstructed dose and planned dose to OAR, optimization could not limit the OAR dose to the original plan with only 12 fractions left. If the re-optimization was done at the 40th fraction, it was impossible to compensate in the last 2 fractions. Large deviations of total dose to bladder and rectum still existed while dose inhomogeneity to PTV was significantly increased due to hard constraints set in the optimization to reduce OAR dose. In summary, ART did not show improvements in TCP if the patient was setup with CBCT. However, EUD of rectum and bladder was increased significantly due to tissue deformation which varied daily. With the power of ART, margins added to the CTV could be further reduced to preserve critical organs surrounding the target. (Abstract shortened by UMI.)
Liu, Wei; Schild, Steven E.; Chang, Joe Y.; Liao, Zhongxing; Chang, Yu-Hui; Wen, Zhifei; Shen, Jiajian; Stoker, Joshua B.; Ding, Xiaoning; Hu, Yanle; Sahoo, Narayan; Herman, Michael G.; Vargas, Carlos; Keole, Sameer; Wong, William; Bues, Martin
2015-01-01
Background To compare the impact of uncertainties and interplay effect on 3D and 4D robustly optimized intensity-modulated proton therapy (IMPT) plans for lung cancer in an exploratory methodology study. Methods IMPT plans were created for 11 non-randomly selected non-small-cell lung cancer (NSCLC) cases: 3D robustly optimized plans on average CTs with internal gross tumor volume density overridden to irradiate internal target volume, and 4D robustly optimized plans on 4D CTs to irradiate clinical target volume (CTV). Regular fractionation (66 Gy[RBE] in 33 fractions) were considered. In 4D optimization, the CTV of individual phases received non-uniform doses to achieve a uniform cumulative dose. The root-mean-square-dose volume histograms (RVH) measured the sensitivity of the dose to uncertainties, and the areas under the RVH curve (AUCs) were used to evaluate plan robustness. Dose evaluation software modeled time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Dose-volume histogram indices comparing CTV coverage, homogeneity, and normal tissue sparing were evaluated using Wilcoxon signed-rank test. Results 4D robust optimization plans led to smaller AUC for CTV (14.26 vs. 18.61 (p=0.001), better CTV coverage (Gy[RBE]) [D95% CTV: 60.6 vs 55.2 (p=0.001)], and better CTV homogeneity [D5%–D95% CTV: 10.3 vs 17.7 (p=0.002)] in the face of uncertainties. With interplay effect considered, 4D robust optimization produced plans with better target coverage [D95% CTV: 64.5 vs 63.8 (p=0.0068)], comparable target homogeneity, and comparable normal tissue protection. The benefits from 4D robust optimization were most obvious for the 2 typical stage III lung cancer patients. Conclusions Our exploratory methodology study showed that, compared to 3D robust optimization, 4D robust optimization produced significantly more robust and interplay-effect-resistant plans for targets with comparable dose distributions for normal tissues. A further study with a larger and more realistic patient population is warranted to generalize the conclusions. PMID:26725727
Is addiction a failure of rationality?
Ferguson, Brian
2012-01-01
This note argues that addiction itself can be seen as a form of double failure, specifically the failure to stick to a predetermined optimal lifetime consumption path for an addictive commodity, which failure might be the result of bad luck, and the failure to adjust the level of consumption of the addictive commodity once the consumer is off their optimal path, which might be seen as a failure of judgment.
Effects of repeated doses of caffeine on performance and alertness: new data and secondary analyses.
Hewlett, Paul; Smith, Andrew
2007-08-01
The effects of caffeine on mood and performance are well established. Some authors suggest that caffeine merely reverses effects of caffeine withdrawal rather than having direct behavioural effects. It has also been suggested that withdrawal may be removed by a first dose of caffeine and further doses have little subsequent effect. These issues are examined here. The present study aimed to determine whether caffeine withdrawal influenced mood and performance by comparing regular consumers who had been withdrawn from caffeine overnight with non-consumers. Following this repeated caffeine doses were administered to test the claim that repeated dosing has no extra effect on mood or performance. Secondary analyses of data collected after a day of normal caffeine consumption were also carried out to examine some alternative explanations of their results which showed effects of caffeine after a day of normal caffeine consumption. One hundred and twenty volunteers participated in the study. Regular caffeine consumption was assessed by questionnaire and this showed that 36 of the volunteers did not regularly consume caffeinated beverages. Volunteers were instructed to abstain from caffeine overnight and then completed a baseline session measuring mood and a range of cognitive functions at 08.00 the next day. Following this volunteers were given 0, or 1 mg/kg caffeine in a milkshake, glucose solution or water (at 09:00), followed by a second 0 or 1 mg/kg caffeine dose (at 09:40) and the test battery repeated at 10:00. The baseline data showed no effect of overnight caffeine withdrawal on mood or performance. In contrast, caffeine challenge improved vigilance performance and prevented decreases in alertness induced by completion of the task battery. The magnitude of these effects increased as a function of the number of doses of caffeine given. Secondary analyses of data from Christopher et al. (2003) also confirmed that effects of caffeine did not depend on length of withdrawal. The present findings show no effect of overnight caffeine withdrawal on mood and performance. Caffeine challenge did have the predicted effect on alertness and vigilance, with the size of the effects increasing with caffeine dose. These findings suggest that the effects of caffeine are not due to reversal of effects of withdrawal, a view confirmed by secondary analyses of data collected after a day of normal caffeine consumption. Copyright 2007 John Wiley & Sons, Ltd.
Lahanas, M; Baltas, D; Giannouli, S; Milickovic, N; Zamboglou, N
2000-05-01
We have studied the accuracy of statistical parameters of dose distributions in brachytherapy using actual clinical implants. These include the mean, minimum and maximum dose values and the variance of the dose distribution inside the PTV (planning target volume), and on the surface of the PTV. These properties have been studied as a function of the number of uniformly distributed sampling points. These parameters, or the variants of these parameters, are used directly or indirectly in optimization procedures or for a description of the dose distribution. The accurate determination of these parameters depends on the sampling point distribution from which they have been obtained. Some optimization methods ignore catheters and critical structures surrounded by the PTV or alternatively consider as surface dose points only those on the contour lines of the PTV. D(min) and D(max) are extreme dose values which are either on the PTV surface or within the PTV. They must be avoided for specification and optimization purposes in brachytherapy. Using D(mean) and the variance of D which we have shown to be stable parameters, achieves a more reliable description of the dose distribution on the PTV surface and within the PTV volume than does D(min) and D(max). Generation of dose points on the real surface of the PTV is obligatory and the consideration of catheter volumes results in a realistic description of anatomical dose distributions.
Nalichowski, Adrian; Burmeister, Jay
2013-07-01
To compare optimization characteristics, plan quality, and treatment delivery efficiency between total marrow irradiation (TMI) plans using the new TomoTherapy graphic processing unit (GPU) based dose engine and CPU/cluster based dose engine. Five TMI plans created on an anthropomorphic phantom were optimized and calculated with both dose engines. The planning treatment volume (PTV) included all the bones from head to mid femur except for upper extremities. Evaluated organs at risk (OAR) consisted of lung, liver, heart, kidneys, and brain. The following treatment parameters were used to generate the TMI plans: field widths of 2.5 and 5 cm, modulation factors of 2 and 2.5, and pitch of either 0.287 or 0.43. The optimization parameters were chosen based on the PTV and OAR priorities and the plans were optimized with a fixed number of iterations. The PTV constraint was selected to ensure that at least 95% of the PTV received the prescription dose. The plans were evaluated based on D80 and D50 (dose to 80% and 50% of the OAR volume, respectively) and hotspot volumes within the PTVs. Gamma indices (Γ) were also used to compare planar dose distributions between the two modalities. The optimization and dose calculation times were compared between the two systems. The treatment delivery times were also evaluated. The results showed very good dosimetric agreement between the GPU and CPU calculated plans for any of the evaluated planning parameters indicating that both systems converge on nearly identical plans. All D80 and D50 parameters varied by less than 3% of the prescription dose with an average difference of 0.8%. A gamma analysis Γ(3%, 3 mm) < 1 of the GPU plan resulted in over 90% of calculated voxels satisfying Γ < 1 criterion as compared to baseline CPU plan. The average number of voxels meeting the Γ < 1 criterion for all the plans was 97%. In terms of dose optimization/calculation efficiency, there was a 20-fold reduction in planning time with the new GPU system. The average optimization/dose calculation time utilizing the traditional CPU/cluster based system was 579 vs 26.8 min for the GPU based system. There was no difference in the calculated treatment delivery time per fraction. Beam-on time varied based on field width and pitch and ranged between 15 and 28 min. The TomoTherapy GPU based dose engine is capable of calculating TMI treatment plans with plan quality nearly identical to plans calculated using the traditional CPU/cluster based system, while significantly reducing the time required for optimization and dose calculation.
Sub-chronic safety evaluation of the ethanol extract of Aralia elata leaves in Beagle dogs.
Li, Fengjin; He, Xiaoli; Niu, Wenying; Feng, Yuenan; Bian, Jingqi; Kuang, Haixue; Xiao, Hongbin
2016-08-01
Aralia elata Seem. (A. elata) is a traditional Chinese medicine to treat some diseases. This investigation aims to evaluate the pharmaceutical safety of the ethanol extract of A. elata leaves, namely ethanol leaves extract (ELE), in Beagle dogs. In sub-chronic oral toxicity study, dogs were treated with the ELE at doses of 50, 100 and 200 mg/kg for 12 weeks and followed by 4 weeks recovery period. During experimental period, clinical signs, mortality, body temperature, food consumption and body weight were recorded. Analysis of electrocardiogram, urinalysis, ophthalmoscopy, hematology, serum biochemistry, organ weights and histopathology were performed. The results showed that both food consumption and body weight significantly decreased in high-dose group. Treatment-related side effects and mortality were observed in high-dose female dogs. Some parameters showed significant alterations in electrocardiogram, urinalysis, serum biochemistry and relative organ weights. These alterations were not related to dose or consistent across gender, which were ascribed to incidental and biological variability. The findings in this study indicated that the no-observed adverse effect level (NOAEL) of the ELE was 100 mg/kg in dogs and provided a vital reference for selecting a safe application dosage for human consumption. Copyright © 2016 Elsevier Inc. All rights reserved.
Cengiz, Pelin; Gokcinar, Derya; Karabeyoglu, Isil; Topcu, Hulya; Cicek, Gizem Selen; Gogus, Nermin
2014-05-01
To evaluate the effect of intraoperative low-dose ketamine with general anesthesia on postoperative pain after total knee replacement surgery. A randomized, double-blind comparative study. Ankara Numune Training and Research Hospital, Turkey, from January and June 2011. Sixty adults undergoing total knee arthroplasty were enrolled in this study. The patients were randomly allocated into two groups of equal size to receive either racemic ketamine infusion (6 μg/kg/minute) or the same volume of saline. A visual analogue scale (VAS) was used to measure each patient's level of pain at 1, 3, 6, 12, and 24 hours after surgery. Time to first analgesic request, postoperative morphine consumption and the incidence of side effects were also recorded. Low-dose ketamine infusion prolonged the time to first analgesic request. It also reduced postoperative cumulative morphine consumption at 1, 3, 6, 12, and 24 hours postsurgery (p < 0.001). Postoperative VAS scores were also significantly lower in the ketamine group than placebo, at all observation times. Incidences of side effects were similar in both study groups. Intraoperative continuous low-dose ketamine infusion reduced pain and postoperative analgesic consumption without affecting the incidence of side effects.
PV integration into a CSP plant
NASA Astrophysics Data System (ADS)
Carvajal, Javier López; Barea, Jose M.; Barragan, Jose; Ortega, Carlos
2017-06-01
This paper describes a preliminary techno-economic analysis of the integration of a PV plant into an optimized Parabolic Trough Plant in order to reduce the online consumptions and thus, increase the net electricity injected into the grid. The idea is to assess the feasibility of such project and see what configuration would be the optimal. An extra effort has been made in terms of modelling as the analysis has to be done to the integrated CSP + PV plant instead of analyzing them independently. Two different technologies have been considered for the PV plant, fix and one-axis tracking. Additionally three different scenarios have been considered for the CSP plant auxiliary consumptions as they are essential for determining the optimal PV plant (the higher the auxiliary consumption the higher the optimal PV plant). As could be expected, the results for all cases with PV show an improvement in terms of electricity generation and also in terms of LCOE with respect to the CSP plant. Such improvement is slightly higher with tracking technology for this specific study. Although this exercise has been done to an already designed CSP plant (so only the PV plant had to be optimized), the methodology could be applied for the optimization of an integrated CSP + PV plant during the design phase.
Fuel optimal maneuvers for spacecraft with fixed thrusters
NASA Technical Reports Server (NTRS)
Carter, T. C.
1982-01-01
Several mathematical models, including a minimum integral square criterion problem, were used for the qualitative investigation of fuel optimal maneuvers for spacecraft with fixed thrusters. The solutions consist of intervals of "full thrust" and "coast" indicating that thrusters do not need to be designed as "throttleable" for fuel optimal performance. For the primary model considered, singular solutions occur only if the optimal solution is "pure translation". "Time optimal" singular solutions can be found which consist of intervals of "coast" and "full thrust". The shape of the optimal fuel consumption curve as a function of flight time was found to depend on whether or not the initial state is in the region admitting singular solutions. Comparisons of fuel optimal maneuvers in deep space with those relative to a point in circular orbit indicate that qualitative differences in the solutions can occur. Computation of fuel consumption for certain "pure translation" cases indicates that considerable savings in fuel can result from the fuel optimal maneuvers.
Criado-Álvarez, J J; González González, J; Romo Barrientos, C; Mohedano Moriano, A; Montero Rubio, J C; Pérez Veiga, J P
2016-09-16
Attention-deficit/hyperactivity disorder (ADHD) is one of the most common behavioural disorders of childhood; its prevalence in Spain is estimated at 5-9%. Available treatments for this condition include methylphenidate, atomoxetine, and lisdexamfetamine, whose consumption increases each year. The prevalence of ADHD was estimated by calculating the defined daily dose per 1,000 population per day of each drug and the total doses (therapeutic group N06BA) between 1992 and 2015 in each of the provinces of Castile-La Mancha (Spain). Trends, joinpoints, and annual percentages of change were analysed using joinpoint regression models. The minimum prevalence of ADHD in the population of Castile-La Mancha aged 5 to 19 was estimated at 13.22 cases per 1,000 population per day; prevalence varied across provinces (p<.05). Overall consumption has increased from 1992 to 2015, with an annual percentages of change of 10.3% and several joinpoints (2000, 2009, and 2012). methylphenidate represents 89.6% of total drug consumption, followed by lisdexamfetamine at 8%. Analysing drug consumption enables us to estimate the distribution of ADHD patients in Castile-La Mancha. Our data show an increase in the consumption of these drugs as well as differences in drug consumption between provinces, which reflect differences in ADHD management in clinical practice. Copyright © 2016. Publicado por Elsevier España, S.L.U.
Pradal, Delphine; Vauchel, Peggy; Decossin, Stéphane; Dhulster, Pascal; Dimitrov, Krasimir
2016-09-01
Ultrasound-assisted extraction (UAE) of antioxidant polyphenols from chicory grounds was studied in order to propose a suitable valorization of this food industry by-product. The main parameters influencing the extraction process were identified. A new mathematical model for multi-criteria optimization of UAE was proposed. This kinetic model permitted the following and the prediction of the yield of extracted polyphenols, the antioxidant activity of the obtained extracts and the energy consumption during the extraction process in wide ranges of temperature (20-60°C), ethanol content in the solvent (0-60% (vol.) in ethanol-water mixtures) and ultrasound power (0-100W). After experimental validation of the model, several simulations at different technological restrictions were performed to illustrate the potentiality of the model to find the optimal conditions for obtaining a given yield within minimal process duration or with minimal energy consumption. The advantage of ultrasound assistance was clearly demonstrated both for the reduction of extraction duration and for the reduction of energy consumption. Copyright © 2016 Elsevier B.V. All rights reserved.
Minimization of energy and surface roughness of the products machined by milling
NASA Astrophysics Data System (ADS)
Belloufi, A.; Abdelkrim, M.; Bouakba, M.; Rezgui, I.
2017-08-01
Metal cutting represents a large portion in the manufacturing industries, which makes this process the largest consumer of energy. Energy consumption is an indirect source of carbon footprint, we know that CO2 emissions come from the production of energy. Therefore high energy consumption requires a large production, which leads to high cost and a large amount of CO2 emissions. At this day, a lot of researches done on the Metal cutting, but the environmental problems of the processes are rarely discussed. The right selection of cutting parameters is an effective method to reduce energy consumption because of the direct relationship between energy consumption and cutting parameters in machining processes. Therefore, one of the objectives of this research is to propose an optimization strategy suitable for machining processes (milling) to achieve the optimum cutting conditions based on the criterion of the energy consumed during the milling. In this paper the problem of energy consumed in milling is solved by an optimization method chosen. The optimization is done according to the different requirements in the process of roughing and finishing under various technological constraints.
NASA Astrophysics Data System (ADS)
Yarmand, Hamed; Winey, Brian; Craft, David
2013-09-01
Stereotactic body radiation therapy (SBRT) is characterized by delivering a high amount of dose in a short period of time. In SBRT the dose is delivered using open fields (e.g., beam’s-eye-view) known as ‘apertures’. Mathematical methods can be used for optimizing treatment planning for delivery of sufficient dose to the cancerous cells while keeping the dose to surrounding organs at risk (OARs) minimal. Two important elements of a treatment plan are quality and delivery time. Quality of a plan is measured based on the target coverage and dose to OARs. Delivery time heavily depends on the number of beams used in the plan as the setup times for different beam directions constitute a large portion of the delivery time. Therefore the ideal plan, in which all potential beams can be used, will be associated with a long impractical delivery time. We use the dose to OARs in the ideal plan to find the plan with the minimum number of beams which is guaranteed to be epsilon-optimal (i.e., a predetermined maximum deviation from the ideal plan is guaranteed). Since the treatment plan optimization is inherently a multi-criteria-optimization problem, the planner can navigate the ideal dose distribution Pareto surface and select a plan of desired target coverage versus OARs sparing, and then use the proposed technique to reduce the number of beams while guaranteeing epsilon-optimality. We use mixed integer programming (MIP) for optimization. To reduce the computation time for the resultant MIP, we use two heuristics: a beam elimination scheme and a family of heuristic cuts, known as ‘neighbor cuts’, based on the concept of ‘adjacent beams’. We show the effectiveness of the proposed technique on two clinical cases, a liver and a lung case. Based on our technique we propose an algorithm for fast generation of epsilon-optimal plans.
A GPU-accelerated and Monte Carlo-based intensity modulated proton therapy optimization system.
Ma, Jiasen; Beltran, Chris; Seum Wan Chan Tseung, Hok; Herman, Michael G
2014-12-01
Conventional spot scanning intensity modulated proton therapy (IMPT) treatment planning systems (TPSs) optimize proton spot weights based on analytical dose calculations. These analytical dose calculations have been shown to have severe limitations in heterogeneous materials. Monte Carlo (MC) methods do not have these limitations; however, MC-based systems have been of limited clinical use due to the large number of beam spots in IMPT and the extremely long calculation time of traditional MC techniques. In this work, the authors present a clinically applicable IMPT TPS that utilizes a very fast MC calculation. An in-house graphics processing unit (GPU)-based MC dose calculation engine was employed to generate the dose influence map for each proton spot. With the MC generated influence map, a modified least-squares optimization method was used to achieve the desired dose volume histograms (DVHs). The intrinsic CT image resolution was adopted for voxelization in simulation and optimization to preserve spatial resolution. The optimizations were computed on a multi-GPU framework to mitigate the memory limitation issues for the large dose influence maps that resulted from maintaining the intrinsic CT resolution. The effects of tail cutoff and starting condition were studied and minimized in this work. For relatively large and complex three-field head and neck cases, i.e., >100,000 spots with a target volume of ∼ 1000 cm(3) and multiple surrounding critical structures, the optimization together with the initial MC dose influence map calculation was done in a clinically viable time frame (less than 30 min) on a GPU cluster consisting of 24 Nvidia GeForce GTX Titan cards. The in-house MC TPS plans were comparable to a commercial TPS plans based on DVH comparisons. A MC-based treatment planning system was developed. The treatment planning can be performed in a clinically viable time frame on a hardware system costing around 45,000 dollars. The fast calculation and optimization make the system easily expandable to robust and multicriteria optimization.
NASA Astrophysics Data System (ADS)
Bonchiş, N.; Balint, Şt.
2010-09-01
In this paper the Ramsey optimal growth of the capital stock and consumption on finite horizon is analyzed when the growth rate of consumers is strictly positive. The main purpose is to establish the dependence of the optimal capital stock and consumption evolution on the growth rate of consumers. The analysis reveals: for any initial value k0≥0 there exists a unique optimal evolution path of length N+1 for the capital stock; if k0 is strictly positive then all the elements of the optimal capital stock evolution path are strictly positives except the last one which is zero; the optimal capital stock evolution of length N+1 starting from k0≥0 satisfies the Euler equation; the value function VN is strictly increasing, strictly concave and continuous on R+. The family of functions {VN-T}T = 0…N-1 satisfies the Bellman equation and it is the unique solution of this equation which is both continuous and satisfies the transversality condition. The Mangasarian Lemma is also satisfied. For N tending to infinity the optimal evolution path of length N of the capital stock tends to those on the infinite time horizon. For any k0>0 the value function in k0 decreases when the consumers growth rate increases.
Samokhvalov, Andriy V; Rehm, Jürgen; Roerecke, Michael
2015-12-01
Pancreatitis is a highly prevalent medical condition associated with a spectrum of endocrine and exocrine pancreatic insufficiencies. While high alcohol consumption is an established risk factor for pancreatitis, its relationship with specific types of pancreatitis and a potential threshold have not been systematically examined. We conducted a systematic literature search for studies on the association between alcohol consumption and pancreatitis based on PRISMA guidelines. Non-linear and linear random-effect dose-response meta-analyses using restricted cubic spline meta-regressions and categorical meta-analyses in relation to abstainers were conducted. Seven studies with 157,026 participants and 3618 cases of pancreatitis were included into analyses. The dose-response relationship between average volume of alcohol consumption and risk of pancreatitis was monotonic with no evidence of non-linearity for chronic pancreatitis (CP) for both sexes (p = 0.091) and acute pancreatitis (AP) in men (p = 0.396); it was non-linear for AP in women (p = 0.008). Compared to abstention, there was a significant decrease in risk (RR = 0.76, 95%CI: 0.60-0.97) of AP in women below the threshold of 40 g/day. No such association was found in men (RR = 1.1, 95%CI: 0.69-1.74). The RR for CP at 100 g/day was 6.29 (95%CI: 3.04-13.02). The dose-response relationships between alcohol consumption and risk of pancreatitis were monotonic for CP and AP in men, and non-linear for AP in women. Alcohol consumption below 40 g/day was associated with reduced risk of AP in women. Alcohol consumption beyond this level was increasingly detrimental for any type of pancreatitis. The work was financially supported by a grant from the National Institute on Alcohol Abuse and Alcoholism (R21AA023521) to the last author.
NASA Astrophysics Data System (ADS)
Widesott, L.; Strigari, L.; Pressello, M. C.; Benassi, M.; Landoni, V.
2008-03-01
We investigated the role and the weight of the parameters involved in the intensity modulated radiation therapy (IMRT) optimization based on the generalized equivalent uniform dose (gEUD) method, for prostate and head-and-neck plans. We systematically varied the parameters (gEUDmax and weight) involved in the gEUD-based optimization of rectal wall and parotid glands. We found that the proper value of weight factor, still guaranteeing planning treatment volumes coverage, produced similar organs at risks dose-volume (DV) histograms for different gEUDmax with fixed a = 1. Most of all, we formulated a simple relation that links the reference gEUDmax and the associated weight factor. As secondary objective, we evaluated plans obtained with the gEUD-based optimization and ones based on DV criteria, using the normal tissue complication probability (NTCP) models. gEUD criteria seemed to improve sparing of rectum and parotid glands with respect to DV-based optimization: the mean dose, the V40 and V50 values to the rectal wall were decreased of about 10%, the mean dose to parotids decreased of about 20-30%. But more than the OARs sparing, we underlined the halving of the OARs optimization time with the implementation of the gEUD-based cost function. Using NTCP models we enhanced differences between the two optimization criteria for parotid glands, but no for rectum wall.
Shen, L; Levine, S H; Catchen, G L
1987-07-01
This paper describes an optimization method for determining the beta dose distribution in tissue, and it describes the associated testing and verification. The method uses electron transport theory and optimization techniques to analyze the responses of a three-element thermoluminescent dosimeter (TLD) system. Specifically, the method determines the effective beta energy distribution incident on the dosimeter system, and thus the system performs as a beta spectrometer. Electron transport theory provides the mathematical model for performing the optimization calculation. In this calculation, parameters are determined that produce calculated doses for each of the chip/absorber components in the three-element TLD system. The resulting optimized parameters describe an effective incident beta distribution. This method can be used to determine the beta dose specifically at 7 mg X cm-2 or at any depth of interest. The doses at 7 mg X cm-2 in tissue determined by this method are compared to those experimentally determined using an extrapolation chamber. For a great variety of pure beta sources having different incident beta energy distributions, good agreement is found. The results are also compared to those produced by a commonly used empirical algorithm. Although the optimization method produces somewhat better results, the advantage of the optimization method is that its performance is not sensitive to the specific method of calibration.
Hanford Environmental Dose Reconstruction Project. Monthly report
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cannon, S.D.; Finch, S.M.
1992-10-01
The objective of the Hanford Environmental Dose Reconstruction (HEDR) Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The independent Technical Steering Panel (TSP) provides technical direction. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed from release to impact on humans (dose estimates):Source Terms, Environmental Transport, Environmental Monitoring Data, Demography, Food Consumption, and Agriculture, and Environmental Pathways and Dose Estimates.
Patterns of glucose lowering drugs utilization in Portugal and in the Netherlands. Trends over time.
Torre, Carla; Guerreiro, José; de Oliveira Martins, Sofia; Raposo, João Filipe; Martins, Ana Paula; Leufkens, Hubert
2015-12-01
To compare the temporal trends in the consumption patterns of glucose lowering drugs (GLD) between Portugal and the Netherlands from 2004 to 2013 and to examine possible reasons behind the cross-national variation found. All GLD (ATC pharmacological subgroup A10B) were selected for analysis. Consumption data were obtained for the 10-year period. Portuguese and Dutch drug estimates were obtained from nationwide databases. The consumption of GLD increased in Portugal from 52.9 defined daily dose per 1000 inhabitants per day (DHD) in 2004 to 70.0 DHD in 2013 and in the Netherlands from 44.9 DHD in 2004 to 50.7 DHD in 2013. In Portugal, the use of fixed-dose combinations, especially with dipeptidyl peptidase-4 inhibitors (DPP-4) increased remarkably and in 2013 represented almost a quarter of total GLD consumption. In the Netherlands, the use of combinations was residual. The consumption of GLD rose over the 10-year period in both countries. However, Portuguese overall consumption and costs of GLD were higher. The differentially rapid uptake of DPP-4 inhibitors in Portugal was the main driver of the cost difference. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.
Latent uncertainties of the precalculated track Monte Carlo method
DOE Office of Scientific and Technical Information (OSTI.GOV)
Renaud, Marc-André; Seuntjens, Jan; Roberge, David
Purpose: While significant progress has been made in speeding up Monte Carlo (MC) dose calculation methods, they remain too time-consuming for the purpose of inverse planning. To achieve clinically usable calculation speeds, a precalculated Monte Carlo (PMC) algorithm for proton and electron transport was developed to run on graphics processing units (GPUs). The algorithm utilizes pregenerated particle track data from conventional MC codes for different materials such as water, bone, and lung to produce dose distributions in voxelized phantoms. While PMC methods have been described in the past, an explicit quantification of the latent uncertainty arising from the limited numbermore » of unique tracks in the pregenerated track bank is missing from the paper. With a proper uncertainty analysis, an optimal number of tracks in the pregenerated track bank can be selected for a desired dose calculation uncertainty. Methods: Particle tracks were pregenerated for electrons and protons using EGSnrc and GEANT4 and saved in a database. The PMC algorithm for track selection, rotation, and transport was implemented on the Compute Unified Device Architecture (CUDA) 4.0 programming framework. PMC dose distributions were calculated in a variety of media and compared to benchmark dose distributions simulated from the corresponding general-purpose MC codes in the same conditions. A latent uncertainty metric was defined and analysis was performed by varying the pregenerated track bank size and the number of simulated primary particle histories and comparing dose values to a “ground truth” benchmark dose distribution calculated to 0.04% average uncertainty in voxels with dose greater than 20% of D{sub max}. Efficiency metrics were calculated against benchmark MC codes on a single CPU core with no variance reduction. Results: Dose distributions generated using PMC and benchmark MC codes were compared and found to be within 2% of each other in voxels with dose values greater than 20% of the maximum dose. In proton calculations, a small (≤1 mm) distance-to-agreement error was observed at the Bragg peak. Latent uncertainty was characterized for electrons and found to follow a Poisson distribution with the number of unique tracks per energy. A track bank of 12 energies and 60000 unique tracks per pregenerated energy in water had a size of 2.4 GB and achieved a latent uncertainty of approximately 1% at an optimal efficiency gain over DOSXYZnrc. Larger track banks produced a lower latent uncertainty at the cost of increased memory consumption. Using an NVIDIA GTX 590, efficiency analysis showed a 807 × efficiency increase over DOSXYZnrc for 16 MeV electrons in water and 508 × for 16 MeV electrons in bone. Conclusions: The PMC method can calculate dose distributions for electrons and protons to a statistical uncertainty of 1% with a large efficiency gain over conventional MC codes. Before performing clinical dose calculations, models to calculate dose contributions from uncharged particles must be implemented. Following the successful implementation of these models, the PMC method will be evaluated as a candidate for inverse planning of modulated electron radiation therapy and scanned proton beams.« less
Latent uncertainties of the precalculated track Monte Carlo method.
Renaud, Marc-André; Roberge, David; Seuntjens, Jan
2015-01-01
While significant progress has been made in speeding up Monte Carlo (MC) dose calculation methods, they remain too time-consuming for the purpose of inverse planning. To achieve clinically usable calculation speeds, a precalculated Monte Carlo (PMC) algorithm for proton and electron transport was developed to run on graphics processing units (GPUs). The algorithm utilizes pregenerated particle track data from conventional MC codes for different materials such as water, bone, and lung to produce dose distributions in voxelized phantoms. While PMC methods have been described in the past, an explicit quantification of the latent uncertainty arising from the limited number of unique tracks in the pregenerated track bank is missing from the paper. With a proper uncertainty analysis, an optimal number of tracks in the pregenerated track bank can be selected for a desired dose calculation uncertainty. Particle tracks were pregenerated for electrons and protons using EGSnrc and geant4 and saved in a database. The PMC algorithm for track selection, rotation, and transport was implemented on the Compute Unified Device Architecture (cuda) 4.0 programming framework. PMC dose distributions were calculated in a variety of media and compared to benchmark dose distributions simulated from the corresponding general-purpose MC codes in the same conditions. A latent uncertainty metric was defined and analysis was performed by varying the pregenerated track bank size and the number of simulated primary particle histories and comparing dose values to a "ground truth" benchmark dose distribution calculated to 0.04% average uncertainty in voxels with dose greater than 20% of Dmax. Efficiency metrics were calculated against benchmark MC codes on a single CPU core with no variance reduction. Dose distributions generated using PMC and benchmark MC codes were compared and found to be within 2% of each other in voxels with dose values greater than 20% of the maximum dose. In proton calculations, a small (≤ 1 mm) distance-to-agreement error was observed at the Bragg peak. Latent uncertainty was characterized for electrons and found to follow a Poisson distribution with the number of unique tracks per energy. A track bank of 12 energies and 60000 unique tracks per pregenerated energy in water had a size of 2.4 GB and achieved a latent uncertainty of approximately 1% at an optimal efficiency gain over DOSXYZnrc. Larger track banks produced a lower latent uncertainty at the cost of increased memory consumption. Using an NVIDIA GTX 590, efficiency analysis showed a 807 × efficiency increase over DOSXYZnrc for 16 MeV electrons in water and 508 × for 16 MeV electrons in bone. The PMC method can calculate dose distributions for electrons and protons to a statistical uncertainty of 1% with a large efficiency gain over conventional MC codes. Before performing clinical dose calculations, models to calculate dose contributions from uncharged particles must be implemented. Following the successful implementation of these models, the PMC method will be evaluated as a candidate for inverse planning of modulated electron radiation therapy and scanned proton beams.
Gaikowski, Mark P.; Wolf, Jeffery C.; Endris, Richard G.; Gingerich, William H.
2003-01-01
Aquaflor, a feed premix containing the broad spectrum antibacterial agent florfenicol (50% w/w), is being developed for use to control enteric septicemia (ESC) in channel catfish Ictalurus punctatus caused by the gram-negative enterobacterium Edwardsiella ictaluri. The recommended dose of Aquaflor to control ESC is 10 mg/kg body weight (BW)/day for 10 days. The study objective was to determine the safety of Aquaflor administered in feed to channel catfish at doses of 0 (control), 10, 30, and 50 mg/kg BW/day for 20 consecutive days. Parameters evaluated included daily mortality, behavioral (appetite, distribution, flight/fright response), and water chemistry observations, initial and terminal weight measurements, and gross and microscopic pathology. Medicated feed consumption was 67-86% of target with group mean doses of 8.5 mg/kg BW/day, 24.6 mg/kg BW/day, and 34.9 mg/kg BW/day. There were no mortalities or clinically observable changes noted at any of the dose levels tested. Aquaflor-related changes were limited to the food consumption and histopathology data. Although Aquaflor-related decreased feed consumption was noted in the 30 and 50 mg/kg BW/day groups, there were no differences in fish growth among the treatment groups. Aquaflor-related histopathology findings were limited to a histomorphologically evident dose-dependent decrease in hematopoietic/lymphopoietic tissue in the anterior kidneys, posterior kidneys, and spleens of channel catfish.
Gaikowski, M.P.; Wolf, J.C.; Endris, R.G.; Gingerich, W.H.
2003-01-01
Aquaflor, a feed premix containing the broad spectrum antibacterial agent florfenicol (50% w/w), is being developed for use to control enteric septicemia (ESC) in channel catfish Ictalurus punctatus caused by the gram-negative enterobacterium Edwardsiella ictaluri. The recommended dose of Aquaflor to control ESC is 10 mg/kg body weight (BW)/day for 10 days. The study objective was to determine the safety of Aquaflor administered in feed to channel catfish at doses of 0 (control), 10, 30, and 50 mg/kg BW/day for 20 consecutive days. Parameters evaluated included daily mortality, behavioral (appetite, distribution, flight/fright response), and water chemistry observations, initial and terminal weight measurements, and gross and microscopic pathology. Medicated feed consumption was 67-86% of target with group mean doses of 8.5 mg/kg BW/day, 24.6 mg/kg BW/day, and 34.9 mg/kg BW/day. There were no mortalities or clinically observable changes noted at any of the dose levels tested. Aquaflor-related changes were limited to the food consumption and histopathology data. Although Aquaflor-related decreased feed consumption was noted in the 30 and 50 mg/kg BW/day groups, there were no differences in fish growth among the treatment groups. Aquaflor-related histopathology findings were limited to a histomorphologically evident dose-dependent decrease in hematopoietic/lymphopoietic tissue in the anterior kidneys, posterior kidneys, and spleens of channel catfish.
PERCEPTION OF MERCURY RISK INFORMATION
Approximately 8% of American women have blood Mercury levels exceeding the EPA reference dose (a dose below which symptoms would be unlikely). The children of these women are at risk of neurological deficits (lower IQ scores) primarily because of the mother's consumption of conta...
Santesteban Moriones, Virginia; Ibáñez Santos, Javier
2017-02-01
Introduction: Very few nutritional supplements have scientifically demonstrated their effectiveness as an ergogenic aid. This review will examine creatine monohydrate (MC), the β-hydroxy-β-methylbutyrate (HMB), sodium bicarbonate (BS), the β-alanine and caffeine. Objectives: To analyze the effi cacy, mechanisms of action, dose, side effects and some sports that can benefit from their consumption. Methods: Searching in PubMed bibliographic database reviews from the last 15 years and original articles from the last 5 years of the studied substances. Results: Doses of 20 mg/day for 4-7 days are effective in improving strength and muscular power and performance in short and repeated sprints. HMB at doses of 3 g/day for at least 2 weeks contributes to increased lean mass and fat-free mass. The intake of 0.3 g/kg of BS improves performance on tests of 400-1,500 meters in athletics and intermittent sprints. Meanwhile, doses of 80 mg/kg/day of β-alanine for 4-10 weeks may improve performance in high-intensity intermittent exercise. Finally, caffeine at doses of 2 mg/kg improves responsiveness and 3-6 mg/kg improves performance in endurance tests. Conclusions: The revised supplements have shown their efficacy in physical performance, but it is needed to keep in mind that most studies have been conducted with recreational-level athletes. Generally, the better the individual´s fitness level is the less improvement in physical performance the supplement shows. However, an increase of only 1% may sometimes allow the athlete to advance several positions in a final. Finally, we should draw attention to the importance of optimizing nutrition before considering the introduction of sports supplements, especially in children and youth. All analyzed substances have scientific basis supporting its ergogenic effect. All of them can be found in the market with Certificate of Quality and Purit
Jayasuriya, W J A B; Suresh, T S; Abeytunga, D; Fernando, G H; Wanigatunga, C A
2012-01-01
This study investigates the oral hypoglycemic activity of Pleurotus ostreatus (P.o.) and P. cystidiosus (P.c.) mushrooms on normal and alloxan-induced diabetic Wistar rats. Different doses (250, 500, 750, 1000, and 1250 mg/kg/body weight) of suspensions of freeze-dried and powdered (SFDP) P.o. and P.c. were administered to normal rats, and postprandial serum glucose levels were measured. Optimal time of activity was investigated using the dose 500 mg/kg. Hypoglycemic effect of a single dose of SFDP P.o. and P.c. (500 mg/kg) were investigated using diabetic male and female rats at different stages of estrous cycle and compared with metformin and glibenclamide. Chronic hypoglycemic activity of SFDP P.o. and P.c. (500 mg/kg) was studied using serum glucose levels and glycosylated hemoglobin levels. Maximally effective dose of SFDP P.o. and P.c. was 500 mg/kg. The highest reduction in the serum glucose level was observed 120 minutes after administration of mushrooms. A single dose of P.o. and P.c. significantly (P < 0.05) reduced the serum glucose levels of male diabetic rats. The hypoglycemic activity in female rats was highest in proestrous stage. The hypoglycemic effect of P.o. and P.c. is comparable with metformin and glibenclamide. Daily single administrations of P.o. and P.c. to diabetic rats exert apparent control on the homeostasis of blood glucose. SFDP P.o. and P.c. possessed marked and significant oral hypoglycemic activity. This study suggests the consumption of P.o. and P.c. mushrooms might bring health benefits to mankind as it shows hypoglycemic activity in rats.
Boufouss, El Hafed; Francis, Laurent A; Kilchytska, Valeriya; Gérard, Pierre; Simon, Pascal; Flandre, Denis
2013-12-13
This paper presents an ultra-low power CMOS voltage reference circuit which is robust under biomedical extreme conditions, such as high temperature and high total ionized dose (TID) radiation. To achieve such performances, the voltage reference is designed in a suitable 130 nm Silicon-on-Insulator (SOI) industrial technology and is optimized to work in the subthreshold regime of the transistors. The design simulations have been performed over the temperature range of -40-200 °C and for different process corners. Robustness to radiation was simulated using custom model parameters including TID effects, such as mobilities and threshold voltages degradation. The proposed circuit has been tested up to high total radiation dose, i.e., 1 Mrad (Si) performed at three different temperatures (room temperature, 100 °C and 200 °C). The maximum drift of the reference voltage V(REF) depends on the considered temperature and on radiation dose; however, it remains lower than 10% of the mean value of 1.5 V. The typical power dissipation at 2.5 V supply voltage is about 20 μW at room temperature and only 75 μW at a high temperature of 200 °C. To understand the effects caused by the combination of high total ionizing dose and temperature on such voltage reference, the threshold voltages of the used SOI MOSFETs were extracted under different conditions. The evolution of V(REF) and power consumption with temperature and radiation dose can then be explained in terms of the different balance between fixed oxide charge and interface states build-up. The total occupied area including pad-ring is less than 0.09 mm2.
NASA Astrophysics Data System (ADS)
Morén, B.; Larsson, T.; Carlsson Tedgren, Å.
2018-03-01
High dose-rate brachytherapy is a method for cancer treatment where the radiation source is placed within the body, inside or close to a tumour. For dose planning, mathematical optimization techniques are being used in practice and the most common approach is to use a linear model which penalizes deviations from specified dose limits for the tumour and for nearby organs. This linear penalty model is easy to solve, but its weakness lies in the poor correlation of its objective value and the dose-volume objectives that are used clinically to evaluate dose distributions. Furthermore, the model contains parameters that have no clear clinical interpretation. Another approach for dose planning is to solve mixed-integer optimization models with explicit dose-volume constraints which include parameters that directly correspond to dose-volume objectives, and which are therefore tangible. The two mentioned models take the overall goals for dose planning into account in fundamentally different ways. We show that there is, however, a mathematical relationship between them by deriving a linear penalty model from a dose-volume model. This relationship has not been established before and improves the understanding of the linear penalty model. In particular, the parameters of the linear penalty model can be interpreted as dual variables in the dose-volume model.
Reynaud, Michel; Aubin, Henri-Jean; Trinquet, Francoise; Zakine, Benjamin; Dano, Corinne; Dematteis, Maurice; Trojak, Benoit; Paille, Francois; Detilleux, Michel
2017-07-01
Alcohol dependence is a major public health issue with a need for new pharmacological treatments. The ALPADIR study assessed the efficacy and safety of baclofen at the target dose of 180 mg/day for the maintenance of abstinence and the reduction in alcohol consumption in alcohol-dependent patients. Three hundred and twenty adult patients (158 baclofen and 162 placebo) were randomized after alcohol detoxification. After a 7-week titration, the maintenance dose was provided for 17 weeks, then progressively decreased over 2 weeks before stopping. The percentage of abstinent patients during 20 consecutive weeks (primary endpoint) was low (baclofen: 11.9%; placebo: 10.5%) and not significantly different between groups (OR 1.20; 95%CI: 0.58 to 2.50; P = 0.618). A reduction in alcohol consumption was observed from month 1 in both groups, but the difference of 10.9 g/day at month 6 between groups, in favour of baclofen, was not statistically significant (P = 0.095). In a subgroup of patients with high drinking risk level at baseline, the reduction was greater with a difference at month 6 of 15.6 g/day between groups in favour of baclofen (P = 0.089). The craving assessed with Obsessive-Compulsive Drinking Scale significantly decreased in the baclofen group (P = 0.017). No major safety concern was observed. This study did not demonstrate the superiority of baclofen in the maintenance of abstinence at the target dose of 180 mg/day. A tendency towards a reduction in alcohol consumption and a significantly decreased craving were observed in favour of baclofen. Baclofen was assessed versus placebo for maintenance of abstinence and reduction in alcohol consumption in alcohol-dependent patients. This study did not demonstrate the superiority of baclofen in the maintenance of abstinence. A tendency towards a reduction in alcohol consumption and a significantly decreased craving were observed in favour of baclofen. © The Author 2017. Medical Council on Alcohol and Oxford University Press. All rights reserved.
van Breda, Simone G J; van Agen, Ebienus; van Sanden, Suzy; Burzykowski, Tomasz; Kienhuis, Anne S; Kleinjans, Jos C S; van Delft, Joost H M
2005-08-01
There is abundant epidemiological evidence that vegetable consumption decreases colorectal cancer (CRC) risk. However, the molecular targets in the genome are mostly unknown. The present study investigated the effects of vegetable consumption on gene expression in the colon mucosa of female C57Bl/6 mice using cDNA microarray technology. Mice were fed one of 8 diets: a control diet containing no vegetables (diet 1); a diet containing 100 g/kg (diet 2, 10% dose), 200 g/kg (diet 3, 20% dose), or 400 g/kg (diet 4, 40% dose) of a vegetable mixture; or a diet containing 70 g/kg of cauliflower (diet 5, 7% dose), 73 g/kg of carrots (diet 6, 7.3% dose), 226 g/kg of peas (diet 7, 22.6% dose); or 31 g/kg of onions (diet 8, 3.1% dose). The vegetable mixture used in diets 2 to 4 consisted of the 4 individual vegetables used in diets 5 to 8: cauliflower (30% wet wt), carrots (30% wet wt), peas (30% wet wt), and onions (10% wet wt). To assess gene expression changes, colonic mucosal cells were collected after the mice were killed. Total RNA was isolated and microarray technology was used to measure the expression levels of 602 genes simultaneously. For 39 genes, significant dose-dependent effects were found, although in general the relations were not linear. For 15 genes, the altered expression could indeed explain reduced cancer risk at various stages of CRC development. Eleven genes were modulated by the vegetable mixture as well as by one or more of the individual vegetables. For 7 of the genes, the modulation by the mixture was due to the effect of a particular vegetable. These genes are of particular interest because they were consistently affected and could be involved in the prevention of CRC by vegetable consumption.
Ding, Ming; Bhupathiraju, Shilpa N; Satija, Ambika; van Dam, Rob M; Hu, Frank B
2014-02-11
Considerable controversy exists on the association between coffee consumption and cardiovascular disease (CVD) risk. A meta-analysis was performed to assess the dose-response relationship of long-term coffee consumption with CVD risk. PubMed and EMBASE were searched for prospective cohort studies of the relationship between coffee consumption and CVD risk, which included coronary heart disease, stroke, heart failure, and CVD mortality. Thirty-six studies were included with 1 279 804 participants and 36 352 CVD cases. A nonlinear relationship of coffee consumption with CVD risk was identified (P for heterogeneity=0.09, P for trend <0.001, P for nonlinearity <0.001). Compared with the lowest category of coffee consumption (median, 0 cups per day), the relative risk of CVD was 0.95 (95% confidence interval, 0.87-1.03) for the highest category (median, 5 cups per day) category, 0.85 (95% confidence interval, 0.80-0.90) for the second highest category (median, 3.5 cups per day), and 0.89 (95% confidence interval, 0.84-0.94) for the third highest category (median, 1.5 cups per day). Looking at separate outcomes, coffee consumption was nonlinearly associated with both coronary heart disease (P for heterogeneity=0.001, P for trend <0.001, P for nonlinearity <0.001) and stroke (P for heterogeneity=0.07, P for trend <0.001, P for nonlinearity <0.001; P for trend differences >0.05) risks. A nonlinear association between coffee consumption and CVD risk was observed in this meta-analysis. Moderate coffee consumption was inversely significantly associated with CVD risk, with the lowest CVD risk at 3 to 5 cups per day, and heavy coffee consumption was not associated with elevated CVD risk.
Ding, Ming; Bhupathiraju, Shilpa N; Satija, Ambika; van Dam, Rob M; Hu, Frank B
2013-01-01
Background Considerable controversy exists regarding the association between coffee consumption and cardiovascular disease (CVD) risk. A meta-analysis was performed to assess the dose-response relationship of long-term coffee consumption with CVD risk. Methods and Results Pubmed and EMBASE were searched for prospective cohort studies of the relationship between coffee consumption and CVD risk, which included coronary heart disease, stroke, heart failure, and CVD mortality. Thirty-six studies were included with 1,279,804 participants and 36,352 CVD cases. A non-linear relationship of coffee consumption with CVD risk was identified (P for heterogeneity = 0.09, P for trend < 0.001, P for non-linearity < 0.001). Compared with the lowest category of coffee consumption (median: 0 cups/d), the relative risk of CVD was 0.95 (95% CI, 0.87 to 1.03) for the highest (median: 5 cups/d) category, 0.85 (0.80 to 0.90) for the second highest (median: 3.5 cups/d), and 0.89 (0.84 to 0.94) for the third highest category (median: 1.5 cups/d). Looking at separate outcomes, coffee consumption was non-linearly associated with both CHD (P for heterogeneity = 0.001, P for trend < 0.001, P for non-linearity < 0.001) and stroke risks (P for heterogeneity = 0.07, P for trend < 0.001, P for non-linearity< 0.001) (P for trend differences > 0.05). Conclusions A non-linear association between coffee consumption with CVD risk was observed in this meta-analysis. Moderate coffee consumption was inversely significantly associated with CVD risk, with the lowest CVD risk at 3 to 5 cups/d, and heavy coffee consumption was not associated with elevated CVD risk. PMID:24201300
Design and optimization of zero-energy-consumption based solar energy residential building systems
NASA Astrophysics Data System (ADS)
Zheng, D. L.; Yu, L. J.; Tan, H. W.
2017-11-01
Energy consumption of residential buildings has grown fast in recent years, thus raising a challenge on zero energy residential building (ZERB) systems, which aim at substantially reducing energy consumption of residential buildings. Thus, how to facilitate ZERB has become a hot but difficult topic. In the paper, we put forward the overall design principle of ZERB based on analysis of the systems’ energy demand. In particular, the architecture for both schematic design and passive technology is optimized and both energy simulation analysis and energy balancing analysis are implemented, followed by committing the selection of high-efficiency appliance and renewable energy sources for ZERB residential building. In addition, Chinese classical residential building has been investigated in the proposed case, in which several critical aspects such as building optimization, passive design, PV panel and HVAC system integrated with solar water heater, Phase change materials, natural ventilation, etc., have been taken into consideration.
[Optimization of Energy Saving Measures with ABR-MBR Integrated Process].
Wu, Peng; Lu, Shuang-jun; Xu, Yue-zhong; Liu, Jie; Shen, Yao-liang
2015-08-01
High energy consumption and membrane fouling are important factors that limit the wide use of membrane bioreactor (MBR). In order to reduce energy consumption and delay the process of membrane fouling, the process of anaerobic baffled reactor (ABR)-MBR was used to treat domestic sewage. The structure of the process and conditions of nitrogen and phosphorus removal were optimized in this study. The results showed that energy consumption was reduced by 43% through optimizing the structure of ABR-MBR process. Meanwhile, the process achieved a high level of COD, NH: -N, TN and TP removal, with the average removal efficiencies of 91%, 85%, 76% and 86%, respectively. In addition, the added particulate media could effectively delay membrane fouling, while the formation process of membrane fouling was changed. The extracted amount of carbohydrates increased while the amount of proteins decreased. Finally, the potential was enhanced for the practical application of MBR.
Optimization of self-study room open problem based on green and low-carbon campus construction
NASA Astrophysics Data System (ADS)
Liu, Baoyou
2017-04-01
The optimization of self-study room open arrangement problem in colleges and universities is conducive to accelerate the fine management of the campus and promote green and low-carbon campus construction. Firstly, combined with the actual survey data, the self-study area and living area were divided into different blocks, and the electricity consumption in each self-study room and distance between different living and studying areas were normalized. Secondly, the minimum of total satisfaction index and the minimum of the total electricity consumption were selected as the optimization targets respectively. The mathematical models of linear programming were established and resolved by LINGO software. The results showed that the minimum of total satisfaction index was 4055.533 and the total minimum electricity consumption was 137216 W. Finally, some advice had been put forward on how to realize the high efficient administration of the study room.
Selective robust optimization: A new intensity-modulated proton therapy optimization strategy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Yupeng; Niemela, Perttu; Siljamaki, Sami
2015-08-15
Purpose: To develop a new robust optimization strategy for intensity-modulated proton therapy as an important step in translating robust proton treatment planning from research to clinical applications. Methods: In selective robust optimization, a worst-case-based robust optimization algorithm is extended, and terms of the objective function are selectively computed from either the worst-case dose or the nominal dose. Two lung cancer cases and one head and neck cancer case were used to demonstrate the practical significance of the proposed robust planning strategy. The lung cancer cases had minimal tumor motion less than 5 mm, and, for the demonstration of the methodology,more » are assumed to be static. Results: Selective robust optimization achieved robust clinical target volume (CTV) coverage and at the same time increased nominal planning target volume coverage to 95.8%, compared to the 84.6% coverage achieved with CTV-based robust optimization in one of the lung cases. In the other lung case, the maximum dose in selective robust optimization was lowered from a dose of 131.3% in the CTV-based robust optimization to 113.6%. Selective robust optimization provided robust CTV coverage in the head and neck case, and at the same time improved controls over isodose distribution so that clinical requirements may be readily met. Conclusions: Selective robust optimization may provide the flexibility and capability necessary for meeting various clinical requirements in addition to achieving the required plan robustness in practical proton treatment planning settings.« less
NASA Astrophysics Data System (ADS)
Seeley, Kaelyn; Cunha, J. Adam; Hong, Tae Min
2017-01-01
We discuss an improvement in brachytherapy--a prostate cancer treatment method that directly places radioactive seeds inside target cancerous regions--by optimizing the current standard for delivering dose. Currently, the seeds' spatiotemporal placement is determined by optimizing the dose based on a set of physical, user-defined constraints. One particular approach is the ``inverse planning'' algorithms that allow for tightly fit isodose lines around the target volumes in order to reduce dose to the patient's organs at risk. However, these dose distributions are typically computed assuming the same biological response to radiation for different types of tissues. In our work, we consider radiobiological parameters to account for the differences in the individual sensitivities and responses to radiation for tissues surrounding the target. Among the benefits are a more accurate toxicity rate and more coverage to target regions for planning high-dose-rate treatments as well as permanent implants.
Microfluidics: a groundbreaking technology for PET tracer production?
Rensch, Christian; Jackson, Alexander; Lindner, Simon; Salvamoser, Ruben; Samper, Victor; Riese, Stefan; Bartenstein, Peter; Wängler, Carmen; Wängler, Björn
2013-07-05
Application of microfluidics to Positron Emission Tomography (PET) tracer synthesis has attracted increasing interest within the last decade. The technical advantages of microfluidics, in particular the high surface to volume ratio and resulting fast thermal heating and cooling rates of reagents can lead to reduced reaction times, increased synthesis yields and reduced by-products. In addition automated reaction optimization, reduced consumption of expensive reagents and a path towards a reduced system footprint have been successfully demonstrated. The processing of radioactivity levels required for routine production, use of microfluidic-produced PET tracer doses in preclinical and clinical imaging as well as feasibility studies on autoradiolytic decomposition have all given promising results. However, the number of microfluidic synthesizers utilized for commercial routine production of PET tracers is very limited. This study reviews the state of the art in microfluidic PET tracer synthesis, highlighting critical design aspects, strengths, weaknesses and presenting several characteristics of the diverse PET market space which are thought to have a significant impact on research, development and engineering of microfluidic devices in this field. Furthermore, the topics of batch- and single-dose production, cyclotron to quality control integration as well as centralized versus de-centralized market distribution models are addressed.
Ikeo, T; Nagao, T
1985-10-01
We compared the effects of denopamine (TA-064) and isoproterenol on hemodynamics, myocardial oxygen consumption and the left ventricular (LV) dimension in halothane-N2O anesthetized dogs. Denopamine (0.25-1 micrograms/kg/min, i.v., infusion X 15 min) produced a maximum increase in LV dp/dtmax by 64% of the control, without affecting aortic pressure significantly. Doses of isoproterenol (0.01-0.04 micrograms/kg/min, i.v., infusion X 15 min) were selected to produce a positive inotropic action similar to that of denopamine. Denopamine produced significantly less increasing effects in heart rate, cardiac output and myocardial oxygen consumption and had more reducing effects in LV internal diameter than isoproterenol, while isoproterenol tended to produce a more potent increase in coronary blood flow, but a smaller decrease in LV end-diastolic pressure than denopamine. PQ interval was similarly reduced. Denopamine caused no substantial increase in myocardial oxygen consumption at a lower dose, at which LV dp/dtmax was significantly increased. A weak effect of denopamine on myocardial oxygen consumption may result partly from a weak positive chronotropic effect and partly from a reduction of preload and cardiac size.
Holloway, B. R.; Howe, R.; Rao, B. S.; Stribling, D.; Mayers, R. M.; Briscoe, M. G.; Jackson, J. M.
1991-01-01
1. ICI D7114 is a novel, beta-adrenoceptor agonist which stimulates whole body oxygen consumption in conscious rats, cats and dogs and brown adipose tissue (BAT) activity in conscious rats. Treatment of rats with ICI D7114 stimulated oxygen consumption (ED50, 0.04 mg kg-1, p.o.) and BAT mitochondrial guanosine diphosphate (GDP)-binding (ED50, 0.15 mg kg-1, p.o.) with no chronotropic effects on the heart at these doses. 2. Reference beta-adrenoceptor agonists, isoprenaline and clenbuterol, also stimulated oxygen consumption and BAT activity but were less selective because they also produced effects on heart rate at these doses. 3. Treatment of conscious rats with ICI D7114 did not attenuate the chronotropic effects on the heart of a subsequent isoprenaline challenge. 4. Administration of ICI D7114 or of its acid metabolite had no effect in a cat soleus muscle model of tremor or on blood potassium levels in the conscious dog, indicating lack of effects at beta 2-adrenoceptors. 5. The results indicate that ICI D7114 may have activity at atypical beta-adrenoceptors in brown adipose tissue leading to increased whole body oxygen consumption. PMID:1686210
Automatic CT simulation optimization for radiation therapy: A general strategy.
Li, Hua; Yu, Lifeng; Anastasio, Mark A; Chen, Hsin-Chen; Tan, Jun; Gay, Hiram; Michalski, Jeff M; Low, Daniel A; Mutic, Sasa
2014-03-01
In radiation therapy, x-ray computed tomography (CT) simulation protocol specifications should be driven by the treatment planning requirements in lieu of duplicating diagnostic CT screening protocols. The purpose of this study was to develop a general strategy that allows for automatically, prospectively, and objectively determining the optimal patient-specific CT simulation protocols based on radiation-therapy goals, namely, maintenance of contouring quality and integrity while minimizing patient CT simulation dose. The authors proposed a general prediction strategy that provides automatic optimal CT simulation protocol selection as a function of patient size and treatment planning task. The optimal protocol is the one that delivers the minimum dose required to provide a CT simulation scan that yields accurate contours. Accurate treatment plans depend on accurate contours in order to conform the dose to actual tumor and normal organ positions. An image quality index, defined to characterize how simulation scan quality affects contour delineation, was developed and used to benchmark the contouring accuracy and treatment plan quality within the predication strategy. A clinical workflow was developed to select the optimal CT simulation protocols incorporating patient size, target delineation, and radiation dose efficiency. An experimental study using an anthropomorphic pelvis phantom with added-bolus layers was used to demonstrate how the proposed prediction strategy could be implemented and how the optimal CT simulation protocols could be selected for prostate cancer patients based on patient size and treatment planning task. Clinical IMRT prostate treatment plans for seven CT scans with varied image quality indices were separately optimized and compared to verify the trace of target and organ dosimetry coverage. Based on the phantom study, the optimal image quality index for accurate manual prostate contouring was 4.4. The optimal tube potentials for patient sizes of 38, 43, 48, 53, and 58 cm were 120, 140, 140, 140, and 140 kVp, respectively, and the corresponding minimum CTDIvol for achieving the optimal image quality index 4.4 were 9.8, 32.2, 100.9, 241.4, and 274.1 mGy, respectively. For patients with lateral sizes of 43-58 cm, 120-kVp scan protocols yielded up to 165% greater radiation dose relative to 140-kVp protocols, and 140-kVp protocols always yielded a greater image quality index compared to the same dose-level 120-kVp protocols. The trace of target and organ dosimetry coverage and the γ passing rates of seven IMRT dose distribution pairs indicated the feasibility of the proposed image quality index for the predication strategy. A general strategy to predict the optimal CT simulation protocols in a flexible and quantitative way was developed that takes into account patient size, treatment planning task, and radiation dose. The experimental study indicated that the optimal CT simulation protocol and the corresponding radiation dose varied significantly for different patient sizes, contouring accuracy, and radiation treatment planning tasks.
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
Smart sensing to drive real-time loads scheduling algorithm in a domotic architecture
NASA Astrophysics Data System (ADS)
Santamaria, Amilcare Francesco; Raimondo, Pierfrancesco; De Rango, Floriano; Vaccaro, Andrea
2014-05-01
Nowadays the focus on power consumption represent a very important factor regarding the reduction of power consumption with correlated costs and the environmental sustainability problems. Automatic control load based on power consumption and use cycle represents the optimal solution to costs restraint. The purpose of these systems is to modulate the power request of electricity avoiding an unorganized work of the loads, using intelligent techniques to manage them based on real time scheduling algorithms. The goal is to coordinate a set of electrical loads to optimize energy costs and consumptions based on the stipulated contract terms. The proposed algorithm use two new main notions: priority driven loads and smart scheduling loads. The priority driven loads can be turned off (stand by) according to a priority policy established by the user if the consumption exceed a defined threshold, on the contrary smart scheduling loads are scheduled in a particular way to don't stop their Life Cycle (LC) safeguarding the devices functions or allowing the user to freely use the devices without the risk of exceeding the power threshold. The algorithm, using these two kind of notions and taking into account user requirements, manages loads activation and deactivation allowing the completion their operation cycle without exceeding the consumption threshold in an off-peak time range according to the electricity fare. This kind of logic is inspired by industrial lean manufacturing which focus is to minimize any kind of power waste optimizing the available resources.
DIFFUSION AND PERCEPTION OF MERCURY RISK INFORMATION
Approximately 8% of American women have blood Mercury levels exceeding the EPA reference dose (a dose below which symptoms would be unlikely). The children of these women are at risk of neurological deficits (lower IQ scores) primarily because of the mother’s consumption of...
Kim, Seong-Min; Lim, So-Mang; Yoo, Jeong-Ah; Woo, Moon-Jea; Cho, Kyung-Hyun
2015-11-01
Background Although the health effects of vitamin C are well known, its physiological effect on serum lipoproteins and microRNA still remain to be investigated, especially daily consumption of a high dosage. Objectives To investigate the physiological effect of vitamin C on serum lipoprotein metabolism in terms of its anti-oxidant and anti-glycation activities, and gene expression via microRNA regulation. Methods We analyzed blood parameters and lipoprotein parameters in young subjects (n = 46, 22 ± 2 years old) including smokers who consumed a high dose of vitamin C (1250 mg) daily for 8 weeks. Results Antioxidant activity of serum was enhanced with the elevation of Vit C content in plasma during 8 weeks consumption. In the LDL fraction, the apo-B48 band disappeared at 8 weeks post-consumption in all subjects. In the HDL fraction, apoA-I expression was enhanced by 20% at 8 weeks, especially in male smokers. In the lipoprotein fraction, all subjects showed significantly reduced contents of advanced glycated end products and reactive oxygen species (ROS). Triglyceride (TG) contents in each LDL and HDL fraction were significantly reduced in all groups following the Vit C consumption, suggesting that the lipoprotein was changed to be more anti-inflammatory and atherogenic properties. Phagocytosis of LDL, which was purified from each individual, into macrophages was significantly reduced at 8-weeks post-consumption of vitamin C. Anti-inflammatory and anti-senescence effects of HDL from all subjects were enhanced after the 8-weeks consumption. The expression level of microRNA 155 in HDL3 was reduced by 49% and 75% in non-smokers and smokers, respectively. Conclusion The daily consumption of a high dose of vitamin C for 8 weeks resulted in enhanced anti-senescence and anti-atherosclerotic effects via an improvement of lipoprotein parameters and microRNA expression through anti-oxidation and anti-glycation, especially in smokers.
USDA-ARS?s Scientific Manuscript database
We report a unique case of a 3-mo-old female with consumptive hypothyroidism and liver hemangioendothelioma who required pharmacological doses of thyroid hormones and was cured following liver transplantation. Liver hemangioendotheliomas are capable of producing an excess of the thyroid hormone inac...
USDA-ARS?s Scientific Manuscript database
Background: In cross-sectional studies and short-term clinical trials, it has been suggested that there is a positive dose-response relation between alcohol consumption and HDL concentrations. However, prospective data have been limited. Objective: We sought to determine the association between tota...
Griffin, William C.; Nguyen, Shaun A.; Deleon, Christopher P.; Middaugh, Lawrence D.
2012-01-01
We tested the hypothesis that the irreversible gamma-amino butyric acid (GABA) transaminase inhibitor, γ-vinyl GABA (Vigabatrin; VGB) would reduce ethanol reinforcement and enhance the discriminative stimulus effect of ethanol, effectively reducing ethanol intake. The present studies used adult C57BL/6J (B6) mice in well-established operant, two-bottle choice consumption, locomotor activity and ethanol discrimination procedures, to examine comprehensively the effects of VGB on ethanol-supported behaviors. VGB dose-dependently reduced operant responding for ethanol as well as ethanol consumption for long periods of time. Importantly, a low dose (200 mg/kg) of VGB was selective for reducing ethanol responding without altering intake of food or water reinforcement. Higher VGB doses (>200 mg/kg) still reduced ethanol intake, but also significantly increased water consumption and, more modestly, increased food consumption. While not affecting locomotor activity on its own, VGB interacted with ethanol to reduce the stimulatory effects of ethanol on locomotion. Finally, VGB (200 mg/kg) significantly enhanced the discriminative stimulus effects of ethanol as evidenced by significant left-ward and up-ward shifts in ethanol generalization curves. Interestingly, VGB treatment was associated with slight increases in blood ethanol concentrations. The reduction in ethanol intake by VGB appears to be related to the ability of VGB to potentiate the pharmacological effects of ethanol. PMID:22336593
Szilágyiová, Petra; Slušná, Jana; Babela, Robert
2017-11-01
To the Editor, Drug utilization is an important field of drug policy and an integral part of public health internationally. This area of research attracts increasing interest but the pioneering work was done 50 years ago when the first drug consumption report from six European countries for the period of 1966-1967 showed great differences in drug utilization between population groups (WHO, 1968). These results gave important stimulus for creation of Anatomical Therapeutic Chemical (ATC) classification and technical unit of measurement called the Defined Daily Dose (DDD) which is specified as "the assumed average maintenance dose per day for a drug used for its main indication in adults" that dealt with the objections against traditional units of measurement in drug utilization studies (WHO, 2016). The ATC/DDD methodology has in the meantime proved its suitability in drug utilization monitoring and research. As mentioned previously, consumption of pharmaceuticals is often used as a basis for comparison between countries. Based on our professional expertise, we decided to analyze the consumption of cardiovascular medicines by DDD in the Czech Republic and Slovak Republic within all ATC groups reported to OECD (OECD, 2016a). According to OECD indicator results, the Slovak Republic showed in 2014 a higher pharmaceutical consumption by DDD in ATC group C (cardiovascular system) compared to the Czech Republic (OECD, 2016a).
Joint optimization of green vehicle scheduling and routing problem with time-varying speeds
Zhang, Dezhi; Wang, Xin; Ni, Nan; Zhang, Zhuo
2018-01-01
Based on an analysis of the congestion effect and changes in the speed of vehicle flow during morning and evening peaks in a large- or medium-sized city, the piecewise function is used to capture the rules of the time-varying speed of vehicles, which are very important in modelling their fuel consumption and CO2 emission. A joint optimization model of the green vehicle scheduling and routing problem with time-varying speeds is presented in this study. Extra wages during nonworking periods and soft time-window constraints are considered. A heuristic algorithm based on the adaptive large neighborhood search algorithm is also presented. Finally, a numerical simulation example is provided to illustrate the optimization model and its algorithm. Results show that, (1) the shortest route is not necessarily the route that consumes the least energy, (2) the departure time influences the vehicle fuel consumption and CO2 emissions and the optimal departure time saves on fuel consumption and reduces CO2 emissions by up to 5.4%, and (3) extra driver wages have significant effects on routing and departure time slot decisions. PMID:29466370
Joint optimization of green vehicle scheduling and routing problem with time-varying speeds.
Zhang, Dezhi; Wang, Xin; Li, Shuangyan; Ni, Nan; Zhang, Zhuo
2018-01-01
Based on an analysis of the congestion effect and changes in the speed of vehicle flow during morning and evening peaks in a large- or medium-sized city, the piecewise function is used to capture the rules of the time-varying speed of vehicles, which are very important in modelling their fuel consumption and CO2 emission. A joint optimization model of the green vehicle scheduling and routing problem with time-varying speeds is presented in this study. Extra wages during nonworking periods and soft time-window constraints are considered. A heuristic algorithm based on the adaptive large neighborhood search algorithm is also presented. Finally, a numerical simulation example is provided to illustrate the optimization model and its algorithm. Results show that, (1) the shortest route is not necessarily the route that consumes the least energy, (2) the departure time influences the vehicle fuel consumption and CO2 emissions and the optimal departure time saves on fuel consumption and reduces CO2 emissions by up to 5.4%, and (3) extra driver wages have significant effects on routing and departure time slot decisions.
An extended continuum model considering optimal velocity change with memory and numerical tests
NASA Astrophysics Data System (ADS)
Qingtao, Zhai; Hongxia, Ge; Rongjun, Cheng
2018-01-01
In this paper, an extended continuum model of traffic flow is proposed with the consideration of optimal velocity changes with memory. The new model's stability condition and KdV-Burgers equation considering the optimal velocities change with memory are deduced through linear stability theory and nonlinear analysis, respectively. Numerical simulation is carried out to study the extended continuum model, which explores how optimal velocity changes with memory affected velocity, density and energy consumption. Numerical results show that when considering the effects of optimal velocity changes with memory, the traffic jams can be suppressed efficiently. Both the memory step and sensitivity parameters of optimal velocity changes with memory will enhance the stability of traffic flow efficiently. Furthermore, numerical results demonstrates that the effect of optimal velocity changes with memory can avoid the disadvantage of historical information, which increases the stability of traffic flow on road, and so it improve the traffic flow stability and minimize cars' energy consumptions.
Oxytocin Reduces Ethanol Self-Administration in Mice.
King, Courtney E; Griffin, William C; Luderman, Lauryn N; Kates, Malcolm M; McGinty, Jacqueline F; Becker, Howard C
2017-05-01
Excessive ethanol (EtOH) consumption remains an important health concern and effective treatments are lacking. The central oxytocin system has emerged as a potentially important therapeutic target for alcohol and drug addiction. These studies tested the hypothesis that oxytocin reduces EtOH consumption. Male C57BL/6J mice were given access to EtOH (20% v/v) using a model of binge-like drinking ("drinking in the dark") that also included the use of lickometer circuits to evaluate the temporal pattern of intake as well as 2-bottle choice drinking in the home cage. In addition, EtOH (12% v/v) and sucrose (5% w/v) self-administration on fixed- and progressive-ratio schedules were also evaluated. A wide range of systemically administered oxytocin doses were tested (0 to 10 mg/kg) in these models. Oxytocin (0, 0.3, 1, 3, or 10 mg/kg) dose dependently reduced EtOH consumption (maximal 45% reduction) in the binge drinking model, with lower effective doses having minimal effects on general locomotor activity. Oxytocin's effect was blocked by pretreatment with an oxytocin receptor antagonist, and the pattern of contacts (licks) at the EtOH bottle suggested a reduction in motivation to drink EtOH. Oxytocin decreased 2-bottle choice drinking without altering general fluid intake. Oxytocin also reduced operant responding for EtOH and sucrose in a dose-related manner. However, oxytocin decreased responding and motivation (breakpoint values) for EtOH at doses that did not alter responding for sucrose. These results indicate that oxytocin reduces EtOH consumption in different models of self-administration. The effects are not likely due to a general sedative effect of the neuropeptide. Further, oxytocin reduces motivation for EtOH at doses that do not alter responding for a natural reward (sucrose). While some evidence supports a role for oxytocin receptors in mediating these effects, additional studies are needed to further elucidate underlying mechanisms. Nevertheless, these results support the therapeutic potential of oxytocin as a treatment for alcohol use disorder. Copyright © 2017 by the Research Society on Alcoholism.
Hunt, G J
1997-04-01
First, some of the early work is reviewed on exposure pathways in connection with proposed and early liquid radioactive waste discharges from Sellafield. The main historical features of these discharges, affected by relevant plant operations, are then briefly described. The important radiological exposure pathways resulting from the discharges and people's consumption and occupancy habits are considered. To place the changing scenario onto a consistent basis using present-day methodology, a reconstruction of exposures has been carried out using environmental monitoring data and models. The three major pathways are examined of Porphyra/laverbread consumption in South Wales, fish and shellfish consumption near Sellafield, and external exposure over local and more distant sediments. The results show that over the period 1952 to about 1970 the laverbread pathway was probably critical, taking a cautious approach. Effective dose rates fluctuated at around 1 mSv y(-1) from about 1956 to 1971. From about 1970 to 1985, the fish and shellfish pathway was likely to have been critical, with effective dose rates peaking at about 2 mSv y(-1) in 1975-1976. External exposure was likely to have been of lesser importance than the other two pathways until about 1985, when with the retention of previously-released radiocesium on sediments it has become dominant. This phenomenon applies particularly further afield where radiocesium concentrations have been slower to decline; in the Ribble estuary, houseboat dwellers have been the critical group from about 1985. Effective doses have been at about 0.3 mSv y(-1) and declining; they are due to the effects of radiocesium discharges in earlier years. Dose rates have remained within contemporary ICRP dose limits.
Quiroz, Gabriel; Guerra-Díaz, Nicolás; Iturriaga-Vásquez, Patricio; Rivera-Meza, Mario; Quintanilla, María Elena; Sotomayor-Zárate, Ramón
2018-09-03
Alcohol abuse is a worldwide health problem with high economic costs to health systems. Emerging evidence suggests that modulation of brain nicotinic acetylcholine receptors (nAChRs) may be a therapeutic target for alcohol dependence. In this work, we assess the effectiveness of four doses of erysodine (1.5, 2.0, 4.0 or 8.0 mg/kg/day, i.p.), a competitive antagonist of nAChRs, on voluntary ethanol consumption behavior in alcohol-preferring UChB rats, administered during three consecutive days. Results show that erysodine administration produces a dose-dependent reduction in ethanol consumption respect to saline injection (control group). The highest doses of erysodine (4 and 8 mg/kg) reduce (45 and 66%, respectively) the ethanol intake during treatment period and first day of post-treatment compared to control group. While, the lowest doses of erysodine (1.5 and 2 mg/kg) only reduce ethanol intake during one day of treatment period. These effective reductions in ethanol intake were 23 and 29% for 1.5 and 2 mg/kg erysodine, respectively. Locomotor activity induced by a high dose of erysodine (10 mg/kg) was similar to those observed with saline injection in control rats, showing that the reduction in ethanol intake was not produced by hypolocomotor effect induced by erysodine. This is the first report showing that erysodine reduces ethanol intake in UChB rats in a dose-dependent manner. Our results highlight the role of nAChRs in the reward effects of ethanol and its modulation as a potentially effective pharmacological alternative for alcohol dependence treatment. Copyright © 2018 Elsevier B.V. All rights reserved.
Romberg, Raymonda; van Dorp, Eveline; Hollander, Justus; Kruit, Michel; Binning, Alexander; Smith, Terry; Dahan, Albert
2007-01-01
To determine the dose-response effect of intravenous morphine-6-glucuronide (M6G) on acute postoperative pain. Patients undergoing knee replacement surgery under spinal anesthesia were randomly assigned to 1 of 4 single intravenous M6G doses, 0 (placebo), 10, 20, or 30 mg/70 kg, administered 150 minutes after the spinal anesthetic was given. Analgesic effects were evaluated by determining the cumulative patient controlled analgesia (PCA) morphine dose, consumed over a 12 and 24 hours period, after the initial dose of M6G. For pain assessments, a 10 cm visual analog scale was used. Data from 41 patients were evaluated (n=10, 10, 10, and 11 in the 0, 10, 20, and 30 mg M6G groups). Only at the highest M6G dose (30 mg/70 kg), morphine PCA consumption was significantly less compared with placebo: over the first 12 postoperative hours mean PCA morphine consumption was 3.0+/-2.0 mg/h after placebo and 1.4+/-0.5 mg/h after 30 mg M6G (P=0.03); over the first 24 h mean PCA morphine consumption was 2.5+/-2.1 mg after placebo and 1.0+/-0.4 mg after 30 mg M6G (P=0.04) (mean+/-SD). Visual analog scale values were similar across all groups during these time periods. The analgesic effect of M6G in postoperative pain was demonstrated with 30 mg/70 kg M6G superior to placebo. At this dose, M6G has a long duration of action as determined by a reduction in the use of morphine PCA over 12 and 24 hours.
A Unified Model of Performance for Predicting the Effects of Sleep and Caffeine.
Ramakrishnan, Sridhar; Wesensten, Nancy J; Kamimori, Gary H; Moon, James E; Balkin, Thomas J; Reifman, Jaques
2016-10-01
Existing mathematical models of neurobehavioral performance cannot predict the beneficial effects of caffeine across the spectrum of sleep loss conditions, limiting their practical utility. Here, we closed this research gap by integrating a model of caffeine effects with the recently validated unified model of performance (UMP) into a single, unified modeling framework. We then assessed the accuracy of this new UMP in predicting performance across multiple studies. We hypothesized that the pharmacodynamics of caffeine vary similarly during both wakefulness and sleep, and that caffeine has a multiplicative effect on performance. Accordingly, to represent the effects of caffeine in the UMP, we multiplied a dose-dependent caffeine factor (which accounts for the pharmacokinetics and pharmacodynamics of caffeine) to the performance estimated in the absence of caffeine. We assessed the UMP predictions in 14 distinct laboratory- and field-study conditions, including 7 different sleep-loss schedules (from 5 h of sleep per night to continuous sleep loss for 85 h) and 6 different caffeine doses (from placebo to repeated 200 mg doses to a single dose of 600 mg). The UMP accurately predicted group-average psychomotor vigilance task performance data across the different sleep loss and caffeine conditions (6% < error < 27%), yielding greater accuracy for mild and moderate sleep loss conditions than for more severe cases. Overall, accounting for the effects of caffeine resulted in improved predictions (after caffeine consumption) by up to 70%. The UMP provides the first comprehensive tool for accurate selection of combinations of sleep schedules and caffeine countermeasure strategies to optimize neurobehavioral performance. © 2016 Associated Professional Sleep Societies, LLC.
Liu, Wei; Liao, Zhongxing; Schild, Steven E; Liu, Zhong; Li, Heng; Li, Yupeng; Park, Peter C; Li, Xiaoqiang; Stoker, Joshua; Shen, Jiajian; Keole, Sameer; Anand, Aman; Fatyga, Mirek; Dong, Lei; Sahoo, Narayan; Vora, Sujay; Wong, William; Zhu, X Ronald; Bues, Martin; Mohan, Radhe
2015-01-01
We compared conventionally optimized intensity modulated proton therapy (IMPT) treatment plans against worst-case scenario optimized treatment plans for lung cancer. The comparison of the 2 IMPT optimization strategies focused on the resulting plans' ability to retain dose objectives under the influence of patient setup, inherent proton range uncertainty, and dose perturbation caused by respiratory motion. For each of the 9 lung cancer cases, 2 treatment plans were created that accounted for treatment uncertainties in 2 different ways. The first used the conventional method: delivery of prescribed dose to the planning target volume that is geometrically expanded from the internal target volume (ITV). The second used a worst-case scenario optimization scheme that addressed setup and range uncertainties through beamlet optimization. The plan optimality and plan robustness were calculated and compared. Furthermore, the effects on dose distributions of changes in patient anatomy attributable to respiratory motion were investigated for both strategies by comparing the corresponding plan evaluation metrics at the end-inspiration and end-expiration phase and absolute differences between these phases. The mean plan evaluation metrics of the 2 groups were compared with 2-sided paired Student t tests. Without respiratory motion considered, we affirmed that worst-case scenario optimization is superior to planning target volume-based conventional optimization in terms of plan robustness and optimality. With respiratory motion considered, worst-case scenario optimization still achieved more robust dose distributions to respiratory motion for targets and comparable or even better plan optimality (D95% ITV, 96.6% vs 96.1% [P = .26]; D5%- D95% ITV, 10.0% vs 12.3% [P = .082]; D1% spinal cord, 31.8% vs 36.5% [P = .035]). Worst-case scenario optimization led to superior solutions for lung IMPT. Despite the fact that worst-case scenario optimization did not explicitly account for respiratory motion, it produced motion-resistant treatment plans. However, further research is needed to incorporate respiratory motion into IMPT robust optimization. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Liu, W; Schild, S; Bues, M
Purpose: We compared conventionally optimized intensity-modulated proton therapy (IMPT) treatment plans against the worst-case robustly optimized treatment plans for lung cancer. The comparison of the two IMPT optimization strategies focused on the resulting plans' ability to retain dose objectives under the influence of patient set-up, inherent proton range uncertainty, and dose perturbation caused by respiratory motion. Methods: For each of the 9 lung cancer cases two treatment plans were created accounting for treatment uncertainties in two different ways: the first used the conventional Method: delivery of prescribed dose to the planning target volume (PTV) that is geometrically expanded from themore » internal target volume (ITV). The second employed the worst-case robust optimization scheme that addressed set-up and range uncertainties through beamlet optimization. The plan optimality and plan robustness were calculated and compared. Furthermore, the effects on dose distributions of the changes in patient anatomy due to respiratory motion was investigated for both strategies by comparing the corresponding plan evaluation metrics at the end-inspiration and end-expiration phase and absolute differences between these phases. The mean plan evaluation metrics of the two groups were compared using two-sided paired t-tests. Results: Without respiratory motion considered, we affirmed that worst-case robust optimization is superior to PTV-based conventional optimization in terms of plan robustness and optimality. With respiratory motion considered, robust optimization still leads to more robust dose distributions to respiratory motion for targets and comparable or even better plan optimality [D95% ITV: 96.6% versus 96.1% (p=0.26), D5% - D95% ITV: 10.0% versus 12.3% (p=0.082), D1% spinal cord: 31.8% versus 36.5% (p =0.035)]. Conclusion: Worst-case robust optimization led to superior solutions for lung IMPT. Despite of the fact that robust optimization did not explicitly account for respiratory motion it produced motion-resistant treatment plans. However, further research is needed to incorporate respiratory motion into IMPT robust optimization.« less
Li, Yu; Luo, Xin-Xin; Yan, Feng-Dong; Wei, Zhang-Bin; Tu, Jun
2017-05-01
To observe the anti-hyperglycemic effect of Puerariae Lobatae Radix in hepatocyte insulin resistance(IR) models, and investigate its preliminary molecular mechanism. IR-HepG2 cell model was stably established with 1×10-9 mol•L⁻¹ insulin plus 3.75×10-6 mol•L-1 dexamethasone treatment for 48 h according to optimized protocol in our research group. After IR-HepG2 cells were treated with different concentrations(5%,10% and 15%) of Puerariae Lobatae Radix-containing serum, cell viability was detected by CCK-8 assay; the glucose consumptions in IR-HepG2 cells were separately detected at different time points (12, 15, 18, 21, 24, 30, 36 h) by using glucose oxidase method; intracellular glycogen content was detected by anthrone method; and the protein expression levels of leptin receptor (Ob-R), insulin receptor substrate-2 (IRS2), glucose transporter 1(GLUT1) and GLUT2 were detected by Western blot assay. The results showed that Puerariae Lobatae Radix-containing serum (5%, 10% and 15%) had no significant effect on IR-HepG2 cell viability; 5% and 10% Puerariae Lobatae Radix-containing serum significantly increased glucose consumption of IR-HepG2 cells (P<0.01) at 18, 21 and 24 h; 15% Puerariae Lobatae Radix-containing serum elevated the glucose consumption of IR-HepG2 cells at 15 h (P<0.05), and significantly elevated the glucose consumption at 18, 21, 24 and 30 h (P<0.01) in a dose-dependent manner. The optimized time of anti-hyperglycemic effect was defined as 24 h, and further study showed that Puerariae Lobatae Radix-containing serum could increase intracellular glycogen content after 24 h treatment (P<0.01), and up-regulate IRS2, Ob-R, GLUT1 and GLUT2 protein expression levels. Our results indicated that Puerariae Lobatae Radix-containing serum could achieve the anti-hyperglycemic effect through important PI3K/PDK signaling pathway partially by up-regulating the expression levels of Ob-R and IRS2, GLUT1 and GLUT2 in IR-HepG2 cells, accelerating the glucose transport into hepatocytes and increasing hepatic glycogen synthesis to enhance the anti-hyperglycemic effect of IR-HepG2 cells. Copyright© by the Chinese Pharmaceutical Association.
Liu, Chenbin; Schild, Steven E; Chang, Joe Y; Liao, Zhongxing; Korte, Shawn; Shen, Jiajian; Ding, Xiaoning; Hu, Yanle; Kang, Yixiu; Keole, Sameer R; Sio, Terence T; Wong, William W; Sahoo, Narayan; Bues, Martin; Liu, Wei
2018-06-01
To investigate how spot size and spacing affect plan quality, robustness, and interplay effects of robustly optimized intensity modulated proton therapy (IMPT) for lung cancer. Two robustly optimized IMPT plans were created for 10 lung cancer patients: first by a large-spot machine with in-air energy-dependent large spot size at isocenter (σ: 6-15 mm) and spacing (1.3 σ), and second by a small-spot machine with in-air energy-dependent small spot size (σ: 2-6 mm) and spacing (5 mm). Both plans were generated by optimizing radiation dose to internal target volume on averaged 4-dimensional computed tomography scans using an in-house-developed IMPT planning system. The dose-volume histograms band method was used to evaluate plan robustness. Dose evaluation software was developed to model time-dependent spot delivery to incorporate interplay effects with randomized starting phases for each field per fraction. Patient anatomy voxels were mapped phase-to-phase via deformable image registration, and doses were scored using in-house-developed software. Dose-volume histogram indices, including internal target volume dose coverage, homogeneity, and organs at risk (OARs) sparing, were compared using the Wilcoxon signed-rank test. Compared with the large-spot machine, the small-spot machine resulted in significantly lower heart and esophagus mean doses, with comparable target dose coverage, homogeneity, and protection of other OARs. Plan robustness was comparable for targets and most OARs. With interplay effects considered, significantly lower heart and esophagus mean doses with comparable target dose coverage and homogeneity were observed using smaller spots. Robust optimization with a small spot-machine significantly improves heart and esophagus sparing, with comparable plan robustness and interplay effects compared with robust optimization with a large-spot machine. A small-spot machine uses a larger number of spots to cover the same tumors compared with a large-spot machine, which gives the planning system more freedom to compensate for the higher sensitivity to uncertainties and interplay effects for lung cancer treatments. Copyright © 2018 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Barragán, A. M., E-mail: ana.barragan@uclouvain.be; Differding, S.; Lee, J. A.
Purpose: To prove the ability of protons to reproduce a dose gradient that matches a dose painting by numbers (DPBN) prescription in the presence of setup and range errors, by using contours and structure-based optimization in a commercial treatment planning system. Methods: For two patients with head and neck cancer, voxel-by-voxel prescription to the target volume (GTV{sub PET}) was calculated from {sup 18}FDG-PET images and approximated with several discrete prescription subcontours. Treatments were planned with proton pencil beam scanning. In order to determine the optimal plan parameters to approach the DPBN prescription, the effects of the scanning pattern, number ofmore » fields, number of subcontours, and use of range shifter were separately tested on each patient. Different constant scanning grids (i.e., spot spacing = Δx = Δy = 3.5, 4, and 5 mm) and uniform energy layer separation [4 and 5 mm WED (water equivalent distance)] were analyzed versus a dynamic and automatic selection of the spots grid. The number of subcontours was increased from 3 to 11 while the number of beams was set to 3, 5, or 7. Conventional PTV-based and robust clinical target volumes (CTV)-based optimization strategies were considered and their robustness against range and setup errors assessed. Because of the nonuniform prescription, ensuring robustness for coverage of GTV{sub PET} inevitably leads to overdosing, which was compared for both optimization schemes. Results: The optimal number of subcontours ranged from 5 to 7 for both patients. All considered scanning grids achieved accurate dose painting (1% average difference between the prescribed and planned doses). PTV-based plans led to nonrobust target coverage while robust-optimized plans improved it considerably (differences between worst-case CTV dose and the clinical constraint was up to 3 Gy for PTV-based plans and did not exceed 1 Gy for robust CTV-based plans). Also, only 15% of the points in the GTV{sub PET} (worst case) were above 5% of DPBN prescription for robust-optimized plans, while they were more than 50% for PTV plans. Low dose to organs at risk (OARs) could be achieved for both PTV and robust-optimized plans. Conclusions: DPBN in proton therapy is feasible with the use of a sufficient number subcontours, automatically generated scanning patterns, and no more than three beams are needed. Robust optimization ensured the required target coverage and minimal overdosing, while PTV-approach led to nonrobust plans with excessive overdose. Low dose to OARs can be achieved even in the presence of a high-dose escalation as in DPBN.« less
A Distribution-class Locational Marginal Price (DLMP) Index for Enhanced Distribution Systems
NASA Astrophysics Data System (ADS)
Akinbode, Oluwaseyi Wemimo
The smart grid initiative is the impetus behind changes that are expected to culminate into an enhanced distribution system with the communication and control infrastructure to support advanced distribution system applications and resources such as distributed generation, energy storage systems, and price responsive loads. This research proposes a distribution-class analog of the transmission LMP (DLMP) as an enabler of the advanced applications of the enhanced distribution system. The DLMP is envisioned as a control signal that can incentivize distribution system resources to behave optimally in a manner that benefits economic efficiency and system reliability and that can optimally couple the transmission and the distribution systems. The DLMP is calculated from a two-stage optimization problem; a transmission system OPF and a distribution system OPF. An iterative framework that ensures accurate representation of the distribution system's price sensitive resources for the transmission system problem and vice versa is developed and its convergence problem is discussed. As part of the DLMP calculation framework, a DCOPF formulation that endogenously captures the effect of real power losses is discussed. The formulation uses piecewise linear functions to approximate losses. This thesis explores, with theoretical proofs, the breakdown of the loss approximation technique when non-positive DLMPs/LMPs occur and discusses a mixed integer linear programming formulation that corrects the breakdown. The DLMP is numerically illustrated in traditional and enhanced distribution systems and its superiority to contemporary pricing mechanisms is demonstrated using price responsive loads. Results show that the impact of the inaccuracy of contemporary pricing schemes becomes significant as flexible resources increase. At high elasticity, aggregate load consumption deviated from the optimal consumption by up to about 45 percent when using a flat or time-of-use rate. Individual load consumption deviated by up to 25 percent when using a real-time price. The superiority of the DLMP is more pronounced when important distribution network conditions are not reflected by contemporary prices. The individual load consumption incentivized by the real-time price deviated by up to 90 percent from the optimal consumption in a congested distribution network. While the DLMP internalizes congestion management, the consumption incentivized by the real-time price caused overloads.
Carrara, Mauro; Cusumano, Davide; Giandini, Tommaso; Tenconi, Chiara; Mazzarella, Ester; Grisotto, Simone; Massari, Eleonora; Mazzeo, Davide; Cerrotta, Annamaria; Pappalardi, Brigida; Fallai, Carlo; Pignoli, Emanuele
2017-12-01
A direct planning approach with multi-channel vaginal cylinders (MVCs) used for HDR brachytherapy of vaginal cancers is particularly challenging. Purpose of this study was to compare the dosimetric performances of different forward and inverse methods used for the optimization of MVC-based vaginal treatments for endometrial cancer, with a particular attention to the definition of strategies useful to limit the high doses to the vaginal mucosa. Twelve postoperative vaginal HDR brachytherapy treatments performed with MVCs were considered. Plans were retrospectively optimized with three different methods: Dose Point Optimization followed by Graphical Optimization (DPO + GrO), Inverse Planning Simulated Annealing with two different class solutions as starting conditions (surflPSA and homogIPSA) and Hybrid Inverse Planning Optimization (HIPO). Several dosimetric parameters related to target coverage, hot spot extensions and sparing of organs at risk were analyzed to evaluate the quality of the achieved treatment plans. Dose homogeneity index (DHI), conformal index (COIN) and a further parameter quantifying the proportion of the central catheter loading with respect to the overall loading (i.e., the central catheter loading index: CCLI) were also quantified. The achieved PTV coverage parameters were highly correlated with each other but uncorrelated with the hot spot quantifiers. HomogIPSA and HIPO achieved higher DHIs and CCLIs and lower volumes of high doses than DPO + GrO and surflPSA. Within the investigated optimization methods, HIPO and homoglPSA showed the highest dose homogeneity to the target. In particular, homogIPSA resulted also the most effective in reducing hot spots to the vaginal mucosa. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
Jurković, Drazen; Stimac, Danijela; Bajramović, Dubravko; Tiljak, Hrvoje; Stevanović, Ranko
2014-06-01
The aim of this paper is to determine the differences in the outpatient consumption of cardiovascular drugs between Croatian regions: the City of Zagreb and Lika-Senj County. The data on the number of packages and the purchase price for each drug have been obtained from all pharmacies in Lika-Senj County and all pharmacies in the City of Zagreb. Defined daily doses/1000 inhabitants/day (DDD/1000/day) was calculated for every drug in accordance with its code name and Anatomical Therapeutic Chemical/Defined Daily Dose (ATC/DDD) index of the World Health Organization (WHO) for 2007. For drug combinations without defined daily doses, equivalent doses (ED) were used. The quality of drug prescribing within the group of cardiovascular drugs was assessed using the Drug Utilization (DU90%) method and the adherence of the DU90% segment to the guidelines for prescribing individual drug groups. The statistical significance of differences in results between the City of Zagreb and Lika-Senj County was tested using the chi-square test at the level of statistical significance p < 0.05. The comparison of the share of the five most often prescribed drug groups in Lika-Senj County has shown statistically significant differences when compared to the City of Zagreb (chi2 = 28.93, df = 4, p < 0.001). The total outpatient consumption of cardiovascular drugs in the City of Zagreb and Lika-Senj County differs significantly. The consumption, quality of prescribing drugs and cost/DDD in the City of Zagreb is higher than in Lika-Senj County; in the City of Zagreb, newer and more expensive drugs are prescribed to a higher extent.
Hua, B; Lee, A; Fan, L; Li, K; Zhang, Y; Poon, M-C; Zhao, Y
2017-05-01
Pharmacokinetics (PK) modelling suggests improvement of trough levels are achieved by using more frequent infusion strategy. However, no clinical study data exists to confirm or quantify improvement in trough level, particularly for low-dose prophylaxis in patients with haemophilia A. To provide evidence that low dose daily (ED) prophylaxis can increase trough levels without increasing FVIII consumption compared to every-other-day (EOD) infusion. A cross-over study on 5 IU kg -1 FVIII daily vs. 10 IU kg -1 EOD infusions, each for 14 days was conducted at the PUMCH-HTC. On the ED schedule, trough (immediate prior to infusion), and peak FVIII:C levels (30 min after infusion) were measured on days 1-5; and trough levels alone on days 7, 9, 11 and 13. For the EOD schedule, troughs, peaks and 4-h postinfusion were measured on day 1; troughs and peaks on days 3, 5, and 7; troughs alone on days 9, 11 and 13 and 24-h postinfusion on days 2, 4 and 6. FVIII inhibitors were assessed on days 0 and 14 during both infusion schedules. Six patients were enrolled. PK evidence showed that daily prophylaxis achieved higher (~2 times) steady-state FVIII trough levels compared to EOD with the same total factor consumption. The daily prophylaxis had good acceptability among patients and reduced chronic pain in the joints in some patients. Our PK study shows low-dose factor VIII daily infusion results in higher trough level than with EOD infusion with similar factor VIII consumption in Chinese adult haemophilia A patients. © 2017 John Wiley & Sons Ltd.
Wu, Lei; Sun, Dali; He, Yao
2017-06-01
Previous epidemiological studies have provided inconsistent conclusions on the impact of coffee consumption in the developing of cognitive disorders. However, no previous meta-analysis has pooled the evidence from the prospective cohort studies to assess the influence of coffee drinking and its potential dose-response patterns on the risk of developing cognitive disorders specifically. Two databases (PubMed and Embase) were searched for evidence of cohort studies from inception to February 2016. We used a generic inverse-variance method with a random-effects model to pool the fully adjusted relative risks (RRs) and the corresponding 95% confidence intervals (CIs). In the dose-response analyses, a generalized least-squares trend estimation model was applied to computing the study-specific slopes. Nine prospective cohort studies involving 34,282 participants were included in our study. The duration of follow-up years ranged from 1.3 to 28. Compared with <1 cup, daily drinking of 1-2 cups of coffee was inversely linked with the occurrence of cognitive disorders (i.e., Alzheimer's disease, dementia, cognitive decline, and cognitive impairment), and the pooled RR (95% CI) was 0.82 (0.71, 0.94) with evidence of non-significant heterogeneity (I 2 = 25%). Non-significant differences were presented for the association between coffee consumption (>3 vs. <1 cup/d) and incident cognitive disorders. The dose-response analysis showed a "J-shaped" curve relationship of the risk of developing cognitive disorders with coffee consumption. A "J-shaped" association was presented between coffee intake and incident cognitive disorders, with the lowest risk of incident cognitive disorders at a daily consumption level of 1-2 cups of coffee. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Shrime, Mark G; Bauer, Scott R; McDonald, Anna C; Chowdhury, Nubaha H; Coltart, Cordelia E M; Ding, Eric L
2011-11-01
A growing body of evidence suggests that the consumption of foods rich in polyphenolic compounds, particularly cocoa, may have cardioprotective effects. No review, however, has yet examined the effect of flavonoid-rich cocoa (FRC) on all major cardiovascular risk factors or has examined potential dose-response relationships for these effects. A systematic review and meta-analysis of randomized, controlled trials was performed to evaluate the effect of FRC on cardiovascular risk factors and to assess a dose-response relationship. Inclusion and exclusion criteria as well as dependent and independent variables were determined a priori. Data were collected for: blood pressure, pulse, total cholesterol, HDL cholesterol, LDL cholesterol, TG, BMI, C-reactive protein, flow-mediated vascular dilation (FMD), fasting glucose, fasting insulin, serum isoprostane, and insulin sensitivity/resistance indices. Twenty-four papers, with 1106 participants, met the criteria for final analysis. In response to FRC consumption, systolic blood pressure decreased by 1.63 mm Hg (P = 0.033), LDL cholesterol decreased by 0.077 mmol/L (P = 0.038), and HDL cholesterol increased by 0.046 mmol/L (P = 0.037), whereas total cholesterol, TG, and C-reactive protein remained the same. Moreover, insulin resistance decreased (HOMA-IR: -0.94 points; P < 0.001), whereas FMD increased (1.53%; P < 0.001). A nonlinear dose-response relationship was found between FRC and FMD (P = 0.004), with maximum effect observed at a flavonoid dose of 500 mg/d; a similar relationship may exist with HDL cholesterol levels (P = 0.06). FRC consumption significantly improves blood pressure, insulin resistance, lipid profiles, and FMD. These short-term benefits warrant larger long-term investigations into the cardioprotective role of FRC.
Komen, Helga; Brunt, L Michael; Deych, Elena; Blood, Jane; Kharasch, Evan D
2018-05-25
Approximately 50 million US patients undergo ambulatory surgery annually. Postoperative opioid overprescribing is problematic, yet many patients report inadequate pain relief. In major inpatient surgery, intraoperative single-dose methadone produces better analgesia and reduces opioid use compared with conventional repeated dosing of short-duration opioids. This investigation tested the hypothesis that in same-day ambulatory surgery, intraoperative methadone, compared with short-duration opioids, reduces opioid consumption and pain, and determined an effective intraoperative induction dose of methadone for same-day ambulatory surgery. A double-blind, dose-escalation protocol randomized 60 patients (2:1) to intraoperative single-dose intravenous methadone (initially 0.1 then 0.15 mg/kg ideal body weight) or conventional as-needed dosing of short-duration opioids (eg, fentanyl, hydromorphone; controls). Intraoperative and postoperative opioid consumption, pain, and opioid side effects were assessed before discharge. Patient home diaries recorded pain, opioid use, and opioid side effects daily for 30 days postoperatively. Primary outcome was in-hospital (intraoperative and postoperative) opioid use. Secondary outcomes were 30 days opioid consumption, pain intensity, and opioid side effects. Median (interquartile range) methadone doses were 6 (5-6) and 9 (8-9) mg in the 0.1 and 0.15 mg/kg methadone groups, respectively. Total opioid consumption (morphine equivalents) in the postanesthesia care unit was significantly less compared with controls (9.3 mg, 1.3-11.0) in subjects receiving 0.15 mg/kg methadone (0.1 mg, 0.1-3.3; P < .001) but not 0.1 mg/kg methadone (5.0 mg, 3.3-8.1; P = .60). Dose-escalation ended at 0.15 mg/kg methadone. Total in-hospital nonmethadone opioid use after short-duration opioid, 0.1 mg/kg methadone, and 0.15 mg/kg methadone was 35.3 (25.0-44.0), 7.1 (3.7-10.0), and 3.3 (0.1-5.8) mg morphine equivalents, respectively (P < .001 for both versus control). In-hospital pain scores and side effects were not different between groups. In the 30 days after discharge, patients who received methadone 0.15 mg/kg had less pain at rest (P = .02) and used fewer opioid pills than controls (P < .0001), whereas patients who received 0.1 mg/kg had no difference in pain at rest (P = .69) and opioid use compared to controls (P = .08). In same-day discharge surgery, this pilot study identified a single intraoperative dose of methadone (0.15 mg/kg ideal body weight), which decreased intraoperative and postoperative opioid requirements and postoperative pain, compared with conventional intermittent short-duration opioids, with similar side effects.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Liu, Wei, E-mail: Liu.Wei@mayo.edu; Schild, Steven E.; Chang, Joe Y.
Purpose: The purpose of this study was to compare the impact of uncertainties and interplay on 3-dimensional (3D) and 4D robustly optimized intensity modulated proton therapy (IMPT) plans for lung cancer in an exploratory methodology study. Methods and Materials: IMPT plans were created for 11 nonrandomly selected non-small cell lung cancer (NSCLC) cases: 3D robustly optimized plans on average CTs with internal gross tumor volume density overridden to irradiate internal target volume, and 4D robustly optimized plans on 4D computed tomography (CT) to irradiate clinical target volume (CTV). Regular fractionation (66 Gy [relative biological effectiveness; RBE] in 33 fractions) was considered.more » In 4D optimization, the CTV of individual phases received nonuniform doses to achieve a uniform cumulative dose. The root-mean-square dose-volume histograms (RVH) measured the sensitivity of the dose to uncertainties, and the areas under the RVH curve (AUCs) were used to evaluate plan robustness. Dose evaluation software modeled time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Dose-volume histogram (DVH) indices comparing CTV coverage, homogeneity, and normal tissue sparing were evaluated using Wilcoxon signed rank test. Results: 4D robust optimization plans led to smaller AUC for CTV (14.26 vs 18.61, respectively; P=.001), better CTV coverage (Gy [RBE]) (D{sub 95%} CTV: 60.6 vs 55.2, respectively; P=.001), and better CTV homogeneity (D{sub 5%}-D{sub 95%} CTV: 10.3 vs 17.7, resspectively; P=.002) in the face of uncertainties. With interplay effect considered, 4D robust optimization produced plans with better target coverage (D{sub 95%} CTV: 64.5 vs 63.8, respectively; P=.0068), comparable target homogeneity, and comparable normal tissue protection. The benefits from 4D robust optimization were most obvious for the 2 typical stage III lung cancer patients. Conclusions: Our exploratory methodology study showed that, compared to 3D robust optimization, 4D robust optimization produced significantly more robust and interplay-effect-resistant plans for targets with comparable dose distributions for normal tissues. A further study with a larger and more realistic patient population is warranted to generalize the conclusions.« less
Design of shared unit-dose drug distribution network using multi-level particle swarm optimization.
Chen, Linjie; Monteiro, Thibaud; Wang, Tao; Marcon, Eric
2018-03-01
Unit-dose drug distribution systems provide optimal choices in terms of medication security and efficiency for organizing the drug-use process in large hospitals. As small hospitals have to share such automatic systems for economic reasons, the structure of their logistic organization becomes a very sensitive issue. In the research reported here, we develop a generalized multi-level optimization method - multi-level particle swarm optimization (MLPSO) - to design a shared unit-dose drug distribution network. Structurally, the problem studied can be considered as a type of capacitated location-routing problem (CLRP) with new constraints related to specific production planning. This kind of problem implies that a multi-level optimization should be performed in order to minimize logistic operating costs. Our results show that with the proposed algorithm, a more suitable modeling framework, as well as computational time savings and better optimization performance are obtained than that reported in the literature on this subject.
Optimal Consumption in a Brownian Model with Absorption and Finite Time Horizon
DOE Office of Scientific and Technical Information (OSTI.GOV)
Grandits, Peter, E-mail: pgrand@fam.tuwien.ac.at
2013-04-15
We construct {epsilon}-optimal strategies for the following control problem: Maximize E[{integral}{sub [0,{tau})}e{sup -{beta}s} dC{sub s}+e{sup -{beta}{tau}}X{sub {tau}}] , where X{sub t}=x+{mu}t+{sigma}W{sub t}-C{sub t}, {tau}{identical_to}inf{l_brace}t>0|X{sub t}=0{r_brace} Logical-And T, T>0 is a fixed finite time horizon, W{sub t} is standard Brownian motion, {mu}, {sigma} are constants, and C{sub t} describes accumulated consumption until time t. It is shown that {epsilon}-optimal strategies are given by barrier strategies with time-dependent barriers.
Acute Alcohol Effects on Attentional Bias in Heavy and Moderate Drinkers
Weafer, Jessica; Fillmore, Mark T.
2012-01-01
Heavy drinkers show an increased attentional bias to alcohol-related stimuli compared to moderate drinkers, and this bias is thought to promote motivation for alcohol consumption (Field & Cox, 2008). Studies have begun to examine acute alcohol effects on attentional bias, however little is known regarding how these effects might differ based on drinker type. Further, the degree to which attentional bias in response to alcohol is associated with excessive alcohol consumption remains unexplored. For the current study, 20 heavy drinkers and 20 moderate drinkers completed a visual probe task in response to placebo and two active doses of alcohol (0.45 g/kg and 0.65 g/kg). Participants’ eye-movements were monitored and attentional bias was calculated as the difference in time spent focused on alcohol compared to neutral images. Participants’ alcohol consumption was assessed by a timeline follow-back calendar and a laboratory ad lib consumption task. Results showed that heavy drinkers displayed significantly greater attentional bias than did moderate drinkers following placebo. However, heavy drinkers displayed a dose-dependent decrease in attentional bias following alcohol, whereas the drug had no effect in moderate drinkers. Individual differences in attentional bias under placebo were strongly associated with both self-reported and laboratory alcohol consumption, yet bias following alcohol administration did not predict either measure of consumption. These findings suggest that attentional bias is strongest before a drinking episode begins. As such, an attentional bias might be most influential in terms of initiation of alcohol consumption, and less of a factor in promoting continued consumption within the drinking episode. PMID:22732051
NASA Astrophysics Data System (ADS)
Gaddy, Melissa R.; Yıldız, Sercan; Unkelbach, Jan; Papp, Dávid
2018-01-01
Spatiotemporal fractionation schemes, that is, treatments delivering different dose distributions in different fractions, can potentially lower treatment side effects without compromising tumor control. This can be achieved by hypofractionating parts of the tumor while delivering approximately uniformly fractionated doses to the surrounding tissue. Plan optimization for such treatments is based on biologically effective dose (BED); however, this leads to computationally challenging nonconvex optimization problems. Optimization methods that are in current use yield only locally optimal solutions, and it has hitherto been unclear whether these plans are close to the global optimum. We present an optimization framework to compute rigorous bounds on the maximum achievable normal tissue BED reduction for spatiotemporal plans. The approach is demonstrated on liver tumors, where the primary goal is to reduce mean liver BED without compromising any other treatment objective. The BED-based treatment plan optimization problems are formulated as quadratically constrained quadratic programming (QCQP) problems. First, a conventional, uniformly fractionated reference plan is computed using convex optimization. Then, a second, nonconvex, QCQP model is solved to local optimality to compute a spatiotemporally fractionated plan that minimizes mean liver BED, subject to the constraints that the plan is no worse than the reference plan with respect to all other planning goals. Finally, we derive a convex relaxation of the second model in the form of a semidefinite programming problem, which provides a rigorous lower bound on the lowest achievable mean liver BED. The method is presented on five cases with distinct geometries. The computed spatiotemporal plans achieve 12-35% mean liver BED reduction over the optimal uniformly fractionated plans. This reduction corresponds to 79-97% of the gap between the mean liver BED of the uniform reference plans and our lower bounds on the lowest achievable mean liver BED. The results indicate that spatiotemporal treatments can achieve substantial reductions in normal tissue dose and BED, and that local optimization techniques provide high-quality plans that are close to realizing the maximum potential normal tissue dose reduction.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zarepisheh, M; Li, R; Xing, L
Purpose: Station Parameter Optimized Radiation Therapy (SPORT) was recently proposed to fully utilize the technical capability of emerging digital LINACs, in which the station parameters of a delivery system, (such as aperture shape and weight, couch position/angle, gantry/collimator angle) are optimized altogether. SPORT promises to deliver unprecedented radiation dose distributions efficiently, yet there does not exist any optimization algorithm to implement it. The purpose of this work is to propose an optimization algorithm to simultaneously optimize the beam sampling and aperture shapes. Methods: We build a mathematical model whose variables are beam angles (including non-coplanar and/or even nonisocentric beams) andmore » aperture shapes. To solve the resulting large scale optimization problem, we devise an exact, convergent and fast optimization algorithm by integrating three advanced optimization techniques named column generation, gradient method, and pattern search. Column generation is used to find a good set of aperture shapes as an initial solution by adding apertures sequentially. Then we apply the gradient method to iteratively improve the current solution by reshaping the aperture shapes and updating the beam angles toward the gradient. Algorithm continues by pattern search method to explore the part of the search space that cannot be reached by the gradient method. Results: The proposed technique is applied to a series of patient cases and significantly improves the plan quality. In a head-and-neck case, for example, the left parotid gland mean-dose, brainstem max-dose, spinal cord max-dose, and mandible mean-dose are reduced by 10%, 7%, 24% and 12% respectively, compared to the conventional VMAT plan while maintaining the same PTV coverage. Conclusion: Combined use of column generation, gradient search and pattern search algorithms provide an effective way to optimize simultaneously the large collection of station parameters and significantly improves quality of resultant treatment plans as compared with conventional VMAT or IMRT treatments.« less
Hibbeln, Joseph R; SanGiovanni, John Paul; Golding, Jean; Emmett, Pauline M; Northstone, Kate; Davis, John M; Schuckit, Marc; Heron, Jon
2017-11-01
Reducing meat consumption is often advised; however, inadvertent nutritional deficiencies during pregnancy may result in residual neurodevelopmental harms to offspring. This study assessed possible effects of maternal diets in pregnancy on adverse substance use among adolescent offspring. Pregnant women and their 13-year-old offspring taking part in a prospective birth cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC), provided Food Frequency Questionnaire data from which dietary patterns were derived using principal components analysis. Multivariable logistic regression models including potential confounders evaluated adverse alcohol, cannabis, and tobacco use of the children at 15 years of age. Lower maternal meat consumption was associated with greater problematic substance use among 15-year-old offspring in dose-response patterns. Comparing never to daily meat consumption after adjustment, risks were greater for all categories of problem substance use: alcohol, odds ratio OR = 1.75, 95% CI = (1.23, 2.56), p < 0.001; tobacco use OR = 1.85, 95% CI = (1.28, 2.63), p < 0.001; and cannabis OR = 2.70, 95% CI = (1.89, 4.00), p < 0.001. Given the likelihood of residual confounding, potential causality was evaluated using stratification for maternal allelic variants that impact biological activity of cobalamin (vitamin B12) and iron. Lower meat consumption disproportionally increased the risks of offspring substance misuse among mothers with optimally functional (homozygous) variants (rs1801198) of the gene transcobalamin 2 gene (TCN2) which encodes the vitamin B12 transport protein transcobalamin 2 implicating a causal role for cobalamin deficits. Functional maternal variants in iron metabolism were unrelated to the adverse substance use. Risks potentially attributable to cobalamin deficits during pregnancy include adverse adolescent alcohol, cannabis, and tobacco use (14, 37, and 23, respectively). Lower prenatal meat consumption was associated with increased risks of adolescent substance misuse. Interactions between TCN2 variant status and meat intake implicate cobalamin deficiencies. Copyright © 2017 by the Research Society on Alcoholism.
Burger, Joanna
2013-01-01
Studies of fish consumption focus on recreational or subsistence fishing, on awareness and adherence to advisories, consumption patterns, and contaminants in fish. Yet the general public obtains their fish from commercial sources. In this paper I examine fish consumption patterns of recreational fishermen in New Jersey to determine: 1) consumption rates for self-caught fish and for other fish, 2) meals consumed per year, 3) average meal size, and average daily intake of mercury, and 4) variations in these parameters for commonly-consumed fish, and different methods of computing intake. Over 300 people were interviewed at fishing sites and fishing clubs along the New Jersey shore. Consumption patterns of anglers varied by species of fish. From 2 to 90 % of the anglers ate the different fish species, and between 9 and 75 % gave fish away to family or friends. Self-caught fish made up 7 to 92 % of fish diets. On average, self-caught fish were eaten for only 2 to 6 months of the year, whereas other fish (commercial or restaurant) were eaten up to 10 months a year. Anglers consumed from 5 to 36 meals of different fish a year, which resulted in intake of mercury ranging from 0.01 to 0.22 ug/kg/day. Average intake of Mako shark, swordfish, and tuna (sushi, canned tuna, self-caught tuna) exceeded the U.S. Environmental Protection Agency's oral, chronic reference dose for mercury of 0.1 ug/kg/day. However, computing intake using consumption for the highest month results in average mercury intake exceeding the reference dose for striped bass and bluefish as well. These data, and the variability in consumption patterns, have implications for risk assessors, risk managers, and health professionals.
Burger, Joanna
2013-01-01
Studies of fish consumption focus on recreational or subsistence fishing, on awareness and adherence to advisories, consumption patterns, and contaminants in fish. Yet the general public obtains their fish from commercial sources. In this paper I examine fish consumption patterns of recreational fishermen in New Jersey to determine: 1) consumption rates for self-caught fish and for other fish, 2) meals consumed per year, 3) average meal size, and average daily intake of mercury, and 4) variations in these parameters for commonly-consumed fish, and different methods of computing intake. Over 300 people were interviewed at fishing sites and fishing clubs along the New Jersey shore. Consumption patterns of anglers varied by species of fish. From 2 to 90 % of the anglers ate the different fish species, and between 9 and 75 % gave fish away to family or friends. Self-caught fish made up 7 to 92 % of fish diets. On average, self-caught fish were eaten for only 2 to 6 months of the year, whereas other fish (commercial or restaurant) were eaten up to 10 months a year. Anglers consumed from 5 to 36 meals of different fish a year, which resulted in intake of mercury ranging from 0.01 to 0.22 ug/kg/day. Average intake of Mako shark, swordfish, and tuna (sushi, canned tuna, self-caught tuna) exceeded the U.S. Environmental Protection Agency’s oral, chronic reference dose for mercury of 0.1 ug/kg/day. However, computing intake using consumption for the highest month results in average mercury intake exceeding the reference dose for striped bass and bluefish as well. These data, and the variability in consumption patterns, have implications for risk assessors, risk managers, and health professionals. PMID:23914136
[Quality prescription indicators in defined daily doses. Are we getting it right?].
Caamaño-Isorna, Francisco; Alvarez-Gil, Rosa
2008-01-01
Quality prescription indicators of use potential level (UPLI) are defined as the proportion that represents consumption of specific active principles as opposed to the total consumption of the anatomical therapeutic category. The UPLIs that have gradually been defined in Spain employ the defined daily dose (DDD) as the unit of measurement. Although the DDD is not necessarily the same as the therapeutic equivalent dose (TED), some authors have argued that the DDD is a standard unit of measurement and is therefore valid. However, this view may not be correct, given that the relationships between the TED and the DDD differ, depending on the drug, even within the same anatomical therapeutic category. Therefore, the use of DDDs in UPLI s may lead to prescription of a medicine being encouraged or discouraged depending on its TED/DDD ratio.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rehani, M.
2016-06-15
The main topic of the session is to show how dose optimization is being implemented in various regions of the world, including Europe, Australia, North America and other regions. A multi-national study conducted under International Atomic Energy Agency (IAEA) across more than 50 less resourced countries gave insight into patient radiation doses and safety practices in CT, mammography, radiography and interventional procedures, both for children and adults. An important outcome was the capability development on dose assessment and management. An overview of recent European projects related to CT radiation dose and optimization both to adults and children will be presented.more » Existing data on DRLs together with a European methodology proposed on establishing and using DRLs for paediatric radiodiagnostic imaging and interventional radiology practices will be shown. Compared with much of Europe at least, many Australian imaging practices are relatively new to the task of diagnostic imaging dose optimisation. In 2008 the Australian Government prescribed a requirement to periodically compare patient radiation doses with diagnostic reference levels (DRLs), where DRLs have been established. Until recently, Australia had only established DRLs for computed tomography (CT). Regardless, both professional society and individual efforts to improved data collection and develop optimisation strategies across a range of modalities continues. Progress in this field, principally with respect to CT and interventional fluoroscopy will be presented. In the US, dose reduction and optimization efforts for computed tomography have been promoted and mandated by several organizations and accrediting entities. This presentation will cover the general motivation, implementation, and implications of such efforts. Learning Objectives: Understand importance of the dose optimization in Diagnostic Radiology. See how this goal is achieved in different regions of the World. Learn about the global trend in the dose optimization and future prospectives. M. Rehani, The work was a part of the work of IAEA where I was an employee and IAEA is a United Nations organization.« less
MO-DE-204-00: International Symposium: Patient Dose Reduction in Diagnostic Radiology
DOE Office of Scientific and Technical Information (OSTI.GOV)
NONE
2016-06-15
The main topic of the session is to show how dose optimization is being implemented in various regions of the world, including Europe, Australia, North America and other regions. A multi-national study conducted under International Atomic Energy Agency (IAEA) across more than 50 less resourced countries gave insight into patient radiation doses and safety practices in CT, mammography, radiography and interventional procedures, both for children and adults. An important outcome was the capability development on dose assessment and management. An overview of recent European projects related to CT radiation dose and optimization both to adults and children will be presented.more » Existing data on DRLs together with a European methodology proposed on establishing and using DRLs for paediatric radiodiagnostic imaging and interventional radiology practices will be shown. Compared with much of Europe at least, many Australian imaging practices are relatively new to the task of diagnostic imaging dose optimisation. In 2008 the Australian Government prescribed a requirement to periodically compare patient radiation doses with diagnostic reference levels (DRLs), where DRLs have been established. Until recently, Australia had only established DRLs for computed tomography (CT). Regardless, both professional society and individual efforts to improved data collection and develop optimisation strategies across a range of modalities continues. Progress in this field, principally with respect to CT and interventional fluoroscopy will be presented. In the US, dose reduction and optimization efforts for computed tomography have been promoted and mandated by several organizations and accrediting entities. This presentation will cover the general motivation, implementation, and implications of such efforts. Learning Objectives: Understand importance of the dose optimization in Diagnostic Radiology. See how this goal is achieved in different regions of the World. Learn about the global trend in the dose optimization and future prospectives. M. Rehani, The work was a part of the work of IAEA where I was an employee and IAEA is a United Nations organization.« less
MO-DE-204-03: Radiology Dose Optimisation - An Australian Perspective
DOE Office of Scientific and Technical Information (OSTI.GOV)
Schick, D.
2016-06-15
The main topic of the session is to show how dose optimization is being implemented in various regions of the world, including Europe, Australia, North America and other regions. A multi-national study conducted under International Atomic Energy Agency (IAEA) across more than 50 less resourced countries gave insight into patient radiation doses and safety practices in CT, mammography, radiography and interventional procedures, both for children and adults. An important outcome was the capability development on dose assessment and management. An overview of recent European projects related to CT radiation dose and optimization both to adults and children will be presented.more » Existing data on DRLs together with a European methodology proposed on establishing and using DRLs for paediatric radiodiagnostic imaging and interventional radiology practices will be shown. Compared with much of Europe at least, many Australian imaging practices are relatively new to the task of diagnostic imaging dose optimisation. In 2008 the Australian Government prescribed a requirement to periodically compare patient radiation doses with diagnostic reference levels (DRLs), where DRLs have been established. Until recently, Australia had only established DRLs for computed tomography (CT). Regardless, both professional society and individual efforts to improved data collection and develop optimisation strategies across a range of modalities continues. Progress in this field, principally with respect to CT and interventional fluoroscopy will be presented. In the US, dose reduction and optimization efforts for computed tomography have been promoted and mandated by several organizations and accrediting entities. This presentation will cover the general motivation, implementation, and implications of such efforts. Learning Objectives: Understand importance of the dose optimization in Diagnostic Radiology. See how this goal is achieved in different regions of the World. Learn about the global trend in the dose optimization and future prospectives. M. Rehani, The work was a part of the work of IAEA where I was an employee and IAEA is a United Nations organization.« less
Dosimetric evaluation of total marrow irradiation using 2 different planning systems
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nalichowski, Adrian, E-mail: nalichoa@karmanos.org; Eagle, Don G.; Burmeister, Jay
This study compared 2 different treatment planning systems (TPSs) for quality and efficiency of total marrow irradiation (TMI) plans. The TPSs used in this study were VOxel-Less Optimization (VoLO) (Accuray Inc, Sunnyvale, CA) using helical dose delivery on a Tomotherapy Hi-Art treatment unit and Eclipse (Varian Medical Systems Inc, Palo Alto, CA) using volumetric modulated arc therapy (VMAT) dose delivery on a Varian iX treatment unit. A total dose of 1200 cGy was prescribed to cover 95% of the planning target volume (PTV). The plans were optimized and calculated based on a single CT data and structure set using themore » Alderson Rando phantom (The Phantom Laboratory, Salem, NY) and physician contoured target and organ at risk (OAR) volumes. The OARs were lungs, heart, liver, kidneys, brain, and small bowel. The plans were evaluated based on plan quality, time to optimize the plan and calculate the dose, and beam on time. The resulting mean and maximum doses to the PTV were 1268 and 1465 cGy for VoLO and 1284 and 1541 cGy for Eclipse, respectively. For 5 of 6 OAR structures the VoLO system achieved lower mean and D10 doses ranging from 22% to 52% and 3% to 44%, respectively. Total computational time including only optimization and dose calculation were 0.9 hours for VoLO and 3.8 hours for Eclipse. These times do not include user-dependent target delineation and field setup. Both planning systems are capable of creating high-quality plans for total marrow irradiation. The VoLO planning system was able to achieve more uniform dose distribution throughout the target volume and steeper dose fall off, resulting in superior OAR sparing. VoLO's graphics processing unit (GPU)–based optimization and dose calculation algorithm also allowed much faster creation of TMI plans.« less
TU-AB-BRC-12: Optimized Parallel MonteCarlo Dose Calculations for Secondary MU Checks
DOE Office of Scientific and Technical Information (OSTI.GOV)
French, S; Nazareth, D; Bellor, M
Purpose: Secondary MU checks are an important tool used during a physics review of a treatment plan. Commercial software packages offer varying degrees of theoretical dose calculation accuracy, depending on the modality involved. Dose calculations of VMAT plans are especially prone to error due to the large approximations involved. Monte Carlo (MC) methods are not commonly used due to their long run times. We investigated two methods to increase the computational efficiency of MC dose simulations with the BEAMnrc code. Distributed computing resources, along with optimized code compilation, will allow for accurate and efficient VMAT dose calculations. Methods: The BEAMnrcmore » package was installed on a high performance computing cluster accessible to our clinic. MATLAB and PYTHON scripts were developed to convert a clinical VMAT DICOM plan into BEAMnrc input files. The BEAMnrc installation was optimized by running the VMAT simulations through profiling tools which indicated the behavior of the constituent routines in the code, e.g. the bremsstrahlung splitting routine, and the specified random number generator. This information aided in determining the most efficient compiling parallel configuration for the specific CPU’s available on our cluster, resulting in the fastest VMAT simulation times. Our method was evaluated with calculations involving 10{sup 8} – 10{sup 9} particle histories which are sufficient to verify patient dose using VMAT. Results: Parallelization allowed the calculation of patient dose on the order of 10 – 15 hours with 100 parallel jobs. Due to the compiler optimization process, further speed increases of 23% were achieved when compared with the open-source compiler BEAMnrc packages. Conclusion: Analysis of the BEAMnrc code allowed us to optimize the compiler configuration for VMAT dose calculations. In future work, the optimized MC code, in conjunction with the parallel processing capabilities of BEAMnrc, will be applied to provide accurate and efficient secondary MU checks.« less
SU-D-12A-06: A Comprehensive Parameter Analysis for Low Dose Cone-Beam CT Reconstruction
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lu, W; Southern Medical University, Guangzhou; Yan, H
Purpose: There is always a parameter in compressive sensing based iterative reconstruction (IR) methods low dose cone-beam CT (CBCT), which controls the weight of regularization relative to data fidelity. A clear understanding of the relationship between image quality and parameter values is important. The purpose of this study is to investigate this subject based on experimental data and a representative advanced IR algorithm using Tight-frame (TF) regularization. Methods: Three data sets of a Catphan phantom acquired at low, regular and high dose levels are used. For each tests, 90 projections covering a 200-degree scan range are used for reconstruction. Threemore » different regions-of-interest (ROIs) of different contrasts are used to calculate contrast-to-noise ratios (CNR) for contrast evaluation. A single point structure is used to measure modulation transfer function (MTF) for spatial-resolution evaluation. Finally, we analyze CNRs and MTFs to study the relationship between image quality and parameter selections. Results: It was found that: 1) there is no universal optimal parameter. The optimal parameter value depends on specific task and dose level. 2) There is a clear trade-off between CNR and resolution. The parameter for the best CNR is always smaller than that for the best resolution. 3) Optimal parameters are also dose-specific. Data acquired under a high dose protocol require less regularization, yielding smaller optimal parameter values. 4) Comparing with conventional FDK images, TF-based CBCT images are better under a certain optimally selected parameters. The advantages are more obvious for low dose data. Conclusion: We have investigated the relationship between image quality and parameter values in the TF-based IR algorithm. Preliminary results indicate optimal parameters are specific to both the task types and dose levels, providing guidance for selecting parameters in advanced IR algorithms. This work is supported in part by NIH (1R01CA154747-01)« less
Dose in x-ray computed tomography
NASA Astrophysics Data System (ADS)
Kalender, Willi A.
2014-02-01
Radiation dose in x-ray computed tomography (CT) has become a topic of high interest due to the increasing numbers of CT examinations performed worldwide. This review aims to present an overview of current concepts for both scanner output metrics and for patient dosimetry and will comment on their strengths and weaknesses. Controversial issues such as the appropriateness of the CT dose index (CTDI) are discussed in detail. A review of approaches to patient dose assessment presently in practice, of the dose levels encountered and options for further dose optimization are also given and discussed. Patient dose assessment remains a topic for further improvement and for international consensus. All approaches presently in use are based on Monte Carlo (MC) simulations. Estimates for effective dose are established, but they are crude and not patient-specific; organ dose estimates are rarely available. Patient- and organ-specific dose estimates can be provided with adequate accuracy and independent of CTDI phantom measurements by fast MC simulations. Such information, in particular on 3D dose distributions, is important and helpful in optimization efforts. Dose optimization has been performed very successfully in recent years and even resulted in applications with effective dose values of below 1 mSv. In general, a trend towards lower dose values based on technical innovations has to be acknowledged. Effective dose values are down to clearly below 10 mSv on average, and there are a number of applications such as cardiac and pediatric CT which are performed routinely below 1 mSv on modern equipment.
Numerical solution of a conspicuous consumption model with constant control delay☆
Huschto, Tony; Feichtinger, Gustav; Hartl, Richard F.; Kort, Peter M.; Sager, Sebastian; Seidl, Andrea
2011-01-01
We derive optimal pricing strategies for conspicuous consumption products in periods of recession. To that end, we formulate and investigate a two-stage economic optimal control problem that takes uncertainty of the recession period length and delay effects of the pricing strategy into account. This non-standard optimal control problem is difficult to solve analytically, and solutions depend on the variable model parameters. Therefore, we use a numerical result-driven approach. We propose a structure-exploiting direct method for optimal control to solve this challenging optimization problem. In particular, we discretize the uncertainties in the model formulation by using scenario trees and target the control delays by introduction of slack control functions. Numerical results illustrate the validity of our approach and show the impact of uncertainties and delay effects on optimal economic strategies. During the recession, delayed optimal prices are higher than the non-delayed ones. In the normal economic period, however, this effect is reversed and optimal prices with a delayed impact are smaller compared to the non-delayed case. PMID:22267871
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yu, V; Nguyen, D; Pajonk, F
Purpose: To explore the feasibility of improving GBM treatment outcome with temporal-spatial dose optimization of an ordinary differential equation (ODE) that models the differentiation and distinct radiosensitivity between cancer stem cells (CSC) and differentiated cancer cells (DCC). Methods: The ODE was formulated into a non-convex optimization problem with the objective to minimize remaining total cancer cells 500 days from the onset of radiotherapy when the total cancer cell number was 3.5×10{sup 7}, while maintaining normal tissue biological effective dose (BED) of 100Gy resulted from standard prescription of 2Gyx30. Assuming spatially separated CSC and DCC, optimization was also performed to exploremore » the potential benefit from dose-painting the two compartments. Dose escalation to a sub-cell-population in the GTV was also examined assuming that a 2 cm margin around the GTV allows sufficient dose drop-off to 100Gy BED. The recurrence time was determined as the time at which the total cancer cell number regrows to 10{sup 9} cells. Results: The recurrence time with variable fractional doses administered once per week, bi-week and month for one year were found to be 615, 593 and 570 days, superior to the standard-prescription recurrence time of 418 days. The optimal dose-fraction size progression for both uniform and dose-painting to the tumor is low and relatively constant in the beginning and gradually increases to more aggressive fractions at end of the treatment course. Dose escalation to BED of 200Gy to the whole tumor alongside with protracted weekly treatment was found to further delay recurrence to 733 days. Dose-painting of 200 and 500Gy BED to CSC on a year-long weekly schedule further extended recurrence to 736 and 1076 days, respectively. Conclusion: GBM treatment outcome can possibly be improved with a chronic treatment approach. Further dose escalation to the entire tumor or CSC targeted killing is needed to achieve total tumor control. This work is supported by the NSF Graduate Research Fellowship (DGE-1144087)« less
Meinzer, Caitlyn; Martin, Renee; Suarez, Jose I
2017-09-08
In phase II trials, the most efficacious dose is usually not known. Moreover, given limited resources, it is difficult to robustly identify a dose while also testing for a signal of efficacy that would support a phase III trial. Recent designs have sought to be more efficient by exploring multiple doses through the use of adaptive strategies. However, the added flexibility may potentially increase the risk of making incorrect assumptions and reduce the total amount of information available across the dose range as a function of imbalanced sample size. To balance these challenges, a novel placebo-controlled design is presented in which a restricted Bayesian response adaptive randomization (RAR) is used to allocate a majority of subjects to the optimal dose of active drug, defined as the dose with the lowest probability of poor outcome. However, the allocation between subjects who receive active drug or placebo is held constant to retain the maximum possible power for a hypothesis test of overall efficacy comparing the optimal dose to placebo. The design properties and optimization of the design are presented in the context of a phase II trial for subarachnoid hemorrhage. For a fixed total sample size, a trade-off exists between the ability to select the optimal dose and the probability of rejecting the null hypothesis. This relationship is modified by the allocation ratio between active and control subjects, the choice of RAR algorithm, and the number of subjects allocated to an initial fixed allocation period. While a responsive RAR algorithm improves the ability to select the correct dose, there is an increased risk of assigning more subjects to a worse arm as a function of ephemeral trends in the data. A subarachnoid treatment trial is used to illustrate how this design can be customized for specific objectives and available data. Bayesian adaptive designs are a flexible approach to addressing multiple questions surrounding the optimal dose for treatment efficacy within the context of limited resources. While the design is general enough to apply to many situations, future work is needed to address interim analyses and the incorporation of models for dose response.
Improved Nitrogen Removal Effect In Continuous Flow A2/O Process Using Typical Extra Carbon Source
NASA Astrophysics Data System (ADS)
Wu, Haiyan; Gao, Junyan; Yang, Dianhai; Zhou, Qi; Cai, Bijing
2010-11-01
In order to provide a basis for optimal selection of carbon source, three typical external carbon sources (i.e. methanol, sodium acetate and leachate) were applied to examine nitrogen removal efficiency of continuous flow A2/O system with the influent from the effluent of grit chamber in the second Kunming wastewater treatment plant. The best dosage was determined, and the specific nitrogen removal rate and carbon consumption rate were calculated with regard to individual external carbon source in A2/O system. Economy and technology analysis was also conducted to select the suitable carbon source with a low operation cost. Experimental results showed that the external typical carbon source caused a remarkable enhancement of system nitrate degradation ability. In comparison with the blank test, the average TN and NH3-N removal efficiency of system with different dosing quantities of external carbon source was improved by 15.2% and 34.2%, respectively. The optimal dosage of methanol, sodium acetate and leachate was respectively up to 30 mg/L, 40 mg/L and 100 mg COD/L in terms of a high nitrogen degradation effect. The highest removal efficiency of COD, TN and NH3-N reached respectively 92.3%, 73.9% and 100% with methanol with a dosage of 30 mg/L. The kinetic analysis and calculation revealed that the greatest denitrification rate was 0.0107 mg TN/mg MLVSSṡd with sodium acetate of 60 mg/L. As to carbon consumption rate, however, the highest value occurred in the blank test with a rate of 0.1955 mg COD/mg MLVSSṡd. Also, further economic analysis proved leachate to be pragmatic external carbon source whose cost was far cheaper than methanol.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chajon, Enrique; Dumas, Isabelle; Touleimat, Mahmoud B.Sc.
2007-11-01
Purpose: The purpose of this study was to evaluate the inverse planning simulated annealing (IPSA) software for the optimization of dose distribution in patients with cervix carcinoma treated with MRI-based pulsed-dose rate intracavitary brachytherapy. Methods and Materials: Thirty patients treated with a technique using a customized vaginal mold were selected. Dose-volume parameters obtained using the IPSA method were compared with the classic manual optimization method (MOM). Target volumes and organs at risk were delineated according to the Gynecological Brachytherapy Group/European Society for Therapeutic Radiology and Oncology recommendations. Because the pulsed dose rate program was based on clinical experience with lowmore » dose rate, dwell time values were required to be as homogeneous as possible. To achieve this goal, different modifications of the IPSA program were applied. Results: The first dose distribution calculated by the IPSA algorithm proposed a heterogeneous distribution of dwell time positions. The mean D90, D100, and V100 calculated with both methods did not differ significantly when the constraints were applied. For the bladder, doses calculated at the ICRU reference point derived from the MOM differed significantly from the doses calculated by the IPSA method (mean, 58.4 vs. 55 Gy respectively; p = 0.0001). For the rectum, the doses calculated at the ICRU reference point were also significantly lower with the IPSA method. Conclusions: The inverse planning method provided fast and automatic solutions for the optimization of dose distribution. However, the straightforward use of IPSA generated significant heterogeneity in dwell time values. Caution is therefore recommended in the use of inverse optimization tools with clinical relevance study of new dosimetric rules.« less
Hassona, Rifaat K; Sam, A K; Osman, O I; Sirelkhatim, D A; LaRosa, J
2008-04-15
An assessment of Committed Effective Dose (CED) due to consumption of Red Sea fish containing (210)Po and (137)Cs was performed for 23 different marine fish samples collected from the local market at Port Sudan. The fish were classified according to their feeding habits into three categories: carnivores, herbivores, and omnivores. Measured activity concentrations of (210)Po were found in the ranges 0.25-6.42 (carnivores), 0.7-5 (omnivores) and 1.5-3.8 (herbivores) Bq/kg fresh weight. In the same study, activity concentrations of Cs-137 were determined to be in the ranges 0.1-0.46 (carnivores), 0.09-0.35 (omnivores) and 0.09-0.32 (herbivores) Bq/kg fresh weight, which were several times lower than those of (210)Po. Appropriate conversion factors were used to derive the CED, which was found to be 0.012, 0.01 and 0.01 (microSv/yr) in carnivores, omnivores and herbivores, respectively, for (137)Cs. This contributes about 0.4% of the total dose exclusively by ingestion of fish. For (210)Po, it was found to be 3.47, 4.81 and 4.14 (microSv/yr) in carnivores, omnivores and herbivores, respectively, which represents 99.6% of the total dose (exclusively by ingestion of fish). The results of CED calculations suggest that the dose received by the Sudanese population from the consumption of marine fish is rather small and that the contribution of (137)Cs is negligible compared to (210)Po.
MO-AB-BRA-01: A Global Level Set Based Formulation for Volumetric Modulated Arc Therapy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nguyen, D; Lyu, Q; Ruan, D
2016-06-15
Purpose: The current clinical Volumetric Modulated Arc Therapy (VMAT) optimization is formulated as a non-convex problem and various greedy heuristics have been employed for an empirical solution, jeopardizing plan consistency and quality. We introduce a novel global direct aperture optimization method for VMAT to overcome these limitations. Methods: The global VMAT (gVMAT) planning was formulated as an optimization problem with an L2-norm fidelity term and an anisotropic total variation term. A level set function was used to describe the aperture shapes and adjacent aperture shapes were penalized to control MLC motion range. An alternating optimization strategy was implemented to solvemore » the fluence intensity and aperture shapes simultaneously. Single arc gVMAT plans, utilizing 180 beams with 2° angular resolution, were generated for a glioblastoma multiforme (GBM), lung (LNG), and 2 head and neck cases—one with 3 PTVs (H&N3PTV) and one with 4 PTVs (H&N4PTV). The plans were compared against the clinical VMAT (cVMAT) plans utilizing two overlapping coplanar arcs. Results: The optimization of the gVMAT plans had converged within 600 iterations. gVMAT reduced the average max and mean OAR dose by 6.59% and 7.45% of the prescription dose. Reductions in max dose and mean dose were as high as 14.5 Gy in the LNG case and 15.3 Gy in the H&N3PTV case. PTV coverages (D95, D98, D99) were within 0.25% of the prescription dose. By globally considering all beams, the gVMAT optimizer allowed some beams to deliver higher intensities, yielding a dose distribution that resembles a static beam IMRT plan with beam orientation optimization. Conclusions: The novel VMAT approach allows for the search of an optimal plan in the global solution space and generates deliverable apertures directly. The single arc VMAT approach fully utilizes the digital linacs’ capability in dose rate and gantry rotation speed modulation. Varian Medical Systems, NIH grant R01CA188300, NIH grant R43CA183390.« less
Gaikowski, Mark P.; Whitsel, Melissa K.; Charles, Shawn; Schleis, Susan M.; Crouch, Louis S.; Endris, Richard G.
2015-01-01
Aquaflor® [50% w w−1 florfenicol (FFC)], is approved for use in freshwater-reared warmwater finfish which include tilapia Oreochromis spp. in the United States to control mortality from Streptococcus iniae. The depletion of florfenicol amine (FFA), the marker residue of FFC, was evaluated after feeding FFC-medicated feed to deliver a nominal 20 mg FFC kg−1 BW d−1 dose (1.33× the label use of 15 mg FFC kg−1 BW d−1) to Nile tilapia O. niloticus and hybrid tilapia O. niloticus × O. aureus held in a recirculating aquaculture system (RAS) at production-scale holding densities. Florfenicol amine concentrations were determined in fillets taken from 10 fish before dosing and from 20 fish at nine time points after dosing (from 1 to 240 h post-dosing). Water samples were assayed for FFC before, during and after the dosing period. Parameters monitored included daily feed consumption and biofilter function (levels of ammonia, nitrite and nitrate). Mean fillet FFA concentration decreased from 13.77 μg g−1 at 1-h post dosing to 0.39 μg g−1 at 240-h post dosing. Water FFC concentration decreased from a maximum of 1400 ng mL−1 at 1 day post-dosing to 847 ng mL−1 at 240 h post-dosing. There were no adverse effects noted on fish, feed consumption or biofilter function associated with FFC-medicated feed administration to tilapia.
Energy Consumption Information Services for Smart Home Inhabitants
NASA Astrophysics Data System (ADS)
Schwanzer, Michael; Fensel, Anna
We investigate services giving users an adequate insight on his or her energy consumption habits in order to optimize it in the long run. The explored energy awareness services are addressed to inhabitants of smart homes, equipped with smart meters, advanced communication facilities, sensors and actuators. To analyze the potential of such services, a game at a social network Facebook has been designed and implemented, and the information about players' responses and interactions within the game environment has been collected and analyzed. The players have had their virtual home energy usage visualized in different ways, and had to optimize the energy consumption basing on their own perceptions of the consumption information. Evaluations reveal, in particular, that users are specifically responsive to information shown as a real-time graph and as costs in Euro, and are able to produce and share with each other policies for managing their smart home environments.
An Efficient Offloading Scheme For MEC System Considering Delay and Energy Consumption
NASA Astrophysics Data System (ADS)
Sun, Yanhua; Hao, Zhe; Zhang, Yanhua
2018-01-01
With the increasing numbers of mobile devices, mobile edge computing (MEC) which provides cloud computing capabilities proximate to mobile devices in 5G networks has been envisioned as a promising paradigm to enhance users experience. In this paper, we investigate a joint consideration of delay and energy consumption offloading scheme (JCDE) for MEC system in 5G heterogeneous networks. An optimization is formulated to minimize the delay as well as energy consumption of the offloading system, which the delay and energy consumption of transmitting and calculating tasks are taken into account. We adopt an iterative greedy algorithm to solve the optimization problem. Furthermore, simulations were carried out to validate the utility and effectiveness of our proposed scheme. The effect of parameter variations on the system is analysed as well. Numerical results demonstrate delay and energy efficiency promotion of our proposed scheme compared with another paper’s scheme.
Real time monitoring system used in route planning for the electric vehicle
NASA Astrophysics Data System (ADS)
Ionescu, LM; Mazare, A.; Serban, G.; Ionita, S.
2017-10-01
The electric vehicle is a new consumer of electricity that is becoming more and more widespread. Under these circumstances, new strategies for optimizing power consumption and increasing vehicle autonomy must be designed. These must include route planning along with consumption, fuelling points and points of interest. The hardware and software solution proposed by us allows: non-invasive monitoring of power consumption, energy autonomy - it does not add any extra consumption, data transmission to a server and data fusion with the route, the points of interest of the route and the power supply points. As a result: an optimal route planning service will be provided to the driver, considering the route, the requirements of the electric vehicle and the consumer profile. The solution can be easily installed on any type of electric car - it does not involve any intervention on the equipment.
NASA Astrophysics Data System (ADS)
Kang, Donghun; Lee, Jungeon; Jung, Jongpil; Lee, Chul-Hee; Kyung, Chong-Min
2014-09-01
In mobile video systems powered by battery, reducing the encoder's compression energy consumption is critical to prolong its lifetime. Previous Energy-rate-distortion (E-R-D) optimization methods based on a software codec is not suitable for practical mobile camera systems because the energy consumption is too large and encoding rate is too low. In this paper, we propose an E-R-D model for the hardware codec based on the gate-level simulation framework to measure the switching activity and the energy consumption. From the proposed E-R-D model, an energy minimizing algorithm for mobile video camera sensor have been developed with the GOP (Group of Pictures) size and QP(Quantization Parameter) as run-time control variables. Our experimental results show that the proposed algorithm provides up to 31.76% of energy consumption saving while satisfying the rate and distortion constraints.
A two‐point scheme for optimal breast IMRT treatment planning
2013-01-01
We propose an approach to determining optimal beam weights in breast/chest wall IMRT treatment plans. The goal is to decrease breathing effect and to maximize skin dose if the skin is included in the target or, otherwise, to minimize the skin dose. Two points in the target are utilized to calculate the optimal weights. The optimal plan (i.e., the plan with optimal beam weights) consists of high energy unblocked beams, low energy unblocked beams, and IMRT beams. Six breast and five chest wall cases were retrospectively planned with this scheme in Eclipse, including one breast case where CTV was contoured by the physician. Compared with 3D CRT plans composed of unblocked and field‐in‐field beams, the optimal plans demonstrated comparable or better dose uniformity, homogeneity, and conformity to the target, especially at beam junction when supraclavicular nodes are involved. Compared with nonoptimal plans (i.e., plans with nonoptimized weights), the optimal plans had better dose distributions at shallow depths close to the skin, especially in cases where breathing effect was taken into account. This was verified with experiments using a MapCHECK device attached to a motion simulation table (to mimic motion caused by breathing). PACS number: 87.55 de PMID:24257291
Multiparameter optimization of mammography: an update
NASA Astrophysics Data System (ADS)
Jafroudi, Hamid; Muntz, E. P.; Jennings, Robert J.
1994-05-01
Previously in this forum we have reported the application of multiparameter optimization techniques to the design of a minimum dose mammography system. The approach used a reference system to define the physical imaging performance required and the dose to which the dose for the optimized system should be compared. During the course of implementing the resulting design in hardware suitable for laboratory testing, the state of the art in mammographic imaging changed, so that the original reference system, which did not have a grid, was no longer appropriate. A reference system with a grid was selected in response to this change, and at the same time the optimization procedure was modified, to make it more general and to facilitate study of the optimized design under a variety of conditions. We report the changes in the procedure, and the results obtained using the revised procedure and the up- to-date reference system. Our results, which are supported by laboratory measurements, indicate that the optimized design can image small objects as well as the reference system using only about 30% of the dose required by the reference system. Hardware meeting the specification produced by the optimization procedure and suitable for clinical use is currently under evaluation in the Diagnostic Radiology Department at the Clinical Center, NH.
Optimization of wireless sensor networks based on chicken swarm optimization algorithm
NASA Astrophysics Data System (ADS)
Wang, Qingxi; Zhu, Lihua
2017-05-01
In order to reduce the energy consumption of wireless sensor network and improve the survival time of network, the clustering routing protocol of wireless sensor networks based on chicken swarm optimization algorithm was proposed. On the basis of LEACH agreement, it was improved and perfected that the points on the cluster and the selection of cluster head using the chicken group optimization algorithm, and update the location of chicken which fall into the local optimum by Levy flight, enhance population diversity, ensure the global search capability of the algorithm. The new protocol avoided the die of partial node of intensive using by making balanced use of the network nodes, improved the survival time of wireless sensor network. The simulation experiments proved that the protocol is better than LEACH protocol on energy consumption, also is better than that of clustering routing protocol based on particle swarm optimization algorithm.
Optimal charge control strategies for stationary photovoltaic battery systems
NASA Astrophysics Data System (ADS)
Li, Jiahao; Danzer, Michael A.
2014-07-01
Battery systems coupled to photovoltaic (PV) modules for example fulfill one major function: they locally decouple PV generation and consumption of electrical power leading to two major effects. First, they reduce the grid load, especially at peak times and therewith reduce the necessity of a network expansion. And second, they increase the self-consumption in households and therewith help to reduce energy expenses. For the management of PV batteries charge control strategies need to be developed to reach the goals of both the distribution system operators and the local power producer. In this work optimal control strategies regarding various optimization goals are developed on the basis of the predicted household loads and PV generation profiles using the method of dynamic programming. The resulting charge curves are compared and essential differences discussed. Finally, a multi-objective optimization shows that charge control strategies can be derived that take all optimization goals into account.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wan Chan Tseung, Hok Seum, E-mail: wanchantseung.hok@mayo.edu; Ma, Jiasen; Kreofsky, Cole R.
Purpose: Our aim is to demonstrate the feasibility of fast Monte Carlo (MC)–based inverse biological planning for the treatment of head and neck tumors in spot-scanning proton therapy. Methods and Materials: Recently, a fast and accurate graphics processor unit (GPU)–based MC simulation of proton transport was developed and used as the dose-calculation engine in a GPU-accelerated intensity modulated proton therapy (IMPT) optimizer. Besides dose, the MC can simultaneously score the dose-averaged linear energy transfer (LET{sub d}), which makes biological dose (BD) optimization possible. To convert from LET{sub d} to BD, a simple linear relation was assumed. By use of thismore » novel optimizer, inverse biological planning was applied to 4 patients, including 2 small and 1 large thyroid tumor targets, as well as 1 glioma case. To create these plans, constraints were placed to maintain the physical dose (PD) within 1.25 times the prescription while maximizing target BD. For comparison, conventional intensity modulated radiation therapy (IMRT) and IMPT plans were also created using Eclipse (Varian Medical Systems) in each case. The same critical-structure PD constraints were used for the IMRT, IMPT, and biologically optimized plans. The BD distributions for the IMPT plans were obtained through MC recalculations. Results: Compared with standard IMPT, the biologically optimal plans for patients with small tumor targets displayed a BD escalation that was around twice the PD increase. Dose sparing to critical structures was improved compared with both IMRT and IMPT. No significant BD increase could be achieved for the large thyroid tumor case and when the presence of critical structures mitigated the contribution of additional fields. The calculation of the biologically optimized plans can be completed in a clinically viable time (<30 minutes) on a small 24-GPU system. Conclusions: By exploiting GPU acceleration, MC-based, biologically optimized plans were created for small–tumor target patients. This optimizer will be used in an upcoming feasibility trial on LET{sub d} painting for radioresistant tumors.« less
Lee, Jin Kyu; Chung, Kyu-Sung; Choi, Choong Hyeok
2015-01-01
We sought to compare a group (Group L) (n=21) of patients that underwent total knee arthroplasty and received a single preoperative dose of pregabalin combined with a COX-2 inhibitor with a control group (Group C) (n=20) that only received a COX-2 inhibitor in terms of (1) acute postoperative pain intensity, (2) analgesic consumption, and (3) functional recovery. Mean cumulative fentanyl consumption during the first 48 hours was lower in Group L than in Group C (P<0.05). The pain scores at rest were lower in Group L at 6 and 12 hours after surgery (P<0.05). No significant intergroup difference was noted in functional recovery. The addition of pregabalin led to an additive reduction in early postoperative pain and analgesic consumption. Copyright © 2014 Elsevier Inc. All rights reserved.
Apples prevent mammary tumors in rats.
Liu, Rui Hai; Liu, Jiaren; Chen, Bingqing
2005-03-23
Regular consumption of fruits and vegetables has been consistently shown to be associated with reduced risk of developing chronic diseases such as cancer and cardiovascular disease. Apples are commonly consumed and are the major contributors of phytochemicals in human diets. It was previously reported that apple extracts exhibit strong antioxidant and antiproliferative activities and that the major part of total antioxidant activity is from the combination of phytochemicals. Phytochemicals, including phenolics and flavonoids, are suggested to be the bioactive compounds contributing to the health benefits of apples. Here it is shown that whole apple extracts prevent mammary cancer in a rat model in a dose-dependent manner at doses comparable to human consumption of one, three, and six apples a day. This study demonstrated that whole apple extracts effectively inhibited mammary cancer growth in the rat model; thus, consumption of apples may be an effective strategy for cancer protection.
Optimizing dosing of oncology drugs.
Minasian, L; Rosen, O; Auclair, D; Rahman, A; Pazdur, R; Schilsky, R L
2014-11-01
The purpose of this article is to acknowledge the challenges in optimizing the dosing of oncology drugs and to propose potential approaches to address these challenges in order to optimize effectiveness, minimize toxicity, and promote adherence in patients. These approaches could provide better opportunities to understand the sources of variability in drug exposure and clinical outcomes during the development and premarketing evaluation of investigational new drugs.
A Data Driven Pre-cooling Framework for Energy Cost Optimization in Commercial Buildings
DOE Office of Scientific and Technical Information (OSTI.GOV)
Vishwanath, Arun; Chandan, Vikas; Mendoza, Cameron
Commercial buildings consume significant amount of energy. Facility managers are increasingly grappling with the problem of reducing their buildings’ peak power, overall energy consumption and energy bills. In this paper, we first develop an optimization framework – based on a gray box model for zone thermal dynamics – to determine a pre-cooling strategy that simultaneously shifts the peak power to low energy tariff regimes, and reduces both the peak power and overall energy consumption by exploiting the flexibility in a building’s thermal comfort range. We then evaluate the efficacy of the pre-cooling optimization framework by applying it to building managementmore » system data, spanning several days, obtained from a large commercial building located in a tropical region of the world. The results from simulations show that optimal pre-cooling reduces peak power by over 50%, energy consumption by up to 30% and energy bills by up to 37%. Next, to enable ease of use of our framework, we also propose a shortest path based heuristic algorithmfor solving the optimization problemand show that it has comparable erformance with the optimal solution. Finally, we describe an application of the proposed optimization framework for developing countries to reduce the dependency on expensive fossil fuels, which are often used as a source for energy backup.We conclude by highlighting our real world deployment of the optimal pre-cooling framework via a software service on the cloud platform of a major provider. Our pre-cooling methodology, based on the gray box optimization framework, incurs no capital expense and relies on data readily available from a building management system, thus enabling facility managers to take informed decisions for improving the energy and cost footprints of their buildings« less
Maridakis, Victor; Herring, Matthew P; O'Connor, Patrick J
2009-01-01
This double-blind, placebo-controlled, within-subjects (N = 18) experiment compared the sensitivity to change of cognitive performance and mood measures of mental energy following consumption of either 100 or 200-mg caffeine or a 440-calorie breakfast. Breakfast and 200-mg caffeine improved mood and cognitive performance. The sensitivity to change of the measures did not differ in response to any treatment (all p values > .05). The mood and cognitive measures of mental energy used here have similar sensitivity to detecting change in response to a moderate dose of caffeine and breakfast consumption.
Thyroid Function Changes Related to Use of Iodinated Water in United States Space Program
NASA Technical Reports Server (NTRS)
McMonigal, Kathleen A.; Braverman, Lewis E.; Dunn, John T.; Stanbury, John B.; Wear, Mary L.; Hamm, Peggy B.; Sauer, Richard L.; Billica, Roger D.; Pool, Sam L.
1999-01-01
The National Aeronautics and Space Administration (NASA) has used iodination as a method of microbial disinfection of potable water systems in United States spacecraft and long-duration habitability modules. A review of the effects on the thyroid following consumption o iodinated water by NASA astronauts was conducted. Pharmacological doses of iodine consumed by astronauts transiently decreased thyroid function, as reflected in serum TSH values. Although the adverse effects of excess iodine consumption in susceptible individuals are well documented, exposure to high doses of iodine during space flight did not result in a statistically significant increase in long-term thyroid disease in the astronaut population.
Effects of HMX exposure upon metabolic rate of northern bobwhite quail (Colinus virginianus) in ovo.
Liu, Jun; Cox, Stephen B; Beall, Blake; Brunjes, Kristina J; Pan, Xiaoping; Kendall, Ronald J; Anderson, Todd A; McMurry, Scott T; Cobb, George P; Smith, Philip N
2008-05-01
We evaluated the use of the gas exchange rate as an ecologically relevant indicator of chemical stress in avian embryos/eggs. Northern bobwhite quail (Colinus virginianus) were exposed to octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) via feed containing nominal concentrations of 0, 12.5, 50.0, and 125.0 mg kg(-1). Metabolic rates (oxygen consumption) of developing quail eggs were then measured via respirometry to examine potential effects of HMX exposure. Metabolic rates were examined on 5, 9, and 21 d of incubation. Next, concentrations of HMX in embryos/eggs were determined by liquid chromatography-mass spectrometry. Mean (+/-SE) concentrations of HMX in eggs were 21.0+/-5.9, 1113+/-79.0, 3864+/-154.0, and 7426+/-301.1 ng g(-1) in control, low, medium and high dose groups, respectively. There were significant differences in oxygen consumption among the three embryo ages, however differences among the ages were not consistent among dose groups (age x dose group interaction p<0.0001). Oxygen consumption rates did not vary as a function of HMX in embryos (p=0.18). No evidence was observed for alterations of in ovo metabolic rates associated with HMX exposure.
Thompson, Helen M; Wilkins, Selwyn; Harkin, Sarah; Milner, Sarah; Walters, Keith F A
2015-07-01
The objective of this study was to quantify whether the presence of three different neonicotinoid insecticides (imidacloprid, thiamethoxam or clothianidin) in sucrose solution results in antifeedant effects in individual worker bumblebees (Bombus terrestris), and, if so, whether this effect is reversible if bees are subsequently offered untreated feed. Bees exposed to imidacloprid displayed a significant dose-dependent reduction in consumption at 10 and 100 µg L(-1), which was reversed when untreated feed was offered. No consistent avoidance/antifeedant response to nectar substitute with thiamethoxam was detected at the more field-realistic dose rates of 1 and 10 µg L(-1), and exposure to the very high 100 µg L(-1) dose rate was followed by 100% mortality of experimental insects. No reduction in food intake was recorded at 1 µg clothianidin L(-1), reduced consumption was noted at 10 µg clothianidin L(-1) and 100% mortality occurred when bees were exposed to rates of 100 µg clothianidin L(-1). This study provides evidence of a direct antifeedant effect of imidacloprid and clothianidin in individual bumblebees but highlights that this may be a compound-specific effect. © 2014 Crown copyright. Pest Management Science © 2014 Society of Chemical Industry.
Xylitol gummy bear snacks: a school-based randomized clinical trial
Ly, Kiet A; Riedy, Christine A; Milgrom, Peter; Rothen, Marilynn; Roberts, Marilyn C; Zhou, Lingmei
2008-01-01
Background Habitual consumption of xylitol reduces mutans streptococci (MS) levels but the effect on Lactobacillus spp. is less clear. Reduction is dependent on daily dose and frequency of consumption. For xylitol to be successfully used in prevention programs to reduce MS and prevent caries, effective xylitol delivery methods must be identified. This study examines the response of MS, specifically S. mutans/sobrinus and Lactobacillus spp., levels to xylitol delivered via gummy bears at optimal exposures. Methods Children, first to fifth grade (n = 154), from two elementary schools in rural Washington State, USA, were randomized to xylitol 15.6 g/day (X16, n = 53) or 11.7 g/day (X12, n = 49), or maltitol 44.7 g/day (M45, n = 52). Gummy bear snacks were pre-packaged in unit-doses, labeled with ID numbers, and distributed three times/day during school hours. No snacks were sent home. Plaque was sampled at baseline and six weeks and cultured on modified Mitis Salivarius agar for S. mutans/sobrinus and Rogosa SL agar for Lactobacillus spp. enumeration. Results There were no differences in S. mutans/sobrinus and Lactobacillus spp. levels in plaque between the groups at baseline. At six weeks, log10 S. mutans/sobrinus levels showed significant reductions for all groups (p = 0.0001): X16 = 1.13 (SD = 1.65); X12 = 0.89 (SD = 1.11); M45 = 0.91 (SD = 1.46). Reductions were not statistically different between groups. Results for Lactobacillus spp. were mixed. Group X16 and M45 showed 0.31 (SD = 2.35), and 0.52 (SD = 2.41) log10 reductions, respectively, while X12 showed a 0.11 (SD = 2.26) log10 increase. These changes were not significant. Post-study discussions with school staff indicated that it is feasible to implement an in-classroom gummy bear snack program. Parents are accepting and children willing to consume gummy bear snacks daily. Conclusion Reductions in S. mutans/sobrinus levels were observed after six weeks of gummy bear snack consumption containing xylitol at 11.7 or 15.6 g/day or maltitol at 44.7 g/day divided in three exposures. Lactobacillus spp. levels were essentially unchanged in all groups. These results suggest that a xylitol gummy bear snack may be an alternative to xylitol chewing gum for dental caries prevention. Positive results with high dose maltitol limit the validity of xylitol findings. A larger clinical trial is needed to confirm the xylitol results. Trial registration [ISRCTN63160504] PMID:18657266
Zsigraiova, Zdena; Semiao, Viriato; Beijoco, Filipa
2013-04-01
This work proposes an innovative methodology for the reduction of the operation costs and pollutant emissions involved in the waste collection and transportation. Its innovative feature lies in combining vehicle route optimization with that of waste collection scheduling. The latter uses historical data of the filling rate of each container individually to establish the daily circuits of collection points to be visited, which is more realistic than the usual assumption of a single average fill-up rate common to all the system containers. Moreover, this allows for the ahead planning of the collection scheduling, which permits a better system management. The optimization process of the routes to be travelled makes recourse to Geographical Information Systems (GISs) and uses interchangeably two optimization criteria: total spent time and travelled distance. Furthermore, rather than using average values, the relevant parameters influencing fuel consumption and pollutant emissions, such as vehicle speed in different roads and loading weight, are taken into consideration. The established methodology is applied to the glass-waste collection and transportation system of Amarsul S.A., in Barreiro. Moreover, to isolate the influence of the dynamic load on fuel consumption and pollutant emissions a sensitivity analysis of the vehicle loading process is performed. For that, two hypothetical scenarios are tested: one with the collected volume increasing exponentially along the collection path; the other assuming that the collected volume decreases exponentially along the same path. The results evidence unquestionable beneficial impacts of the optimization on both the operation costs (labor and vehicles maintenance and fuel consumption) and pollutant emissions, regardless the optimization criterion used. Nonetheless, such impact is particularly relevant when optimizing for time yielding substantial improvements to the existing system: potential reductions of 62% for the total spent time, 43% for the fuel consumption and 40% for the emitted pollutants. This results in total cost savings of 57%, labor being the greatest contributor, representing over €11,000 per year for the two vehicles collecting glass-waste. Moreover, it is shown herein that the dynamic loading process of the collection vehicle impacts on both the fuel consumption and on pollutant emissions. Copyright © 2012 Elsevier Ltd. All rights reserved.
Speed and convergence properties of gradient algorithms for optimization of IMRT.
Zhang, Xiaodong; Liu, Helen; Wang, Xiaochun; Dong, Lei; Wu, Qiuwen; Mohan, Radhe
2004-05-01
Gradient algorithms are the most commonly employed search methods in the routine optimization of IMRT plans. It is well known that local minima can exist for dose-volume-based and biology-based objective functions. The purpose of this paper is to compare the relative speed of different gradient algorithms, to investigate the strategies for accelerating the optimization process, to assess the validity of these strategies, and to study the convergence properties of these algorithms for dose-volume and biological objective functions. With these aims in mind, we implemented Newton's, conjugate gradient (CG), and the steepest decent (SD) algorithms for dose-volume- and EUD-based objective functions. Our implementation of Newton's algorithm approximates the second derivative matrix (Hessian) by its diagonal. The standard SD algorithm and the CG algorithm with "line minimization" were also implemented. In addition, we investigated the use of a variation of the CG algorithm, called the "scaled conjugate gradient" (SCG) algorithm. To accelerate the optimization process, we investigated the validity of the use of a "hybrid optimization" strategy, in which approximations to calculated dose distributions are used during most of the iterations. Published studies have indicated that getting trapped in local minima is not a significant problem. To investigate this issue further, we first obtained, by trial and error, and starting with uniform intensity distributions, the parameters of the dose-volume- or EUD-based objective functions which produced IMRT plans that satisfied the clinical requirements. Using the resulting optimized intensity distributions as the initial guess, we investigated the possibility of getting trapped in a local minimum. For most of the results presented, we used a lung cancer case. To illustrate the generality of our methods, the results for a prostate case are also presented. For both dose-volume and EUD based objective functions, Newton's method far outperforms other algorithms in terms of speed. The SCG algorithm, which avoids expensive "line minimization," can speed up the standard CG algorithm by at least a factor of 2. For the same initial conditions, all algorithms converge essentially to the same plan. However, we demonstrate that for any of the algorithms studied, starting with previously optimized intensity distributions as the initial guess but for different objective function parameters, the solution frequently gets trapped in local minima. We found that the initial intensity distribution obtained from IMRT optimization utilizing objective function parameters, which favor a specific anatomic structure, would lead to a local minimum corresponding to that structure. Our results indicate that from among the gradient algorithms tested, Newton's method appears to be the fastest by far. Different gradient algorithms have the same convergence properties for dose-volume- and EUD-based objective functions. The hybrid dose calculation strategy is valid and can significantly accelerate the optimization process. The degree of acceleration achieved depends on the type of optimization problem being addressed (e.g., IMRT optimization, intensity modulated beam configuration optimization, or objective function parameter optimization). Under special conditions, gradient algorithms will get trapped in local minima, and reoptimization, starting with the results of previous optimization, will lead to solutions that are generally not significantly different from the local minimum.
Dzierżanowski, Tomasz; Ciałkowska-Rysz, Aleksandra
2017-03-01
Based on the international reports, consumption of opioid analgesics in Poland is relatively low. There is limited information on possible impediments to optimal opioid use. This study was aimed to identify possible barriers to access to opioid analgesics and causes of failure to comply with current clinical guidelines. Consumption data per capita in 2000-2015 were analyzed in terms of oral morphine equivalents in total, per prescription type, per reimbursement status, to identify the impact of regulations specific for Poland. The consumption of opioid analgesics has been consistently growing from 36.0 in 2000 to 103.4 mg oral morphine equivalents (OME) per capita in 2015, mainly thanks to strong opioid consumption growth. Tramadol is the most commonly used opioid in Poland. Fentanyl and buprenorphine transdermal formulations are the most frequently used strong opioid analgesics in terms of OME. The vast majority (92.8 %) of opioids were distributed upon for outpatient use in 2015, with a almost fourfold growth of consumption of strong opioids and almost threefold of weak opioids between 2000 and 2015. Strong opioids were 41 % of OME used upon prescription in 2015. Acceleration of consumption growth has been observed since 2013. The prescription pattern does not abide by the current clinical guidelines for pain treatment, and the most often used opioids in Poland are tramadol, buprenorphine, and fentanyl. The use of opioids in Poland grows fast, with acceleration since 2013. The most important legal impediments of optimal opioid analgesics use have been lack of reimbursement, special prescription forms, and complicated prescribing rules.
Treatment regimens of classical and newer taxanes.
Joerger, Markus
2016-02-01
The classical taxanes (paclitaxel, docetaxel), the newer taxane cabazitaxel and the nanoparticle-bound nab-paclitaxel are among the most widely used anticancer drugs. The taxanes share the characteristics of extensive hepatic metabolism and biliary excretion, the need for dose adaptation in patients with liver dysfunction, and a substantial pharmacokinetic variability even after taking into account known covariates. Data from clinical studies suggest that optimal scheduling of the taxanes is dependent not only on the specific taxane compound, but also on the tumor type and line of treatment. Still, the optimal dosing regimen (weekly vs 3 weekly) and optimal dose of the taxanes are controversial, as is the value of pharmacological personalization of taxane dosing. In this article, an overview is given on the pharmacological properties of the taxanes, including metabolism, pharmacokinetics-pharmacodynamics and aspects in the clinical use of taxanes. The latter includes the ongoing debate on the most active and safe regimen, the recommended initial dose and the issue of therapeutic drug dosing.
NASA Astrophysics Data System (ADS)
Yang, Jia Sheng
2018-06-01
In this paper, we investigate a H∞ memory controller with input limitation minimization (HMCIM) for offshore jacket platforms stabilization. The main objective of this study is to reduce the control consumption as well as protect the actuator when satisfying the requirement of the system performance. First, we introduce a dynamic model of offshore platform with low order main modes based on mode reduction method in numerical analysis. Then, based on H∞ control theory and matrix inequality techniques, we develop a novel H∞ memory controller with input limitation. Furthermore, a non-convex optimization model to minimize input energy consumption is proposed. Since it is difficult to solve this non-convex optimization model by optimization algorithm, we use a relaxation method with matrix operations to transform this non-convex optimization model to be a convex optimization model. Thus, it could be solved by a standard convex optimization solver in MATLAB or CPLEX. Finally, several numerical examples are given to validate the proposed models and methods.
Guiu-Souto, Jacobo; Sánchez-García, Manuel; Vázquez-Vázquez, Rubén; Otero, Carlos; Luna, Victor; Mosquera, Javier; Busto, Ramón Lobato; Aguiar, Pablo; Ruibal, Álvaro; Pardo-Montero, Juan; Pombar-Cameán, Miguel
2016-06-01
The last recommendations of the International Commission on Radiological Protection for eye lens dose suggest an important reduction on the radiation limits associated with early and late tissue reactions. The aim of this work is to quantify and optimize the eye lens dose associated to nurse staff during positron emission tomography (PET) procedures. PET is one of the most important diagnostic methods of oncological and neurological cancer disease involving an important number of workers exposed to the high energy isotope F-18. We characterize the relevant stages as preparation and administration of monodose syringes in terms of occupational dose. A direct reading silicon dosimeter was used to measure the lens dose to staff. The highest dose of radiation was observed during preparation of the fluorodesoxyglucose (FDG) syringes. By optimizing a suitable vials' distribution of FDG we find an important reduction in occupational doses. Extrapolation of our data to other clinical scenarios indicates that, depending on the work load and/or syringes activity, safety limits of the dose might be exceeded.
Optimal iodine-131 dose for eliminating hyperthyroidism in Graves' disease
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nordyke, R.A.; Gilbert, F.I. Jr.
1991-03-01
Since hypothyroidism is commonplace after treatment of Graves' disease with radioiodine, the goal should be cure of hyperthyroidism rather than avoidance of hypothyroidism. To find the optimal dose to accomplish cure, we treated 605 patients with stepwise increasing doses of 3, 4, 5, 6, 8, and 10 mCi, analyzing the relationship of dose, age, sex, gland weight, and thyroidal uptake to cure. Estimates of cure at doses above 10 mCi were made from the literature. Cure was directly related to dose between 5 and 10 mCi. There was no significant relationship between cure and age (chi-square, p = 0.74), sexmore » (chi-square, p = 0.12), and 24-hr uptake if over 30% (chi-square for slope, p greater than 0.10). Cure and gland weight had an inverse relationship (chi-square for slope, 0.01 less than p less than 0.02). We concluded that the optimal 131I dose for curing hyperthyroidism is approximated by starting with 10 mCi and increasing it for unusually large glands or for special patient circumstances.« less
Cross-jurisdictional management of a trophy-hunted species.
Hochard, Jacob; Finnoff, David
2017-05-07
Gray wolves (Canis lupus) are managed for competing uses in the Greater Yellowstone Ecosystem (GYE). Tourism benefits Yellowstone National Park (YNP) visitors while trophy hunting benefits hunters outside of the park. We investigate the policy scope of gray wolf management across jurisdictional boundaries by incorporating three foundations of the behavioral ecology of wolves: refuge-seeking behavior, optimal foraging group size and territoriality. Tradeoffs between and within consumptive and non-consumptive human benefits and wolf population fitness and life history indicators are quantified as a set of elasticities, providing clear implications to resource managers. Our approach highlights that hunting intensity affects the provision of consumptive and non-consumptive human benefits across jurisdictional boundaries and ought to be managed accordingly. We also show that population levels are an incomplete indicator of species fitness, which may depend on how hunting policies impact underlying group ecology. Our findings suggest traditional optimization approaches to wildlife management may lead to suboptimal policy recommendations when the boundaries on the natural system are oversimplified. Highlighting the human element of wildlife management, we show that understanding tourist and hunter responses to wildlife population abundances is critical to balancing provision of consumptive and non-consumptive human uses. Copyright © 2017 Elsevier Ltd. All rights reserved.
Wu, Qixue; Snyder, Karen Chin; Liu, Chang; Huang, Yimei; Zhao, Bo; Chetty, Indrin J; Wen, Ning
2016-09-30
Treatment of patients with multiple brain metastases using a single-isocenter volumetric modulated arc therapy (VMAT) has been shown to decrease treatment time with the tradeoff of larger low dose to the normal brain tissue. We have developed an efficient Projection Summing Optimization Algorithm to optimize the treatment geometry in order to reduce dose to normal brain tissue for radiosurgery of multiple metastases with single-isocenter VMAT. The algorithm: (a) measures coordinates of outer boundary points of each lesion to be treated using the Eclipse Scripting Application Programming Interface, (b) determines the rotations of couch, collimator, and gantry using three matrices about the cardinal axes, (c) projects the outer boundary points of the lesion on to Beam Eye View projection plane, (d) optimizes couch and collimator angles by selecting the least total unblocked area for each specific treatment arc, and (e) generates a treatment plan with the optimized angles. The results showed significant reduction in the mean dose and low dose volume to normal brain, while maintaining the similar treatment plan qualities on the thirteen patients treated previously. The algorithm has the flexibility with regard to the beam arrangements and can be integrated in the treatment planning system for clinical application directly.
Comprehensive optimization process of paranasal sinus radiography.
Saarakkala, S; Nironen, K; Hermunen, H; Aarnio, J; Heikkinen, J O
2009-04-01
The optimization of radiological examinations is important in order to reduce unnecessary patient radiation exposure. To perform a comprehensive optimization process for paranasal sinus radiography at Mikkeli Central Hospital, Finland. Patients with suspicion of acute sinusitis were imaged with a Kodak computed radiography (CR) system (n=20) and with a Philips digital radiography (DR) system (n=30) using focus-detector distances (FDDs) of 110 cm, 150 cm, or 200 cm. Patients' radiation exposure was determined in terms of entrance surface dose and dose-area product. Furthermore, an anatomical phantom was used for the estimation of point doses inside the head. Clinical image quality was evaluated by an experienced radiologist, and physical image quality was evaluated from the digital radiography phantom. Patient doses were significantly lower and image quality better with the DR system compared to the CR system. The differences in patient dose and physical image quality were small with varying FDD. Clinical image quality of the DR system was lowest with FDD of 200 cm. Further, imaging with FDD of 150 cm was technically easier for the technologist to perform than with FDD of 110 cm. After optimization, it was recommended that the DR system with FDD of 150 cm should always be used at Mikkeli Central Hospital. We recommend this kind of comprehensive approach in all optimization processes of radiological examinations.
Takahashi, Fumihiro; Morita, Satoshi
2018-02-08
Phase II clinical trials are conducted to determine the optimal dose of the study drug for use in Phase III clinical trials while also balancing efficacy and safety. In conducting these trials, it may be important to consider subpopulations of patients grouped by background factors such as drug metabolism and kidney and liver function. Determining the optimal dose, as well as maximizing the effectiveness of the study drug by analyzing patient subpopulations, requires a complex decision-making process. In extreme cases, drug development has to be terminated due to inadequate efficacy or severe toxicity. Such a decision may be based on a particular subpopulation. We propose a Bayesian utility approach (BUART) to randomized Phase II clinical trials which uses a first-order bivariate normal dynamic linear model for efficacy and safety in order to determine the optimal dose and study population in a subsequent Phase III clinical trial. We carried out a simulation study under a wide range of clinical scenarios to evaluate the performance of the proposed method in comparison with a conventional method separately analyzing efficacy and safety in each patient population. The proposed method showed more favorable operating characteristics in determining the optimal population and dose.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Taleei, R; Qin, N; Jiang, S
2016-06-15
Purpose: Biological treatment plan optimization is of great interest for proton therapy. It requires extensive Monte Carlo (MC) simulations to compute physical dose and biological quantities. Recently, a gPMC package was developed for rapid MC dose calculations on a GPU platform. This work investigated its suitability for proton therapy biological optimization in terms of accuracy and efficiency. Methods: We performed simulations of a proton pencil beam with energies of 75, 150 and 225 MeV in a homogeneous water phantom using gPMC and FLUKA. Physical dose and energy spectra for each ion type on the central beam axis were scored. Relativemore » Biological Effectiveness (RBE) was calculated using repair-misrepair-fixation model. Microdosimetry calculations were performed using Monte Carlo Damage Simulation (MCDS). Results: Ranges computed by the two codes agreed within 1 mm. Physical dose difference was less than 2.5 % at the Bragg peak. RBE-weighted dose agreed within 5 % at the Bragg peak. Differences in microdosimetric quantities such as dose average lineal energy transfer and specific energy were < 10%. The simulation time per source particle with FLUKA was 0.0018 sec, while gPMC was ∼ 600 times faster. Conclusion: Physical dose computed by FLUKA and gPMC were in a good agreement. The RBE differences along the central axis were small, and RBE-weighted dose difference was found to be acceptable. The combined accuracy and efficiency makes gPMC suitable for proton therapy biological optimization.« less
Role of step size and max dwell time in anatomy based inverse optimization for prostate implants
Manikandan, Arjunan; Sarkar, Biplab; Rajendran, Vivek Thirupathur; King, Paul R.; Sresty, N.V. Madhusudhana; Holla, Ragavendra; Kotur, Sachin; Nadendla, Sujatha
2013-01-01
In high dose rate (HDR) brachytherapy, the source dwell times and dwell positions are vital parameters in achieving a desirable implant dose distribution. Inverse treatment planning requires an optimal choice of these parameters to achieve the desired target coverage with the lowest achievable dose to the organs at risk (OAR). This study was designed to evaluate the optimum source step size and maximum source dwell time for prostate brachytherapy implants using an Ir-192 source. In total, one hundred inverse treatment plans were generated for the four patients included in this study. Twenty-five treatment plans were created for each patient by varying the step size and maximum source dwell time during anatomy-based, inverse-planned optimization. Other relevant treatment planning parameters were kept constant, including the dose constraints and source dwell positions. Each plan was evaluated for target coverage, urethral and rectal dose sparing, treatment time, relative target dose homogeneity, and nonuniformity ratio. The plans with 0.5 cm step size were seen to have clinically acceptable tumor coverage, minimal normal structure doses, and minimum treatment time as compared with the other step sizes. The target coverage for this step size is 87% of the prescription dose, while the urethral and maximum rectal doses were 107.3 and 68.7%, respectively. No appreciable difference in plan quality was observed with variation in maximum source dwell time. The step size plays a significant role in plan optimization for prostate implants. Our study supports use of a 0.5 cm step size for prostate implants. PMID:24049323
Design of a modulated orthovoltage stereotactic radiosurgery system.
Fagerstrom, Jessica M; Bender, Edward T; Lawless, Michael J; Culberson, Wesley S
2017-07-01
To achieve stereotactic radiosurgery (SRS) dose distributions with sharp gradients using orthovoltage energy fluence modulation with inverse planning optimization techniques. A pencil beam model was used to calculate dose distributions from an orthovoltage unit at 250 kVp. Kernels for the model were derived using Monte Carlo methods. A Genetic Algorithm search heuristic was used to optimize the spatial distribution of added tungsten filtration to achieve dose distributions with sharp dose gradients. Optimizations were performed for depths of 2.5, 5.0, and 7.5 cm, with cone sizes of 5, 6, 8, and 10 mm. In addition to the beam profiles, 4π isocentric irradiation geometries were modeled to examine dose at 0.07 mm depth, a representative skin depth, for the low energy beams. Profiles from 4π irradiations of a constant target volume, assuming maximally conformal coverage, were compared. Finally, dose deposition in bone compared to tissue in this energy range was examined. Based on the results of the optimization, circularly symmetric tungsten filters were designed to modulate the orthovoltage beam across the apertures of SRS cone collimators. For each depth and cone size combination examined, the beam flatness and 80-20% and 90-10% penumbrae were calculated for both standard, open cone-collimated beams as well as for optimized, filtered beams. For all configurations tested, the modulated beam profiles had decreased penumbra widths and flatness statistics at depth. Profiles for the optimized, filtered orthovoltage beams also offered decreases in these metrics compared to measured linear accelerator cone-based SRS profiles. The dose at 0.07 mm depth in the 4π isocentric irradiation geometries was higher for the modulated beams compared to unmodulated beams; however, the modulated dose at 0.07 mm depth remained <0.025% of the central, maximum dose. The 4π profiles irradiating a constant target volume showed improved statistics for the modulated, filtered distribution compared to the standard, open cone-collimated distribution. Simulations of tissue and bone confirmed previously published results that a higher energy beam (≥ 200 keV) would be preferable, but the 250 kVp beam was chosen for this work because it is available for future measurements. A methodology has been described that may be used to optimize the spatial distribution of added filtration material in an orthovoltage SRS beam to result in dose distributions with decreased flatness and penumbra statistics compared to standard open cones. This work provides the mathematical foundation for a novel, orthovoltage energy fluence-modulated SRS system. © 2017 American Association of Physicists in Medicine.
A New Distributed Optimization for Community Microgrids Scheduling
DOE Office of Scientific and Technical Information (OSTI.GOV)
Starke, Michael R; Tomsovic, Kevin
This paper proposes a distributed optimization model for community microgrids considering the building thermal dynamics and customer comfort preference. The microgrid central controller (MCC) minimizes the total cost of operating the community microgrid, including fuel cost, purchasing cost, battery degradation cost and voluntary load shedding cost based on the customers' consumption, while the building energy management systems (BEMS) minimize their electricity bills as well as the cost associated with customer discomfort due to room temperature deviation from the set point. The BEMSs and the MCC exchange information on energy consumption and prices. When the optimization converges, the distributed generation scheduling,more » energy storage charging/discharging and customers' consumption as well as the energy prices are determined. In particular, we integrate the detailed thermal dynamic characteristics of buildings into the proposed model. The heating, ventilation and air-conditioning (HVAC) systems can be scheduled intelligently to reduce the electricity cost while maintaining the indoor temperature in the comfort range set by customers. Numerical simulation results show the effectiveness of proposed model.« less
Optimizing Cellular Networks Enabled with Renewal Energy via Strategic Learning.
Sohn, Insoo; Liu, Huaping; Ansari, Nirwan
2015-01-01
An important issue in the cellular industry is the rising energy cost and carbon footprint due to the rapid expansion of the cellular infrastructure. Greening cellular networks has thus attracted attention. Among the promising green cellular network techniques, the renewable energy-powered cellular network has drawn increasing attention as a critical element towards reducing carbon emissions due to massive energy consumption in the base stations deployed in cellular networks. Game theory is a branch of mathematics that is used to evaluate and optimize systems with multiple players with conflicting objectives and has been successfully used to solve various problems in cellular networks. In this paper, we model the green energy utilization and power consumption optimization problem of a green cellular network as a pilot power selection strategic game and propose a novel distributed algorithm based on a strategic learning method. The simulation results indicate that the proposed algorithm achieves correlated equilibrium of the pilot power selection game, resulting in optimum green energy utilization and power consumption reduction.
Patient Dose Management: Focus on Practical Actions
2016-01-01
Medical radiation is a very important part of modern medicine, and should be only used when needed and optimized. Justification and optimization of radiation examinations must be performed. The first step of reduction of medical exposure is to know the radiation dose in currently performed examinations. This review covers radiation units, how various imaging modalities report dose, and the current status of radiation dose reports and legislation. Also, practical tips that can be applied to clinical practice are introduced. Afterwards, the importance of radiology exposure related education is emphasized and the current status of education for medical personal and the public is explained, and appropriate education strategies are suggested. Commonly asked radiation dose related example questions and answers are provided in detail to allow medical personnel to answer patients. Lastly, we talk about computerized programs that can be used in medical facilities for managing patient dose. While patient dose monitoring and management should be used to decrease and optimize overall radiation dose, it should not be used to assess individual cancer risk. One must always remember that medically justified examinations should always be performed, and unneeded examinations should be avoided in the first place. PMID:26908988
DOE Office of Scientific and Technical Information (OSTI.GOV)
Syh, J; Syh, J; Patel, B
2014-06-15
Purpose: The multichannel cylindrical vaginal applicator is a variation of traditional single channel cylindrical vaginal applicator. The multichannel applicator has additional peripheral channels that provide more flexibility in the planning process. The dosimetric advantage is to reduce dose to adjacent organ at risk (OAR) such as bladder and rectum while maintaining target coverage with the dose optimization from additional channels. Methods: Vaginal HDR brachytherapy plans are all CT based. CT images were acquired in 2 mm thickness to keep integrity of cylinder contouring. The CTV of 5mm Rind with prescribed treatment length was reconstructed from 5mm expansion of inserted cylinder.more » The goal was 95% of CTV covered by 95% of prescribed dose in both single channel planning (SCP)and multichannel planning (MCP) before proceeding any further optimization for dose reduction to critical structures with emphasis on D2cc and V2Gy . Results: This study demonstrated noticeable dose reduction to OAR was apparent in multichannel plans. The D2cc of the rectum and bladder were showing the reduced dose for multichannel versus single channel. The V2Gy of the rectum was 93.72% and 83.79% (p=0.007) for single channel and multichannel respectively (Figure 1 and Table 1). To assure adequate coverage to target while reducing the dose to the OAR without any compromise is the main goal in using multichannel vaginal applicator in HDR brachytherapy. Conclusion: Multichannel plans were optimized using anatomical based inverse optimization algorithm of inverse planning simulation annealing. The optimization solution of the algorithm was to improve the clinical target volume dose coverage while reducing the dose to critical organs such as bladder, rectum and bowels. The comparison between SCP and MCP demonstrated MCP is superior to SCP where the dwell positions were based on geometric array only. It concluded that MCP is preferable and is able to provide certain features superior to SCP.« less
An inverse association between tea consumption and colorectal cancer risk.
Chen, Yuetong; Wu, Yuan; Du, Mulong; Chu, Haiyan; Zhu, Lingjun; Tong, Na; Zhang, Zhengdong; Wang, Meilin; Gu, Dongying; Chen, Jinfei
2017-06-06
It is well known that the tea extracts, mainly polyphenols as chemo-preventive elements, could act as cancer progression blockers. Although the association between tea consumption and colorectal cancer risk has been widely investigated, the results still remain inconsistent. We conducted a dose-response meta-analysis to evaluate their relationships by enrolling qualified 29 literatures. The summary odds ratio (OR) of colorectal cancer for the highest vs. lowest tea consumption was 0.93 with 0.87-1.00 of 95% confidence intervals (CIs) among all studies with modest heterogeneity (P = 0.001, I2 = 43.4%). Stratified analysis revealed that tea, especially green tea, had a protective effect among female and rectal cancer patients. Particularly, the dose-response analysis showed that there was a significant inverse association between an increment of 1 cup/day of tea consumption and colorectal cancer risk in the subgroup of the green tea drinking (OR = 0.98, 95% CI = 0.96-1.01, Pnonlinear = 0.003) and female (OR = 0.68, 95% CI = 0.56-0.81, Pnonlinear < 0.001). Our findings indicate that tea consumption has an inverse impact on colorectal cancer risk, which may have significant public health implications in the prevention of colorectal cancer and further similar researches.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yarmand, H; Winey, B; Craft, D
2014-06-15
Purpose: To efficiently find quality-guaranteed treatment plans with the minimum number of beams for stereotactic body radiation therapy using RayStation. Methods: For a pre-specified pool of candidate beams we use RayStation (a treatment planning software for clinical use) to identify the deliverable plan which uses all the beams with the minimum dose to organs at risk (OARs) and dose to the tumor and other structures in specified ranges. Then use the dose matrix information for the generated apertures from RayStation to solve a linear program to find the ideal plan with the same objective and constraints allowing use of allmore » beams. Finally we solve a mixed integer programming formulation of the beam angle optimization problem (BAO) with the objective of minimizing the number of beams while remaining in a predetermined epsilon-optimality of the ideal plan with respect to the dose to OARs. Since the treatment plan optimization is a multicriteria optimization problem, the planner can exploit the multicriteria optimization capability of RayStation to navigate the ideal dose distribution Pareto surface and select a plan of desired target coverage versus OARs sparing, and then use the proposed technique to reduce the number of beams while guaranteeing quality. For the numerical experiments two liver cases and one lung case with 33 non-coplanar beams are considered. Results: The ideal plan uses an impractically large number of beams. The proposed technique reduces the number of beams to the range of practical application (5 to 9 beams) while remaining in the epsilon-optimal range of 1% to 5% optimality gap. Conclusion: The proposed method can be integrated into a general algorithm for fast navigation of the ideal dose distribution Pareto surface and finding the treatment plan with the minimum number of beams, which corresponds to the delivery time, in epsilon-optimality range of the desired ideal plan. The project was supported by the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center and partially by RaySearch Laboratories.« less
NASA Astrophysics Data System (ADS)
Borot de Battisti, M.; de Senneville, B. Denis; Hautvast, G.; Binnekamp, D.; Lagendijk, J. J. W.; Maenhout, M.; Moerland, M. A.
2017-05-01
MR-guided high-dose-rate (HDR) brachytherapy has gained increasing interest as a treatment for patients with localized prostate cancer because of the superior value of MRI for tumor and surrounding tissues localization. To enable needle insertion into the prostate with the patient in the MR bore, a single needle MR-compatible robotic system involving needle-by-needle dose delivery has been developed at our institution. Throughout the intervention, dose delivery may be impaired by: (1) sub-optimal needle positioning caused by e.g. needle bending, (2) intra-operative internal organ motion such as prostate rotations or swelling, or intra-procedural rectum or bladder filling. This may result in failure to reach clinical constraints. To assess the first aforementioned challenge, a recent study from our research group demonstrated that the deposited dose may be greatly improved by real-time adaptive planning with feedback on the actual needle positioning. However, the needle insertion sequence is left to the doctor and therefore, this may result in sub-optimal dose delivery. In this manuscript, a new method is proposed to determine and update automatically the needle insertion sequence. This strategy is based on the determination of the most sensitive needle track. The sensitivity of a needle track is defined as its impact on the dose distribution in case of sub-optimal positioning. A stochastic criterion is thus presented to determine each needle track sensitivity based on needle insertion simulations. To assess the proposed sequencing strategy, HDR prostate brachytherapy was simulated on 11 patients with varying number of needle insertions. Sub-optimal needle positioning was simulated at each insertion (modeled by typical random angulation errors). In 91% of the scenarios, the dose distribution improved when the needle was inserted into the most compared to the least sensitive needle track. The computation time for sequencing was less than 6 s per needle track. The proposed needle insertion sequencing can therefore assist in delivering an optimal dose in HDR prostate brachytherapy.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kofler, J.
The main topic of the session is to show how dose optimization is being implemented in various regions of the world, including Europe, Australia, North America and other regions. A multi-national study conducted under International Atomic Energy Agency (IAEA) across more than 50 less resourced countries gave insight into patient radiation doses and safety practices in CT, mammography, radiography and interventional procedures, both for children and adults. An important outcome was the capability development on dose assessment and management. An overview of recent European projects related to CT radiation dose and optimization both to adults and children will be presented.more » Existing data on DRLs together with a European methodology proposed on establishing and using DRLs for paediatric radiodiagnostic imaging and interventional radiology practices will be shown. Compared with much of Europe at least, many Australian imaging practices are relatively new to the task of diagnostic imaging dose optimisation. In 2008 the Australian Government prescribed a requirement to periodically compare patient radiation doses with diagnostic reference levels (DRLs), where DRLs have been established. Until recently, Australia had only established DRLs for computed tomography (CT). Regardless, both professional society and individual efforts to improved data collection and develop optimisation strategies across a range of modalities continues. Progress in this field, principally with respect to CT and interventional fluoroscopy will be presented. In the US, dose reduction and optimization efforts for computed tomography have been promoted and mandated by several organizations and accrediting entities. This presentation will cover the general motivation, implementation, and implications of such efforts. Learning Objectives: Understand importance of the dose optimization in Diagnostic Radiology. See how this goal is achieved in different regions of the World. Learn about the global trend in the dose optimization and future prospectives. M. Rehani, The work was a part of the work of IAEA where I was an employee and IAEA is a United Nations organization.« less
TH-E-BRF-01: Exploiting Tumor Shrinkage in Split-Course Radiotherapy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Unkelbach, J; Craft, D; Hong, T
2014-06-15
Purpose: In split-course radiotherapy, a patient is treated in several stages separated by weeks or months. This regimen has been motivated by radiobiological considerations. However, using modern image-guidance, it also provides an approach to reduce normal tissue dose by exploiting tumor shrinkage. In this work, we consider the optimal design of split-course treatments, motivated by the clinical management of large liver tumors for which normal liver dose constraints prohibit the administration of an ablative radiation dose in a single treatment. Methods: We introduce a dynamic tumor model that incorporates three factors: radiation induced cell kill, tumor shrinkage, and tumor cellmore » repopulation. The design of splitcourse radiotherapy is formulated as a mathematical optimization problem in which the total dose to the liver is minimized, subject to delivering the prescribed dose to the tumor. Based on the model, we gain insight into the optimal administration of radiation over time, i.e. the optimal treatment gaps and dose levels. Results: We analyze treatments consisting of two stages in detail. The analysis confirms the intuition that the second stage should be delivered just before the tumor size reaches a minimum and repopulation overcompensates shrinking. Furthermore, it was found that, for a large range of model parameters, approximately one third of the dose should be delivered in the first stage. The projected benefit of split-course treatments in terms of liver sparing depends on model assumptions. However, the model predicts large liver dose reductions by more than a factor of two for plausible model parameters. Conclusion: The analysis of the tumor model suggests that substantial reduction in normal tissue dose can be achieved by exploiting tumor shrinkage via an optimal design of multi-stage treatments. This suggests taking a fresh look at split-course radiotherapy for selected disease sites where substantial tumor regression translates into reduced target volumes.« less
NASA Technical Reports Server (NTRS)
Zimmer, J. Paul; Lewis, Sherry M.; Moyer, Jerry L.
1993-01-01
Gavage, water bottle, and diet incorporation are 3 dosing methods used orally to administer test compounds to rodents. These 3 methods were compared in mice to determine which represented the most quantitative delivery system. For dietary incorporation, a high-moisture bolus form of NIH-31 rodent meal was developed using hydroxypropyl methylcellulose as an autoclave-stable binding agent. A high-moisture bolus were selected to increase the acceptability of the dosed diet and to promote quantitative consumption through reduced wastage. The test compound used was D-xylose, a pentose sugar that may be quantitatively detected, colorimetrically, in urine following oral dosing. Six male and 6 female B6D2FI mice were placed in metabolism cages and dosed with a known quantity of D-xylose by each of the 3 methods. Urine was collected before and after each method of administration and analysed for total D-xylose; the per cent recovery was based upon the amount of D-xylose consumed. Quantitative consumption was apparently greatest for water bottle dosing with an average recovery of 56.0% of the original D-xylose dose. High-moisture bolus incorporation ranked second with 50.0% D-xylose recovery, and gavage was third with 41.0% D-xylose recovery.
Wang, Xia; Ouyang, Yingying; Liu, Jun; Zhu, Minmin; Zhao, Gang; Bao, Wei; Hu, Frank B
2014-07-29
To examine and quantify the potential dose-response relation between fruit and vegetable consumption and risk of all cause, cardiovascular, and cancer mortality. Medline, Embase, and the Cochrane library searched up to 30 August 2013 without language restrictions. Reference lists of retrieved articles. Prospective cohort studies that reported risk estimates for all cause, cardiovascular, and cancer mortality by levels of fruit and vegetable consumption. Random effects models were used to calculate pooled hazard ratios and 95% confidence intervals and to incorporate variation between studies. The linear and non-linear dose-response relations were evaluated with data from categories of fruit and vegetable consumption in each study. Sixteen prospective cohort studies were eligible in this meta-analysis. During follow-up periods ranging from 4.6 to 26 years there were 56,423 deaths (11,512 from cardiovascular disease and 16,817 from cancer) among 833,234 participants. Higher consumption of fruit and vegetables was significantly associated with a lower risk of all cause mortality. Pooled hazard ratios of all cause mortality were 0.95 (95% confidence interval 0.92 to 0.98) for an increment of one serving a day of fruit and vegetables (P=0.001), 0.94 (0.90 to 0.98) for fruit (P=0.002), and 0.95 (0.92 to 0.99) for vegetables (P=0.006). There was a threshold around five servings of fruit and vegetables a day, after which the risk of all cause mortality did not reduce further. A significant inverse association was observed for cardiovascular mortality (hazard ratio for each additional serving a day of fruit and vegetables 0.96, 95% confidence interval 0.92 to 0.99), while higher consumption of fruit and vegetables was not appreciably associated with risk of cancer mortality. This meta-analysis provides further evidence that a higher consumption of fruit and vegetables is associated with a lower risk of all cause mortality, particularly cardiovascular mortality. © Wang et al 2014.
Hagström, Hannes; Hemmingsson, Tomas; Discacciati, Andrea; Andreasson, Anna
2018-03-01
High alcohol consumption is associated with an increased risk of severe liver disease. Current recommendations suggest it is safe for men to consume 30 grams of alcohol per day. We investigated the association between alcohol consumption early in life and later development of severe liver disease. We used data on alcohol consumption at conscription to military service from 43,296 men (18-20 years) in Sweden between 1969 and 1970. Outcomes were defined as incident diagnoses of severe liver disease from systematic national registration of clinical events until the end of 2009. A Cox regression model adjusted for body mass index, smoking, use of narcotics, cognitive ability and cardiovascular capacity was applied. During a mean follow-up of 37.8 years, 383 men developed severe liver disease. Alcohol consumption was associated with an increased risk of development of severe liver disease in a dose-response pattern (adjusted hazard ratio for every one gram/day increase 1.02; 95% CI 1.01-1.02). No evidence of a threshold effect was found. Importantly, a clear trend pointed towards an increased risk of severe liver disease in men who consumed less than 30 grams of alcohol per day. Alcohol consumption in young men is associated with an increased risk of severe liver disease, up to 39 years later in life. The risk was dose-dependent, with no sign of a threshold effect. Current guidelines for safe alcohol intake in men might have to be revised. We investigated more than 43,000 Swedish men in their late teens enlisted for conscription in 1969-1970. After almost 40 years of follow-up, we found that alcohol consumption was a significant risk factor for developing severe liver disease, independent of confounders. This risk was dose-dependent, and was most pronounced in men consuming two drinks per day or more. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
[Effect of antihypoxants on the consumption of oxygen in animals with traumatic brain injury].
Novikov, V E; Ponamareva, N S; Kokhonov, K V
2008-01-01
The effect of drugs on the dynamics of oxygen consumption in experimental animals with traumatic brain injury (TBI) has been measured. It is established that the antihypoxants bemithyl, amtizole, trymeen, and ethomersol in a dose of 25 mg/kg decrease the consumption of oxygen and reduced oxygen demands of tissues in the acute posttraumatic period. These phenomena can play a significant role in the mechanism of the protective action of drugs under conditions of TBI.
Gill, Christopher J; DeSilva, Mary Bachman; Hamer, Davidson H; Keyi, Xu; Wilson, Ira B; Sabin, Lora
2015-11-01
Adherence to antiretroviral medications is usually expressed in terms of the proportion of doses taken. However, the timing of doses taken may also be an important dimension to overall adherence. Little is known about whether patients who mistime doses are also more likely to skip doses. Using data from the completed Adherence for Life randomized controlled trial, we created visual and statistical models to capture and analyze dose timing data collected longitudinally with electronic drug monitors (EDM). From scatter plots depicting dose time versus calendar date, we identified dominant patterns of dose taking and calculated key features [slope of line over calendar date; residual mean standard error (RMSE)]. Each was assessed for its ability to categorize subjects with 'sub-optimal' (<95 % of doses taken) using area under the receiver operating characteristic (AROC) curve analysis. Sixty eight subjects contributed EDM data, with ~300 to 400 observations/subject. While regression line slopes did not predict 'sub-optimal' adherence (AROC 0.51, 95 % CI 0.26-0.75), the variability in dose timing (RMSE) was strongly predictive (AROC 0.79, 95 % CI 0.62-0.97). Compared with the lowest quartile of RMSE (minimal dose time variability), each successive quartile roughly doubled the odds of 'sub-optimal' adherence (OR 2.1, 95 % CI 1.3-3.4). Patterns of dose timing and mistiming are strongly related to overall adherence behavior. Notably, individuals who skip doses are more likely to mistime doses, with the degree of risk positively correlated with the extent of dose timing variability.
On the Run-Time Optimization of the Boolean Logic of a Program.
ERIC Educational Resources Information Center
Cadolino, C.; Guazzo, M.
1982-01-01
Considers problem of optimal scheduling of Boolean expression (each Boolean variable represents binary outcome of program module) on single-processor system. Optimization discussed consists of finding operand arrangement that minimizes average execution costs representing consumption of resources (elapsed time, main memory, number of…
Jenicek, P; Kutil, J; Benes, O; Todt, V; Zabranska, J; Dohanyos, M
2013-01-01
The anaerobic digestion of primary and waste activated sludge generates biogas that can be converted into energy to power the operation of a sewage wastewater treatment plant (WWTP). But can the biogas generated by anaerobic sludge digestion ever completely satisfy the electricity requirements of a WWTP with 'standard' energy consumption (i.e. industrial pollution not treated, no external organic substrate added)? With this question in mind, we optimized biogas production at Prague's Central Wastewater Treatment Plant in the following ways: enhanced primary sludge separation; thickened waste activated sludge; implemented a lysate centrifuge; increased operational temperature; improved digester mixing. With these optimizations, biogas production increased significantly to 12.5 m(3) per population equivalent per year. In turn, this led to an equally significant increase in specific energy production from approximately 15 to 23.5 kWh per population equivalent per year. We compared these full-scale results with those obtained from WWTPs that are already energy self-sufficient, but have exceptionally low energy consumption. Both our results and our analysis suggest that, with the correct optimization of anaerobic digestion technology, even WWTPs with 'standard' energy consumption can either attain or come close to attaining energy self-sufficiency.
Li, Ruiying; Liu, Xiaoxi; Xie, Wei; Huang, Ning
2014-12-10
Sensor-deployment-based lifetime optimization is one of the most effective methods used to prolong the lifetime of Wireless Sensor Network (WSN) by reducing the distance-sensitive energy consumption. In this paper, data retransmission, a major consumption factor that is usually neglected in the previous work, is considered. For a homogeneous WSN, monitoring a circular target area with a centered base station, a sensor deployment model based on regular hexagonal grids is analyzed. To maximize the WSN lifetime, optimization models for both uniform and non-uniform deployment schemes are proposed by constraining on coverage, connectivity and success transmission rate. Based on the data transmission analysis in a data gathering cycle, the WSN lifetime in the model can be obtained through quantifying the energy consumption at each sensor location. The results of case studies show that it is meaningful to consider data retransmission in the lifetime optimization. In particular, our investigations indicate that, with the same lifetime requirement, the number of sensors needed in a non-uniform topology is much less than that in a uniform one. Finally, compared with a random scheme, simulation results further verify the advantage of our deployment model.
NASA Astrophysics Data System (ADS)
Nur, Rusdi; Suyuti, Muhammad Arsyad; Susanto, Tri Agus
2017-06-01
Aluminum is widely utilized in the industrial sector. There are several advantages of aluminum, i.e. good flexibility and formability, high corrosion resistance and electrical conductivity, and high heat. Despite of these characteristics, however, pure aluminum is rarely used because of its lacks of strength. Thus, most of the aluminum used in the industrial sectors was in the form of alloy form. Sustainable machining can be considered to link with the transformation of input materials and energy/power demand into finished goods. Machining processes are responsible for environmental effects accepting to their power consumption. The cutting conditions have been optimized to minimize the cutting power, which is the power consumed for cutting. This paper presents an experimental study of sustainable machining of Al-11%Si base alloy that was operated without any cooling system to assess the capacity in reducing power consumption. The cutting force was measured and the cutting power was calculated. Both of cutting force and cutting power were analyzed and modeled by using the central composite design (CCD). The result of this study indicated that the cutting speed has an effect on machining performance and that optimum cutting conditions have to be determined, while sustainable machining can be followed in terms of minimizing power consumption and cutting force. The model developed from this study can be used for evaluation process and optimization to determine optimal cutting conditions for the performance of the whole process.
Yang, Jing; Xu, Mai; Zhao, Wei; Xu, Baoguo
2010-01-01
For monitoring burst events in a kind of reactive wireless sensor networks (WSNs), a multipath routing protocol (MRP) based on dynamic clustering and ant colony optimization (ACO) is proposed. Such an approach can maximize the network lifetime and reduce the energy consumption. An important attribute of WSNs is their limited power supply, and therefore some metrics (such as energy consumption of communication among nodes, residual energy, path length) were considered as very important criteria while designing routing in the MRP. Firstly, a cluster head (CH) is selected among nodes located in the event area according to some parameters, such as residual energy. Secondly, an improved ACO algorithm is applied in the search for multiple paths between the CH and sink node. Finally, the CH dynamically chooses a route to transmit data with a probability that depends on many path metrics, such as energy consumption. The simulation results show that MRP can prolong the network lifetime, as well as balance of energy consumption among nodes and reduce the average energy consumption effectively.
Energy Optimization Using a Case-Based Reasoning Strategy
Herrera-Viedma, Enrique
2018-01-01
At present, the domotization of homes and public buildings is becoming increasingly popular. Domotization is most commonly applied to the field of energy management, since it gives the possibility of managing the consumption of the devices connected to the electric network, the way in which the users interact with these devices, as well as other external factors that influence consumption. In buildings, Heating, Ventilation and Air Conditioning (HVAC) systems have the highest consumption rates. The systems proposed so far have not succeeded in optimizing the energy consumption associated with a HVAC system because they do not monitor all the variables involved in electricity consumption. For this reason, this article presents an agent approach that benefits from the advantages provided by a Multi-Agent architecture (MAS) deployed in a Cloud environment with a wireless sensor network (WSN) in order to achieve energy savings. The agents of the MAS learn social behavior thanks to the collection of data and the use of an artificial neural network (ANN). The proposed system has been assessed in an office building achieving an average energy savings of 41% in the experimental group offices. PMID:29543729
Energy Optimization Using a Case-Based Reasoning Strategy.
González-Briones, Alfonso; Prieto, Javier; De La Prieta, Fernando; Herrera-Viedma, Enrique; Corchado, Juan M
2018-03-15
At present, the domotization of homes and public buildings is becoming increasingly popular. Domotization is most commonly applied to the field of energy management, since it gives the possibility of managing the consumption of the devices connected to the electric network, the way in which the users interact with these devices, as well as other external factors that influence consumption. In buildings, Heating, Ventilation and Air Conditioning (HVAC) systems have the highest consumption rates. The systems proposed so far have not succeeded in optimizing the energy consumption associated with a HVAC system because they do not monitor all the variables involved in electricity consumption. For this reason, this article presents an agent approach that benefits from the advantages provided by a Multi-Agent architecture (MAS) deployed in a Cloud environment with a wireless sensor network (WSN) in order to achieve energy savings. The agents of the MAS learn social behavior thanks to the collection of data and the use of an artificial neural network (ANN). The proposed system has been assessed in an office building achieving an average energy savings of 41% in the experimental group offices.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kang, S; Kim, D; Kim, T
2016-06-15
Purpose: To propose a simple and effective cost value function to search optimal planning phase (gating window) and demonstrated its feasibility for respiratory correlated radiation therapy. Methods: We acquired 4DCT of 10 phases for 10 lung patients who have tumor located near OARs such as esophagus, heart, and spinal cord (i.e., central lung cancer patients). A simplified mathematical optimization function was established by using overlap volume histogram (OVH) between the target and organ at risk (OAR) at each phase and the tolerance dose of selected OARs to achieve surrounding OARs dose-sparing. For all patients and all phases, delineation of themore » target volume and selected OARs (esophagus, heart, and spinal cord) was performed (by one observer to avoid inter-observer variation), then cost values were calculated for all phases. After the breathing phases were ranked according to cost value function, the relationship between score and dose distribution at highest and lowest cost value phases were evaluated by comparing the mean/max dose. Results: A simplified mathematical cost value function showed noticeable difference from phase to phase, implying it is possible to find optimal phases for gating window. The lowest cost value which may result in lower mean/max dose to OARs was distributed at various phases for all patients. The mean doses of the OARs significantly decreased about 10% with statistical significance for all 3 OARs at the phase with the lowest cost value. Also, the max doses of the OARs were decreased about 2∼5% at the phase with the lowest cost value compared to the phase with the highest cost value. Conclusion: It is demonstrated that optimal phases (in dose distribution perspective) for gating window could exist differently through each patient and the proposed cost value function can be a useful tool for determining such phases without performing dose optimization calculations. This research was supported by the Mid-career Researcher Program through NRF funded by the Ministry of Science, ICT & Future Planning of Korea (NRF-2014R1A2A1A10050270) and by the Radiation Technology R&D program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (No. 2013M2A2A7038291)« less
The impact of different dose response parameters on biologically optimized IMRT in breast cancer
NASA Astrophysics Data System (ADS)
Costa Ferreira, Brigida; Mavroidis, Panayiotis; Adamus-Górka, Magdalena; Svensson, Roger; Lind, Bengt K.
2008-05-01
The full potential of biologically optimized radiation therapy can only be maximized with the prediction of individual patient radiosensitivity prior to treatment. Unfortunately, the available biological parameters, derived from clinical trials, reflect an average radiosensitivity of the examined populations. In the present study, a breast cancer patient of stage I II with positive lymph nodes was chosen in order to analyse the effect of the variation of individual radiosensitivity on the optimal dose distribution. Thus, deviations from the average biological parameters, describing tumour, heart and lung response, were introduced covering the range of patient radiosensitivity reported in the literature. Two treatment configurations of three and seven biologically optimized intensity-modulated beams were employed. The different dose distributions were analysed using biological and physical parameters such as the complication-free tumour control probability (P+), the biologically effective uniform dose (\\bar{\\bar{D}} ), dose volume histograms, mean doses, standard deviations, maximum and minimum doses. In the three-beam plan, the difference in P+ between the optimal dose distribution (when the individual patient radiosensitivity is known) and the reference dose distribution, which is optimal for the average patient biology, ranges up to 13.9% when varying the radiosensitivity of the target volume, up to 0.9% when varying the radiosensitivity of the heart and up to 1.3% when varying the radiosensitivity of the lung. Similarly, in the seven-beam plan, the differences in P+ are up to 13.1% for the target, up to 1.6% for the heart and up to 0.9% for the left lung. When the radiosensitivity of the most important tissues in breast cancer radiation therapy was simultaneously changed, the maximum gain in outcome was as high as 7.7%. The impact of the dose response uncertainties on the treatment outcome was clinically insignificant for the majority of the simulated patients. However, the jump from generalized to individualized radiation therapy may significantly increase the therapeutic window for patients with extreme radio sensitivity or radioresistance, provided that these are identified. Even for radiosensitive patients a simple treatment technique is sufficient to maximize the outcome, since no significant benefits were obtained with a more complex technique using seven intensity-modulated beams portals.
Machine learning techniques for energy optimization in mobile embedded systems
NASA Astrophysics Data System (ADS)
Donohoo, Brad Kyoshi
Mobile smartphones and other portable battery operated embedded systems (PDAs, tablets) are pervasive computing devices that have emerged in recent years as essential instruments for communication, business, and social interactions. While performance, capabilities, and design are all important considerations when purchasing a mobile device, a long battery lifetime is one of the most desirable attributes. Battery technology and capacity has improved over the years, but it still cannot keep pace with the power consumption demands of today's mobile devices. This key limiter has led to a strong research emphasis on extending battery lifetime by minimizing energy consumption, primarily using software optimizations. This thesis presents two strategies that attempt to optimize mobile device energy consumption with negligible impact on user perception and quality of service (QoS). The first strategy proposes an application and user interaction aware middleware framework that takes advantage of user idle time between interaction events of the foreground application to optimize CPU and screen backlight energy consumption. The framework dynamically classifies mobile device applications based on their received interaction patterns, then invokes a number of different power management algorithms to adjust processor frequency and screen backlight levels accordingly. The second strategy proposes the usage of machine learning techniques to learn a user's mobile device usage pattern pertaining to spatiotemporal and device contexts, and then predict energy-optimal data and location interface configurations. By learning where and when a mobile device user uses certain power-hungry interfaces (3G, WiFi, and GPS), the techniques, which include variants of linear discriminant analysis, linear logistic regression, non-linear logistic regression, and k-nearest neighbor, are able to dynamically turn off unnecessary interfaces at runtime in order to save energy.
Spatiotemporal radiotherapy planning using a global optimization approach
NASA Astrophysics Data System (ADS)
Adibi, Ali; Salari, Ehsan
2018-02-01
This paper aims at quantifying the extent of potential therapeutic gain, measured using biologically effective dose (BED), that can be achieved by altering the radiation dose distribution over treatment sessions in fractionated radiotherapy. To that end, a spatiotemporally integrated planning approach is developed, where the spatial and temporal dose modulations are optimized simultaneously. The concept of equivalent uniform BED (EUBED) is used to quantify and compare the clinical quality of spatiotemporally heterogeneous dose distributions in target and critical structures. This gives rise to a large-scale non-convex treatment-plan optimization problem, which is solved using global optimization techniques. The proposed spatiotemporal planning approach is tested on two stylized cancer cases resembling two different tumor sites and sensitivity analysis is performed for radio-biological and EUBED parameters. Numerical results validate that spatiotemporal plans are capable of delivering a larger BED to the target volume without increasing the BED in critical structures compared to conventional time-invariant plans. In particular, this additional gain is attributed to the irradiation of different regions of the target volume at different treatment sessions. Additionally, the trade-off between the potential therapeutic gain and the number of distinct dose distributions is quantified, which suggests a diminishing marginal gain as the number of dose distributions increases.
Trnková, Petra; Baltas, Dimos; Karabis, Andreas; Stock, Markus; Dimopoulos, Johannes; Georg, Dietmar; Pötter, Richard; Kirisits, Christian
2010-12-01
The purpose of this study was to compare two inverse planning algorithms for cervical cancer brachytherapy and a conventional manual treatment planning according to the MUW (Medical University of Vienna) protocol. For 20 patients, manually optimized, and, inversely optimized treatment plans with Hybrid Inverse treatment Planning and Optimization (HIPO) and with Inverse Planning Simulated Annealing (IPSA) were created. Dosimetric parameters, absolute volumes of normal tissue receiving reference doses, absolute loading times of tandem, ring and interstitial needles, Paddick and COIN conformity indices were evaluated. HIPO was able to achieve a similar dose distribution to manual planning with the restriction of high dose regions. It reduced the loading time of needles and the overall treatment time. The values of both conformity indices were the lowest. IPSA was able to achieve acceptable dosimetric results. However, it overloaded the needles. This resulted in high dose regions located in the normal tissue. The Paddick index for the volume of two times prescribed dose was outstandingly low. HIPO can produce clinically acceptable treatment plans with the elimination of high dose regions in normal tissue. Compared to IPSA, it is an inverse optimization method which takes into account current clinical experience gained from manual treatment planning.
Baltas, Dimos; Karabis, Andreas; Stock, Markus; Dimopoulos, Johannes; Georg, Dietmar; Pötter, Richard; Kirisits, Christian
2011-01-01
Purpose The purpose of this study was to compare two inverse planning algorithms for cervical cancer brachytherapy and a conventional manual treatment planning according to the MUW (Medical University of Vienna) protocol. Material and methods For 20 patients, manually optimized, and, inversely optimized treatment plans with Hybrid Inverse treatment Planning and Optimization (HIPO) and with Inverse Planning Simulated Annealing (IPSA) were created. Dosimetric parameters, absolute volumes of normal tissue receiving reference doses, absolute loading times of tandem, ring and interstitial needles, Paddick and COIN conformity indices were evaluated. Results HIPO was able to achieve a similar dose distribution to manual planning with the restriction of high dose regions. It reduced the loading time of needles and the overall treatment time. The values of both conformity indices were the lowest. IPSA was able to achieve acceptable dosimetric results. However, it overloaded the needles. This resulted in high dose regions located in the normal tissue. The Paddick index for the volume of two times prescribed dose was outstandingly low. Conclusions HIPO can produce clinically acceptable treatment plans with the elimination of high dose regions in normal tissue. Compared to IPSA, it is an inverse optimization method which takes into account current clinical experience gained from manual treatment planning. PMID:27853479
Thomopoulos, Thomas P; Ntouvelis, Evangelos; Diamantaras, Andreas-Antonios; Tzanoudaki, Marianna; Baka, Margarita; Hatzipantelis, Emmanuel; Kourti, Maria; Polychronopoulou, Sophia; Sidi, Vasiliki; Stiakaki, Eftichia; Moschovi, Maria; Kantzanou, Maria; Petridou, Eleni Th
2015-12-01
To systematically review studies and meta-analyze the literature on the association of maternal and/or index child's coffee, tea, and cola consumption with subsequent development of childhood leukemia and its major subtypes. Eligible studies were identified through a detailed algorithm and hand-search of eligible articles' references; thereafter, summary-effect estimates were calculated by leukemia subtype and dose-response meta-analyses were performed. Twelve case-control studies, comprising a total of 3649 cases and 5705 controls, were included. High maternal coffee consumption was positively associated with acute lymphoblastic leukemia (ALL; OR: 1.43, 95%CI: 1.22-1.68) and acute myeloid leukemia (AML; OR: 2.52, 95%CI: 1.59-3.57). Any or low to moderate maternal cola consumption was also positively associated with overall leukemia (AL) and ALL, A linear trend between coffee and cola consumption and childhood leukemia was observed in the dose-response analyses. On the contrary, low to moderate tea consumption was inversely associated with AL (OR: 0.85, 95%CI: 0.75-0.97), although the trend was non-significant. A null association between offspring's cola consumption and leukemia was noted. Our findings confirm the detrimental association between maternal coffee consumption and childhood leukemia risk and provide indications for a similar role of maternal cola intake. In contrast, an inverse association with tea was found, implying that other micronutrients contained in this beverage could potentially counterbalance the deleterious effects of caffeine. Further research should focus on the intake of specific micronutrients, different types of coffee and tea, specific immunophenotypes of the disease, and the modifying effect of genetic polymorphisms. Copyright © 2015. Published by Elsevier Ltd.
Optimization of dose and image quality in adult and pediatric computed tomography scans
NASA Astrophysics Data System (ADS)
Chang, Kwo-Ping; Hsu, Tzu-Kun; Lin, Wei-Ting; Hsu, Wen-Lin
2017-11-01
Exploration to maximize CT image and reduce radiation dose was conducted while controlling for multiple factors. The kVp, mAs, and iteration reconstruction (IR), affect the CT image quality and radiation dose absorbed. The optimal protocols (kVp, mAs, IR) are derived by figure of merit (FOM) based on CT image quality (CNR) and CT dose index (CTDIvol). CT image quality metrics such as CT number accuracy, SNR, low contrast materials' CNR and line pair resolution were also analyzed as auxiliary assessments. CT protocols were carried out with an ACR accreditation phantom and a five-year-old pediatric head phantom. The threshold values of the adult CT scan parameters, 100 kVp and 150 mAs, were determined from the CT number test and line pairs in ACR phantom module 1and module 4 respectively. The findings of this study suggest that the optimal scanning parameters for adults be set at 100 kVp and 150-250 mAs. However, for improved low- contrast resolution, 120 kVp and 150-250 mAs are optimal. Optimal settings for pediatric head CT scan were 80 kVp/50 mAs, for maxillary sinus and brain stem, while 80 kVp /300 mAs for temporal bone. SNR is not reliable as the independent image parameter nor the metric for determining optimal CT scan parameters. The iteration reconstruction (IR) approach is strongly recommended for both adult and pediatric CT scanning as it markedly improves image quality without affecting radiation dose.
Einstein, Andrew J.; Januzis, Natalie; Nguyen, Giao; Li, Jennifer S.; Fleming, Gregory A.; Yoshizumi, Terry K.
2016-01-01
Objectives To quantify the impact of image optimization on absorbed radiation dose and associated risk in children undergoing cardiac catheterization. Background Various imaging and fluoroscopy system technical parameters including camera magnification, source-to-image distance, collimation, anti-scatter grids, beam quality, and pulse rates, all affect radiation dose but have not been well studied in younger children. Methods We used anthropomorphic phantoms (ages: newborn and 5-years-old) to measure surface radiation exposure from various imaging approaches and estimated absorbed organ doses and effective doses (ED) using Monte Carlo simulations. Models developed in the National Academies’ Biological Effects of Ionizing Radiation VII report were used to compare an imaging protocol optimized for dose reduction versus suboptimal imaging (+20cm source-to-image-distance, +1 magnification setting, no collimation) on lifetime attributable risk (LAR) of cancer. Results For the newborn and 5-year-old phantoms respectively ED changes were as follows: +157% and +232% for an increase from 6-inch to 10-inch camera magnification; +61% and +59% for a 20cm increase in source-to-image-distance; −42% and −48% with addition of 1-inch periphery collimation; −31% and −46% with removal of the anti-scatter grid. Compared to an optimized protocol, suboptimal imaging increased ED by 2.75-fold (newborn) and 4-fold (5-year-old). Estimated cancer LAR from 30-minutes of postero-anterior fluoroscopy using optimized versus sub-optimal imaging respectively was: 0.42% versus 1.23% (newborn female), 0.20% vs 0.53% (newborn male), 0.47% versus 1.70% (5-year-old female) and 0.16% vs 0.69% (5-year-old male). Conclusions Radiation-related risks to children undergoing cardiac catheterization can be substantial but are markedly reduced with an optimized imaging approach. PMID:27315598
Svatos, M.; Zankowski, C.; Bednarz, B.
2016-01-01
Purpose: The future of radiation therapy will require advanced inverse planning solutions to support single-arc, multiple-arc, and “4π” delivery modes, which present unique challenges in finding an optimal treatment plan over a vast search space, while still preserving dosimetric accuracy. The successful clinical implementation of such methods would benefit from Monte Carlo (MC) based dose calculation methods, which can offer improvements in dosimetric accuracy when compared to deterministic methods. The standard method for MC based treatment planning optimization leverages the accuracy of the MC dose calculation and efficiency of well-developed optimization methods, by precalculating the fluence to dose relationship within a patient with MC methods and subsequently optimizing the fluence weights. However, the sequential nature of this implementation is computationally time consuming and memory intensive. Methods to reduce the overhead of the MC precalculation have been explored in the past, demonstrating promising reductions of computational time overhead, but with limited impact on the memory overhead due to the sequential nature of the dose calculation and fluence optimization. The authors propose an entirely new form of “concurrent” Monte Carlo treat plan optimization: a platform which optimizes the fluence during the dose calculation, reduces wasted computation time being spent on beamlets that weakly contribute to the final dose distribution, and requires only a low memory footprint to function. In this initial investigation, the authors explore the key theoretical and practical considerations of optimizing fluence in such a manner. Methods: The authors present a novel derivation and implementation of a gradient descent algorithm that allows for optimization during MC particle transport, based on highly stochastic information generated through particle transport of very few histories. A gradient rescaling and renormalization algorithm, and the concept of momentum from stochastic gradient descent were used to address obstacles unique to performing gradient descent fluence optimization during MC particle transport. The authors have applied their method to two simple geometrical phantoms, and one clinical patient geometry to examine the capability of this platform to generate conformal plans as well as assess its computational scaling and efficiency, respectively. Results: The authors obtain a reduction of at least 50% in total histories transported in their investigation compared to a theoretical unweighted beamlet calculation and subsequent fluence optimization method, and observe a roughly fixed optimization time overhead consisting of ∼10% of the total computation time in all cases. Finally, the authors demonstrate a negligible increase in memory overhead of ∼7–8 MB to allow for optimization of a clinical patient geometry surrounded by 36 beams using their platform. Conclusions: This study demonstrates a fluence optimization approach, which could significantly improve the development of next generation radiation therapy solutions while incurring minimal additional computational overhead. PMID:27277051
Grosso, Giuseppe; Micek, Agnieszka; Godos, Justyna; Sciacca, Salvatore; Pajak, Andrzej; Martínez-González, Miguel A; Giovannucci, Edward L; Galvano, Fabio
2016-12-01
Coffee consumption has been associated with several benefits toward human health. However, its association with mortality risk has yielded contrasting results, including a non-linear relation to all-cause and cardiovascular disease (CVD) mortality and no association with cancer mortality. As smoking habits may affect the association between coffee and health outcomes, the aim of the present study was to update the latest dose-response meta-analysis of prospective cohort studies on the association between coffee consumption and mortality risk and conduct stratified analyses by smoking status and other potential confounders. A systematic search was conducted in electronic databases to identify relevant studies, risk estimates were retrieved from the studies, and dose-response analysis was modeled by using restricted cubic splines. A total of 31 studies comprising 1610,543 individuals and 183,991 cases of all-cause, 34,574 of CVD, and 40,991 of cancer deaths were selected. Analysis showed decreased all-cause [relative risk (RR) = 0.86, 95 % confidence interval (CI) = 0.82, 0.89)] and CVD mortality risk (RR = 0.85, 95 % CI = 0.77, 0.93) for consumption of up to 4 cups/day of coffee, while higher intakes were associated with no further lower risk. When analyses were restricted only to non-smokers, a linear decreased risk of all-cause (RR = 0.94, 95 % CI = 0.93, 0.96), CVD (RR = 0.94, 95 % CI = 0.91, 0.97), and cancer mortality (RR = 0.98, 95 % CI = 0.96, 1.00) for 1 cup/day increase was found. The search for other potential confounders, including dose-response analyses in subgroups by gender, geographical area, year of publication, and type of coffee, showed no relevant differences between strata. In conclusion, coffee consumption is associated with decreased risk of mortality from all-cause, CVD, and cancer; however, smoking modifies the observed risk when studying the role of coffee on human health.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Laoui, S; Dietrich, S; Sehgal, V
2016-06-15
Purpose: Radiation dose delivery for endometrial cancer using HDR techniques is limited by dose to bladder and rectum. A dosimetric study was performed using Varian Capri vaginal brachytherapy applicator to determine the optimal channel configuration which minimizes dose to bladder and rectum, while providing good target coverage. Methods: A total of 17 patients, 63 plans clinically delivered, and 252 simulated plans using Varian BrachyVision planning system were generated to investigate optimal channel configuration which results in minimum dose to bladder and rectum while providing adequate target coverage. The Capri applicator consists of 13 lumens arranged in two concentric rings, onemore » central lumen and six lumens per ring. Manual dose shaping is invariably required to lower the dose to critical organs. Three-dimensional plans were simulated for 4 channel arrangements, all 13 channels, channel 12 o’clock (close to bladder) and 6 o’clock (close to rectum) deactivated, central channel deactivated, and central channel in addition to 12 o’clock and 6 o’clock deactivated. A relationship between V100, the volume that receives the prescribed dose, and the amount of curie-seconds required to deliver it, was established. Results: Using all 13 channels results in maximum dose to bladder and rectum. Deactivating central channel in addition to 12 o’clock and 6 o’clock resulted in minimizing bladder and rectum doses but compromised target coverage. The relationship between V100, the volume that receives the prescribed dose, and the curie seconds was found to be linear. Conclusion: Deactivating channels 12 o’clock and 6 o’clock was shown to be the optimal configuration leading to minimum dose to bladder and rectum without compromising target coverage. The linear relationship between V100 and the curie- seconds can be used as a verification parameter.« less
General 4-week toxicity study with EMS in the rat.
Pfister, Thomas; Eichinger-Chapelon, Anne
2009-11-12
In this subacute toxicity study, ethyl methanesulfonate (EMS) was administered daily by oral gavage to SPF-bred Wistar rats of both sexes at dose levels of 20, 60 and 180/120 mg/kg body weight (bw)/day for a period of 28 days (for 19 days in the high-dose group). A control group was treated similarly with the vehicle, bidistilled water, only. The groups comprised 10 animals per sex, which were sacrificed after 28 days, respectively 19 days in the high-dose group, of treatment. Additional five rats per sex and group were treated accordingly and then allowed a 14 days treatment-free recovery period. Additional six rats per sex and group (three rats per sex in the control group) were treated accordingly and used for hemoglobin adduct analysis after EMS exposure. All animals survived until their scheduled necropsy. Treatment with EMS had a direct dose-dependent effect on food consumption and consequently on body weight at doses > or =20mg/kgbw/day in male rats and at > or =60 mg/kgbw/day in females rats. Hence, treatment with the high dose of 180 mg/kgbw/day had to be interrupted for 9 days after which, the animals were re-dosed at 120 mg/kgbw/day. This dose was also poorly tolerated over the remaining two treatment weeks causing again a marked reduction in food consumption and body weight. A dose of 60 mg/kgbw/day was moderately tolerated over 4 weeks treatment with mean daily food consumption and body weight distinctly lower than in controls. Primary targets of systemic toxicity were the hematopoietic system, thymolymphatic system and sexual organs. Characteristic changes in hematology parameters were decreased red blood cell counts, hematocrit, and hemoglobin concentration. White blood cell counts were also decreased due to reduced lymphocyte and granulocyte populations of each fraction. The corresponding histopathology findings were fatty atrophy of bone marrow and minimal hypocellularity of the white pulp of the spleen. Similarly, treatment with EMS caused an involution of the thymolymphatic system characterized by decreased organ weight of thymus, lymph nodes, and spleen microscopically associated with atrophy of the thymus and hypocellularity of Peyer's patches, lymph nodes and the white pulp of the spleen. The effects on sexual organs included lower organ weight/reduced size for testes, epididymides, seminal vesicles, prostate, and uterus. Tubular atrophy, single cell necrosis of the germ cells and in epididymides reduced spermatozoa were recorded microscopically. The described findings occurred at doses of 60 and 180/120 mg/kgbw/day and were dose-dependent with regard to incidence and severity. Other target organs were the pancreas (acinar cell vacuolation), thyroid gland (follicular cell hypertrophy), and salivary gland (secretory depletion of convoluted ducts). The systemic exposure to EMS was monitored by hemoglobin ethylvaline adduct measurement. The concentration of hemoglobin ethylvaline adducts was linear with the dose and accumulated 11-26-fold over the treatment period. In summary, decreases in food consumption and body weight were the dose-limiting effects of treatment with EMS. Organ toxicity was characterized by depression of cell proliferation (hematopoiesis and spermatogenesis) and changes suggestive of reduced metabolism and/or physiological imbalances (e.g. thymolymphatic system and thyroid gland) without signs of inflammatory or necrotic lesions. For some findings, especially the effects on the thymolymphatic system and sexual organs, it cannot be excluded that starvation-like condition contributed to the occurrence of such changes. The low dose of 20 mg/kgbw/day was basically free of adverse effects despite of a clear evidence for hemoglobin adducts.
Ivnitsky, Jury Ju; Schäfer, Timur V; Malakhovsky, Vladimir N; Rejniuk, Vladimir L
2004-10-01
Rats poisoned with one LD50 of thiopental or amytal are shown to increase oxygen consumption when intraperitoneally given sucinate, malate, citrate, alpha-ketoglutarate, dimethylsuccinate or glutamate (the Krebs cycle intermediates or their precursors) but not when given glucose, pyruvate, acetate, benzoate or nicotinate (energy substrates of other metabolic stages etc). Survival was increased with succinate or malate from control groups, which ranged from 30-83% to 87-100%. These effects were unrelated to respiratory depression or hypoxia as judged by little or no effect of succinate on ventilation indices and by the lack of effect of oxygen administration. Body cooling of comatose rats at ambient temperature approximately 19 degrees C became slower with succinate, the rate of cooling correlated well with oxygen consumption decrease. Succinate had no potency to modify oxygen consumption and body temperature in intact rats. A condition for antidote effect of the Krebs intermediate was sufficiently high dosage (5 mmol/kg), further dose increase made no odds. Repeated dosing of succinate had more marked protective effect, than a single one, to oxygen consumption and tended to promote the attenuation of lethal effect of barbiturates. These data suggest that suppression of whole body oxygen consumption with barbiturate overdose could be an important contributor to both body cooling and mortality. Intermediates of Krebs cycle, not only succinate, may have a pronounced therapeutic effect under the proper treatment regimen. Availability of Krebs cycle intermediates may be a limiting factor for the whole body oxygen consumption in barbiturate coma, its role in brain needs further elucidation.
Ding, Ming; Bhupathiraju, Shilpa N.; Chen, Mu; van Dam, Rob M.; Hu, Frank B.
2014-01-01
OBJECTIVE Previous meta-analyses identified an inverse association of coffee consumption with the risk of type 2 diabetes. However, an updated meta-analysis is needed because new studies comparing the trends of association for caffeinated and decaffeinated coffee have since been published. RESEARCH DESIGN AND METHODS PubMed and Embase were searched for cohort or nested case-control studies that assessed the relationship of coffee consumption and risk of type 2 diabetes from 1966 to February 2013. A restricted cubic spline random-effects model was used. RESULTS Twenty-eight prospective studies were included in the analysis, with 1,109,272 study participants and 45,335 cases of type 2 diabetes. The follow-up duration ranged from 10 months to 20 years. Compared with no or rare coffee consumption, the relative risk (RR; 95% CI) for diabetes was 0.92 (0.90–0.94), 0.85 (0.82–0.88), 0.79 (0.75–0.83), 0.75 (0.71–0.80), 0.71 (0.65–0.76), and 0.67 (0.61–0.74) for 1–6 cups/day, respectively. The RR of diabetes for a 1 cup/day increase was 0.91 (0.89–0.94) for caffeinated coffee consumption and 0.94 (0.91–0.98) for decaffeinated coffee consumption (P for difference = 0.17). CONCLUSIONS Coffee consumption was inversely associated with the risk of type 2 diabetes in a dose-response manner. Both caffeinated and decaffeinated coffee was associated with reduced diabetes risk. PMID:24459154
NASA Astrophysics Data System (ADS)
Alabdulkarem, Abdullah
Liquefied natural gas (LNG) plants are energy intensive. As a result, the power plants operating these LNG plants emit high amounts of CO2 . To mitigate global warming that is caused by the increase in atmospheric CO2, CO2 capture and sequestration (CCS) using amine absorption is proposed. However, the major challenge of implementing this CCS system is the associated power requirement, increasing power consumption by about 15--25%. Therefore, the main scope of this work is to tackle this challenge by minimizing CCS power consumption as well as that of the entire LNG plant though system integration and rigorous optimization. The power consumption of the LNG plant was reduced through improving the process of liquefaction itself. In this work, a genetic algorithm (GA) was used to optimize a propane pre-cooled mixed-refrigerant (C3-MR) LNG plant modeled using HYSYS software. An optimization platform coupling Matlab with HYSYS was developed. New refrigerant mixtures were found, with savings in power consumption as high as 13%. LNG plants optimization with variable natural gas feed compositions was addressed and the solution was proposed through applying robust optimization techniques, resulting in a robust refrigerant which can liquefy a range of natural gas feeds. The second approach for reducing the power consumption is through process integration and waste heat utilization in the integrated CCS system. Four waste heat sources and six potential uses were uncovered and evaluated using HYSYS software. The developed models were verified against experimental data from the literature with good agreement. Net available power enhancement in one of the proposed CCS configuration is 16% more than the conventional CCS configuration. To reduce the CO2 pressurization power into a well for enhanced oil recovery (EOR) applications, five CO2 pressurization methods were explored. New CO2 liquefaction cycles were developed and modeled using HYSYS software. One of the developed liquefaction cycles using NH3 as a refrigerant resulted in 5% less power consumption than the conventional multi-stage compression cycle. Finally, a new concept of providing the CO2 regeneration heat is proposed. The proposed concept is using a heat pump to provide the regeneration heat as well as process heat and CO2 liquefaction heat. Seven configurations of heat pumps integrated with CCS were developed. One of the heat pumps consumes 24% less power than the conventional system or 59% less total equivalent power demand than the conventional system with steam extraction and CO2 compression.
International Society of Sports Nutrition Position Stand: protein and exercise.
Jäger, Ralf; Kerksick, Chad M; Campbell, Bill I; Cribb, Paul J; Wells, Shawn D; Skwiat, Tim M; Purpura, Martin; Ziegenfuss, Tim N; Ferrando, Arny A; Arent, Shawn M; Smith-Ryan, Abbie E; Stout, Jeffrey R; Arciero, Paul J; Ormsbee, Michael J; Taylor, Lem W; Wilborn, Colin D; Kalman, Doug S; Kreider, Richard B; Willoughby, Darryn S; Hoffman, Jay R; Krzykowski, Jamie L; Antonio, Jose
2017-01-01
The International Society of Sports Nutrition (ISSN) provides an objective and critical review related to the intake of protein for healthy, exercising individuals. Based on the current available literature, the position of the Society is as follows:An acute exercise stimulus, particularly resistance exercise, and protein ingestion both stimulate muscle protein synthesis (MPS) and are synergistic when protein consumption occurs before or after resistance exercise.For building muscle mass and for maintaining muscle mass through a positive muscle protein balance, an overall daily protein intake in the range of 1.4-2.0 g protein/kg body weight/day (g/kg/d) is sufficient for most exercising individuals, a value that falls in line within the Acceptable Macronutrient Distribution Range published by the Institute of Medicine for protein.Higher protein intakes (2.3-3.1 g/kg/d) may be needed to maximize the retention of lean body mass in resistance-trained subjects during hypocaloric periods.There is novel evidence that suggests higher protein intakes (>3.0 g/kg/d) may have positive effects on body composition in resistance-trained individuals (i.e., promote loss of fat mass).Recommendations regarding the optimal protein intake per serving for athletes to maximize MPS are mixed and are dependent upon age and recent resistance exercise stimuli. General recommendations are 0.25 g of a high-quality protein per kg of body weight, or an absolute dose of 20-40 g.Acute protein doses should strive to contain 700-3000 mg of leucine and/or a higher relative leucine content, in addition to a balanced array of the essential amino acids (EAAs).These protein doses should ideally be evenly distributed, every 3-4 h, across the day.The optimal time period during which to ingest protein is likely a matter of individual tolerance, since benefits are derived from pre- or post-workout ingestion; however, the anabolic effect of exercise is long-lasting (at least 24 h), but likely diminishes with increasing time post-exercise.While it is possible for physically active individuals to obtain their daily protein requirements through the consumption of whole foods, supplementation is a practical way of ensuring intake of adequate protein quality and quantity, while minimizing caloric intake, particularly for athletes who typically complete high volumes of training. Rapidly digested proteins that contain high proportions of essential amino acids (EAAs) and adequate leucine, are most effective in stimulating MPS. Different types and quality of protein can affect amino acid bioavailability following protein supplementation. Athletes should consider focusing on whole food sources of protein that contain all of the EAAs (i.e., it is the EAAs that are required to stimulate MPS). Endurance athletes should focus on achieving adequate carbohydrate intake to promote optimal performance; the addition of protein may help to offset muscle damage and promote recovery. Pre-sleep casein protein intake (30-40 g) provides increases in overnight MPS and metabolic rate without influencing lipolysis.
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.
[Trends in antibiotic consumption in Spain, 1985-2000].
Lázaro Bengoa, Edurne; Madurga Sanz, Mariano; de Abajo Iglesias, Francisco J
2002-04-27
The purpose of this study was to analyse the trend in antibiotics consumption to draw on the National Health System (NHS) over the last 16 years in Spain and its different Autonomous Communities (AC). Consumption data for all antibiotics used in Spain, either alone or in fixed-dose combinations, were obtained using the database ECOM. This database includes all the packages sold through retail pharmacies and reimbursed by the NHS. Data are expressed as defined dairy doses per 1,000 inhabitants per day (DHD), in accordance with the methodology recommended by the World Health Organization. Demographic data were provided by the National Institute of Statistics. In 1985 the overall consumption of antibiotics was 21.9 DHD, while in 2000 it was 20.4 DHD. It was possible to distinguish three phases over the study period. The first phase lasts until 1989, where a mild decreasing trend was observed (1.1 DHD; 5.0%), mainly due to the fall of fixed-dose combinations of antibiotics and the association of sulfamethoxazole-trimethoprim. The second phase, lasting until 1996, was characterized by a generalized increase in the consumption in all AC, with an average of 2.3 DHD (+ 11.1%), ranging from 0.4 to 4.6 DHD; this increase was mainly due to the marketing of new macrolides, cephalosporins and quinolones. Finally, there was a third phase beginning in 1996, where the consumption of antibiotics came into a sustained and generalized decline, ranging from 0.5 to 5.1 DHD, and depending on the AC (national average 2.7 DHD, 11.7% lower than that in 1996). This latter trend was mainly due to the fall of wide-spectrum penicillins. Differences between AC regarding the level of consumption were huge over the study period, although the pattern of use was quite similar. There was, for instance, a difference of 10.4 DHD between Región de Murcia and Islas Baleares in 2000, or 9.9 DHD between the former and Madrid in the same year. The consumption of antibiotics in Spain and all its AC has declined since 1996, probably related to the campaigns launched by public administrations to promote the rational use of these agents. The main subgroup involved in this trend is wide-spectrum penicillins. Differences in antibiotics use between AC are too big to be accounted for by different epidemic patterns and, therefore, should be analysed further.
Investigation of effective decision criteria for multiobjective optimization in IMRT.
Holdsworth, Clay; Stewart, Robert D; Kim, Minsun; Liao, Jay; Phillips, Mark H
2011-06-01
To investigate how using different sets of decision criteria impacts the quality of intensity modulated radiation therapy (IMRT) plans obtained by multiobjective optimization. A multiobjective optimization evolutionary algorithm (MOEA) was used to produce sets of IMRT plans. The MOEA consisted of two interacting algorithms: (i) a deterministic inverse planning optimization of beamlet intensities that minimizes a weighted sum of quadratic penalty objectives to generate IMRT plans and (ii) an evolutionary algorithm that selects the superior IMRT plans using decision criteria and uses those plans to determine the new weights and penalty objectives of each new plan. Plans resulting from the deterministic algorithm were evaluated by the evolutionary algorithm using a set of decision criteria for both targets and organs at risk (OARs). Decision criteria used included variation in the target dose distribution, mean dose, maximum dose, generalized equivalent uniform dose (gEUD), an equivalent uniform dose (EUD(alpha,beta) formula derived from the linear-quadratic survival model, and points on dose volume histograms (DVHs). In order to quantatively compare results from trials using different decision criteria, a neutral set of comparison metrics was used. For each set of decision criteria investigated, IMRT plans were calculated for four different cases: two simple prostate cases, one complex prostate Case, and one complex head and neck Case. When smaller numbers of decision criteria, more descriptive decision criteria, or less anti-correlated decision criteria were used to characterize plan quality during multiobjective optimization, dose to OARs and target dose variation were reduced in the final population of plans. Mean OAR dose and gEUD (a = 4) decision criteria were comparable. Using maximum dose decision criteria for OARs near targets resulted in inferior populations that focused solely on low target variance at the expense of high OAR dose. Target dose range, (D(max) - D(min)), decision criteria were found to be most effective for keeping targets uniform. Using target gEUD decision criteria resulted in much lower OAR doses but much higher target dose variation. EUD(alpha,beta) based decision criteria focused on a region of plan space that was a compromise between target and OAR objectives. None of these target decision criteria dominated plans using other criteria, but only focused on approaching a different area of the Pareto front. The choice of decision criteria implemented in the MOEA had a significant impact on the region explored and the rate of convergence toward the Pareto front. When more decision criteria, anticorrelated decision criteria, or decision criteria with insufficient information were implemented, inferior populations are resulted. When more informative decision criteria were used, such as gEUD, EUD(alpha,beta), target dose range, and mean dose, MOEA optimizations focused on approaching different regions of the Pareto front, but did not dominate each other. Using simple OAR decision criteria and target EUD(alpha,beta) decision criteria demonstrated the potential to generate IMRT plans that significantly reduce dose to OARs while achieving the same or better tumor control when clinical requirements on target dose variance can be met or relaxed.
DOE Office of Scientific and Technical Information (OSTI.GOV)
McGeachy, P.; Villarreal-Barajas, J. E.; Khan, R.
2014-08-15
We previously reported on a novel, modulated in both energy and intensity; photon radiotherapy (XMRT) optimization technique. The purpose of this investigation was to test this XMRT optimization against conventional intensity modulated radiotherapy (IMRT) optimization on four different organ test geometries. All geometries mimicked clinically relevant scenarios. Both IMRT and XMRT were based on a linear programming approach where the objective function was the mean dose to healthy organs and organ-specific linear dose-point constraints were used. For IMRT, the beam energy was fixed to 6 MV while XMRT optimized in terms of both 6 and 18 MV beams. All plansmore » consisted of a seven beam coplanar arrangement. All organ geometries were contoured on a 25cm diameter cylindrical water phantom in open source radiotherapy research software known as CERR. Solutions for both IMRT and XMRT were obtained for each geometry using a numerical solver Gurobi. Analyzing the quality of the solutions was done by comparing dose distributions and dose volume histograms calculated using CERR. For all four geometries, IMRT and XMRT solutions were comparable in terms of target coverage. For two of the geometries, IMRT provided an advantage in terms of reduced dose to the healthy structures. XMRT showed improved dose reduction to healthy organs for one geometry and a comparable dose distribution to IMRT for the remaining geometry. The inability to exploit the benefits of using multiple energies may be attributed to limited water phantom diameter and having the majority of the organs in close proximity to the transverse axis.« less
Blacker, Bryan C; Snyder, Shannon M; Eggett, Dennis L; Parker, Tory L
2013-05-01
We sought to determine whether consumption of blueberries could reduce postprandial oxidation when consumed with a typical high-carbohydrate, low-fat breakfast. Participants (n 14) received each of the three treatments over 3 weeks in a cross-over design. Treatments consisted of a high blueberry dose (75 g), a low blueberry dose (35 g) and a control (ascorbic acid and sugar content matching that of the high blueberry dose). Serum oxygen radical absorbance capacity (ORAC), serum lipoprotein oxidation (LO) and serum ascorbate, urate and glucose were measured at fasting, and at 1, 2 and 3 h after sample consumption. The mean serum ORAC was significantly higher in the 75 g group than in the control group during the first 2 h postprandially, while serum LO lag time showed a significant trend over the 3 h for both blueberry doses. Changes in serum ascorbate, urate and glucose were not significantly different among the groups. To our knowledge, this is the first report that has demonstrated that increased serum antioxidant capacity is not attributable to the fructose or ascorbate content of blueberries. In summary, a practically consumable quantity of blueberries (75 g) can provide statistically significant oxidative protection in vivo after a high-carbohydrate, low-fat breakfast. Though not tested directly, it is likely that the effects are due to phenolic compounds, either directly or indirectly, as they are a major family of compounds in blueberries with potential bioactive activity.
Optimized Orthovoltage Stereotactic Radiosurgery
NASA Astrophysics Data System (ADS)
Fagerstrom, Jessica M.
Because of its ability to treat intracranial targets effectively and noninvasively, stereotactic radiosurgery (SRS) is a prevalent treatment modality in modern radiation therapy. This work focused on SRS delivering rectangular function dose distributions, which are desirable for some targets such as those with functional tissue included within the target volume. In order to achieve such distributions, this work used fluence modulation and energies lower than those utilized in conventional SRS. In this work, the relationship between prescription isodose and dose gradients was examined for standard, unmodulated orthovoltage SRS dose distributions. Monte Carlo-generated energy deposition kernels were used to calculate 4pi, isocentric dose distributions for a polyenergetic orthovoltage spectrum, as well as monoenergetic orthovoltage beams. The relationship between dose gradients and prescription isodose was found to be field size and energy dependent, and values were found for prescription isodose that optimize dose gradients. Next, a pencil-beam model was used with a Genetic Algorithm search heuristic to optimize the spatial distribution of added tungsten filtration within apertures of cone collimators in a moderately filtered 250 kVp beam. Four cone sizes at three depths were examined with a Monte Carlo model to determine the effects of the optimized modulation compared to open cones, and the simulations found that the optimized cones were able to achieve both improved penumbra and flatness statistics at depth compared to the open cones. Prototypes of the filter designs calculated using mathematical optimization techniques and Monte Carlo simulations were then manufactured and inserted into custom built orthovoltage SRS cone collimators. A positioning system built in-house was used to place the collimator and filter assemblies temporarily in the 250 kVp beam line. Measurements were performed in water using radiochromic film scanned with both a standard white light flatbed scanner as well as a prototype laser densitometry system. Measured beam profiles showed that the modulated beams could more closely approach rectangular function dose profiles compared to the open cones. A methodology has been described and implemented to achieve optimized SRS delivery, including the development of working prototypes. Future work may include the construction of a full treatment platform.
Minimizing water consumption when producing hydropower
NASA Astrophysics Data System (ADS)
Leon, A. S.
2015-12-01
In 2007, hydropower accounted for only 16% of the world electricity production, with other renewable sources totaling 3%. Thus, it is not surprising that when alternatives are evaluated for new energy developments, there is strong impulse for fossil fuel or nuclear energy as opposed to renewable sources. However, as hydropower schemes are often part of a multipurpose water resources development project, they can often help to finance other components of the project. In addition, hydropower systems and their associated dams and reservoirs provide human well-being benefits, such as flood control and irrigation, and societal benefits such as increased recreational activities and improved navigation. Furthermore, hydropower due to its associated reservoir storage, can provide flexibility and reliability for energy production in integrated energy systems. The storage capability of hydropower systems act as a regulating mechanism by which other intermittent and variable renewable energy sources (wind, wave, solar) can play a larger role in providing electricity of commercial quality. Minimizing water consumption for producing hydropower is critical given that overuse of water for energy production may result in a shortage of water for other purposes such as irrigation, navigation or fish passage. This paper presents a dimensional analysis for finding optimal flow discharge and optimal penstock diameter when designing impulse and reaction water turbines for hydropower systems. The objective of this analysis is to provide general insights for minimizing water consumption when producing hydropower. This analysis is based on the geometric and hydraulic characteristics of the penstock, the total hydraulic head and the desired power production. As part of this analysis, various dimensionless relationships between power production, flow discharge and head losses were derived. These relationships were used to withdraw general insights on determining optimal flow discharge and optimal penstock diameter. For instance, it was found that for minimizing water consumption, the ratio of head loss to gross head should not exceed about 15%. Two examples of application are presented to illustrate the procedure for determining optimal flow discharge and optimal penstock diameter for impulse and reaction turbines.
Simultaneous optimization of photons and electrons for mixed beam radiotherapy
NASA Astrophysics Data System (ADS)
Mueller, S.; Fix, M. K.; Joosten, A.; Henzen, D.; Frei, D.; Volken, W.; Kueng, R.; Aebersold, D. M.; Stampanoni, M. F. M.; Manser, P.
2017-07-01
The aim of this work is to develop and investigate an inverse treatment planning process (TPP) for mixed beam radiotherapy (MBRT) capable of performing simultaneous optimization of photon and electron apertures. A simulated annealing based direct aperture optimization (DAO) is implemented to perform simultaneous optimization of photon and electron apertures, both shaped with the photon multileaf collimator (pMLC). Validated beam models are used as input for Monte Carlo dose calculations. Consideration of photon pMLC transmission during DAO and a weight re-optimization of the apertures after deliverable dose calculation are utilized to efficiently reduce the differences between optimized and deliverable dose distributions. The TPP for MBRT is evaluated for an academic situation with a superficial and an enlarged PTV in the depth, a left chest wall case including the internal mammary chain and a squamous cell carcinoma case. Deliverable dose distributions of MBRT plans are compared to those of modulated electron radiotherapy (MERT), photon IMRT and if available to those of clinical VMAT plans. The generated MBRT plans dosimetrically outperform the MERT, photon IMRT and VMAT plans for all investigated situations. For the clinical cases of the left chest wall and the squamous cell carcinoma, the MBRT plans cover the PTV similarly or more homogeneously than the VMAT plans, while OARs are spared considerably better with average reductions of the mean dose to parallel OARs and D 2% to serial OARs by 54% and 26%, respectively. Moreover, the low dose bath expressed as V 10% to normal tissue is substantially reduced by up to 45% compared to the VMAT plans. A TPP for MBRT including simultaneous optimization is successfully implemented and the dosimetric superiority of MBRT plans over MERT, photon IMRT and VMAT plans is demonstrated for academic and clinical situations including superficial targets with and without deep-seated part.
Simultaneous optimization of photons and electrons for mixed beam radiotherapy.
Mueller, S; Fix, M K; Joosten, A; Henzen, D; Frei, D; Volken, W; Kueng, R; Aebersold, D M; Stampanoni, M F M; Manser, P
2017-06-26
The aim of this work is to develop and investigate an inverse treatment planning process (TPP) for mixed beam radiotherapy (MBRT) capable of performing simultaneous optimization of photon and electron apertures. A simulated annealing based direct aperture optimization (DAO) is implemented to perform simultaneous optimization of photon and electron apertures, both shaped with the photon multileaf collimator (pMLC). Validated beam models are used as input for Monte Carlo dose calculations. Consideration of photon pMLC transmission during DAO and a weight re-optimization of the apertures after deliverable dose calculation are utilized to efficiently reduce the differences between optimized and deliverable dose distributions. The TPP for MBRT is evaluated for an academic situation with a superficial and an enlarged PTV in the depth, a left chest wall case including the internal mammary chain and a squamous cell carcinoma case. Deliverable dose distributions of MBRT plans are compared to those of modulated electron radiotherapy (MERT), photon IMRT and if available to those of clinical VMAT plans. The generated MBRT plans dosimetrically outperform the MERT, photon IMRT and VMAT plans for all investigated situations. For the clinical cases of the left chest wall and the squamous cell carcinoma, the MBRT plans cover the PTV similarly or more homogeneously than the VMAT plans, while OARs are spared considerably better with average reductions of the mean dose to parallel OARs and D 2% to serial OARs by 54% and 26%, respectively. Moreover, the low dose bath expressed as V 10% to normal tissue is substantially reduced by up to 45% compared to the VMAT plans. A TPP for MBRT including simultaneous optimization is successfully implemented and the dosimetric superiority of MBRT plans over MERT, photon IMRT and VMAT plans is demonstrated for academic and clinical situations including superficial targets with and without deep-seated part.
Benzodiazepine use and aggressive behaviour: a systematic review.
Albrecht, Bonnie; Staiger, Petra K; Hall, Kate; Miller, Peter; Best, David; Lubman, Dan I
2014-12-01
The relationship between benzodiazepine consumption and subsequent increases in aggressive behaviour in humans is not well understood. The current study aimed to identify, via a systematic review, whether there is an association between benzodiazepine consumption and aggressive responding in adults. A systematic review was conducted and reported in line with the PRISMA statement. English articles within MEDLINE, PsycARTICLES, PsycINFO, Academic Search Complete, and Psychology and Behavioural Sciences Collection databases were searched. Additional studies were identified by searching reference lists of reviewed articles. Only articles that explicitly investigated the relationship between benzodiazepine consumption and subsequent aggressive behaviour, or a lack thereof, in human adults were included. Forty-six studies met the inclusion criteria. It was not possible to conduct a meta-analysis due to the heterogeneity of study design and benzodiazepine type and dose. An association between benzodiazepine use and subsequent aggressive behaviour was found in the majority of the more rigorous studies, although there is a paucity of high-quality research with clinical or forensic populations. Diazepam and alprazolam have received the most attention. Dose-related findings are inconsistent: therapeutic doses may be more likely to be associated with aggressive responding when administered as a once-off, whereas higher doses may be more risky following repeated administration. Trait levels of anxiety and hostility may indicate a vulnerability to the experience of benzodiazepine-related aggression. There appears to be a moderate association between some benzodiazepines and subsequent aggressive behaviour in humans. The circumstances under which aggressive responding may be more likely to follow benzodiazepine use remain unclear, although some evidence suggests dose and/or personality factors may influence this effect. © The Royal Australian and New Zealand College of Psychiatrists 2014.
Toxicological evaluation of morning glory seed: subchronic 90-day feeding study.
Dugan, G M; Gumbmann, M R
1990-08-01
Diets containing 0.8, 2.53 and 8.0% field variety morning glory seed were fed to male and female rats (20 per group) in a 90-day subchronic feeding study. Gross clinical observations, body weight, and feed and water intake were recorded weekly. At 90 days, all surviving rats were autopsied, organs were weighed, and blood chemistry analyses, haematology, and bone-marrow evaluation for evidence of clastogenic effects were performed. Tissues from control (0% seed) and high-dose (8.0% seed) rats were examined histologically. Effects of morning glory seed were noted mainly in the high-dose group of both sexes. These included increases in mortality, feed consumption (on a body-weight basis), water consumption, serum alkaline phosphatase and potassium, white blood cell count, and brain and liver weights (as a percentage of body weight); body-weight gain and serum glucose were decreased. Significant changes seen in high-dose females alone were: increased haemoglobin, serum constituents (urea nitrogen, glutamic-pyruvic transaminase, glutamic-oxaloacetic transaminase, and ornithine carbamyl transferase), and organ weights (heart, kidney, spleen and pancreas as a percentage of body weight), and decreases in serum albumin, total protein, albumin:globulin ratio, and calcium. Significant changes occurring in high-dose males alone were: increased testicular weight (as a percentage of body weight), increased serum phosphorus, and decreased serum cholesterol. Liver degeneration in the high-dose females was greater than that in the controls. Mortality at 8.0% seed in the diet was 40% in males and 10% in females. At 0.8% seed, the only parameter that differed significantly from that of the controls was a final body-weight reduction in females without a corresponding reduction in feed consumption.
Palmisano, Pietro; Ammendola, Ernesto; D'Onofrio, Antonio; Accogli, Michele; Calò, Leonardo; Ruocco, Antonio; Rapacciuolo, Antonio; Del Giorno, Giuseppe; Bianchi, Valter; Malacrida, Maurizio; Valsecchi, Sergio; Gronda, Edoardo
2015-01-01
Prior studies have suggested that a substantial number of eligible heart failure (HF) patients fail to receive β-blocker therapy, or receive it at a suboptimal dose. The aim of this study is to assess the benefit of a predefined management program designed for β-blocker up-titration, evaluating the synergistic effect of cardiac resynchronization therapy (CRT) and β-blockers in a HF population. The Resynchronization Therapy and β-Blocker Titration (RESTORE) study is a prospective, case-control, multicenter cohort study designed to test the hypothesis that a β-blocker up-titration strategy based on a predefined management program maximizes the beneficial effect of CRT, increasing the number of patients reaching the target dose of β-blockers and improving their clinical outcome. All study patients receive an implantable defibrillator for CRT delivery in accordance with current guidelines. Enrollments started in December 2011 and are scheduled to end in December 2014. Approximately 250 consecutive patients will be prospectively enrolled in 6 Italian centers and followed up for 24 months after implantation. The primary endpoint is to demonstrate that CRT may allow titration of β-blockers until the optimal dose, or at least to the effective dose, in patients with HF. This study might provide important information about the benefit of a predefined management program for β-blocker up-titration in patients receiving CRT. Moreover, assessment of health-care utilization and the consumption of resources will allow estimating the potential utility of remote monitoring by means of an automated telemedicine system in facilitating the titration of β-blockers in comparison with a standard in-hospital approach. © 2015 Wiley Periodicals, Inc.
A Unified Model of Performance for Predicting the Effects of Sleep and Caffeine
Ramakrishnan, Sridhar; Wesensten, Nancy J.; Kamimori, Gary H.; Moon, James E.; Balkin, Thomas J.; Reifman, Jaques
2016-01-01
Study Objectives: Existing mathematical models of neurobehavioral performance cannot predict the beneficial effects of caffeine across the spectrum of sleep loss conditions, limiting their practical utility. Here, we closed this research gap by integrating a model of caffeine effects with the recently validated unified model of performance (UMP) into a single, unified modeling framework. We then assessed the accuracy of this new UMP in predicting performance across multiple studies. Methods: We hypothesized that the pharmacodynamics of caffeine vary similarly during both wakefulness and sleep, and that caffeine has a multiplicative effect on performance. Accordingly, to represent the effects of caffeine in the UMP, we multiplied a dose-dependent caffeine factor (which accounts for the pharmacokinetics and pharmacodynamics of caffeine) to the performance estimated in the absence of caffeine. We assessed the UMP predictions in 14 distinct laboratory- and field-study conditions, including 7 different sleep-loss schedules (from 5 h of sleep per night to continuous sleep loss for 85 h) and 6 different caffeine doses (from placebo to repeated 200 mg doses to a single dose of 600 mg). Results: The UMP accurately predicted group-average psychomotor vigilance task performance data across the different sleep loss and caffeine conditions (6% < error < 27%), yielding greater accuracy for mild and moderate sleep loss conditions than for more severe cases. Overall, accounting for the effects of caffeine resulted in improved predictions (after caffeine consumption) by up to 70%. Conclusions: The UMP provides the first comprehensive tool for accurate selection of combinations of sleep schedules and caffeine countermeasure strategies to optimize neurobehavioral performance. Citation: Ramakrishnan S, Wesensten NJ, Kamimori GH, Moon JE, Balkin TJ, Reifman J. A unified model of performance for predicting the effects of sleep and caffeine. SLEEP 2016;39(10):1827–1841. PMID:27397562
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stewart, J; Princess Margaret Cancer Centre, University Health Network, Toronto, CA; Lindsay, P
Purpose: Advances in radiotherapy practice facilitated by collimation systems to shape radiation fields and image guidance to target these conformal beams have motivated proposals for more complex dose patterns to improve the therapeutic ratio. Recent progress in small animal radiotherapy platforms has provided the foundation to validate the efficacy of such interventions, but robustly delivering heterogeneous dose distributions at the scale and accuracy demanded by preclinical studies remains challenging. This work proposes a dual focal spot optimization method to paint spatially heterogeneous dose regions and an online virtual isocenter targeting method to accurately target the dose distributions. Methods: Two-dimensional dosemore » kernels were empirically measured for the 1 mm diameter circular collimator with radiochromic film in a solid water phantom for the small and large x-ray focal spots on the X-RAD 225Cx microirradiator. These kernels were used in an optimization framework which determined a set of animal stage positions, beam-on times, and focal spot settings to optimally deliver a given desired dose distribution. An online method was developed which defined a virtual treatment isocenter based on a single image projection of the collimated radiation field. The method was demonstrated by optimization of a 6 mm circular 2 Gy target adjoining a 4 mm semicircular avoidance region. Results: The dual focal spot technique improved the optimized dose distribution with the proportion of avoidance region receiving more than 0.5 Gy reduced by 40% compared to the large focal spot technique. Targeting tests performed by irradiating ball bearing targets on radiochromic film pieced revealed the online targeting method improved the three-dimensional accuracy from 0.48 mm to 0.15 mm. Conclusion: The dual focal spot optimization and online virtual isocenter targeting framework is a robust option for delivering dose at the preclinical level and provides a new experimental option for unique radiobiological investigations This work is supported, in part, by the Natural Sciences and Engineering Research Council of Canada and a Mitacs-Accelerate fellowship. P.E. Lindsay, and D.A. Jaffray are listed as inventors of the system described herein. This system has been licensed to Precision X-Ray Inc. for commercial development.« less
Dairy product consumption and risk of hip fracture: a systematic review and meta-analysis.
Bian, Shanshan; Hu, Jingmin; Zhang, Kai; Wang, Yunguo; Yu, Miaohui; Ma, Jie
2018-01-22
Dairy product consumption may affect the risk of hip fracture, but previous studies have reported inconsistent findings. The primary aim of our meta-analysis was to examine and quantify the potential association of dairy product consumption with risk of hip fracture. We searched the databases of PubMed and EMBASE for relevant articles from their inception through April 17, 2017. The final analysis included 10 cohort studies and 8 case-control studies. Random-effects models were used to estimate the pooled risk. Subgroup and dose-response analyses were conducted to explore the relationships between the consumption of milk and the risk of hip fracture. After pooling the data from the included studies, the summary relative risk (RR) for hip fracture for highest versus lowest consumption were 0.91 (95% CI: 0.74-1.12), 0.75 (95% CI: 0.66-0.86), 0.68 (95% CI: 0.61-0. 77), 1.02 (95% CI: 0.93-1.12) for milk, yogurt, cheese, and total dairy products in cohort studies, respectively. Higher milk consumption [Odds ratio (OR), 0.71, 95% CI: 0.55-0. 91] was associated with lower risk of hip fracture for highest versus lowest consumption in case-control studies. After quantifying the specific dose of milk, the summary RR/OR for an increased milk consumption of 200 g/day was 1.00 (95% CI: 0.94-1.07), and 0.89 (95%CI: 0.64-1.24) with significant heterogeneity for cohort and case-control studies, respectively; There was a nonlinear association between milk consumption and hip fracture risk in cohort, and case-control studies. Our findings indicate that consumption of yogurt and cheese was associated with lower risk of hip fracture in cohort studies. However, the consumption of total dairy products and cream was not significantly associated with the risk of hip fracture. There was insufficient evidence to deduce the association between milk consumption and risk of hip fracture. A lower threshold of 200 g/day milk intake may have beneficial effects, whereas the effects of a higher threshold of milk intake are unclear.
Li, Xiao-Hua; Yu, Fei-Fei; Zhou, Yu-Hao; He, Jia
2016-03-01
Previous cohort studies have shown that moderate alcohol consumption was associated with a lower risk of type 2 diabetes (T2D). However, whether these associations differ according to the characteristics of patients with T2D remains controversial. The purpose of this study was to explore and summarize the evidence on the strength of the association between alcohol consumption and the subsequent risk of T2D by using a dose-response meta-analytic approach. We identified potential studies by searching the PubMed, Embase, and Cochrane Library databases up to 24 March 2015. Prospective observational studies that evaluated the relation between alcohol consumption and the risk of T2D and reported its effect estimates with 95% CIs were included. Analyses were based on 706,716 individuals (275,711 men and 431,005 women) from 26 studies with 31,621 T2D cases. We detected a nonlinear relation between alcohol consumption and the risk of T2D, which was identified in all cohorts (P-trend < 0.001, P-nonlinearity < 0.001), in men (P-trend < 0.001, P-nonlinearity < 0.001), and in women (P-trend < 0.001, P-nonlinearity < 0.001). Compared with the minimal category of alcohol consumption, light (RR: 0.83; 95% CI: 0.73, 0.95; P = 0.005) and moderate (RR: 0.74; 95% CI: 0.67, 0.82; P < 0.001) alcohol consumption was associated with a lower risk of T2D. However, heavy alcohol consumption had little or no effect on subsequent T2D risk. Furthermore, the summary RR ratio (RRR; male to female) of the comparison between moderate alcohol consumption and the minimal alcohol categories for T2D was significantly higher, and the pooled RRR (current smoker to never smoker) of light alcohol consumption was significantly reduced. Light and moderate alcohol consumption was associated with a lower risk of T2D, whereas heavy alcohol consumption was not related to the risk of T2D. © 2016 American Society for Nutrition.
Is ecological food also radioecological? - 210Po and 210Pb studies.
Strumińska-Parulska, Dagmara; Olszewski, Grzegorz
2018-01-01
Presented are results of a study on accumulation of naturally occurring 210 Po and 210 Pb in ecological and conventional farming food products in Poland: fruits, vegetables and cereals. The main idea behind this research was to determine the activity concentrations of 210 Po and 210 Pb in ecological and commercial food as well as calculate and compare the effective dose (radiation) connected to different origin of analyzed food products consumption. The studies showed the majority of all compared food samples contained similar 210 Po and 210 Pb activities and statistically, the consumption of organic and commercial food would give similar annual effective dose. Copyright © 2017 Elsevier Ltd. All rights reserved.
Maidatsi, P; Gorgias, N; Zaralidou, A; Ourailoglou, V; Giala, M
1998-09-01
Prolonged nerve conduction blockade has been proposed to result from the summed effects of charged and neutral local anaesthetics. Thirty-seven patients were randomly allocated to receive intravenous patient-controlled analgesia alone or combined with intercostal blockade (T7-T11) with a mixture of 0.45% bupivacaine and 0.6% phenol for post-cholecystectomy analgesia. Adequacy of pain relief was measured by patient scores on a 10-cm visual analogue scale and by dose-demand ratio, amounts of loading dose and total consumption of morphine and also the duration of patient-controlled analgesia in each group. No differences were found between groups in post-operative scores, dose-demand ratios and loading doses of morphine. However, in the combined treatment group, a significantly lower total consumption of morphine (P < 0.05), associated with a shorter duration of patient-controlled analgesia (P < 0.02) and a decreased mean number of unsuccessful demands (P < 0.001) were recorded. Intercostal blockade with bupivacaine-phenol supplements intravenous patient-controlled analgesia for post-cholecystectomy pain relief.
Oral toxicity of 3-nitro-1,2,4-triazol-5-one in rats.
Crouse, Lee C B; Lent, Emily May; Leach, Glenn J
2015-01-01
3-Nitro-1,2,4-triazol-5-one (NTO), an insensitive explosive, was evaluated to assess potential environmental and human health effects. A 14-day oral toxicity study in Sprague-Dawley rats was conducted with NTO in polyethylene glycol -200 by gavage at doses of 0, 250, 500, 1000, 1500, or 2000 mg/kg-d. Body mass and food consumption decreased in males (2000 mg/kg-d), and testes mass was reduced at doses of 500 mg/kg-d and greater. Based on the findings in the 14-day study, a 90-day study was conducted at doses of 0, 30, 100, 315, or 1000 mg/kg-d NTO. There was no effect on food consumption, body mass, or neurobehavioral parameters. Males in the 315 and 1000 mg/kg-d groups had reduced testes mass with associated tubular degeneration and atrophy. The testicular effects were the most sensitive adverse effect and were used to derive a benchmark dose (BMD) of 70 mg/kg-d with a 10% effect level (BMDL10) of 40 mg/kg-d. © The Author(s) 2015.
NASA Astrophysics Data System (ADS)
Yan, Hao; Cervino, Laura; Jia, Xun; Jiang, Steve B.
2012-04-01
While compressed sensing (CS)-based algorithms have been developed for the low-dose cone beam CT (CBCT) reconstruction, a clear understanding of the relationship between the image quality and imaging dose at low-dose levels is needed. In this paper, we qualitatively investigate this subject in a comprehensive manner with extensive experimental and simulation studies. The basic idea is to plot both the image quality and imaging dose together as functions of the number of projections and mAs per projection over the whole clinically relevant range. On this basis, a clear understanding of the tradeoff between the image quality and imaging dose can be achieved and optimal low-dose CBCT scan protocols can be developed to maximize the dose reduction while minimizing the image quality loss for various imaging tasks in image-guided radiation therapy (IGRT). Main findings of this work include (1) under the CS-based reconstruction framework, image quality has little degradation over a large range of dose variation. Image quality degradation becomes evident when the imaging dose (approximated with the x-ray tube load) is decreased below 100 total mAs. An imaging dose lower than 40 total mAs leads to a dramatic image degradation, and thus should be used cautiously. Optimal low-dose CBCT scan protocols likely fall in the dose range of 40-100 total mAs, depending on the specific IGRT applications. (2) Among different scan protocols at a constant low-dose level, the super sparse-view reconstruction with the projection number less than 50 is the most challenging case, even with strong regularization. Better image quality can be acquired with low mAs protocols. (3) The optimal scan protocol is the combination of a medium number of projections and a medium level of mAs/view. This is more evident when the dose is around 72.8 total mAs or below and when the ROI is a low-contrast or high-resolution object. Based on our results, the optimal number of projections is around 90 to 120. (4) The clinically acceptable lowest imaging dose level is task dependent. In our study, 72.8 mAs is a safe dose level for visualizing low-contrast objects, while 12.2 total mAs is sufficient for detecting high-contrast objects of diameter greater than 3 mm.
Mustapha, Ibrahim; Ali, Borhanuddin Mohd; Rasid, Mohd Fadlee A.; Sali, Aduwati; Mohamad, Hafizal
2015-01-01
It is well-known that clustering partitions network into logical groups of nodes in order to achieve energy efficiency and to enhance dynamic channel access in cognitive radio through cooperative sensing. While the topic of energy efficiency has been well investigated in conventional wireless sensor networks, the latter has not been extensively explored. In this paper, we propose a reinforcement learning-based spectrum-aware clustering algorithm that allows a member node to learn the energy and cooperative sensing costs for neighboring clusters to achieve an optimal solution. Each member node selects an optimal cluster that satisfies pairwise constraints, minimizes network energy consumption and enhances channel sensing performance through an exploration technique. We first model the network energy consumption and then determine the optimal number of clusters for the network. The problem of selecting an optimal cluster is formulated as a Markov Decision Process (MDP) in the algorithm and the obtained simulation results show convergence, learning and adaptability of the algorithm to dynamic environment towards achieving an optimal solution. Performance comparisons of our algorithm with the Groupwise Spectrum Aware (GWSA)-based algorithm in terms of Sum of Square Error (SSE), complexity, network energy consumption and probability of detection indicate improved performance from the proposed approach. The results further reveal that an energy savings of 9% and a significant Primary User (PU) detection improvement can be achieved with the proposed approach. PMID:26287191
Mustapha, Ibrahim; Mohd Ali, Borhanuddin; Rasid, Mohd Fadlee A; Sali, Aduwati; Mohamad, Hafizal
2015-08-13
It is well-known that clustering partitions network into logical groups of nodes in order to achieve energy efficiency and to enhance dynamic channel access in cognitive radio through cooperative sensing. While the topic of energy efficiency has been well investigated in conventional wireless sensor networks, the latter has not been extensively explored. In this paper, we propose a reinforcement learning-based spectrum-aware clustering algorithm that allows a member node to learn the energy and cooperative sensing costs for neighboring clusters to achieve an optimal solution. Each member node selects an optimal cluster that satisfies pairwise constraints, minimizes network energy consumption and enhances channel sensing performance through an exploration technique. We first model the network energy consumption and then determine the optimal number of clusters for the network. The problem of selecting an optimal cluster is formulated as a Markov Decision Process (MDP) in the algorithm and the obtained simulation results show convergence, learning and adaptability of the algorithm to dynamic environment towards achieving an optimal solution. Performance comparisons of our algorithm with the Groupwise Spectrum Aware (GWSA)-based algorithm in terms of Sum of Square Error (SSE), complexity, network energy consumption and probability of detection indicate improved performance from the proposed approach. The results further reveal that an energy savings of 9% and a significant Primary User (PU) detection improvement can be achieved with the proposed approach.
NASA Astrophysics Data System (ADS)
Zulai, Luis G. T.; Durand, Fábio R.; Abrão, Taufik
2015-05-01
In this article, an energy-efficiency mechanism for next-generation passive optical networks is investigated through heuristic particle swarm optimization. Ten-gigabit Ethernet-wavelength division multiplexing optical code division multiplexing-passive optical network next-generation passive optical networks are based on the use of a legacy 10-gigabit Ethernet-passive optical network with the advantage of using only an en/decoder pair of optical code division multiplexing technology, thus eliminating the en/decoder at each optical network unit. The proposed joint mechanism is based on the sleep-mode power-saving scheme for a 10-gigabit Ethernet-passive optical network, combined with a power control procedure aiming to adjust the transmitted power of the active optical network units while maximizing the overall energy-efficiency network. The particle swarm optimization based power control algorithm establishes the optimal transmitted power in each optical network unit according to the network pre-defined quality of service requirements. The objective is controlling the power consumption of the optical network unit according to the traffic demand by adjusting its transmitter power in an attempt to maximize the number of transmitted bits with minimum energy consumption, achieving maximal system energy efficiency. Numerical results have revealed that it is possible to save 75% of energy consumption with the proposed particle swarm optimization based sleep-mode energy-efficiency mechanism compared to 55% energy savings when just a sleeping-mode-based mechanism is deployed.
Mathison, Bridget D; Kimble, Lindsey L; Kaspar, Kerrie L; Khoo, Christina; Chew, Boon P
2014-05-01
Consumption of polyphenol-rich foods is associated with lower risk from many chronic diseases. We hypothesized that a single dose of cranberry beverage would improve indices of oxidative stress, inflammation, and urinary antibacterial adhesion activity in healthy humans. Six males and 6 females (18-35 years; body mass index, 19-25 kg/m(2)) consumed placebo, cranberry leaf extract beverage, or low-calorie cranberry juice cocktail (LCJC) once in a randomized, double-blind, placebo-controlled cross-over experimental design trial. The washout period between beverages was 1 week. Blood was collected 0, 2, 4, 8, and 24 hours after beverage consumption for measuring oxidative and inflammatory biomarkers. Urine was collected at 0, 0 to 3, 3 to 6, 6 to 9, 9 to 12, and 24 hours postintervention to assess antibacterial adhesion activity. Consumption of cranberry leaf extract beverage elevated (P < .05) blood glutathione peroxidase activity, whereas LCJC consumption increased (P < .05) glutathione concentrations and superoxide dismutase activity compared with placebo. Cranberry leaf extract beverage and LCJC consumption had no effect on the inflammatory biomarkers measured as compared with placebo. At 0 to 3 hours postconsumption, urine from participants who consumed cranberry beverages had higher (P < .05) ex vivo antiadhesion activity against P-fimbriated Escherichia coli compared with placebo. An acute dose of cranberry beverages improved biomarkers of antioxidant status and inhibition of bacterial adhesion in urine. Copyright © 2014 Elsevier Inc. All rights reserved.
Filiberti, Rosa A; Fontana, Vincenzo; De Ceglie, Antonella; Blanchi, Sabrina; Grossi, Enzo; Della Casa, Domenico; Lacchin, Teresa; De Matthaeis, Marina; Ignomirelli, Orazio; Cappiello, Roberta; Rosa, Alessandra; Foti, Monica; Laterza, Francesco; D'Onofrio, Vittorio; Iaquinto, Gaetano; Conio, Massimo
2017-04-01
Knowledge about the association between alcohol and Barrett's oesophagus and reflux oesophagitis is conflicting. In this case-control study we evaluated the role of specific alcoholic beverages (red and white wine, beer and liquors) in 339 Barrett's oesophagus and 462 oesophagitis patients compared with 619 endoscopic controls with other disorders, recruited in twelve Italian endoscopic units. Data on alcohol and other individual characteristics were obtained from structured questionnaires. No clear, monotonic significant dose-response relationship was pointed out for red wine. However, a generalised U-shaped trend of Barrett's oesophagus/oesophagitis risk due to red wine consumption particularly among current drinkers was found. Similar results were also found for white wine. Liquor/spirit consumption seemed to bring about a 1·14-2·30 risk excess, although statistically non-significant, for current Barrett's oesophagus/oesophagitis drinkers. Statistically significant decreasing dose-response relationships were found in Barrett's oesophagus for frequency and duration of beer consumption. Similar, but less clear downward tendencies were also found for oesophagitis patients. In conclusion, although often not statistically significant, our data suggested a reduced risk of Barrett's oesophagus and oesophagitis with a low/moderate intake of wine and beer consumption. A non-significant increased risk of Barrett's oesophagus/oesophagitis was observed with a higher intake of any type of heavy alcohol consumption, but no conclusion can be drawn owing to the high number of non-spirit drinkers and to the small number of drinkers at higher alcohol intake levels.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xu, Z; Wang, I; Yao, R
Purpose: This study is to use plan parameters optimization (Dose rate, collimator angle, couch angle, initial starting phase) to improve the performance of conformal arc radiotherapy plans with motion tracking by increasing the plan performance score (PPS). Methods: Two types of 3D conformal arc plans were created based on QUASAR respiratory motion phantom with spherical and cylindrical targets. Sinusoidal model was applied to the MLC leaves to generate motion tracking plans. A MATLAB program was developed to calculate PPS of each plan (ranges from 0–1) and optimize plan parameters. We first selected the dose rate for motion tracking plans andmore » then used simulated annealing algorithm to search for the combination of the other parameters that resulted in the plan of the maximal PPS. The optimized motion tracking plan was delivered by Varian Truebeam Linac. In-room cameras and stopwatch were used for starting phase selection and synchronization between phantom motion and plan delivery. Gaf-EBT2 dosimetry films were used to measure the dose delivered to the target in QUASAR phantom. Dose profiles and Truebeam trajectory log files were used for plan delivery performance evaluation. Results: For spherical target, the maximal PPS (PPSsph) of the optimized plan was 0.79: (Dose rate: 500MU/min, Collimator: 90°, Couch: +10°, starting phase: 0.83π). For cylindrical target, the maximal PPScyl was 0.75 (Dose rate: 300MU/min, Collimator: 87°, starting phase: 0.97π) with couch at 0°. Differences of dose profiles between motion tracking plans (with the maximal and the minimal PPS) and 3D conformal plans were as follows: PPSsph=0.79: %ΔFWHM: 8.9%, %Dmax: 3.1%; PPSsph=0.52: %ΔFWHM: 10.4%, %Dmax: 6.1%. PPScyl=0.75: %ΔFWHM: 4.7%, %Dmax: 3.6%; PPScyl=0.42: %ΔFWHM: 12.5%, %Dmax: 9.6%. Conclusion: By achieving high plan performance score through parameters optimization, we can improve target dose conformity of motion tracking plan by decreasing total MLC leaf travel distance and leaf speed.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kontaxis, C; Bol, G; Lagendijk, J
2016-06-15
Purpose: To develop a new IMRT treatment planning methodology suitable for the new generation of MR-linear accelerator machines. The pipeline is able to deliver Pareto-optimal plans and can be utilized for conventional treatments as well as for inter- and intrafraction plan adaptation based on real-time MR-data. Methods: A Pareto-optimal plan is generated using the automated multicriterial optimization approach Erasmus-iCycle. The resulting dose distribution is used as input to the second part of the pipeline, an iterative process which generates deliverable segments that target the latest anatomical state and gradually converges to the prescribed dose. This process continues until a certainmore » percentage of the dose has been delivered. Under a conventional treatment, a Segment Weight Optimization (SWO) is then performed to ensure convergence to the prescribed dose. In the case of inter- and intrafraction adaptation, post-processing steps like SWO cannot be employed due to the changing anatomy. This is instead addressed by transferring the missing/excess dose to the input of the subsequent fraction. In this work, the resulting plans were delivered on a Delta4 phantom as a final Quality Assurance test. Results: A conventional static SWO IMRT plan was generated for two prostate cases. The sequencer faithfully reproduced the input dose for all volumes of interest. For the two cases the mean relative dose difference of the PTV between the ideal input and sequenced dose was 0.1% and −0.02% respectively. Both plans were delivered on a Delta4 phantom and passed the clinical Quality Assurance procedures by achieving 100% pass rate at a 3%/3mm gamma analysis. Conclusion: We have developed a new sequencing methodology capable of online plan adaptation. In this work, we extended the pipeline to support Pareto-optimal input and clinically validated that it can accurately achieve these ideal distributions, while its flexible design enables inter- and intrafraction plan adaptation. This research is financially supported by Elekta AB, Stockholm, Sweden.« less
Optimizing global liver function in radiation therapy treatment planning
NASA Astrophysics Data System (ADS)
Wu, Victor W.; Epelman, Marina A.; Wang, Hesheng; Romeijn, H. Edwin; Feng, Mary; Cao, Yue; Ten Haken, Randall K.; Matuszak, Martha M.
2016-09-01
Liver stereotactic body radiation therapy (SBRT) patients differ in both pre-treatment liver function (e.g. due to degree of cirrhosis and/or prior treatment) and radiosensitivity, leading to high variability in potential liver toxicity with similar doses. This work investigates three treatment planning optimization models that minimize risk of toxicity: two consider both voxel-based pre-treatment liver function and local-function-based radiosensitivity with dose; one considers only dose. Each model optimizes different objective functions (varying in complexity of capturing the influence of dose on liver function) subject to the same dose constraints and are tested on 2D synthesized and 3D clinical cases. The normal-liver-based objective functions are the linearized equivalent uniform dose (\\ell \\text{EUD} ) (conventional ‘\\ell \\text{EUD} model’), the so-called perfusion-weighted \\ell \\text{EUD} (\\text{fEUD} ) (proposed ‘fEUD model’), and post-treatment global liver function (GLF) (proposed ‘GLF model’), predicted by a new liver-perfusion-based dose-response model. The resulting \\ell \\text{EUD} , fEUD, and GLF plans delivering the same target \\ell \\text{EUD} are compared with respect to their post-treatment function and various dose-based metrics. Voxel-based portal venous liver perfusion, used as a measure of local function, is computed using DCE-MRI. In cases used in our experiments, the GLF plan preserves up to 4.6 % ≤ft(7.5 % \\right) more liver function than the fEUD (\\ell \\text{EUD} ) plan does in 2D cases, and up to 4.5 % ≤ft(5.6 % \\right) in 3D cases. The GLF and fEUD plans worsen in \\ell \\text{EUD} of functional liver on average by 1.0 Gy and 0.5 Gy in 2D and 3D cases, respectively. Liver perfusion information can be used during treatment planning to minimize the risk of toxicity by improving expected GLF; the degree of benefit varies with perfusion pattern. Although fEUD model optimization is computationally inexpensive and often achieves better GLF than \\ell \\text{EUD} model optimization does, the GLF model directly optimizes a more clinically relevant metric and can further improve fEUD plan quality.
Network Modeling and Energy-Efficiency Optimization for Advanced Machine-to-Machine Sensor Networks
Jung, Sungmo; Kim, Jong Hyun; Kim, Seoksoo
2012-01-01
Wireless machine-to-machine sensor networks with multiple radio interfaces are expected to have several advantages, including high spatial scalability, low event detection latency, and low energy consumption. Here, we propose a network model design method involving network approximation and an optimized multi-tiered clustering algorithm that maximizes node lifespan by minimizing energy consumption in a non-uniformly distributed network. Simulation results show that the cluster scales and network parameters determined with the proposed method facilitate a more efficient performance compared to existing methods. PMID:23202190
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yang, Y. M., E-mail: ymingy@gmail.com; Bednarz, B.; Svatos, M.
Purpose: The future of radiation therapy will require advanced inverse planning solutions to support single-arc, multiple-arc, and “4π” delivery modes, which present unique challenges in finding an optimal treatment plan over a vast search space, while still preserving dosimetric accuracy. The successful clinical implementation of such methods would benefit from Monte Carlo (MC) based dose calculation methods, which can offer improvements in dosimetric accuracy when compared to deterministic methods. The standard method for MC based treatment planning optimization leverages the accuracy of the MC dose calculation and efficiency of well-developed optimization methods, by precalculating the fluence to dose relationship withinmore » a patient with MC methods and subsequently optimizing the fluence weights. However, the sequential nature of this implementation is computationally time consuming and memory intensive. Methods to reduce the overhead of the MC precalculation have been explored in the past, demonstrating promising reductions of computational time overhead, but with limited impact on the memory overhead due to the sequential nature of the dose calculation and fluence optimization. The authors propose an entirely new form of “concurrent” Monte Carlo treat plan optimization: a platform which optimizes the fluence during the dose calculation, reduces wasted computation time being spent on beamlets that weakly contribute to the final dose distribution, and requires only a low memory footprint to function. In this initial investigation, the authors explore the key theoretical and practical considerations of optimizing fluence in such a manner. Methods: The authors present a novel derivation and implementation of a gradient descent algorithm that allows for optimization during MC particle transport, based on highly stochastic information generated through particle transport of very few histories. A gradient rescaling and renormalization algorithm, and the concept of momentum from stochastic gradient descent were used to address obstacles unique to performing gradient descent fluence optimization during MC particle transport. The authors have applied their method to two simple geometrical phantoms, and one clinical patient geometry to examine the capability of this platform to generate conformal plans as well as assess its computational scaling and efficiency, respectively. Results: The authors obtain a reduction of at least 50% in total histories transported in their investigation compared to a theoretical unweighted beamlet calculation and subsequent fluence optimization method, and observe a roughly fixed optimization time overhead consisting of ∼10% of the total computation time in all cases. Finally, the authors demonstrate a negligible increase in memory overhead of ∼7–8 MB to allow for optimization of a clinical patient geometry surrounded by 36 beams using their platform. Conclusions: This study demonstrates a fluence optimization approach, which could significantly improve the development of next generation radiation therapy solutions while incurring minimal additional computational overhead.« less
Woodford, Katrina; Panettieri, Vanessa; Ruben, Jeremy D; Senthi, Sashendra
2016-05-01
Intensity modulated radiotherapy (IMRT) is routinely utilized in the treatment of locally advanced non-small cell lung cancer (NSCLC). RTOG 0617 found that overall survival was impacted by increased low (5 Gy) and intermediate (30 Gy) cardiac doses. We evaluated the impact of esophageal-sparing IMRT on cardiac doses with and without the heart considered in the planning process and predicted toxicity compared to 3D-conventional radiotherapy (3DCRT). Ten consecutive patients with N2 Stage III NSCLC treated to 60 Gy in 30 fractions, between February 2012 and September 2014, were evaluated. For each patient, 3DCRT and esophageal-sparing IMRT plans were generated. IMRT plans were then created with and without the heart considered in the optimization process. To compare plans, the dose delivered to 95% and 99% of the target (D95% and D99%), and doses to the esophagus, lung and heart were compared by determining the volume receiving X dose (VXGy) and the normal tissue complication probability (NTCP) calculated. IMRT reduced maximum esophagus dose to below 60 Gy in all patients and produced significant reductions to V50Gy, V40Gy and esophageal NTCP. The cost of this reduction was a non-statistically, non-clinically significant increase in low dose (5 Gy) lung exposure that did not worsen lung NTCP. IMRT plans produced significant cardiac sparing, with the amount of improvement correlating to the amount of heart overlapping with the target. When included in plan optimization, for selected patients further sparing of the heart and improvement in heart NTCP was possible. Esophageal-sparing IMRT can significantly spare the heart even if it is not considered in the optimization process. Further sparing can be achieved if plan optimization constrains low and intermediate heart doses, without compromising lung doses.
Simultaneously optimizing dose and schedule of a new cytotoxic agent.
Braun, Thomas M; Thall, Peter F; Nguyen, Hoang; de Lima, Marcos
2007-01-01
Traditionally, phase I clinical trial designs are based upon one predefined course of treatment while varying among patients the dose given at each administration. In actual medical practice, patients receive a schedule comprised of several courses of treatment, and some patients may receive one or more dose reductions or delays during treatment. Consequently, the overall risk of toxicity for each patient is a function of both actual schedule of treatment and the differing doses used at each adminstration. Our goal is to provide a practical phase I clinical trial design that more accurately reflects actual medical practice by accounting for both dose per administration and schedule. We propose an outcome-adaptive Bayesian design that simultaneously optimizes both dose and schedule in terms of the overall risk of toxicity, based on time-to-toxicity outcomes. We use computer simulation as a tool to calibrate design parameters. We describe a phase I trial in allogeneic bone marrow transplantation that was designed and is currently being conducted using our new method. Our computer simulations demonstrate that our method outperforms any method that searches for an optimal dose but does not allow schedule to vary, both in terms of the probability of identifying optimal (dose, schedule) combinations, and the numbers of patients assigned to those combinations in the trial. Our design requires greater sample sizes than those seen in traditional phase I studies due to the larger number of treatment combinations examined. Our design also assumes that the effects of multiple administrations are independent of each other and that the hazard of toxicity is the same for all administrations. Our design is the first for phase I clinical trials that is sufficiently flexible and practical to truly reflect clinical practice by varying both dose and the timing and number of administrations given to each patient.
Seco, J; Clark, C H; Evans, P M; Webb, S
2006-05-01
This study focuses on understanding the impact of intensity-modulated radiotherapy (IMRT) delivery effects when applied to plans generated by commercial treatment-planning systems such as Pinnacle (ADAC Laboratories Inc.) and CadPlan/Helios (Varian Medical Systems). These commercial planning systems have had several version upgrades (with improvements in the optimization algorithm), but the IMRT delivery effects have not been incorporated into the optimization process. IMRT delivery effects include head-scatter fluence from IMRT fields, transmission through leaves and the effect of the rounded shape of the leaf ends. They are usually accounted for after optimization when leaf sequencing the "optimal" fluence profiles, to derive the delivered fluence profile. The study was divided into two main parts: (a) analysing the dose distribution within the planning-target volume (PTV), produced by each of the commercial treatment-planning systems, after the delivered fluence had been renormalized to deliver the correct dose to the PTV; and (b) studying the impact of the IMRT delivery technique on the surrounding critical organs such as the spinal cord, lungs, rectum, bladder etc. The study was performed for tumours of (i) the oesophagus and (ii) the prostate and pelvic nodes. An oesophagus case was planned with the Pinnacle planning system for IMRT delivery, via multiple-static fields (MSF) and compensators, using the Elekta SL25 with a multileaf collimator (MLC) component. A prostate and pelvic nodes IMRT plan was performed with the Cadplan/Helios system for a dynamic delivery (DMLC) using the Varian 120-leaf Millennium MLC. In these commercial planning systems, since IMRT delivery effects are not included into the optimization process, fluence renormalization is required such that the median delivered PTV dose equals the initial prescribed PTV dose. In preparing the optimum fluence profile for delivery, the PTV dose has been "smeared" by the IMRT delivery techniques. In the case of the oesophagus, the critical organ, spinal cord, received a greater dose than initially planned, due to the delivery effects. The increase in the spinal cord dose is of the order of 2-3 Gy. In the case of the prostate and pelvic nodes, the IMRT delivery effects led to an increase of approximately 2 Gy in the dose delivered to the secondary PTV, the pelvic nodes. In addition to this, the small bowel, rectum and bladder received an increased dose of the order of 2-3 Gy to 50% of their total volume. IMRT delivery techniques strongly influence the delivered dose distributions for the oesophagus and prostate/pelvic nodes tumour sites and these effects are not yet accounted for in the Pinnacle and the CadPlan/Helios planning systems. Currently, they must be taken into account during the optimization stage by altering the dose limits accepted during optimization so that the final (sequenced) dose is within the constraints.
A robust two-stage design identifying the optimal biological dose for phase I/II clinical trials.
Zang, Yong; Lee, J Jack
2017-01-15
We propose a robust two-stage design to identify the optimal biological dose for phase I/II clinical trials evaluating both toxicity and efficacy outcomes. In the first stage of dose finding, we use the Bayesian model averaging continual reassessment method to monitor the toxicity outcomes and adopt an isotonic regression method based on the efficacy outcomes to guide dose escalation. When the first stage ends, we use the Dirichlet-multinomial distribution to jointly model the toxicity and efficacy outcomes and pick the candidate doses based on a three-dimensional volume ratio. The selected candidate doses are then seamlessly advanced to the second stage for dose validation. Both toxicity and efficacy outcomes are continuously monitored so that any overly toxic and/or less efficacious dose can be dropped from the study as the trial continues. When the phase I/II trial ends, we select the optimal biological dose as the dose obtaining the minimal value of the volume ratio within the candidate set. An advantage of the proposed design is that it does not impose a monotonically increasing assumption on the shape of the dose-efficacy curve. We conduct extensive simulation studies to examine the operating characteristics of the proposed design. The simulation results show that the proposed design has desirable operating characteristics across different shapes of the underlying true dose-toxicity and dose-efficacy curves. The software to implement the proposed design is available upon request. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
Loganathan, Kavithaa; Bromley, David; Chelme-Ayala, Pamela; Gamal El-Din, Mohamed
2015-09-15
Through sustainable water management, oil sands companies are working to reduce their reliance on fresh water by minimizing the amount of water required for their operations and by recycling water from tailings ponds. This study was the first pilot-scale testing of a hybrid technology consisting of froth flotation combined with filtration through precoated submerged stainless steel membranes used to treat recycle water from an oil sands facility. The results indicated that the most important factor affecting the performance of the hybrid system was the influent water quality. Any rise in the levels of suspended solids or total organic carbon of the feed water resulted in changes of chemical consumption rates, flux rates, and operating cycle durations. The selections of chemical type and dosing rates were critical in achieving optimal performance. In particular, the froth application rate heavily affected the overall recovery of the hybrid system as well as the performance of the flotation process. Optimum surfactant usage to generate froth (per liter of treated water) was 0.25 mL/L at approximately 2000 NTU of influent turbidity and 0.015 mL/L at approximately 200 NTU of influent turbidity. At the tested conditions, the optimal coagulant dose was 80 mg/L (as Al) at approximately 2000 NTU of influent turbidity and <40 mg/L (as Al) at approximately 200 NTU of influent turbidity. Precoat loading per unit membrane surface area tested during the pilot study was approximately 30 g/m(2). The results of this study indicated that this hybrid technology can potentially be considered as a pre-treatment step for reverse osmosis treatment of recycle water. Copyright © 2015 Elsevier Ltd. All rights reserved.
Nkiwane, Karen S; Pötter, Richard; Tanderup, Kari; Federico, Mario; Lindegaard, Jacob C; Kirisits, Christian
2013-01-01
Three-dimensional evaluation and comparison of target and organs at risk (OARs) doses from two traditional standard source loading patterns in the frame of MRI-guided cervical cancer brachytherapy for various clinical scenarios based on patient data collected in a multicenter trial setting. Two nonoptimized three-dimensional MRI-based treatment plans, Plan 1 (tandem and vaginal loading) and Plan 2 (tandem loading only), were generated for 134 patients from seven centers participating in the EMBRACE study. Both plans were normalized to point A (Pt. A). Target and OAR doses were evaluated in terms of minimum dose to 90% of the high-risk clinical target volume (HRCTV D90) grouped by tumor stage and minimum dose to the most exposed 2cm³ of the OARs volume. An HRCTV D90 ≥ Pt. A was achieved in 82% and 44% of the patients with Plans 1 and 2, respectively. Median HRCTV D90 with Plans 1 and 2 was 120% and 90% of Pt. A dose, respectively. Both plans had optimal dose coverage in 88% of Stage IB tumors; however, the tandem-only plan resulted in about 50% of dose reduction to the vagina and rectum. For Stages IIB and IIIB, Plan 1 had on average 35% better target coverage but with significant doses to OARs. Standard tandem loading alone results in good target coverage in most Stage IB tumors without violating OAR dose constraints. For Stage IIB tumors, standard vaginal loading improves the therapeutic window, however needs optimization to fulfill the dose prescription for target and OAR. In Stage IIIB, even optimized vaginal loading often does not fulfill the needs for dose prescription. The significant dose variation across various clinical scenarios for both target and OARs indicates the need for image-guided brachytherapy for optimal dose adaptation both for limited and advanced diseases. Copyright © 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.
Optimizing treatment of hypothyroidism.
Clarke, Nick; Kabadi, Udaya M
2004-01-01
Several thyroid hormone preparations are currently available, including levothyroxine sodium (thyroxine), liothyronine (triiodothyronine), and desiccated thyroid extract, as well as a combination of levothyroxine sodium and liothyronine. Levothyroxine sodium monotherapy at an appropriate daily dose provides uniform levels of both thyroxine and triiodothyronine in the circulation without diurnal variation. Therefore, it is the preparation of choice in most patients with hypothyroidism of both the primary and central types. A normal thyrotropin (TSH) level of 1-2 mU/L is considered the determinant of optimal daily levothyroxine sodium dose in patients with primary hypothyroidism, whereas normal thyroxine and triiodothyronine levels in the mid or upper normal range may denote optimal replacement in patients with central hypothyroidism. Optimal daily levothyroxine sodium dose may be determined according to serum TSH level at the time of diagnosis of primary hypothyroidism. Initial administration of close to the full calculated dose of levothyroxine sodium is appropriate for younger patients, reducing the need for follow-up visits and repeated laboratory testing for dose titration. In the elderly and in patients with a history of coronary artery disease (CAD), the well established approach of starting with a low dose and gradually titrating to the full calculated dose is always the best option. Levothyroxine sodium can and should be continued in patients receiving treatment for CAD. Even minor over-replacement during initial titration of levothyroxine sodium should be avoided, because of the risk of cardiac events. Chronic over-replacement may induce osteoporosis, particularly in postmenopausal women, and should also be avoided.
CT dose minimization using personalized protocol optimization and aggressive bowtie
NASA Astrophysics Data System (ADS)
Wang, Hui; Yin, Zhye; Jin, Yannan; Wu, Mingye; Yao, Yangyang; Tao, Kun; Kalra, Mannudeep K.; De Man, Bruno
2016-03-01
In this study, we propose to use patient-specific x-ray fluence control to reduce the radiation dose to sensitive organs while still achieving the desired image quality (IQ) in the region of interest (ROI). The mA modulation profile is optimized view by view, based on the sensitive organs and the ROI, which are obtained from an ultra-low-dose volumetric CT scout scan [1]. We use a clinical chest CT scan to demonstrate the feasibility of the proposed concept: the breast region is selected as the sensitive organ region while the cardiac region is selected as IQ ROI. Two groups of simulations are performed based on the clinical CT dataset: (1) a constant mA scan adjusted based on the patient attenuation (120 kVp, 300 mA), which serves as baseline; (2) an optimized scan with aggressive bowtie and ROI centering combined with patient-specific mA modulation. The results shows that the combination of the aggressive bowtie and the optimized mA modulation can result in 40% dose reduction in the breast region, while the IQ in the cardiac region is maintained. More generally, this paper demonstrates the general concept of using a 3D scout scan for optimal scan planning.
Silkosessak, O; Jacobs, R; Bogaerts, R; Bosmans, H; Panmekiate, S
2014-01-01
Objectives: To determine the optimal kVp setting for a particular cone beam CT (CBCT) device by maximizing technical image quality at a fixed radiation dose. Methods: The 3D Accuitomo 170 (J. Morita Mfg. Corp., Kyoto, Japan) CBCT was used. The radiation dose as a function of kVp was measured in a cylindrical polymethyl methacrylate (PMMA) phantom using a small-volume ion chamber. Contrast-to-noise ratio (CNR) was measured using a PMMA phantom containing four materials (air, aluminium, polytetrafluoroethylene and low-density polyethylene), which was scanned using 180 combinations of kVp/mA, ranging from 60/1 to 90/8. The CNR was measured for each material using PMMA as background material. The pure effect of kVp and mAs on the CNR values was analysed. Using a polynomial fit for CNR as a function of mA for each kVp value, the optimal kVp was determined at five dose levels. Results: Absorbed doses ranged between 0.034 mGy mAs−1 (14 × 10 cm, 60 kVp) and 0.108 mGy mAs−1 (14 × 10 cm, 90 kVp). The relation between kVp and dose was quasilinear (R2 > 0.99). The effect of mA and kVp on CNR could be modelled using a second-degree polynomial. At a fixed dose, there was a tendency for higher CNR values at increasing kVp values, especially at low dose levels. A dose reduction through mA was more efficient than an equivalent reduction through kVp in terms of image quality deterioration. Conclusions: For the investigated CBCT model, the most optimal contrast at a fixed dose was found at the highest available kVp setting. There is great potential for dose reduction through mA with a minimal loss in image quality. PMID:24708447
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gill, K; Aldoohan, S; Collier, J
Purpose: Study image optimization and radiation dose reduction in pediatric shunt CT scanning protocol through the use of different beam-hardening filters Methods: A 64-slice CT scanner at OU Childrens Hospital has been used to evaluate CT image contrast-to-noise ratio (CNR) and measure effective-doses based on the concept of CT dose index (CTDIvol) using the pediatric head shunt scanning protocol. The routine axial pediatric head shunt scanning protocol that has been optimized for the intrinsic x-ray tube filter has been used to evaluate CNR by acquiring images using the ACR approved CT-phantom and radiation dose CTphantom, which was used to measuremore » CTDIvol. These results were set as reference points to study and evaluate the effects of adding different filtering materials (i.e. Tungsten, Tantalum, Titanium, Nickel and Copper filters) to the existing filter on image quality and radiation dose. To ensure optimal image quality, the scanner routine air calibration was run for each added filter. The image CNR was evaluated for different kVps and wide range of mAs values using above mentioned beam-hardening filters. These scanning protocols were run under axial as well as under helical techniques. The CTDIvol and the effective-dose were measured and calculated for all scanning protocols and added filtration, including the intrinsic x-ray tube filter. Results: Beam-hardening filter shapes energy spectrum, which reduces the dose by 27%. No noticeable changes in image low contrast detectability Conclusion: Effective-dose is very much dependent on the CTDIVol, which is further very much dependent on beam-hardening filters. Substantial reduction in effective-dose is realized using beam-hardening filters as compare to the intrinsic filter. This phantom study showed that significant radiation dose reduction could be achieved in CT pediatric shunt scanning protocols without compromising in diagnostic value of image quality.« less
Srivastava, Shashikant; Deshpande, Devyani; Pasipanodya, Jotam; Nuermberger, Eric; Swaminathan, Soumya; Gumbo, Tawanda
2016-01-01
Background. When treated with the same antibiotic dose, children achieve different 0- to 24-hour area under the concentration-time curves (AUC0–24) because of maturation and between-child physiological variability on drug clearance. Children are also infected by Mycobacterium tuberculosis isolates with different antibiotic minimum inhibitory concentrations (MICs). Thus, each child will achieve different AUC0–24/MIC ratios when treated with the same dose. Methods. We used 10 000-subject Monte Carlo experiments to identify the oral doses of linezolid, moxifloxacin, and faropenem that would achieve optimal target exposures associated with optimal efficacy in children with disseminated tuberculosis. The linezolid and moxifloxacin exposure targets were AUC0–24/MIC ratios of 62 and 122, and a faropenem percentage of time above MIC >60%, in combination therapy. A linezolid AUC0–24 of 93.4 mg × hour/L was target for toxicity. Population pharmacokinetic parameters of each drug and between-child variability, as well as MIC distribution, were used, and the cumulative fraction of response (CFR) was calculated. We also considered drug penetration indices into meninges, bone, and peritoneum. Results. The linezolid dose of 15 mg/kg in full-term neonates and infants aged up to 3 months and 10 mg/kg in toddlers, administered once daily, achieved CFR ≥ 90%, with <10% achieving linezolid AUC0–24 associated with toxicity. The moxifloxacin dose of 25 mg/kg/day achieved a CFR > 90% in infants, but the optimal dose was 20 mg/kg/day in older children. The faropenem medoxomil optimal dosage was 30 mg/kg 3–4 times daily. Conclusions. The regimen and doses of linezolid, moxifloxacin, and faropenem identified are proposed to be adequate for all disseminated tuberculosis syndromes, whether drug-resistant or -susceptible. PMID:27742641
Clinical implementation of a knowledge based planning tool for prostate VMAT.
Powis, Richard; Bird, Andrew; Brennan, Matthew; Hinks, Susan; Newman, Hannah; Reed, Katie; Sage, John; Webster, Gareth
2017-05-08
A knowledge based planning tool has been developed and implemented for prostate VMAT radiotherapy plans providing a target average rectum dose value based on previously achievable values for similar rectum/PTV overlap. The purpose of this planning tool is to highlight sub-optimal clinical plans and to improve plan quality and consistency. A historical cohort of 97 VMAT prostate plans was interrogated using a RayStation script and used to develop a local model for predicting optimum average rectum dose based on individual anatomy. A preliminary validation study was performed whereby historical plans identified as "optimal" and "sub-optimal" by the local model were replanned in a blinded study by four experienced planners and compared to the original clinical plan to assess whether any improvement in rectum dose was observed. The predictive model was then incorporated into a RayStation script and used as part of the clinical planning process. Planners were asked to use the script during planning to provide a patient specific prediction for optimum average rectum dose and to optimise the plan accordingly. Plans identified as "sub-optimal" in the validation study observed a statistically significant improvement in average rectum dose compared to the clinical plan when replanned whereas plans that were identified as "optimal" observed no improvement when replanned. This provided confidence that the local model can identify plans that were suboptimal in terms of rectal sparing. Clinical implementation of the knowledge based planning tool reduced the population-averaged mean rectum dose by 5.6Gy. There was a small but statistically significant increase in total MU and femoral head dose and a reduction in conformity index. These did not affect the clinical acceptability of the plans and no significant changes to other plan quality metrics were observed. The knowledge-based planning tool has enabled substantial reductions in population-averaged mean rectum dose for prostate VMAT patients. This suggests plans are improved when planners receive quantitative feedback on plan quality against historical data.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sanchez-Parcerisa, D; Carabe-Fernandez, A
2014-06-01
Purpose. Intensity-modulated proton therapy is usually implemented with multi-field optimization of pencil-beam scanning (PBS) proton fields. However, at the view of the experience with photon-IMRT, proton facilities equipped with double-scattering (DS) delivery and multi-leaf collimation (MLC) could produce highly conformal dose distributions (and possibly eliminate the need for patient-specific compensators) with a clever use of their MLC field shaping, provided that an optimal inverse TPS is developed. Methods. A prototype TPS was developed in MATLAB. The dose calculation process was based on a fluence-dose algorithm on an adaptive divergent grid. A database of dose kernels was precalculated in order tomore » allow for fast variations of the field range and modulation during optimization. The inverse planning process was based on the adaptive simulated annealing approach, with direct aperture optimization of the MLC leaves. A dosimetry study was performed on a phantom formed by three concentrical semicylinders separated by 5 mm, of which the inner-most and outer-most were regarded as organs at risk (OARs), and the middle one as the PTV. We chose a concave target (which is not treatable with conventional DS fields) to show the potential of our technique. The optimizer was configured to minimize the mean dose to the OARs while keeping a good coverage of the target. Results. The plan produced by the prototype TPS achieved a conformity index of 1.34, with the mean doses to the OARs below 78% of the prescribed dose. This Result is hardly achievable with traditional conformal DS technique with compensators, and it compares to what can be obtained with PBS. Conclusion. It is certainly feasible to produce IMPT fields with MLC passive scattering fields. With a fully developed treatment planning system, the produced plans can be superior to traditional DS plans in terms of plan conformity and dose to organs at risk.« less
Yang, Ching-Ching; Yang, Bang-Hung; Tu, Chun-Yuan; Wu, Tung-Hsin; Liu, Shu-Hsin
2017-06-01
This study aimed to evaluate the efficacy of automatic exposure control (AEC) in order to optimize low-dose computed tomography (CT) protocols for patients of different ages undergoing cardiac PET/CT and single-photon emission computed tomography/computed tomography (SPECT/CT). One PET/CT and one SPECT/CT were used to acquire CT images for four anthropomorphic phantoms representative of 1-year-old, 5-year-old and 10-year-old children and an adult. For the hybrid systems investigated in this study, the radiation dose and image quality of cardiac CT scans performed with AEC activated depend mainly on the selection of a predefined image quality index. Multiple linear regression methods were used to analyse image data from anthropomorphic phantom studies to investigate the effects of body size and predefined image quality index on CT radiation dose in cardiac PET/CT and SPECT/CT scans. The regression relationships have a coefficient of determination larger than 0.9, indicating a good fit to the data. According to the regression models, low-dose protocols using the AEC technique were optimized for patients of different ages. In comparison with the standard protocol with AEC activated for adult cardiac examinations used in our clinical routine practice, the optimized paediatric protocols in PET/CT allow 32.2, 63.7 and 79.2% CT dose reductions for anthropomorphic phantoms simulating 10-year-old, 5-year-old and 1-year-old children, respectively. The corresponding results for cardiac SPECT/CT are 8.4, 51.5 and 72.7%. AEC is a practical way to reduce CT radiation dose in cardiac PET/CT and SPECT/CT, but the AEC settings should be determined properly for optimal effect. Our results show that AEC does not eliminate the need for paediatric protocols and CT examinations using the AEC technique should be optimized for paediatric patients to reduce the radiation dose as low as reasonably achievable.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Folkerts, MM; University of California San Diego, La Jolla, California; Long, T
Purpose: To provide a tool to generate large sets of realistic virtual patient geometries and beamlet doses for treatment optimization research. This tool enables countless studies exploring the fundamental interplay between patient geometry, objective functions, weight selections, and achievable dose distributions for various algorithms and modalities. Methods: Generating realistic virtual patient geometries requires a small set of real patient data. We developed a normalized patient shape model (PSM) which captures organ and target contours in a correspondence-preserving manner. Using PSM-processed data, we perform principal component analysis (PCA) to extract major modes of variation from the population. These PCA modes canmore » be shared without exposing patient information. The modes are re-combined with different weights to produce sets of realistic virtual patient contours. Because virtual patients lack imaging information, we developed a shape-based dose calculation (SBD) relying on the assumption that the region inside the body contour is water. SBD utilizes a 2D fluence-convolved scatter kernel, derived from Monte Carlo simulations, and can compute both full dose for a given set of fluence maps, or produce a dose matrix (dose per fluence pixel) for many modalities. Combining the shape model with SBD provides the data needed for treatment plan optimization research. Results: We used PSM to capture organ and target contours for 96 prostate cases, extracted the first 20 PCA modes, and generated 2048 virtual patient shapes by randomly sampling mode scores. Nearly half of the shapes were thrown out for failing anatomical checks, the remaining 1124 were used in computing dose matrices via SBD and a standard 7-beam protocol. As a proof of concept, and to generate data for later study, we performed fluence map optimization emphasizing PTV coverage. Conclusions: We successfully developed and tested a tool for creating customizable sets of virtual patients suitable for large-scale radiation therapy optimization research.« less
SU-E-I-43: Pediatric CT Dose and Image Quality Optimization
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stevens, G; Singh, R
2014-06-01
Purpose: To design an approach to optimize radiation dose and image quality for pediatric CT imaging, and to evaluate expected performance. Methods: A methodology was designed to quantify relative image quality as a function of CT image acquisition parameters. Image contrast and image noise were used to indicate expected conspicuity of objects, and a wide-cone system was used to minimize scan time for motion avoidance. A decision framework was designed to select acquisition parameters as a weighted combination of image quality and dose. Phantom tests were used to acquire images at multiple techniques to demonstrate expected contrast, noise and dose.more » Anthropomorphic phantoms with contrast inserts were imaged on a 160mm CT system with tube voltage capabilities as low as 70kVp. Previously acquired clinical images were used in conjunction with simulation tools to emulate images at different tube voltages and currents to assess human observer preferences. Results: Examination of image contrast, noise, dose and tube/generator capabilities indicates a clinical task and object-size dependent optimization. Phantom experiments confirm that system modeling can be used to achieve the desired image quality and noise performance. Observer studies indicate that clinical utilization of this optimization requires a modified approach to achieve the desired performance. Conclusion: This work indicates the potential to optimize radiation dose and image quality for pediatric CT imaging. In addition, the methodology can be used in an automated parameter selection feature that can suggest techniques given a limited number of user inputs. G Stevens and R Singh are employees of GE Healthcare.« less
Gu, Wenbo; O'Connor, Daniel; Nguyen, Dan; Yu, Victoria Y; Ruan, Dan; Dong, Lei; Sheng, Ke
2018-04-01
Intensity-Modulated Proton Therapy (IMPT) is the state-of-the-art method of delivering proton radiotherapy. Previous research has been mainly focused on optimization of scanning spots with manually selected beam angles. Due to the computational complexity, the potential benefit of simultaneously optimizing beam orientations and spot pattern could not be realized. In this study, we developed a novel integrated beam orientation optimization (BOO) and scanning-spot optimization algorithm for intensity-modulated proton therapy (IMPT). A brain chordoma and three unilateral head-and-neck patients with a maximal target size of 112.49 cm 3 were included in this study. A total number of 1162 noncoplanar candidate beams evenly distributed across 4π steradians were included in the optimization. For each candidate beam, the pencil-beam doses of all scanning spots covering the PTV and a margin were calculated. The beam angle selection and spot intensity optimization problem was formulated to include three terms: a dose fidelity term to penalize the deviation of PTV and OAR doses from ideal dose distribution; an L1-norm sparsity term to reduce the number of active spots and improve delivery efficiency; a group sparsity term to control the number of active beams between 2 and 4. For the group sparsity term, convex L2,1-norm and nonconvex L2,1/2-norm were tested. For the dose fidelity term, both quadratic function and linearized equivalent uniform dose (LEUD) cost function were implemented. The optimization problem was solved using the Fast Iterative Shrinkage-Thresholding Algorithm (FISTA). The IMPT BOO method was tested on three head-and-neck patients and one skull base chordoma patient. The results were compared with IMPT plans created using column generation selected beams or manually selected beams. The L2,1-norm plan selected spatially aggregated beams, indicating potential degeneracy using this norm. L2,1/2-norm was able to select spatially separated beams and achieve smaller deviation from the ideal dose. In the L2,1/2-norm plans, the [mean dose, maximum dose] of OAR were reduced by an average of [2.38%, 4.24%] and[2.32%, 3.76%] of the prescription dose for the quadratic and LEUD cost function, respectively, compared with the IMPT plan using manual beam selection while maintaining the same PTV coverage. The L2,1/2 group sparsity plans were dosimetrically superior to the column generation plans as well. Besides beam orientation selection, spot sparsification was observed. Generally, with the quadratic cost function, 30%~60% spots in the selected beams remained active. With the LEUD cost function, the percentages of active spots were in the range of 35%~85%.The BOO-IMPT run time was approximately 20 min. This work shows the first IMPT approach integrating noncoplanar BOO and scanning-spot optimization in a single mathematical framework. This method is computationally efficient, dosimetrically superior and produces delivery-friendly IMPT plans. © 2018 American Association of Physicists in Medicine.
Is patient size important in dose determination and optimization in cardiology?
NASA Astrophysics Data System (ADS)
Reay, J.; Chapple, C. L.; Kotre, C. J.
2003-12-01
Patient dose determination and optimization have become more topical in recent years with the implementation of the Medical Exposures Directive into national legislation, the Ionising Radiation (Medical Exposure) Regulations. This legislation incorporates a requirement for new equipment to provide a means of displaying a measure of patient exposure and introduces the concept of diagnostic reference levels. It is normally assumed that patient dose is governed largely by patient size; however, in cardiology, where procedures are often very complex, the significance of patient size is less well understood. This study considers over 9000 cardiology procedures, undertaken throughout the north of England, and investigates the relationship between patient size and dose. It uses simple linear regression to calculate both correlation coefficients and significance levels for data sorted by both room and individual clinician for the four most common examinations, left ventrical and/or coronary angiography, single vessel stent insertion and single vessel angioplasty. This paper concludes that the correlation between patient size and dose is weak for the procedures considered. It also illustrates the use of an existing method for removing the effect of patient size from dose survey data. This allows typical doses and, therefore, reference levels to be defined for the purposes of dose optimization.
Acute toxicity and anti-fatigue activity of polysaccharide-rich extract from corn silk.
Zhao, He-Peng; Zhang, Yang; Liu, Zhuo; Chen, Jiang-Yue; Zhang, Song-Yan; Yang, Xiu-Dong; Zhou, Hong-Li
2017-06-01
The aim of this study was to evaluate the safety and potential of PCS as the anti-fatigue functional food. PCS was prepared by water extracting-alcohol precipitating method, and its chemical compositions of monosaccharide were analyzed. Then, acute toxicity and anti-fatigue activity of PCS were evaluated. PCS is composed of Rha, Arab, Xyl, Man, Glu, and Gal, its molar ratio is 0.17: 0.30: 0.26: 0.35: 1.00: 0.57. No mortality and general symptoms of toxicity were observed in the PCS treated mice (7.5, 15, and 20g/kg body weight), the body weight and food consumption were not significantly changed compared with the normal control group. The relative weights of main organ, and biochemical indicators also did not markedly change. PCS can significantly prolong the duration of the swimming time to exhaustion in mice, decrease BUN, LA levels, increase LDH activities, and the contents of HG in the PCS treated mice. The dose of 400mg/kg body weight is the optimal dose for anti-fatigue activity both in male and female mice. In conclusion, PCS is a promising traditional natural-based therapeutic remedy for relieving fatigue with high safety. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Secula, Marius Sebastian; Cretescu, Igor; Cagnon, Benoit; Manea, Liliana Rozemarie; Stan, Corneliu Sergiu; Breaban, Iuliana Gabriela
2013-07-10
The aim of this study was to determine the effects of main factors and interactions on the color removal performance from dye solutions using the electrocoagulation process enhanced by adsorption on Granular Activated Carbon (GAC). In this study, a mathematical approach was conducted using a two-level fractional factorial design ( FFD ) for a given dye solution. Three textile dyes: Acid Blue 74, Basic Red 1, and Reactive Black 5 were used. Experimental factors used and their respective levels were: current density (2.73 or 27.32 A/m²), initial pH of aqueous dye solution (3 or 9), electrocoagulation time (20 or 180 min), GAC dose (0.1 or 0.5 g/L), support electrolyte (2 or 50 mM), initial dye concentration (0.05 or 0.25 g/L) and current type (Direct Current- DC or Alternative Pulsed Current- APC ). GAC-enhanced electrocoagulation performance was analyzed statistically in terms of removal efficiency, electrical energy, and electrode material consumptions, using modeling polynomial equations. The statistical significance of GAC dose level on the performance of GAC enhanced electrocoagulation and the experimental conditions that favor the process operation of electrocoagulation in APC regime were determined. The local optimal experimental conditions were established using a multi-objective desirability function method.
Secula, Marius Sebastian; Cretescu, Igor; Cagnon, Benoit; Manea, Liliana Rozemarie; Stan, Corneliu Sergiu; Breaban, Iuliana Gabriela
2013-01-01
The aim of this study was to determine the effects of main factors and interactions on the color removal performance from dye solutions using the electrocoagulation process enhanced by adsorption on Granular Activated Carbon (GAC). In this study, a mathematical approach was conducted using a two-level fractional factorial design (FFD) for a given dye solution. Three textile dyes: Acid Blue 74, Basic Red 1, and Reactive Black 5 were used. Experimental factors used and their respective levels were: current density (2.73 or 27.32 A/m2), initial pH of aqueous dye solution (3 or 9), electrocoagulation time (20 or 180 min), GAC dose (0.1 or 0.5 g/L), support electrolyte (2 or 50 mM), initial dye concentration (0.05 or 0.25 g/L) and current type (Direct Current—DC or Alternative Pulsed Current—APC). GAC-enhanced electrocoagulation performance was analyzed statistically in terms of removal efficiency, electrical energy, and electrode material consumptions, using modeling polynomial equations. The statistical significance of GAC dose level on the performance of GAC enhanced electrocoagulation and the experimental conditions that favor the process operation of electrocoagulation in APC regime were determined. The local optimal experimental conditions were established using a multi-objective desirability function method. PMID:28811405
Sustainable Mobility Initiative | Transportation Research | NREL
optimize mobility and significantly reduce related energy consumption. This concept of an intelligent measures to explore these technologies' effects on transportation energy use, emissions, and overall system . Efficient driving with smoother starts, stops, and accelerations to reduce energy consumption and
Atcheson, Margaret E.; Myers, Katherine W.; Beauchamp, David A.; Mantua, Nathan J.
2012-01-01
Energetic responses of steelhead Oncorhynchus mykiss to climate-driven changes in marine conditions are expected to affect the species’ ocean distribution, feeding, growth, and survival. With a unique 18-year data series (1991–2008) for steelhead sampled in the open ocean, we simulated interannual variation in prey consumption and growth efficiency of steelhead using a bioenergetics model to evaluate the temperature-dependent growth response of steelhead to past climate events and to estimate growth potential of steelhead under future climate scenarios. Our results showed that annual ocean growth of steelhead is highly variable depending on prey quality, consumption rates, total consumption, and thermal experience. At optimal growing temperatures, steelhead can compensate for a low-energy diet by increasing consumption rates and consuming more prey, if available. Our findings suggest that steelhead have a narrow temperature window in which to achieve optimal growth, which is strongly influenced by climate-driven changes in ocean temperature.
USDA-ARS?s Scientific Manuscript database
Two different dosages of ivermectin were used to medicate a liquid molasses feed supplement for free-choice consumption by cattle. Calves that fed on supplement medicated at 25 ppm with ivermectin had a 14 day mean consumption of 0.62 ± 0.07 kg supplement/animal/day producing an average dose of 15....
Effect of black tea consumption on radial blood pulse spectrum and cognitive health.
Chang, Chi-Wei; Wang, Sheng-Hung; Jan, Ming-Yie; Wang, Wei-Kung
2017-04-01
Black tea consumption has been proven to improve endothelial function and to lower the risk of stroke and cognitive impairment. Several effects of black tea on cardiovascular system had been surveyed. However, the black tea effect on pressure pulse spectrum remains unknown. The study was aimed to investigate the influence of black tea on radial blood pressure and Pulse Spectrum. Fourteen healthy subjects received water and single doses of black tea (0.05g/Kg) in separate weeks. The radial blood pressure and pulse wave were measured and the pressure pulses were evaluated using harmonic analysis. This report confirmed that black tea consumption (dose=0.05g/Kg) significantly increased third, fifth, (P<0.1), sixth, seventh, and eighth harmonics (p<0.05) of radial pressure wave comparing to water control. We proposed that black tea may increase cerebral blood flow (CBF), which was deduced from the results and from the conclusions of previous studies. The results also showed that the harmonic components of pressure pulse could be the vascular kinetic index that assessed the hemodynamic status in each time frame before and after consumption of black tea. Copyright © 2017 Elsevier Ltd. All rights reserved.
Quantitative risk assessment of E. coli in street-vended cassava-based delicacies in the Philippines
NASA Astrophysics Data System (ADS)
Mesias, I. C. P.
2018-01-01
In the Philippines, rootcrop-based food products are gaining popularity in street food trade. However, a number of street-vended food products in the country are reported to be contaminated with E. coli posing possible risk among consumers. In this study, information on quantitative risk assessment of E. coli in street-vended cassava-based delicacies was generated. The assessment started with the prevalence and concentration of E. coli at post production in packages of the cassava-based delicacies. Combase growth predictor was used to trace the microbial population of E. coli in each step of the food chain. The @Risk software package, version 6 (Palisade USA) was used to run the simulations. Scenarios in the post-production to consumption pathway were simulated. The effect was then assessed in relation to exposure to the defined infective dose. In the worst case scenario, a minimum and most likely concentration of 6.3 and 7.8 log CFU of E. coli per serving respectively were observed. The simulation revealed that lowering the temperature in the chain considerably decreased the E. coli concentration prior to consumption and subsequently decreased the percentage of exposure to the infective dose. Exposure to infective dose however was increased with longer lag time from postproduction to consumption.
Determination of MLC model parameters for Monaco using commercial diode arrays.
Kinsella, Paul; Shields, Laura; McCavana, Patrick; McClean, Brendan; Langan, Brian
2016-07-08
Multileaf collimators (MLCs) need to be characterized accurately in treatment planning systems to facilitate accurate intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT). The aim of this study was to examine the use of MapCHECK 2 and ArcCHECK diode arrays for optimizing MLC parameters in Monaco X-ray voxel Monte Carlo (XVMC) dose calculation algorithm. A series of radiation test beams designed to evaluate MLC model parameters were delivered to MapCHECK 2, ArcCHECK, and EBT3 Gafchromic film for comparison. Initial comparison of the calculated and ArcCHECK-measured dose distributions revealed it was unclear how to change the MLC parameters to gain agreement. This ambiguity arose due to an insufficient sampling of the test field dose distributions and unexpected discrepancies in the open parts of some test fields. Consequently, the XVMC MLC parameters were optimized based on MapCHECK 2 measurements. Gafchromic EBT3 film was used to verify the accuracy of MapCHECK 2 measured dose distributions. It was found that adjustment of the MLC parameters from their default values resulted in improved global gamma analysis pass rates for MapCHECK 2 measurements versus calculated dose. The lowest pass rate of any MLC-modulated test beam improved from 68.5% to 93.5% with 3% and 2 mm gamma criteria. Given the close agreement of the optimized model to both MapCHECK 2 and film, the optimized model was used as a benchmark to highlight the relatively large discrepancies in some of the test field dose distributions found with ArcCHECK. Comparison between the optimized model-calculated dose and ArcCHECK-measured dose resulted in global gamma pass rates which ranged from 70.0%-97.9% for gamma criteria of 3% and 2 mm. The simple square fields yielded high pass rates. The lower gamma pass rates were attributed to the ArcCHECK overestimating the dose in-field for the rectangular test fields whose long axis was parallel to the long axis of the ArcCHECK. Considering ArcCHECK measurement issues and the lower gamma pass rates for the MLC-modulated test beams, it was concluded that MapCHECK 2 was a more suitable detector than ArcCHECK for the optimization process. © 2016 The Authors
An Energy-Efficient Mobile Sink-Based Unequal Clustering Mechanism for WSNs.
Gharaei, Niayesh; Abu Bakar, Kamalrulnizam; Mohd Hashim, Siti Zaiton; Hosseingholi Pourasl, Ali; Siraj, Mohammad; Darwish, Tasneem
2017-08-11
Network lifetime and energy efficiency are crucial performance metrics used to evaluate wireless sensor networks (WSNs). Decreasing and balancing the energy consumption of nodes can be employed to increase network lifetime. In cluster-based WSNs, one objective of applying clustering is to decrease the energy consumption of the network. In fact, the clustering technique will be considered effective if the energy consumed by sensor nodes decreases after applying clustering, however, this aim will not be achieved if the cluster size is not properly chosen. Therefore, in this paper, the energy consumption of nodes, before clustering, is considered to determine the optimal cluster size. A two-stage Genetic Algorithm (GA) is employed to determine the optimal interval of cluster size and derive the exact value from the interval. Furthermore, the energy hole is an inherent problem which leads to a remarkable decrease in the network's lifespan. This problem stems from the asynchronous energy depletion of nodes located in different layers of the network. For this reason, we propose Circular Motion of Mobile-Sink with Varied Velocity Algorithm (CM2SV2) to balance the energy consumption ratio of cluster heads (CH). According to the results, these strategies could largely increase the network's lifetime by decreasing the energy consumption of sensors and balancing the energy consumption among CHs.
NASA Astrophysics Data System (ADS)
Wang, Jianhua; Cheng, Lianglun; Wang, Tao; Peng, Xiaodong
2016-03-01
Table look-up operation plays a very important role during the decoding processing of context-based adaptive variable length decoding (CAVLD) in H.264/advanced video coding (AVC). However, frequent table look-up operation can result in big table memory access, and then lead to high table power consumption. Aiming to solve the problem of big table memory access of current methods, and then reduce high power consumption, a memory-efficient table look-up optimized algorithm is presented for CAVLD. The contribution of this paper lies that index search technology is introduced to reduce big memory access for table look-up, and then reduce high table power consumption. Specifically, in our schemes, we use index search technology to reduce memory access by reducing the searching and matching operations for code_word on the basis of taking advantage of the internal relationship among length of zero in code_prefix, value of code_suffix and code_lengh, thus saving the power consumption of table look-up. The experimental results show that our proposed table look-up algorithm based on index search can lower about 60% memory access consumption compared with table look-up by sequential search scheme, and then save much power consumption for CAVLD in H.264/AVC.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Liu, W; Shen, J; Stoker, J
2015-06-15
Purpose: To compare the impact of interplay effect on 3D and 4D robustly optimized intensity-modulated proton therapy (IMPT) plans to treat lung cancer. Methods: Two IMPT plans were created for 11 non-small-cell-lung-cancer cases with 6–14 mm spots. 3D robust optimization generated plans on average CTs with the internal gross tumor volume density overridden to deliver 66 CGyE in 33 fractions to the internal target volume (ITV). 4D robust optimization generated plans on 4D CTs with the delivery of prescribed dose to the clinical target volume (CTV). In 4D optimization, the CTV of individual 4D CT phases received non-uniform doses tomore » achieve a uniform cumulative dose. Dose evaluation software was developed to model time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Patient anatomy voxels were mapped from phase to phase via deformable image registration to score doses. Indices from dose-volume histograms were used to compare target coverage, dose homogeneity, and normal-tissue sparing. DVH indices were compared using Wilcoxon test. Results: Given the presence of interplay effect, 4D robust optimization produced IMPT plans with better target coverage and homogeneity, but slightly worse normal tissue sparing compared to 3D robust optimization (unit: Gy) [D95% ITV: 63.5 vs 62.0 (p=0.014), D5% - D95% ITV: 6.2 vs 7.3 (p=0.37), D1% spinal cord: 29.0 vs 29.5 (p=0.52), Dmean total lung: 14.8 vs 14.5 (p=0.12), D33% esophagus: 33.6 vs 33.1 (p=0.28)]. The improvement of target coverage (D95%,4D – D95%,3D) was related to the ratio RMA3/(TVx10−4), with RMA and TV being respiratory motion amplitude (RMA) and tumor volume (TV), respectively. Peak benefit was observed at ratios between 2 and 10. This corresponds to 125 – 625 cm3 TV with 0.5-cm RMA. Conclusion: 4D optimization produced more interplay-effect-resistant plans compared to 3D optimization. It is most effective when respiratory motion is modest compared to TV. NIH/NCI K25CA168984; Eagles Cancer Research Career Development; The Lawrence W. and Marilyn W. Matteson Fund for Cancer Research; Mayo ASU Seed Grant; The Kemper Marley Foundation.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
McCowan, P. M., E-mail: pmccowan@cancercare.mb.ca; McCurdy, B. M. C.; Medical Physics Department, CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, Manitoba R3E 0V9
Purpose: The in vivo 3D dose delivered to a patient during volumetric modulated arc therapy (VMAT) delivery can be calculated using electronic portal imaging device (EPID) images. These images must be acquired in cine-mode (i.e., “movie” mode) in order to capture the time-dependent delivery information. The angle subtended by each cine-mode EPID image during an arc can be changed via the frame averaging number selected within the image acquisition software. A large frame average number will decrease the EPID’s angular resolution and will result in a decrease in the accuracy of the dose information contained within each image. Alternatively, lessmore » EPID images acquired per delivery will decrease the overall 3D patient dose calculation time, which is appealing for large-scale clinical implementation. Therefore, the purpose of this study was to determine the optimal frame average value per EPID image, defined as the highest frame averaging that can be used without an appreciable loss in 3D dose reconstruction accuracy for VMAT treatments. Methods: Six different VMAT plans and six different SBRT-VMAT plans were delivered to an anthropomorphic phantom. Delivery was carried out on a Varian 2300ix model linear accelerator (Linac) equipped with an aS1000 EPID running at a frame acquisition rate of 7.5 Hz. An additional PC was set up at the Linac console area, equipped with specialized frame-grabber hardware and software packages allowing continuous acquisition of all EPID frames during delivery. Frames were averaged into “frame-averaged” EPID images using MATLAB. Each frame-averaged data set was used to calculate the in vivo dose to the patient and then compared to the single EPID frame in vivo dose calculation (the single frame calculation represents the highest possible angular resolution per EPID image). A mean percentage dose difference of low dose (<20% prescription dose) and high dose regions (>80% prescription dose) was calculated for each frame averaged scenario for each plan. The authors defined their unacceptable loss of accuracy as no more than a ±1% mean dose difference in the high dose region. Optimal frame average numbers were then determined as a function of the Linac’s average gantry speed and the dose per fraction. Results: The authors found that 9 and 11 frame averages were suitable for all VMAT and SBRT-VMAT treatments, respectively. This resulted in no more than a 1% loss to any of the dose region’s mean percentage difference when compared to the single frame reconstruction. The optimized number was dependent on the treatment’s dose per fraction and was determined to be as high as 14 for 12 Gy/fraction (fx), 15 for 8 Gy/fx, 11 for 6 Gy/fx, and 9 for 2 Gy/fx. Conclusions: The authors have determined an optimal EPID frame averaging number for multiple VMAT-type treatments. These are given as a function of the dose per fraction and average gantry speed. These optimized values are now used in the authors’ clinical, 3D, in vivo patient dosimetry program. This provides a reduction in calculation time while maintaining the authors’ required level of accuracy in the dose reconstruction.« less
Analysis of oil consumption in cylinder of diesel engine for optimization of piston rings
NASA Astrophysics Data System (ADS)
Zhang, Junhong; Zhang, Guichang; He, Zhenpeng; Lin, Jiewei; Liu, Hai
2013-01-01
The performance and particulate emission of a diesel engine are affected by the consumption of lubricating oil. Most studies on oil consumption mechanism of the cylinder have been done by using the experimental method, however they are very costly. Therefore, it is very necessary to study oil consumption mechanism of the cylinder and obtain the accurate results by the calculation method. Firstly, four main modes of lubricating oil consumption in cylinder are analyzed and then the oil consumption rate under common working conditions are calculated for the four modes based on an engine. Then, the factors that affect the lubricating oil consumption such as working conditions, the second ring closed gap, the elastic force of the piston rings are also investigated for the four modes. The calculation results show that most of the lubricating oil is consumed by evaporation on the liner surface. Besides, there are three other findings: (1) The oil evaporation from the liner is determined by the working condition of an engine; (2) The increase of the ring closed gap reduces the oil blow through the top ring end gap but increases blow-by; (3) With the increase of the elastic force of the ring, both the left oil film thickness and the oil throw-off at the top ring decrease. The oil scraping of the piston top edge is consequently reduced while the friction loss between the rings and the liner increases. A neural network prediction model of the lubricating oil consumption in cylinder is established based on the BP neural network theory, and then the model is trained and validated. The main piston rings parameters which affect the oil consumption are optimized by using the BP neural network prediction model and the prediction accuracy of this BP neural network is within 8%, which is acceptable for normal engineering applications. The oil consumption is also measured experimentally. The relative errors of the calculated and experimental values are less than 10%, verifying the validity of the simulation results. Applying the established simulation model and the validated BP network model is able to generate numerical results with sufficient accuracy, which significantly reduces experimental work and provides guidance for the optimal design of the piston rings diesel engines.
Cao, Wenhua; Lim, Gino; Li, Xiaoqiang; Li, Yupeng; Zhu, X. Ronald; Zhang, Xiaodong
2014-01-01
The purpose of this study is to investigate the feasibility and impact of incorporating deliverable monitor unit (MU) constraints into spot intensity optimization in intensity modulated proton therapy (IMPT) treatment planning. The current treatment planning system (TPS) for IMPT disregards deliverable MU constraints in the spot intensity optimization (SIO) routine. It performs a post-processing procedure on an optimized plan to enforce deliverable MU values that are required by the spot scanning proton delivery system. This procedure can create a significant dose distribution deviation between the optimized and post-processed deliverable plans, especially when small spot spacings are used. In this study, we introduce a two-stage linear programming (LP) approach to optimize spot intensities and constrain deliverable MU values simultaneously, i.e., a deliverable spot intensity optimization (DSIO) model. Thus, the post-processing procedure is eliminated and the associated optimized plan deterioration can be avoided. Four prostate cancer cases at our institution were selected for study and two parallel opposed beam angles were planned for all cases. A quadratic programming (QP) based model without MU constraints, i.e., a conventional spot intensity optimization (CSIO) model, was also implemented to emulate the commercial TPS. Plans optimized by both the DSIO and CSIO models were evaluated for five different settings of spot spacing from 3 mm to 7 mm. For all spot spacings, the DSIO-optimized plans yielded better uniformity for the target dose coverage and critical structure sparing than did the CSIO-optimized plans. With reduced spot spacings, more significant improvements in target dose uniformity and critical structure sparing were observed in the DSIO- than in the CSIO-optimized plans. Additionally, better sparing of the rectum and bladder was achieved when reduced spacings were used for the DSIO-optimized plans. The proposed DSIO approach ensures the deliverability of optimized IMPT plans that take into account MU constraints. This eliminates the post-processing procedure required by the TPS as well as the resultant deteriorating effect on ultimate dose distributions. This approach therefore allows IMPT plans to adopt all possible spot spacings optimally. Moreover, dosimetric benefits can be achieved using smaller spot spacings. PMID:23835656
Inverse planning in the age of digital LINACs: station parameter optimized radiation therapy (SPORT)
NASA Astrophysics Data System (ADS)
Xing, Lei; Li, Ruijiang
2014-03-01
The last few years have seen a number of technical and clinical advances which give rise to a need for innovations in dose optimization and delivery strategies. Technically, a new generation of digital linac has become available which offers features such as programmable motion between station parameters and high dose-rate Flattening Filter Free (FFF) beams. Current inverse planning methods are designed for traditional machines and cannot accommodate these features of new generation linacs without compromising either dose conformality and/or delivery efficiency. Furthermore, SBRT is becoming increasingly important, which elevates the need for more efficient delivery, improved dose distribution. Here we will give an overview of our recent work in SPORT designed to harness the digital linacs and highlight the essential components of SPORT. We will summarize the pros and cons of traditional beamlet-based optimization (BBO) and direct aperture optimization (DAO) and introduce a new type of algorithm, compressed sensing (CS)-based inverse planning, that is capable of automatically removing the redundant segments during optimization and providing a plan with high deliverability in the presence of a large number of station control points (potentially non-coplanar, non-isocentric, and even multi-isocenters). We show that CS-approach takes the interplay between planning and delivery into account and allows us to balance the dose optimality and delivery efficiency in a controlled way and, providing a viable framework to address various unmet demands of the new generation linacs. A few specific implementation strategies of SPORT in the forms of fixed-gantry and rotational arc delivery are also presented.
Research on Ratio of Dosage of Drugs in Traditional Chinese Prescriptions by Data Mining.
Yu, Xing-Wen; Gong, Qing-Yue; Hu, Kong-Fa; Mao, Wen-Jing; Zhang, Wei-Ming
2017-01-01
Maximizing the effectiveness of prescriptions and minimizing adverse effects of drugs is a key component of the health care of patients. In the practice of traditional Chinese medicine (TCM), it is important to provide clinicians a reference for dosing of prescribed drugs. The traditional Cheng-Church biclustering algorithm (CC) is optimized and the data of TCM prescription dose is analyzed by using the optimization algorithm. Based on an analysis of 212 prescriptions related to TCM treatment of kidney diseases, the study generated 87 prescription dose quantum matrices and each sub-matrix represents the referential value of the doses of drugs in different recipes. The optimized CC algorithm can effectively eliminate the interference of zero in the original dose matrix of TCM prescriptions and avoid zero appearing in output sub-matrix. This results in the ability to effectively analyze the reference value of drugs in different prescriptions related to kidney diseases, so as to provide valuable reference for clinicians to use drugs rationally.
Dosimetric comparison between VMAT and RC3D techniques: case of prostate treatment
NASA Astrophysics Data System (ADS)
Chemingui, Fatima Zohra; Benrachi, Fatima; Bali, Mohamed Saleh; Ladjal, Hamid
2017-09-01
Considered as the second men cancer in Algeria, prostate cancer is treated in 70% by radiation. That's why radiation therapy is therapeutic weapon for prostate cancer. Conformational Radiotherapy in 3D is the most common technique [1-5]. The use of conventionally optimized treatment plans was compared at case scenario of optimized treatment plans VMAT for prostate cancer. The evaluation of the two optimizations strategies focused on the resulting plans ability to retain dose objectives under the influence of patient set up. Dose Volume Histogram in the Planning Target Volume and dose in the Organs At Risks were used to calculate the conformity index, and evaluation ratio of irradiated volume which represent the main tool of comparison [6,7]. The situation was analysed systematically. The 14% dose increase in the target leads to a decrease in the dose in adjacent organs with 39% in the bladder. Therefore, the criterion for better efficacy and less toxicity reveal that VMAT is the best choice.
Ishizawa, Yoshiki; Dobashi, Suguru; Kadoya, Noriyuki; Ito, Kengo; Chiba, Takahito; Takayama, Yoshiki; Sato, Kiyokazu; Takeda, Ken
2018-05-17
An accurate source model of a medical linear accelerator is essential for Monte Carlo (MC) dose calculations. This study aims to propose an analytical photon source model based on particle transport in parameterized accelerator structures, focusing on a more realistic determination of linac photon spectra compared to existing approaches. We designed the primary and secondary photon sources based on the photons attenuated and scattered by a parameterized flattening filter. The primary photons were derived by attenuating bremsstrahlung photons based on the path length in the filter. Conversely, the secondary photons were derived from the decrement of the primary photons in the attenuation process. This design facilitates these sources to share the free parameters of the filter shape and be related to each other through the photon interaction in the filter. We introduced two other parameters of the primary photon source to describe the particle fluence in penumbral regions. All the parameters are optimized based on calculated dose curves in water using the pencil-beam-based algorithm. To verify the modeling accuracy, we compared the proposed model with the phase space data (PSD) of the Varian TrueBeam 6 and 15 MV accelerators in terms of the beam characteristics and the dose distributions. The EGS5 Monte Carlo code was used to calculate the dose distributions associated with the optimized model and reference PSD in a homogeneous water phantom and a heterogeneous lung phantom. We calculated the percentage of points passing 1D and 2D gamma analysis with 1%/1 mm criteria for the dose curves and lateral dose distributions, respectively. The optimized model accurately reproduced the spectral curves of the reference PSD both on- and off-axis. The depth dose and lateral dose profiles of the optimized model also showed good agreement with those of the reference PSD. The passing rates of the 1D gamma analysis with 1%/1 mm criteria between the model and PSD were 100% for 4 × 4, 10 × 10, and 20 × 20 cm 2 fields at multiple depths. For the 2D dose distributions calculated in the heterogeneous lung phantom, the 2D gamma pass rate was 100% for 6 and 15 MV beams. The model optimization time was less than 4 min. The proposed source model optimization process accurately produces photon fluence spectra from a linac using valid physical properties, without detailed knowledge of the geometry of the linac head, and with minimal optimization time. © 2018 American Association of Physicists in Medicine.
Optimization of Price and Quality in Service Systems,
Price and service quality are important variables in the design of optimal service systems. Price is important because of the strong consumption...priorities of service offered. The paper takes a systematic view of this problem, and presents techniques for quantitative determination of the optimal prices and service quality in a wide class of systems. (Author)
Portfolio Optimization with Stochastic Dividends and Stochastic Volatility
ERIC Educational Resources Information Center
Varga, Katherine Yvonne
2015-01-01
We consider an optimal investment-consumption portfolio optimization model in which an investor receives stochastic dividends. As a first problem, we allow the drift of stock price to be a bounded function. Next, we consider a stochastic volatility model. In each problem, we use the dynamic programming method to derive the Hamilton-Jacobi-Bellman…
Zhang, Weizhe; Bai, Enci; He, Hui; Cheng, Albert M.K.
2015-01-01
Reducing energy consumption is becoming very important in order to keep battery life and lower overall operational costs for heterogeneous real-time multiprocessor systems. In this paper, we first formulate this as a combinatorial optimization problem. Then, a successful meta-heuristic, called Shuffled Frog Leaping Algorithm (SFLA) is proposed to reduce the energy consumption. Precocity remission and local optimal avoidance techniques are proposed to avoid the precocity and improve the solution quality. Convergence acceleration significantly reduces the search time. Experimental results show that the SFLA-based energy-aware meta-heuristic uses 30% less energy than the Ant Colony Optimization (ACO) algorithm, and 60% less energy than the Genetic Algorithm (GA) algorithm. Remarkably, the running time of the SFLA-based meta-heuristic is 20 and 200 times less than ACO and GA, respectively, for finding the optimal solution. PMID:26110406
Multi Dimensional Honey Bee Foraging Algorithm Based on Optimal Energy Consumption
NASA Astrophysics Data System (ADS)
Saritha, R.; Vinod Chandra, S. S.
2017-10-01
In this paper a new nature inspired algorithm is proposed based on natural foraging behavior of multi-dimensional honey bee colonies. This method handles issues that arise when food is shared from multiple sources by multiple swarms at multiple destinations. The self organizing nature of natural honey bee swarms in multiple colonies is based on the principle of energy consumption. Swarms of multiple colonies select a food source to optimally fulfill the requirements of its colonies. This is based on the energy requirement for transporting food between a source and destination. Minimum use of energy leads to maximizing profit in each colony. The mathematical model proposed here is based on this principle. This has been successfully evaluated by applying it on multi-objective transportation problem for optimizing cost and time. The algorithm optimizes the needs at each destination in linear time.
Zhimeng, Li; Chuan, He; Dishan, Qiu; Jin, Liu; Manhao, Ma
2013-01-01
Aiming to the imaging tasks scheduling problem on high-altitude airship in emergency condition, the programming models are constructed by analyzing the main constraints, which take the maximum task benefit and the minimum energy consumption as two optimization objectives. Firstly, the hierarchy architecture is adopted to convert this scheduling problem into three subproblems, that is, the task ranking, value task detecting, and energy conservation optimization. Then, the algorithms are designed for the sub-problems, and the solving results are corresponding to feasible solution, efficient solution, and optimization solution of original problem, respectively. This paper makes detailed introduction to the energy-aware optimization strategy, which can rationally adjust airship's cruising speed based on the distribution of task's deadline, so as to decrease the total energy consumption caused by cruising activities. Finally, the application results and comparison analysis show that the proposed strategy and algorithm are effective and feasible. PMID:23864822
Optimal Control of Connected and Automated Vehicles at Roundabouts
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhao, Liuhui; Malikopoulos, Andreas; Rios-Torres, Jackeline
Connectivity and automation in vehicles provide the most intriguing opportunity for enabling users to better monitor transportation network conditions and make better operating decisions to improve safety and reduce pollution, energy consumption, and travel delays. This study investigates the implications of optimally coordinating vehicles that are wirelessly connected to each other and to an infrastructure in roundabouts to achieve a smooth traffic flow without stop-and-go driving. We apply an optimization framework and an analytical solution that allows optimal coordination of vehicles for merging in such traffic scenario. The effectiveness of the efficiency of the proposed approach is validated through simulationmore » and it is shown that coordination of vehicles can reduce total travel time by 3~49% and fuel consumption by 2~27% with respect to different traffic levels. In addition, network throughput is improved by up to 25% due to elimination of stop-and-go driving behavior.« less
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
Lim, Hyeong-Seok; Kim, Su Jin; Noh, Yook-Hwan; Lee, Byung Chul; Jin, Seok-Joon; Park, Hyun Soo; Kim, Soohyeon; Jang, In-Jin; Kim, Sang Eun
2013-03-01
To evaluate the potential usage of D(2) receptor occupancy (D2RO) measured by positron emission tomography (PET) in antipsychotic development. In this randomized, parallel group study, eight healthy male volunteers received oral doses of 0.5 (n = 3), 1 (n = 2), or 3 mg (n = 3) of haloperidol once daily for 7 days. PET's were scanned before haloperidol, and on days 8, 12, with serial pharmacokinetic sampling on day 7. Pharmacokinetics and binding potential to D(2) receptor in putamen and caudate nucleus over time were analyzed using NONMEM, and simulations for the profiles of D2RO over time on various regimens of haloperidol were conducted to find the optimal dosing regimens. One compartment model with a saturable binding compartment, and inhibitory E(max) model in the effect compartment best described the data. Plasma haloperidol concentrations at half-maximal inhibition were 0.791 and 0.650 ng/ml, in putamen and caudate nucleus. Simulation suggested haloperidol 2 mg every 12 h is near the optimal dose. This study showed that sparse D2RO measurements in steady state pharmacodynamic design after multiple dosing could reveal the possibility of treatment effect of D(2) antagonist, and could identify the potential optimal doses for later clinical studies by modeling and simulation.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Unkelbach, J; Perko, Z; Wolfgang, J
Purpose: Stereotactic body radiotherapy (SBRT) has become an established treatment option for liver cancer. For patients with large tumors, the prescription dose is often limited by constraints on the mean liver dose, leading to tumor recurrence. In this work, we demonstrate that spatiotemporal fractionation schemes, ie delivering distinct dose distributions in different fractions, may allow for a 10% increase in biologically effective dose (BED) in the tumor compared to current practice where each fraction delivers the same dose distribution. Methods: We consider rotation therapy delivered with x-ray beams. Treatment plan optimization is performed using objective functions evaluated for the cumulativemore » BED delivered at the end of treatment. This allows for simultaneously optimizing multiple distinct treatment plans for different fractions. Results: The treatment that optimally exploits fractionation effects is designed such that each fraction delivers a similar dose bath to the uninvolved liver while delivering high single fraction doses to complementary parts of the target volume. Thereby, partial hypofractionation in the tumor is achieved along with near uniform fractionation in the surrounding liver - leading to an improvement in the therapeutic ratio. The benefit of such spatiotemporal fractionation schemes depends on tumor geometry and location as well as the number of fractions. For 5-fraction treatments (allowing for 5 distinct dose distributions) an improvement in the order of 10% is observed. Conclusion: Delivering distinct dose distributions in different fractions, purely motivated by fractionation effects rather than geometric changes, may improve the therapeutic ratio. For treatment sites where the prescriptions dose is limited by mean dose constraints in the surrounding organ, such as liver cancer, this approach may facilitate biological dose escalation and improved cure rates.« less
Magnuson, B A; Burdock, G A; Doull, J; Kroes, R M; Marsh, G M; Pariza, M W; Spencer, P S; Waddell, W J; Walker, R; Williams, G M
2007-01-01
Aspartame is a methyl ester of a dipeptide used as a synthetic nonnutritive sweetener in over 90 countries worldwide in over 6000 products. The purpose of this investigation was to review the scientific literature on the absorption and metabolism, the current consumption levels worldwide, the toxicology, and recent epidemiological studies on aspartame. Current use levels of aspartame, even by high users in special subgroups, remains well below the U.S. Food and Drug Administration and European Food Safety Authority established acceptable daily intake levels of 50 and 40 mg/kg bw/day, respectively. Consumption of large doses of aspartame in a single bolus dose will have an effect on some biochemical parameters, including plasma amino acid levels and brain neurotransmitter levels. The rise in plasma levels of phenylalanine and aspartic acid following administration of aspartame at doses less than or equal to 50 mg/kg bw do not exceed those observed postprandially. Acute, subacute and chronic toxicity studies with aspartame, and its decomposition products, conducted in mice, rats, hamsters and dogs have consistently found no adverse effect of aspartame with doses up to at least 4000 mg/kg bw/day. Critical review of all carcinogenicity studies conducted on aspartame found no credible evidence that aspartame is carcinogenic. The data from the extensive investigations into the possibility of neurotoxic effects of aspartame, in general, do not support the hypothesis that aspartame in the human diet will affect nervous system function, learning or behavior. Epidemiological studies on aspartame include several case-control studies and one well-conducted prospective epidemiological study with a large cohort, in which the consumption of aspartame was measured. The studies provide no evidence to support an association between aspartame and cancer in any tissue. The weight of existing evidence is that aspartame is safe at current levels of consumption as a nonnutritive sweetener.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lee, K; Leung, R; Law, G
Background: Commercial treatment planning system Pinnacle3 (Philips, Fitchburg, WI, USA) employs a convolution-superposition algorithm for volumetric-modulated arc radiotherapy (VMAT) optimization and dose calculation. Study of Monte Carlo (MC) dose recalculation of VMAT plans for advanced-stage nasopharyngeal cancers (NPC) is currently limited. Methods: Twenty-nine VMAT prescribed 70Gy, 60Gy, and 54Gy to the planning target volumes (PTVs) were included. These clinical plans achieved with a CS dose engine on Pinnacle3 v9.0 were recalculated by the Monaco TPS v5.0 (Elekta, Maryland Heights, MO, USA) with a XVMC-based MC dose engine. The MC virtual source model was built using the same measurement beam datasetmore » as for the Pinnacle beam model. All MC recalculation were based on absorbed dose to medium in medium (Dm,m). Differences in dose constraint parameters per our institution protocol (Supplementary Table 1) were analyzed. Results: Only differences in maximum dose to left brachial plexus, left temporal lobe and PTV54Gy were found to be statistically insignificant (p> 0.05). Dosimetric differences of other tumor targets and normal organs are found in supplementary Table 1. Generally, doses outside the PTV in the normal organs are lower with MC than with CS. This is also true in the PTV54-70Gy doses but higher dose in the nasal cavity near the bone interfaces is consistently predicted by MC, possibly due to the increased backscattering of short-range scattered photons and the secondary electrons that is not properly modeled by the CS. The straight shoulders of the PTV dose volume histograms (DVH) initially resulted from the CS optimization are merely preserved after MC recalculation. Conclusion: Significant dosimetric differences in VMAT NPC plans were observed between CS and MC calculations. Adjustments of the planning dose constraints to incorporate the physics differences from conventional CS algorithm should be made when VMAT optimization is carried out directly with MC dose engine.« less
Sargento, Luis; Simões, Andre Vicente; Longo, Susana; Lousada, Nuno; Reis, Roberto Palma Dos
2017-05-01
Furosemide is associated with poor prognosis in patients with heart failure and reduced ejection fraction (HFrEF). To evaluate the association between daily furosemide dose prescribed during the dry state and long-term survival in stable, optimally medicated outpatients with HFrEF. Two hundred sixty-six consecutive outpatients with left ventricular ejection fraction <40%, clinically stable in the dry state and on optimal heart failure therapy, were followed up for 3 years in a heart failure unit. The end point was all-cause death. There were no changes in New York Heart Association class and therapeutics, including diuretics, and no decompensation or hospitalization during 6 months. Furosemide doses were categorized as low or none (0-40 mg/d), intermediate (41-80 mg/d), and high (>80 mg). Cox regression was adjusted for significant confounders. The 3-year mortality rate was 33.8%. Mean dose of furosemide was 57.3 ± 21.4 mg/d. A total of 47.6% of patients received the low dose, 42.1% the intermediate dose, and 2.3% the high dose. Receiver operating characteristics for death associated with furosemide dose showed an area under the curve of 0.74 (95% confidence interval [CI]: 0.68-0.79; P < .001), and the best cutoff was >40 mg/d. An increasing daily dose of furosemide was associated with worse prognosis. Those receiving the intermediate dose (hazard ratio [HR] = 4.1; 95% CI: 2.57-6.64; P < .001) or high dose (HR = 19.8; 95% CI: 7.9-49.6; P < .001) had a higher risk of mortality compared to those receiving a low dose. Patients receiving >40 mg/d, in a propensity score-matched cohort, had a greater risk of mortality than those receiving a low dose (HR = 4.02; 95% CI: 1.8-8.8; P = .001) and those not receiving furosemide (HR = 3.9; 95% CI: 0.07-14.2; P = .039). Furosemide administration during the dry state in stable, optimally medicated outpatients with HFrEF is unfavorably associated with long-term survival. The threshold dose was 40 mg/d.
Coffee and tea: perks for health and longevity?
Bhatti, Salman K; O'Keefe, James H; Lavie, Carl J
2013-11-01
Tea and coffee, after water, are the most commonly consumed beverages in the world and are the top sources of caffeine and antioxidant polyphenols in the American diet. The purpose of this review is to assess the health effects of chronic tea and/or coffee consumption. Tea consumption, especially green tea, is associated with significantly reduced risks for stroke, diabetes and depression, and improved levels of glucose, cholesterol, abdominal obesity and blood pressure. Habitual coffee consumption in large epidemiological studies is associated with reduced mortality, both for all-cause and cardiovascular deaths. In addition, coffee intake is associated with risks of heart failure, stroke, diabetes mellitus and some cancers in an inverse dose-dependent fashion. Surprisingly, coffee is associated with neutral to reduced risks for both atrial and ventricular arrhythmias. However, caffeine at high doses can increase anxiety, insomnia, calcium loss and possibly the risk of fractures. Coffee and tea can generally be recommended as health-promoting additions to an adult diet. Adequate dietary calcium intake may be particularly important for tea and coffee drinkers.
Wu, Lei; Sun, Dali
2017-03-22
Previous systematic reviews and meta-analyses have evaluated the association of dairy consumption and the risk of cardiovascular disease (CVD). However, the findings were inconsistent. No quantitative analysis has specifically assessed the effect of yogurt intake on the incident risk of CVD. We searched the PubMed and the Embase databases from inception to 10 January 2017. A generic inverse-variance method was used to pool the fully-adjusted relative risks (RRs) and the corresponding 95% confidence intervals (CIs) with a random-effects model. A generalized least squares trend estimation model was used to calculate the specific slopes in the dose-response analysis. The present systematic review and meta-analysis identified nine prospective cohort articles involving a total of 291,236 participants. Compared with the lowest category, highest category of yogurt consumption was not significantly related with the incident risk of CVD, and the RR (95% CI) was 1.01 (0.95, 1.08) with an evidence of significant heterogeneity (I² = 52%). However, intake of ≥200 g/day yogurt was significantly associated with a lower risk of CVD in the subgroup analysis. There was a trend that a higher level of yogurt consumption was associated with a lower incident risk of CVD in the dose-response analysis. A daily dose of ≥200 g yogurt intake might be associated with a lower incident risk of CVD. Further cohort studies and randomized controlled trials are still demanded to establish and confirm the observed association in populations with different characteristics.
Wu, Lei; Sun, Dali
2017-01-01
Previous systematic reviews and meta-analyses have evaluated the association of dairy consumption and the risk of cardiovascular disease (CVD). However, the findings were inconsistent. No quantitative analysis has specifically assessed the effect of yogurt intake on the incident risk of CVD. We searched the PubMed and the Embase databases from inception to 10 January 2017. A generic inverse-variance method was used to pool the fully-adjusted relative risks (RRs) and the corresponding 95% confidence intervals (CIs) with a random-effects model. A generalized least squares trend estimation model was used to calculate the specific slopes in the dose-response analysis. The present systematic review and meta-analysis identified nine prospective cohort articles involving a total of 291,236 participants. Compared with the lowest category, highest category of yogurt consumption was not significantly related with the incident risk of CVD, and the RR (95% CI) was 1.01 (0.95, 1.08) with an evidence of significant heterogeneity (I2 = 52%). However, intake of ≥200 g/day yogurt was significantly associated with a lower risk of CVD in the subgroup analysis. There was a trend that a higher level of yogurt consumption was associated with a lower incident risk of CVD in the dose-response analysis. A daily dose of ≥200 g yogurt intake might be associated with a lower incident risk of CVD. Further cohort studies and randomized controlled trials are still demanded to establish and confirm the observed association in populations with different characteristics. PMID:28327514
Hu, Jiang; Webster, Donna; Cao, Joyce; Shao, Andrew
2018-06-01
A systematic review of published toxicology and human intervention studies was performed to characterize potential hazards associated with consumption of green tea and its preparations. A review of toxicological evidence from laboratory studies revealed the liver as the target organ and hepatotoxicity as the critical effect, which was strongly associated with certain dosing conditions (e.g. bolus dose via gavage, fasting), and positively correlated with total catechin and epigallocatechingallate (EGCG) content. A review of adverse event (AE) data from 159 human intervention studies yielded findings consistent with toxicological evidence in that a limited range of concentrated, catechin-rich green tea preparations resulted in hepatic AEs in a dose-dependent manner when ingested in large bolus doses, but not when consumed as brewed tea or extracts in beverages or as part of food. Toxico- and pharmacokinetic evidence further suggests internal dose of catechins is a key determinant in the occurrence and severity of hepatotoxicity. A safe intake level of 338 mg EGCG/day for adults was derived from toxicological and human safety data for tea preparations ingested as a solid bolus dose. An Observed Safe Level (OSL) of 704 mg EGCG/day might be considered for tea preparations in beverage form based on human AE data. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Schämann, M.; Bücker, M.; Hessel, S.; Langmann, U.
2008-05-01
High data rates combined with high mobility represent a challenge for the design of cellular devices. Advanced algorithms are required which result in higher complexity, more chip area and increased power consumption. However, this contrasts to the limited power supply of mobile devices. This presentation discusses the application of an HSDPA receiver which has been optimized regarding power consumption with the focus on the algorithmic and architectural level. On algorithmic level the Rake combiner, Prefilter-Rake equalizer and MMSE equalizer are compared regarding their BER performance. Both equalizer approaches provide a significant increase of performance for high data rates compared to the Rake combiner which is commonly used for lower data rates. For both equalizer approaches several adaptive algorithms are available which differ in complexity and convergence properties. To identify the algorithm which achieves the required performance with the lowest power consumption the algorithms have been investigated using SystemC models regarding their performance and arithmetic complexity. Additionally, for the Prefilter Rake equalizer the power estimations of a modified Griffith (LMS) and a Levinson (RLS) algorithm have been compared with the tool ORINOCO supplied by ChipVision. The accuracy of this tool has been verified with a scalable architecture of the UMTS channel estimation described both in SystemC and VHDL targeting a 130 nm CMOS standard cell library. An architecture combining all three approaches combined with an adaptive control unit is presented. The control unit monitors the current condition of the propagation channel and adjusts parameters for the receiver like filter size and oversampling ratio to minimize the power consumption while maintaining the required performance. The optimization strategies result in a reduction of the number of arithmetic operations up to 70% for single components which leads to an estimated power reduction of up to 40% while the BER performance is not affected. This work utilizes SystemC and ORINOCO for the first estimation of power consumption in an early step of the design flow. Thereby algorithms can be compared in different operating modes including the effects of control units. Here an algorithm having higher peak complexity and power consumption but providing more flexibility showed less consumption for normal operating modes compared to the algorithm which is optimized for peak performance.
Lavigne, J-P; Bourg, G; Combescure, C; Botto, H; Sotto, A
2008-04-01
This study evaluated the antibacterial efficacy of the consumption of cranberry capsules vs. placebo in the urine of healthy volunteers. A first double-blind, randomised, crossover trial involved eight volunteers who had followed three regimens, with or without cranberry, with a wash-out period of at least 6 days between each regimen. Twelve hours after consumption of cranberry or placebo hard capsules, the first urine of the morning was collected. Different Escherichia coli strains were cultured in the urine samples. Urinary antibacterial adhesion activity was measured in vitro using the human T24 epithelial cell-line, and in vivo using the Caenorhabditis elegans killing model. With the in-vitro model, 108 mg of cranberry induced a significant reduction in bacterial adherence to T24 cells as compared with placebo (p <0.001). A significant dose-dependent decrease in bacterial adherence in vitro was noted after the consumption of 108 and 36 mg of cranberry (p <0.001). The in-vivo model confirmed that E. coli strains had a reduced ability to kill C. elegans after growth in the urine of patients who consumed cranberry capsules. Overall, these in-vivo and in-vitro studies suggested that consumption of cranberry juice represents an interesting new strategy to prevent recurrent urinary tract infection.
Lavigne, Jean-Philippe; Bourg, Gisèle; Combescure, Christophe; Botto, Henri; Sotto, Albert
2008-01-01
This study evaluated the antibacterial efficacy of the consumption of cranberry capsules vs. placebo in the urine of healthy volunteers. A first double-blind, randomised, crossover trial involved eight volunteers who had followed three regimens, with or without cranberry, with a wash-out period of at least 6 days between each regimen. Twelve hours after consumption of cranberry or placebo hard capsules, the first urine of the morning was collected. Different Escherichia coli strains were cultured in the urine samples. Urinary antibacterial adhesion activity was measured in vitro using the human T24 epithelial cell-line, and in vivo using the Caenorhabditis elegans killing model. With the in-vitro model, 108 mg of cranberry induced a significant reduction in bacterial adherence to T24 cells as compared with placebo (p <0.001). A significant dose-dependent decrease in bacterial adherence in vitro was noted after the consumption of 108 and 36 mg of cranberry (p <0.001). The in-vivo model confirmed that E. coli strains had a reduced ability to kill C. elegans after growth in the urine of patients who consumed cranberry capsules. Overall, these in-vivo and in-vitro studies suggested that consumption of cranberry juice represents an interesting new strategy to prevent recurrent urinary tract infection. PMID:18190583
Brantly, Alexandra M.; Drobonick, Alexandra L.; King, Hannah T.; Mesta, Daniel C.; Richards, Caroline G.; Lal, Manjari; Lai, Manshun
2018-01-01
Negative hedonic sensory qualities of HIV antiretroviral drugs often reduce patient adherence particularly in pediatric populations requiring oral consumption. This study examines the palatability of an innovative delivery mechanism utilizing a freeze-drying-in-blister approach to create fast-dissolving tablets (FDTs) containing a fixed-dose combination of lopinavir and ritonavir (LPV/r). Consumption patterns of solutions during brief-access and long-term testing and baby foodstuff consumption were analyzed to evaluate the orosensory detection and avoidance of placebo FDTs containing no LPV/r (FDT−) and FDTs containing LPV/r (FDT+). Rats showed no change in consumption patterns for the placebo FDT− compared with control solutions. Rats can detect but do not avoid FDT+ at body-weight-adjusted dosages in both brief-access (30-s) and long-term (23 h) consumption tests. There is an aversive response to concentrated doses of FDT+ during brief-access tests that cannot be masked by 25% sucrose. However, the strongest FDT+ concentration was not rejected when mixed with 50 g of applesauce, banana sauce, or rice cereal baby foodstuffs. The averseness of the FDT+ was associated with the presence of LPV/r and not the FDT− formulation itself. The novel FDT formulation appears to be a palatable delivery mechanism for oral antiretroviral pharmaceuticals especially when mixed with baby foodstuffs. PMID:29593900
Pittman, David W; Brantly, Alexandra M; Drobonick, Alexandra L; King, Hannah T; Mesta, Daniel C; Richards, Caroline G; Lal, Manjari; Lai, Manshun
2018-01-01
Negative hedonic sensory qualities of HIV antiretroviral drugs often reduce patient adherence particularly in pediatric populations requiring oral consumption. This study examines the palatability of an innovative delivery mechanism utilizing a freeze-drying-in-blister approach to create fast-dissolving tablets (FDTs) containing a fixed-dose combination of lopinavir and ritonavir (LPV/r). Consumption patterns of solutions during brief-access and long-term testing and baby foodstuff consumption were analyzed to evaluate the orosensory detection and avoidance of placebo FDTs containing no LPV/r (FDT-) and FDTs containing LPV/r (FDT+). Rats showed no change in consumption patterns for the placebo FDT- compared with control solutions. Rats can detect but do not avoid FDT+ at body-weight-adjusted dosages in both brief-access (30-s) and long-term (23 h) consumption tests. There is an aversive response to concentrated doses of FDT+ during brief-access tests that cannot be masked by 25% sucrose. However, the strongest FDT+ concentration was not rejected when mixed with 50 g of applesauce, banana sauce, or rice cereal baby foodstuffs. The averseness of the FDT+ was associated with the presence of LPV/r and not the FDT- formulation itself. The novel FDT formulation appears to be a palatable delivery mechanism for oral antiretroviral pharmaceuticals especially when mixed with baby foodstuffs.
Does high antibiotic consumption still reflect bad practices?
Levent, T; Delfosse, F; Lambiotte, F; Dezorzi, S; Gosteau, L; Vasseur, M
2012-07-01
The authors had for aim to assess the quality of antibiotic prescription in an intensive care unit because of their high rate of consumption. A prospective 5-month study was made of the first 50 prescriptions of ciprofloxacin, levofloxacin, teicoplanin, vancomycin, and imipenem. Treatment was considered adequate at day 5 if the indication was relevant, with the right doses, and if the prescription was adapted to the antibiogram. Fifty treatments were evaluated (38 patients included). Eighty-four percent (42/50) was adequate at day 5. Glycopeptides and fluoroquinolones accounted for 2/3 of prescriptions. The absence of de-escalation was the most common mistake. The severity of presentations was evident with a mean SSI at 68 (22-113), and a mean BMI at 28 (18.5 - 50). Eighty-four percent (32/38) of patients were exposed to invasive devices, 47% died in the ICU. Most prescriptions were adequate. The patient profile could explain the high rate of antibiotic consumption. Bacteriological monitoring revealed an increased prevalence of resistant bacteria, which could explain a high rate of consumption along with adaptation of the dose to overweight. De-escalation, using aminosides more frequently, and shorter prescribed courses of fluoroquinolones should improve consumption rates does not always reflect bad practices, but may be adequate when considering bacterial ecology and patient profile. Copyright © 2012 Elsevier Masson SAS. All rights reserved.
NASA Astrophysics Data System (ADS)
Borot de Battisti, M.; Maenhout, M.; de Senneville, B. Denis; Hautvast, G.; Binnekamp, D.; Lagendijk, J. J. W.; van Vulpen, M.; Moerland, M. A.
2015-10-01
Focal high-dose-rate (HDR) for prostate cancer has gained increasing interest as an alternative to whole gland therapy as it may contribute to the reduction of treatment related toxicity. For focal treatment, optimal needle guidance and placement is warranted. This can be achieved under MR guidance. However, MR-guided needle placement is currently not possible due to space restrictions in the closed MR bore. To overcome this problem, a MR-compatible, single-divergent needle-implant robotic device is under development at the University Medical Centre, Utrecht: placed between the legs of the patient inside the MR bore, this robot will tap the needle in a divergent pattern from a single rotation point into the tissue. This rotation point is just beneath the perineal skin to have access to the focal prostate tumor lesion. Currently, there is no treatment planning system commercially available which allows optimization of the dose distribution with such needle arrangement. The aim of this work is to develop an automatic inverse dose planning optimization tool for focal HDR prostate brachytherapy with needle insertions in a divergent configuration. A complete optimizer workflow is proposed which includes the determination of (1) the position of the center of rotation, (2) the needle angulations and (3) the dwell times. Unlike most currently used optimizers, no prior selection or adjustment of input parameters such as minimum or maximum dose or weight coefficients for treatment region and organs at risk is required. To test this optimizer, a planning study was performed on ten patients (treatment volumes ranged from 8.5 cm3to 23.3 cm3) by using 2-14 needle insertions. The total computation time of the optimizer workflow was below 20 min and a clinically acceptable plan was reached on average using only four needle insertions.
Li, Yongbao; Tian, Zhen; Song, Ting; Wu, Zhaoxia; Liu, Yaqiang; Jiang, Steve; Jia, Xun
2017-01-07
Monte Carlo (MC)-based spot dose calculation is highly desired for inverse treatment planning in proton therapy because of its accuracy. Recent studies on biological optimization have also indicated the use of MC methods to compute relevant quantities of interest, e.g. linear energy transfer. Although GPU-based MC engines have been developed to address inverse optimization problems, their efficiency still needs to be improved. Also, the use of a large number of GPUs in MC calculation is not favorable for clinical applications. The previously proposed adaptive particle sampling (APS) method can improve the efficiency of MC-based inverse optimization by using the computationally expensive MC simulation more effectively. This method is more efficient than the conventional approach that performs spot dose calculation and optimization in two sequential steps. In this paper, we propose a computational library to perform MC-based spot dose calculation on GPU with the APS scheme. The implemented APS method performs a non-uniform sampling of the particles from pencil beam spots during the optimization process, favoring those from the high intensity spots. The library also conducts two computationally intensive matrix-vector operations frequently used when solving an optimization problem. This library design allows a streamlined integration of the MC-based spot dose calculation into an existing proton therapy inverse planning process. We tested the developed library in a typical inverse optimization system with four patient cases. The library achieved the targeted functions by supporting inverse planning in various proton therapy schemes, e.g. single field uniform dose, 3D intensity modulated proton therapy, and distal edge tracking. The efficiency was 41.6 ± 15.3% higher than the use of a GPU-based MC package in a conventional calculation scheme. The total computation time ranged between 2 and 50 min on a single GPU card depending on the problem size.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wu, Q; Snyder, K; Liu, C
Purpose: To develop an optimization algorithm to reduce normal brain dose by optimizing couch and collimator angles for single isocenter multiple targets treatment of stereotactic radiosurgery. Methods: Three metastatic brain lesions were retrospectively planned using single-isocenter volumetric modulated arc therapy (VMAT). Three matrices were developed to calculate the projection of each lesion on Beam’s Eye View (BEV) by the rotating couch, collimator and gantry respectively. The island blocking problem was addressed by computing the total area of open space between any two lesions with shared MLC leaf pairs. The couch and collimator angles resulting in the smallest open areas weremore » the optimized angles for each treatment arc. Two treatment plans with and without couch and collimator angle optimization were developed using the same objective functions and to achieve 99% of each target volume receiving full prescription dose of 18Gy. Plan quality was evaluated by calculating each target’s Conformity Index (CI), Gradient Index (GI), and Homogeneity index (HI), and absolute volume of normal brain V8Gy, V10Gy, V12Gy, and V14Gy. Results: Using the new couch/collimator optimization strategy, dose to normal brain tissue was reduced substantially. V8, V10, V12, and V14 decreased by 2.3%, 3.6%, 3.5%, and 6%, respectively. There were no significant differences in the conformity index, gradient index, and homogeneity index between two treatment plans with and without the new optimization algorithm. Conclusion: We have developed a solution to the island blocking problem in delivering radiation to multiple brain metastases with shared isocenter. Significant reduction in dose to normal brain was achieved by using optimal couch and collimator angles that minimize total area of open space between any of the two lesions with shared MLC leaf pairs. This technique has been integrated into Eclipse treatment system using scripting API.« less
NASA Astrophysics Data System (ADS)
Li, Yongbao; Tian, Zhen; Song, Ting; Wu, Zhaoxia; Liu, Yaqiang; Jiang, Steve; Jia, Xun
2017-01-01
Monte Carlo (MC)-based spot dose calculation is highly desired for inverse treatment planning in proton therapy because of its accuracy. Recent studies on biological optimization have also indicated the use of MC methods to compute relevant quantities of interest, e.g. linear energy transfer. Although GPU-based MC engines have been developed to address inverse optimization problems, their efficiency still needs to be improved. Also, the use of a large number of GPUs in MC calculation is not favorable for clinical applications. The previously proposed adaptive particle sampling (APS) method can improve the efficiency of MC-based inverse optimization by using the computationally expensive MC simulation more effectively. This method is more efficient than the conventional approach that performs spot dose calculation and optimization in two sequential steps. In this paper, we propose a computational library to perform MC-based spot dose calculation on GPU with the APS scheme. The implemented APS method performs a non-uniform sampling of the particles from pencil beam spots during the optimization process, favoring those from the high intensity spots. The library also conducts two computationally intensive matrix-vector operations frequently used when solving an optimization problem. This library design allows a streamlined integration of the MC-based spot dose calculation into an existing proton therapy inverse planning process. We tested the developed library in a typical inverse optimization system with four patient cases. The library achieved the targeted functions by supporting inverse planning in various proton therapy schemes, e.g. single field uniform dose, 3D intensity modulated proton therapy, and distal edge tracking. The efficiency was 41.6 ± 15.3% higher than the use of a GPU-based MC package in a conventional calculation scheme. The total computation time ranged between 2 and 50 min on a single GPU card depending on the problem size.
Li, Yongbao; Tian, Zhen; Song, Ting; Wu, Zhaoxia; Liu, Yaqiang; Jiang, Steve; Jia, Xun
2016-01-01
Monte Carlo (MC)-based spot dose calculation is highly desired for inverse treatment planning in proton therapy because of its accuracy. Recent studies on biological optimization have also indicated the use of MC methods to compute relevant quantities of interest, e.g. linear energy transfer. Although GPU-based MC engines have been developed to address inverse optimization problems, their efficiency still needs to be improved. Also, the use of a large number of GPUs in MC calculation is not favorable for clinical applications. The previously proposed adaptive particle sampling (APS) method can improve the efficiency of MC-based inverse optimization by using the computationally expensive MC simulation more effectively. This method is more efficient than the conventional approach that performs spot dose calculation and optimization in two sequential steps. In this paper, we propose a computational library to perform MC-based spot dose calculation on GPU with the APS scheme. The implemented APS method performs a non-uniform sampling of the particles from pencil beam spots during the optimization process, favoring those from the high intensity spots. The library also conducts two computationally intensive matrix-vector operations frequently used when solving an optimization problem. This library design allows a streamlined integration of the MC-based spot dose calculation into an existing proton therapy inverse planning process. We tested the developed library in a typical inverse optimization system with four patient cases. The library achieved the targeted functions by supporting inverse planning in various proton therapy schemes, e.g. single field uniform dose, 3D intensity modulated proton therapy, and distal edge tracking. The efficiency was 41.6±15.3% higher than the use of a GPU-based MC package in a conventional calculation scheme. The total computation time ranged between 2 and 50 min on a single GPU card depending on the problem size. PMID:27991456
Kierkels, Roel G J; Wopken, Kim; Visser, Ruurd; Korevaar, Erik W; van der Schaaf, Arjen; Bijl, Hendrik P; Langendijk, Johannes A
2016-12-01
Radiotherapy of the head and neck is challenged by the relatively large number of organs-at-risk close to the tumor. Biologically-oriented objective functions (OF) could optimally distribute the dose among the organs-at-risk. We aimed to explore OFs based on multivariable normal tissue complication probability (NTCP) models for grade 2-4 dysphagia (DYS) and tube feeding dependence (TFD). One hundred head and neck cancer patients were studied. Additional to the clinical plan, two more plans (an OF DYS and OF TFD -plan) were optimized per patient. The NTCP models included up to four dose-volume parameters and other non-dosimetric factors. A fully automatic plan optimization framework was used to optimize the OF NTCP -based plans. All OF NTCP -based plans were reviewed and classified as clinically acceptable. On average, the Δdose and ΔNTCP were small comparing the OF DYS -plan, OF TFD -plan, and clinical plan. For 5% of patients NTCP TFD reduced >5% using OF TFD -based planning compared to the OF DYS -plans. Plan optimization using NTCP DYS - and NTCP TFD -based objective functions resulted in clinically acceptable plans. For patients with considerable risk factors of TFD, the OF TFD steered the optimizer to dose distributions which directly led to slightly lower predicted NTCP TFD values as compared to the other studied plans. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
D-optimal experimental designs to test for departure from additivity in a fixed-ratio mixture ray.
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.
SU-E-T-07: 4DCT Robust Optimization for Esophageal Cancer Using Intensity Modulated Proton Therapy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Liao, L; Department of Industrial Engineering, University of Houston, Houston, TX; Yu, J
2015-06-15
Purpose: To develop a 4DCT robust optimization method to reduce the dosimetric impact from respiratory motion in intensity modulated proton therapy (IMPT) for esophageal cancer. Methods: Four esophageal cancer patients were selected for this study. The different phases of CT from a set of 4DCT were incorporated into the worst-case dose distribution robust optimization algorithm. 4DCT robust treatment plans were designed and compared with the conventional non-robust plans. Result doses were calculated on the average and maximum inhale/exhale phases of 4DCT. Dose volume histogram (DVH) band graphic and ΔD95%, ΔD98%, ΔD5%, ΔD2% of CTV between different phases were used tomore » evaluate the robustness of the plans. Results: Compare to the IMPT plans optimized using conventional methods, the 4DCT robust IMPT plans can achieve the same quality in nominal cases, while yield a better robustness to breathing motion. The mean ΔD95%, ΔD98%, ΔD5% and ΔD2% of CTV are 6%, 3.2%, 0.9% and 1% for the robustly optimized plans vs. 16.2%, 11.8%, 1.6% and 3.3% from the conventional non-robust plans. Conclusion: A 4DCT robust optimization method was proposed for esophageal cancer using IMPT. We demonstrate that the 4DCT robust optimization can mitigate the dose deviation caused by the diaphragm motion.« less
A study of optimization techniques in HDR brachytherapy for the prostate
NASA Astrophysics Data System (ADS)
Pokharel, Ghana Shyam
Several studies carried out thus far are in favor of dose escalation to the prostate gland to have better local control of the disease. But optimal way of delivery of higher doses of radiation therapy to the prostate without hurting neighboring critical structures is still debatable. In this study, we proposed that real time high dose rate (HDR) brachytherapy with highly efficient and effective optimization could be an alternative means of precise delivery of such higher doses. This approach of delivery eliminates the critical issues such as treatment setup uncertainties and target localization as in external beam radiation therapy. Likewise, dosimetry in HDR brachytherapy is not influenced by organ edema and potential source migration as in permanent interstitial implants. Moreover, the recent report of radiobiological parameters further strengthen the argument of using hypofractionated HDR brachytherapy for the management of prostate cancer. Firstly, we studied the essential features and requirements of real time HDR brachytherapy treatment planning system. Automating catheter reconstruction with fast editing tools, fast yet accurate dose engine, robust and fast optimization and evaluation engine are some of the essential requirements for such procedures. Moreover, in most of the cases we performed, treatment plan optimization took significant amount of time of overall procedure. So, making treatment plan optimization automatic or semi-automatic with sufficient speed and accuracy was the goal of the remaining part of the project. Secondly, we studied the role of optimization function and constraints in overall quality of optimized plan. We have studied the gradient based deterministic algorithm with dose volume histogram (DVH) and more conventional variance based objective functions for optimization. In this optimization strategy, the relative weight of particular objective in aggregate objective function signifies its importance with respect to other objectives. Based on our study, DVH based objective function performed better than traditional variance based objective function in creating a clinically acceptable plan when executed under identical conditions. Thirdly, we studied the multiobjective optimization strategy using both DVH and variance based objective functions. The optimization strategy was to create several Pareto optimal solutions by scanning the clinically relevant part of the Pareto front. This strategy was adopted to decouple optimization from decision such that user could select final solution from the pool of alternative solutions based on his/her clinical goals. The overall quality of treatment plan improved using this approach compared to traditional class solution approach. In fact, the final optimized plan selected using decision engine with DVH based objective was comparable to typical clinical plan created by an experienced physicist. Next, we studied the hybrid technique comprising both stochastic and deterministic algorithm to optimize both dwell positions and dwell times. The simulated annealing algorithm was used to find optimal catheter distribution and the DVH based algorithm was used to optimize 3D dose distribution for given catheter distribution. This unique treatment planning and optimization tool was capable of producing clinically acceptable highly reproducible treatment plans in clinically reasonable time. As this algorithm was able to create clinically acceptable plans within clinically reasonable time automatically, it is really appealing for real time procedures. Next, we studied the feasibility of multiobjective optimization using evolutionary algorithm for real time HDR brachytherapy for the prostate. The algorithm with properly tuned algorithm specific parameters was able to create clinically acceptable plans within clinically reasonable time. However, the algorithm was let to run just for limited number of generations not considered optimal, in general, for such algorithms. This was done to keep time window desirable for real time procedures. Therefore, it requires further study with improved conditions to realize the full potential of the algorithm.