MO-C-18A-01: Advances in Model-Based 3D Image Reconstruction

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

Chen, G; Pan, X; Stayman, J

2014-06-15

Recent years have seen the emergence of CT image reconstruction techniques that exploit physical models of the imaging system, photon statistics, and even the patient to achieve improved 3D image quality and/or reduction of radiation dose. With numerous advantages in comparison to conventional 3D filtered backprojection, such techniques bring a variety of challenges as well, including: a demanding computational load associated with sophisticated forward models and iterative optimization methods; nonlinearity and nonstationarity in image quality characteristics; a complex dependency on multiple free parameters; and the need to understand how best to incorporate prior information (including patient-specific prior images) within themore » reconstruction process. The advantages, however, are even greater – for example: improved image quality; reduced dose; robustness to noise and artifacts; task-specific reconstruction protocols; suitability to novel CT imaging platforms and noncircular orbits; and incorporation of known characteristics of the imager and patient that are conventionally discarded. This symposium features experts in 3D image reconstruction, image quality assessment, and the translation of such methods to emerging clinical applications. Dr. Chen will address novel methods for the incorporation of prior information in 3D and 4D CT reconstruction techniques. Dr. Pan will show recent advances in optimization-based reconstruction that enable potential reduction of dose and sampling requirements. Dr. Stayman will describe a “task-based imaging” approach that leverages models of the imaging system and patient in combination with a specification of the imaging task to optimize both the acquisition and reconstruction process. Dr. Samei will describe the development of methods for image quality assessment in such nonlinear reconstruction techniques and the use of these methods to characterize and optimize image quality and dose in a spectrum of clinical applications. Learning Objectives: Learn the general methodologies associated with model-based 3D image reconstruction. Learn the potential advantages in image quality and dose associated with model-based image reconstruction. Learn the challenges associated with computational load and image quality assessment for such reconstruction methods. Learn how imaging task can be incorporated as a means to drive optimal image acquisition and reconstruction techniques. Learn how model-based reconstruction methods can incorporate prior information to improve image quality, ease sampling requirements, and reduce dose.« less

Transdermal film-loaded finasteride microplates to enhance drug skin permeation: Two-step optimization study.

PubMed

Ahmed, Tarek A; El-Say, Khalid M

2016-06-10

The goal was to develop an optimized transdermal finasteride (FNS) film loaded with drug microplates (MIC), utilizing two-step optimization, to decrease the dosing schedule and inconsistency in gastrointestinal absorption. First; 3-level factorial design was implemented to prepare optimized FNS-MIC of minimum particle size. Second; Box-Behnken design matrix was used to develop optimized transdermal FNS-MIC film. Interaction among MIC components was studied using physicochemical characterization tools. Film components namely; hydroxypropyl methyl cellulose (X1), dimethyl sulfoxide (X2) and propylene glycol (X3) were optimized for their effects on the film thickness (Y1) and elongation percent (Y2), and for FNS steady state flux (Y3), permeability coefficient (Y4), and diffusion coefficient (Y5) following ex-vivo permeation through the rat skin. Morphological study of the optimized MIC and transdermal film was also investigated. Results revealed that stabilizer concentration and anti-solvent percent were significantly affecting MIC formulation. Optimized FNS-MIC of particle size 0.93μm was successfully prepared in which there was no interaction observed among their components. An enhancement in the aqueous solubility of FNS-MIC by more than 23% was achieved. All the studied variables, most of their interaction and quadratic effects were significantly affecting the studied variables (Y1-Y5). Morphological observation illustrated non-spherical, short rods, flakes like small plates that were homogeneously distributed in the optimized transdermal film. Ex-vivo study showed enhanced FNS permeation from film loaded MIC when compared to that contains pure drug. So, MIC is a successful technique to enhance aqueous solubility and skin permeation of poor water soluble drug especially when loaded into transdermal films. Copyright © 2016 Elsevier B.V. All rights reserved.

Engineering of small interfering RNA-loaded lipidoid-poly(DL-lactic-co-glycolic acid) hybrid nanoparticles for highly efficient and safe gene silencing: A quality by design-based approach.

PubMed

Thanki, Kaushik; Zeng, Xianghui; Justesen, Sarah; Tejlmann, Sarah; Falkenberg, Emily; Van Driessche, Elize; Mørck Nielsen, Hanne; Franzyk, Henrik; Foged, Camilla

2017-11-01

Safety and efficacy of therapeutics based on RNA interference, e.g., small interfering RNA (siRNA), are dependent on the optimal engineering of the delivery technology, which is used for intracellular delivery of siRNA to the cytosol of target cells. We investigated the hypothesis that commonly used and poorly tolerated cationic lipids might be replaced with more efficacious and safe lipidoids as the lipid component of siRNA-loaded lipid-polymer hybrid nanoparticles (LPNs) for achieving more efficient gene silencing at lower and safer doses. However, formulation design of such a complex formulation is highly challenging due to a strong interplay between several contributing factors. Hence, critical formulation variables, i.e. the lipidoid content and siRNA:lipidoid ratio, were initially identified, followed by a systematic quality-by-design approach to define the optimal operating space (OOS), eventually resulting in the identification of a robust, highly efficacious and safe formulation. A 17-run design of experiment with an I-optimal approach was performed to systematically assess the effect of selected variables on critical quality attributes (CQAs), i.e. physicochemical properties (hydrodynamic size, zeta potential, siRNA encapsulation/loading) and the biological performance (in vitro gene silencing and cell viability). Model fitting of the obtained data to construct predictive models revealed non-linear relationships for all CQAs, which can be readily overlooked in one-factor-at-a-time optimization approaches. The response surface methodology further enabled the identification of an OOS that met the desired quality target product profile. The optimized lipidoid-modified LPNs revealed more than 50-fold higher in vitro gene silencing at well-tolerated doses and approx. a twofold increase in siRNA loading as compared to reference LPNs modified with the commonly used cationic lipid dioleyltrimethylammonium propane (DOTAP). Thus, lipidoid-modified LPNs show highly promising prospects for efficient and safe intracellular delivery of siRNA. Copyright © 2017 Elsevier B.V. All rights reserved.

High-dose Versus Low-dose Tranexamic Acid to Reduce Transfusion Requirements in Pediatric Scoliosis Surgery.

PubMed

Johnson, Daniel J; Johnson, Christine C; Goobie, Susan M; Nami, Nina; Wetzler, Joshua A; Sponseller, Paul D; Frank, Steven M

2017-12-01

Our objective was to quantify blood loss and transfusion requirements for high-dose and low-dose tranexamic acid (TXA) dosing regimens in pediatric patients undergoing spinal fusion for correction of idiopathic scoliosis. Previous investigators have established the efficacy of TXA in pediatric scoliosis surgery; however, the dosing regimens vary widely and the optimal dose has not been established. We retrospectively analyzed electronic medical records for 116 patients who underwent spinal fusion surgery for idiopathic scoliosis by a single surgeon and were treated with TXA. In total, 72 patients received a 10 mg/kg loading dose with a 1 mg/kg/h maintenance dose (low-dose) and 44 patients received 50 mg/kg loading dose with a 5 mg/kg/h maintenance dose (high-dose). Estimated blood loss and transfusion requirements were compared between dosing groups. Patient characteristics were nearly identical between the 2 groups. Compared with the low-dose TXA group, the high-dose TXA group had decreased estimated blood loss (695 vs. 968 mL, P=0.01), and a decrease in both intraoperative (0.3 vs. 0.9 units, P=0.01) and whole hospitalization (0.4 vs. 1.0 units, P=0.04) red blood cell transfusion requirements. The higher-dose TXA was associated with decreased intraoperative (P=0.01), and whole hospital transfusion (P=0.01) requirements, even after risk-adjustment for potential confounding variables. High-dose TXA is more effective than low-dose TXA in reducing blood loss and transfusion requirements in pediatric idiopathic scoliosis patients undergoing surgery. Level-III, retrospective cohort study.

The effect of glucose dose and fasting interval on cognitive function: a double-blind, placebo-controlled, six-way crossover study.

PubMed

Owen, Lauren; Scholey, Andrew B; Finnegan, Yvonne; Hu, Henglong; Sünram-Lea, Sandra I

2012-04-01

Previous research has identified a number of factors that appear to moderate the behavioural response to glucose administration. These include physiological state, dose, types of cognitive tasks used and level of cognitive demand. Another potential moderating factor is the length of the fasting interval prior to a glucose load. Therefore, we aimed to examine the effect of glucose dose and fasting interval on mood and cognitive function. The current study utilised a double-blind, placebo-controlled, balanced, six period crossover design to examine potential interactions between length of fasting interval (2 versus 12 hours) and optimal dose for cognition enhancement. Results demonstrated that the higher dose (60 g) increased working memory performance following an overnight fast, whereas the lower dose (25 g) enhanced working memory performance following a 2-h fast. The data suggest that optimal glucose dosage may differ under different conditions of depleted blood glucose resources. In addition, glucoregulation was observed to be a moderating factor. However, further research is needed to develop a model of the moderating and mediating factors under which glucose facilitation is best achieved.

The pharmacogenetics and pharmacodynamics of clopidogrel response: an analysis from the PRINC (Plavix Response in Coronary Intervention) trial.

PubMed

Gladding, Patrick; Webster, Mark; Zeng, Irene; Farrell, Helen; Stewart, Jim; Ruygrok, Peter; Ormiston, John; El-Jack, Seif; Armstrong, Guy; Kay, Patrick; Scott, Douglas; Gunes, Arzu; Dahl, Marja-Liisa

2008-12-01

This study assessed the effect of pharmacogenetics on the antiplatelet effect of clopidogrel. Variability in clopidogrel response might be influenced by polymorphisms in genes coding for drug metabolism enzymes (cytochrome P450 [CYP] family), transport proteins (P-glycoprotein) and/or target proteins for the drug (adenosine diphosphate-receptor P2Y12). Sixty patients undergoing elective percutaneous coronary intervention in the randomized PRINC (Plavix Response in Coronary Intervention) trial had platelet function measured using the VerifyNow P2Y12 analyzer after a 600-mg or split 1,200-mg loading dose and after a 75- or 150-mg daily maintenance dosage. Polymerase chain reaction-based genotyping evaluated polymorphisms in the CYP2C19, CYP2C9, CYP3A4, CYP3A5, ABCB1, P2Y12, and CES genes. CYP2C19*1*1 carriers had greater platelet inhibition 2 h after a 600-mg dose (median: 23%, range: 0% to 66%), compared with platelet inhibition in CYP2C19*2 or *4 carriers (10%, 0% to 56%, p = 0.029) and CYP2C19*17 carriers (9%, 0% to 98%, p = 0.026). CYP2C19*2 or *4 carriers had greater platelet inhibition with the higher loading dose than with the lower dose at 4 h (37%, 8% to 87% vs. 14%, 0% to 22%, p = 0.002) and responded better with the higher maintenance dose regimen (51%, 15% to 86% vs. 14%, 0% to 67%, p = 0.042). Carriers of the CYP2C19*2 and *4 alleles showed reduced platelet inhibition after a clopidogrel 600-mg loading dose but responded to higher loading and maintenance dose regimens. Genotyping for the relevant gene polymorphisms may help to individualize and optimize clopidogrel treatment. (Australia New Zealand Clinical Trials Registry; ACTRN12606000129583).

Design of gefitinib-loaded poly (l-lactic acid) microspheres via a supercritical anti-solvent process for dry powder inhalation.

PubMed

Lin, Qing; Liu, Guijin; Zhao, Ziyi; Wei, Dongwei; Pang, Jiafeng; Jiang, Yanbin

2017-10-30

To develop a safer, more stable and potent formulation of gefitinib (GFB), micro-spheres of GFB encapsulated into poly (l-lactic acid) (PLLA) have been prepared by supercritical anti-solvent (SAS) technology in this study. Operating factors were optimized using a selected OA 16 (4 5 ) orthogonal array design, and the properties of the raw material and SAS processed samples were characterized by different methods The results show that the GFB-loaded PLLA particles prepared were spherical, having a smaller and narrower particle size compared with raw GFB. The optimal GFB-loaded PLLA sample was prepared with less aggregation, highest GFB loading (15.82%) and smaller size (D 50 =2.48μm, which meets the size of dry powder inhalers). The results of XRD and DSC indicate that GFB is encapsulated into PLLA matrix in a polymorphic form different from raw GFB. FT-IR results show that the chemical structure of GFB does not change after the SAS process. The results of in vitro release show that the optimal sample release was slower compared with raw GFB particles. Moreover, the results of in vitro anti-cancer trials show that the optimal sample had a higher cytotoxicity than raw GFB. After blending with sieved lactose, the flowability and aerosolization performance of the optimal sample for DPI were improved, with angle of repose, emitted dose and fine particles fractions from 38.4° to 23°, 63.21% to >90%, 23.37% to >30%, respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

A comprehensive study on the relationship between the image quality and imaging dose in low-dose cone beam CT

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.

Does help structures play a role in reducing the variation of dwell time in IPSA planning for gynaecological brachytherapy application?

PubMed Central

Mahantshetty, Umesh; Deshpande, DD; Sharma, Smriti; Shrivastava, SK

2011-01-01

Purpose To report our experience of dosimetric comparison of IPSA and manual plans, with a focus on the use of help structures (HS) during optimization. Material and methods 33 patients who underwent MR image-based HDR intracavitary-brachytherapy for cervix cancer based on GYN-ESTRO recommendations were selected for evaluation. Tandem/ovoid (T/O) and Vienna applicators were used. HS of diameter of 5 mm were drawn around the tandem/needles/ovoid and ring. Three plans were generated: manual optimized plan (MOPT), IPSA without help structures (IPSA_woHS) and IPSA with help structures (IPSA_wHS). Dose-volume parameters and the loading pattern were evaluated. Results For T/O, the use of HS did not make significant impact in the dose-volume parameters and in the loading of tandem and ovoids, however steep variation was found in the individual dwell time. In case of Vienna applicator, inclusion of HS in the optimization made a significant impact in loading of needles. The percentage ratio of total time of needles to the tandem (TN/T%) was found to be 14±2.5, 53±9, 22±6 for MOPT, IPSA_woHS and IPSA_wHS, respectively, which implies that in IPSA_woHS the dwell time in needles were half of the dwell time in the tandem, while in MOPT the needles were loaded only in 14%, and in IPSA_wHS it was 22% of the dwell time of tandem. Inclusion of HS in the optimization has reduced the contribution of dwell time of needle in IPSA_wHS. The individual variation of dwell time was also reduced in IPSA_wHS, however drawing of HS is a time consuming procedure and may not be practical for a routine practice. Conclusion The role of HS was evaluated for IPSA for T/O and Vienna-applicator, the use of HS may be beneficial in case of combined intracavitary – interstitial approach. PMID:23346124

Exponential increase in postprandial blood-glucose exposure with increasing carbohydrate loads using a linear carbohydrate-to-insulin ratio.

PubMed

Marran, K J; Davey, B; Lang, A; Segal, D G

2013-04-10

Postprandial glucose excursions contribute significantly to average blood glucose, glycaemic variability and cardiovascular risk. Carbohydrate counting is a method of insulin dosing that balances carbohydrate load to insulin dose using a fixed ratio. Many patients and current insulin pumps calculate insulin delivery for meals based on a linear carbohydrate-to-insulin relationship. It is our hypothesis that a non-linear relationship exists between the amounts of carbohydrate consumed and the insulin required to cover it. To document blood glucose exposure in response to increasing carbohydrate loads on fixed carbohydrate-to-insulin ratios. Five type 1 diabetic subjects receiving insulin pump therapy with good control were recruited. Morning basal rates and carbohydrate- to-insulin ratios were optimised. A Medtronic glucose sensor was used for 5 days to collect data for area-under-the-curve (AUC) analysis, during which standardised meals of increasing carbohydrate loads were consumed. Increasing carbohydrate loads using a fixed carbohydrate-to-insulin ratio resulted in increasing glucose AUC. The relationship was found to be exponential rather than linear. Late postprandial hypoglycaemia followed carbohydrate loads of >60 g and this was often followed by rebound hyperglycaemia that lasted >6 hours. A non-linear relationship exists between carbohydrates consumed and the insulin required to cover them. This has implications for control of postprandial blood sugars, especially when consuming large carbohydrate loads. Further studies are required to look at the optimal ratios, duration and type of insulin boluses required to cover increasing carbohydrate loads.

SU-E-T-09: A Clinical Implementation and Optimized Dosimetry Study of Freiberg Flap Skin Surface Treatment in High Dose Rate Brachytherapy

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

Syh, J; Syh, J; Patel, B

Purpose: This case study was designated to confirm the optimized plan was used to treat skin surface of left leg in three stages. 1. To evaluate dose distribution and plan quality by alternating of the source loading catheters pattern in flexible Freiberg Flap skin surface (FFSS) applicator. 2. To investigate any impact on Dose Volume Histogram (DVH) of large superficial surface target volume coverage. 3. To compare the dose distribution if it was treated with electron beam. Methods: The Freiburg Flap is a flexible mesh style surface mold for skin radiation or intraoperative surface treatments. The Freiburg Flap consists ofmore » multiple spheres that are attached to each other, holding and guiding up to 18 treatment catheters. The Freiburg Flap also ensures a constant distance of 5mm from the treatment catheter to the surface. Three treatment trials with individual planning optimization were employed: 18 channels, 9 channels of FF and 6 MeV electron beam. The comparisons were highlighted in target coverage, dose conformity and dose sparing of surrounding tissues. Results: The first 18 channels brachytherapy plan was generated with 18 catheters inside the skin-wrapped up flap (Figure 1A). A second 9 catheters plan was generated associated with the same calculation points which were assigned to match prescription for target coverage as 18 catheters plan (Figure 1B). The optimized inverse plan was employed to reduce the dose to adjacent structures such as tibia or fibula. The comparison of DVH’s was depicted on Figure 2. External beam of electron RT plan was depicted in Figure 3. Overcall comparisons among these three were illustrated in Conclusion: The 9-channel Freiburg flap flexible skin applicator offers a reasonably acceptable plan without compromising the coverage. Electron beam was discouraged to use to treat curved skin surface because of low target coverage and high dose in adjacent tissues.« less

A pharmacodynamic comparison of prasugrel vs. high-dose clopidogrel in patients with type 2 diabetes mellitus and coronary artery disease: results of the Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 Trial

PubMed Central

Angiolillo, Dominick J.; Badimon, Juan Jose; Saucedo, Jorge F.; Frelinger, Andrew L.; Michelson, Alan D.; Jakubowski, Joseph A.; Zhu, Baojin; Ojeh, Clement K.; Baker, Brian A.; Effron, Mark B.

2011-01-01

Aims Patients with diabetes mellitus (DM) have increased platelet reactivity and reduced platelet response to clopidogrel compared with patients without DM. Prasugrel, a more potent antiplatelet agent, is associated with greater reductions in ischaemic events compared with clopidogrel, particularly in patients with DM. The aim of this study was to perform serial pharmacodynamic assessments of prasugrel with high-dose clopidogrel in patients with DM. Methods and results Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 was a prospective, randomized, double-blind, crossover study in patients with type 2 DM and coronary artery disease (CAD). Patients (n= 35) were randomly assigned to either prasugrel 60 mg loading dose (LD)/10 mg maintenance dose (MD) or clopidogrel 600 mg LD/150 mg MD over two 1-week treatment periods separated by a 2-week washout period. Platelet function was assessed by VerifyNow® P2Y12 assay, light transmission aggregometry, and vasodilator-stimulated phosphoprotein phosphorylation at 0, 1, 4, and 24 h and 7 days. Greater platelet inhibition by VerifyNow® P2Y12 was achieved by prasugrel compared with clopidogrel at 4 h post-LD (least squares mean, 89.3 vs. 27.7%, P< 0.0001; primary endpoint). The difference in platelet inhibition between prasugrel and clopidogrel was significant from 1 h through 7 days (P < 0.0001). Similar results were obtained using all other platelet function measures. Prasugrel resulted in fewer poor responders at all time points irrespective of definition used. Conclusion In patients with type 2 DM and CAD, standard-dose prasugrel is associated with greater platelet inhibition and better response profiles during both the loading and maintenance periods when compared with double-dose clopidogrel. Clinical trial identifier: www.clinicaltrials.gov—NCT00642174 PMID:21252171

Folate-conjugated chitosan-polylactide nanoparticles for enhanced intracellular uptake of anticancer drug

NASA Astrophysics Data System (ADS)

Huang, Shengtang; Wan, Ying; Wang, Zheng; Wu, Jiliang

2013-12-01

Chitosan was conjugated with folic acid (FA) and the resulting chitosan derivatives with a FA-substitution degree of around 6 % was used to synthesize FA-conjugated chitosan-polylactide (FA-CH-PLA) copolymers to build a drug carrier with active targeting characteristics for the anticancer drug of paclitaxel (PTX). Selected FA-CH-PLAs with various polylactide percentages of about 40 wt% or lower were employed to fabricate nanoparticles using sodium tripolyphosphate as a crosslinker, and different types of nanoparticles were endued with similar average particle-sizes located in a range between 100 and 200 nm. Certain types of PTX-loaded FA-CH-PLA nanoparticles having encapsulation efficiency of around 90 % and initial load of about 12 % were able to release PTX in a controlled manner with significant regulation by polylactide content in FA-CH-PLAs. Targeting characteristic of achieved nanoparticles was confirmed using FA-receptor-expressed MCF-7 breast cancer cells. The uptake of PTX revealed that optimized FA-CH-PLA nanoparticles with an equivalent PTX-dose of around 1 μg/mL could have more than sixfold increasing abilities to facilitate intracellular paclitaxel accumulation in MCF-7 cells after 24 h treatment as compared to free PTX. At a relatively safe equivalent PTX-dose for normal MCF-10A mammary epithelial cells, the obtained results from Hoechst 33342 staining indicated that optimized PTX-loaded FA-CH-PLA nanoparticles had more than threefold increasing abilities to induce MCF-7 cell apoptosis in comparison to free PTX.

Solid self-nanoemulsifying drug delivery systems for oral delivery of polypeptide-k: Formulation, optimization, in-vitro and in-vivo antidiabetic evaluation.

PubMed

Garg, Varun; Kaur, Puneet; Singh, Sachin Kumar; Kumar, Bimlesh; Bawa, Palak; Gulati, Monica; Yadav, Ankit Kumar

2017-11-15

Development of self-nanoemulsifying drug delivery systems (SNEDDS) of polypeptide-k (PPK) is reported with the aim to achieve its oral delivery. Box-Behnken design (BBD) was adopted to develop and optimize the composition of SNEDDS. Oleoyl polyoxyl-6 glycerides (A), Tween 80 (B), and diethylene glycol monoethyl ether (C) were used as oil, surfactant and co-surfactant, respectively as independent variables. The effect of variation in their composition was observed on the mean droplet size (y1), polydispersity index (PDI) (y2), % drug loading (y3) and zeta potential (y4). As per the optimal design, seventeen SNEDDS prototypes were prepared. The optimized composition of SNEDDS formulation was 25% v/v Oleoyl polyoxyl-6 glycerides, 37% v/v Tween 80, 38% v/v diethylene glycol monoethyl ether, and 3% w/v PPK. The optimized formulation revealed values of y1, y2, y3, and y4 as 31.89nm, 0.16, 73.15%, and -15.65mV, respectively. Further the optimized liquid SNEDDS were solidified through spray drying using various hydrophilic and hydrophobic carriers. Among the various carriers, Aerosil 200 was found to provide desirable flow, compression, disintegration and dissolution properties. Both, liquid and solid-SNEDDS have shown release of >90% within 10min. The formulation was found stable with change in pH, dilution, temperature variation and freeze thaw cycles in terms of droplet size, zeta potential, drug precipitation and phase separation. Crystalline PPK was observed in amorphous state in solid SNEDDS when characterized through DSC and PXRD studies. The biochemical, hematological and histopathological results of streptozotocin induced diabetic rats shown promising antidiabetic potential of PPK loaded in SNEDDS at its both the doses (i.e. 400mg/kg and 800mg/kg) as compared to its naïve form at both the doses. The study revealed successful formulation of SNEDDS for oral delivery of PPK. Copyright © 2017 Elsevier B.V. All rights reserved.

Colistin Population Pharmacokinetics after Application of a Loading Dose of 9 MU Colistin Methanesulfonate in Critically Ill Patients

PubMed Central

Friberg, Lena E.; Pontikis, Konstantinos; Ioannidis, Konstantinos; Tsagkari, Vasiliki; Galani, Lamprini; Kostakou, Eirini; Baziaka, Fotini; Paskalis, Charalambos; Koutsoukou, Antonia; Giamarellou, Helen

2015-01-01

Colistin has been revived, in the era of extensively drug-resistant (XDR) Gram-negative infections, as the last-resort treatment in critically ill patients. Recent studies focusing on the optimal dosing strategy of colistin have demonstrated the necessity of a loading dose at treatment initiation (D. Plachouras, M. Karvanen, L. E. Friberg, E. Papadomichelakis, A. Antoniadou, I. Tsangaris, I. Karaiskos, G. Poulakou, F. Kontopidou, A. Armaganidis, O. Cars, and H. Giamarellou, Antimicrob Agents Chemother 53:3430–3436, 2009, http://dx.doi.org/10.1128/AAC.01361-08; A. F. Mohamed, I. Karaiskos, D. Plachouras, M. Karvanen, K. Pontikis, B. Jansson, E. Papadomichelakis, A. Antoniadou, H. Giamarellou, A. Armaganidis, O. Cars, and L. E. Friberg, Antimicrob Agents Chemother 56:4241– 4249, 2012, http://dx.doi.org/10.1128/AAC.06426-11; S. M. Garonzik, J. Li, V. Thamlikitkul, D. L. Paterson, S. Shoham, J. Jacob, F. P. Silveira, A. Forrest, and R. L. Nation, Antimicrob Agents Chemother 55:3284–3294, 2011, http://dx.doi.org/10.1128/AAC.01733-10). In 19 critically ill patients with suspected or microbiologically documented infections caused by XDR Gram-negative strains, a loading dose of 9 MU colistin methanesulfonate (CMS) (∼270 mg colistin base activity) was administered with a maintenance dose of 4.5 MU every 12 h, commenced after 24 h. Patients on renal replacement were excluded. CMS infusion was given over 30 min or 1 h. Repeated blood sampling was performed after the loading dose and after the 5th or 6th dose. Colistin concentrations and measured CMS, determined after hydrolization to colistin and including the partially sulfomethylated derivatives, were determined with a liquid chromatography-tandem mass spectrometry assay. Population pharmacokinetic analysis was conducted in NONMEM with the new data combined with data from previous studies. Measured colistimethate concentrations were described by 4 compartments for distribution and removal of sulfomethyl groups, while colistin disposition followed a 1-compartment model. The average observed maximum colistin A plus B concentration was 2.65 mg/liter after the loading dose (maximum time was 8 h). A significantly higher availability of the measured A and B forms of colistimethate and colistin explained the higher-than-expected concentrations in the present study compared to those in previous studies. Creatinine clearance was a time-varying covariate of colistimethate clearance. The incidence of acute renal injury was 20%. PMID:26369974

Colistin Population Pharmacokinetics after Application of a Loading Dose of 9 MU Colistin Methanesulfonate in Critically Ill Patients.

PubMed

Karaiskos, Ilias; Friberg, Lena E; Pontikis, Konstantinos; Ioannidis, Konstantinos; Tsagkari, Vasiliki; Galani, Lamprini; Kostakou, Eirini; Baziaka, Fotini; Paskalis, Charalambos; Koutsoukou, Antonia; Giamarellou, Helen

2015-12-01

Colistin has been revived, in the era of extensively drug-resistant (XDR) Gram-negative infections, as the last-resort treatment in critically ill patients. Recent studies focusing on the optimal dosing strategy of colistin have demonstrated the necessity of a loading dose at treatment initiation (D. Plachouras, M. Karvanen, L. E. Friberg, E. Papadomichelakis, A. Antoniadou, I. Tsangaris, I. Karaiskos, G. Poulakou, F. Kontopidou, A. Armaganidis, O. Cars, and H. Giamarellou, Antimicrob Agents Chemother 53:3430-3436, 2009, http://dx.doi.org/10.1128/AAC.01361-08; A. F. Mohamed, I. Karaiskos, D. Plachouras, M. Karvanen, K. Pontikis, B. Jansson, E. Papadomichelakis, A. Antoniadou, H. Giamarellou, A. Armaganidis, O. Cars, and L. E. Friberg, Antimicrob Agents Chemother 56:4241- 4249, 2012, http://dx.doi.org/10.1128/AAC.06426-11; S. M. Garonzik, J. Li, V. Thamlikitkul, D. L. Paterson, S. Shoham, J. Jacob, F. P. Silveira, A. Forrest, and R. L. Nation, Antimicrob Agents Chemother 55:3284-3294, 2011, http://dx.doi.org/10.1128/AAC.01733-10). In 19 critically ill patients with suspected or microbiologically documented infections caused by XDR Gram-negative strains, a loading dose of 9 MU colistin methanesulfonate (CMS) (∼ 270 mg colistin base activity) was administered with a maintenance dose of 4.5 MU every 12 h, commenced after 24 h. Patients on renal replacement were excluded. CMS infusion was given over 30 min or 1 h. Repeated blood sampling was performed after the loading dose and after the 5th or 6th dose. Colistin concentrations and measured CMS, determined after hydrolization to colistin and including the partially sulfomethylated derivatives, were determined with a liquid chromatography-tandem mass spectrometry assay. Population pharmacokinetic analysis was conducted in NONMEM with the new data combined with data from previous studies. Measured colistimethate concentrations were described by 4 compartments for distribution and removal of sulfomethyl groups, while colistin disposition followed a 1-compartment model. The average observed maximum colistin A plus B concentration was 2.65 mg/liter after the loading dose (maximum time was 8 h). A significantly higher availability of the measured A and B forms of colistimethate and colistin explained the higher-than-expected concentrations in the present study compared to those in previous studies. Creatinine clearance was a time-varying covariate of colistimethate clearance. The incidence of acute renal injury was 20%. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Randomised, double blind trial of two loading dose regimens of diamorphine in ventilated newborn infants.

PubMed

Barker, D P; Simpson, J; Pawula, M; Barrett, D A; Shaw, P N; Rutter, N

1995-07-01

To compare the safety and efficacy of two loading doses of diamorphine in 27 ventilated newborn infants in a randomised double blind trial. Fifty or 200 mcg/kg were infused intravenously over 30 minutes, followed by a 15 mcg/kg/hour continuous infusion. Serial measurements were made of physiology, behaviour, and stress hormones. Both loading doses produced small but significant falls in blood pressure. The 200 mcg/kg dose produced greater respiratory depression, and two infants deteriorated clinically, requiring resuscitation. Loading reduced respiratory effort in most of the infants, but had little effect on behavioural activity. Stress hormone concentrations were reduced at six hours in both dosage groups; differences between loading doses were not significant. Morphine, morphine-3-glucuronide, and morphine-6-glucuronide were detected in the plasma of all patients. No significant differences in concentrations between loading doses were found. Diamorphine reduces the stress response in ventilated newborn infants. A high loading dose confers no benefit, and may produce undesirable physiological effects. A 50 mcg/kg loading dose seems to be safe and effective.

Randomised, double blind trial of two loading dose regimens of diamorphine in ventilated newborn infants.

PubMed Central

Barker, D. P.; Simpson, J.; Pawula, M.; Barrett, D. A.; Shaw, P. N.; Rutter, N.

1995-01-01

AIMS--To compare the safety and efficacy of two loading doses of diamorphine in 27 ventilated newborn infants in a randomised double blind trial. METHODS--Fifty or 200 mcg/kg were infused intravenously over 30 minutes, followed by a 15 mcg/kg/hour continuous infusion. Serial measurements were made of physiology, behaviour, and stress hormones. RESULTS--Both loading doses produced small but significant falls in blood pressure. The 200 mcg/kg dose produced greater respiratory depression, and two infants deteriorated clinically, requiring resuscitation. Loading reduced respiratory effort in most of the infants, but had little effect on behavioural activity. Stress hormone concentrations were reduced at six hours in both dosage groups; differences between loading doses were not significant. Morphine, morphine-3-glucuronide, and morphine-6-glucuronide were detected in the plasma of all patients. No significant differences in concentrations between loading doses were found. CONCLUSIONS--Diamorphine reduces the stress response in ventilated newborn infants. A high loading dose confers no benefit, and may produce undesirable physiological effects. A 50 mcg/kg loading dose seems to be safe and effective. PMID:7552591

Development of Yersinia pestis F1 antigen-loaded microspheres vaccine against plague

PubMed Central

Huang, Shih-shiung; Li, I-Hsun; Hong, Po-da; Yeh, Ming-kung

2014-01-01

Yersinia pestis F1 antigen-loaded poly(DL-lactide-co-glycolide)/polyethylene glycol (PEG) (PLGA/PEG) microspheres were produced using a water-in-oil-in-water emulsion/solvent extraction technique and assayed for their percent yield, entrapment efficiency, surface morphology, particle size, zeta potential, in vitro release properties, and in vivo animal protect efficacy. The Y. pestis F1 antigen-loaded microspheres (mean particle size 3.8 μm) exhibited a high loading capacity (4.5% w/w), yield (85.2%), and entrapment efficiency (38.1%), and presented a controlled in vitro release profile with a low initial burst (18.5%), then continued to release Y. pestis F1 antigen over 70 days. The distribution (%) of Y. pestis F1 on the microspheres surface, outer layer, and core was 3.1%, 28.9%, and 60.7%, respectively. A steady release rate was noticed to be 0.55 μg Y. pestis F1 antigen/mg microspheres/day of Y. pestis F1 antigen release maintained for 42 days. The cumulative release amount at the 1st, 28th, and 42nd days was 8.2, 26.7, and 31.0 μg Y. pestis F1 antigen/mg microspheres, respectively. The 100 times median lethal dose 50% (LD50) of Y. pestis Yokohama-R strain by intraperitoneal injection challenge in mice test, in which mice received one dose of 40 μg F1 antigen content of PLGA/PEG microspheres, F1 antigen in Al(OH)3, and in comparison with F1 antigen in Al(OH)3 vaccine in two doses, was evaluated after given by subcutaneous immunization of BALB/c mice. The study results show that the greatest survival was observed in the group of mice immunized with one dose of F1 antigen-loaded PLGA/PEG microspheres, and two doses of F1 antigen in Al(OH)3 vaccine (100%). In vivo vaccination studies also demonstrated that F1 vaccines microspheres had a protective ability; its steady-state IgG immune protection in mice plasma dramatic increased from 2 weeks (18,764±3,124) to 7 weeks (126,468±19,176) after vaccination. These findings strongly suggest that F1-antigen loaded microspheres vaccine offer a new therapeutic strategy in optimizing the vaccine incorporation and delivery properties of these potential vaccine targeting carriers. PMID:24550673

Biodegradable implants from poly-(alpha-hydroxy acid) polymers for isoniazid delivery.

PubMed

Hurley, L; Andersen, B R

1999-11-01

In vitro and in vivo study of an isoniazid (INH) drug delivery system. To develop a system for the treatment of tuberculosis using a subcutaneous polymer implant with a large drug load released slowly over a long period. INH delivery by biodegradable poly-(alpha-hydroxy acid) polymers was evaluated using ground polymer and compression molded implants. Rate of drug release and structural stability of the implant in an aqueous environment were measured, as were in vivo evaluations of the duration of measurable levels of INH in serum and urine. Factors that influenced the suitability of an implant in an in vitro system included polymer molecular weight and crystallinity, polymer and drug particle size, drug loading dose, and press temperature and pressure. The implant characteristics that most closely approached optimal conditions include a polymer of 100% L-lactide with low intrinsic viscosity, polymer particle size <75 micron, and INH particle = 126-180 micron, INH loading dose not to exceed 46%, and press conditions of 70 degrees C and 345000 kPa. Studies of subcutaneous implants in rabbits and baboons show that INH is released from the implant for 15 to 26 weeks. An INH-containing polymer was developed that was structurally stable in an aqueous environment and that released INH over a period of at least 15 weeks. Studies with infected animals will be necessary to determine the dose required for prophylaxis and treatment of active disease.

[Optimization of ventricular function during anesthesia induction by administering crystalloids and colloids to heart surgery patients].

PubMed

Ballesteros, M; Boldt, J; Zickmann, B; Knothe, C; Hempelmann, G

1995-01-01

To describe the changes in cardiac function after administration of three different solutions infused after anesthetic induction. Thirty-six patients scheduled for elective aortocoronary bypass surgery were randomly distributed into three groups. Over a period of 25 min after anesthetic induction, 12 received 10 ml/kg of Ringer solution (low dose crystalloid group), 12 received 20 ml/kg of Ringer solution (high dose crystalloid group), and 12 received 10 ml/kg of Ringer solution with 10 ml/kg of hydroxi-ethyl-almidon solution 450,000 D, 0.7 substitution grade (group C-HEA). Minute volume, systemic and pulmonary pressures, osmolality of blood and urine, and plasma and urine sodium concentrations were measured before and after infusion of the assigned liquid. In spite of the volume infused, low dose crystalloid group showed a high incidence of oliguria, increased urinary osmolality and decreased sodium in urine. Cardiac and systolic indices and left ventricular work load remained stable after infusion of the assigned liquid in low and high dose crystalloid groups, whereas they increased significantly ion group C-HEA (+23%, +16% and +20%). Administration of restricted doses of crystalloids after anesthetic induction favors the retention of water and sodium. Higher doses of crystalloids weaken this effect. However, neither of these two regimens leads to a more effective cardiac work load. A combination of crystalloids and colloids administered immediately after anesthetic induction temporarily improves cardiac performance during surgery.

Ramizol® encapsulation into extended release PLGA micro- and nanoparticle systems for subcutaneous and intramuscular administration: in vitro and in vivo evaluation.

PubMed

Wright, Leah; Rao, Shasha; Thomas, Nicky; Boulos, Ramiz A; Prestidge, Clive A

2018-04-11

Novel antibiotic Ramizol ® is advancing to clinical trials for the treatment of gastrointestinal Clostridium difficile associated disease. Despite this, previous studies have shown a rapid plasma clearance upon intravenous administration and low oral bioavailability indicating pure drug is unsuitable for systemic infection treatment following oral dosing. The current study aims to investigate the development of poly-lactic-(co-glycolic) acid (PLGA) particles to overcome this limitation and increase the systemic half-life following subcutaneous and intramuscular dosing. The development of new antibiotic treatments will help in combatting the rising incidence of antimicrobial resistance. Ramizol ® was encapsulated into PLGA nano and microparticles using nanoprecipitation and emulsification solvent evaporation techniques. Formulations were analyzed for particle size, loading level and encapsulation efficiency as well as in vitro drug release profiles. Final formulation was advanced to in vivo pharmacokinetic studies in Sprague-Dawley rats. Formulation technique showed major influence on particle size and loading levels with optimal loading of 9.4% and encapsulation efficiency of 92.06%, observed using emulsification solvent evaporation. Differences in formulation technique were also linked with subsequent differences in release profiles. Pharmacokinetic studies in Sprague-Dawley rats confirmed extended absorption and enhanced bioavailability following subcutaneous and intramuscular dosing with up to an 8-fold increase in T max and T 1/2 when compared to the oral and IV routes. Subcutaneous and intramuscular dosing of PLGA particles successfully increased systemic half-life and bioavailability of Ramizol ® . This formulation will allow further development of Ramizol ® for systemic infection eradication.

Pharmacokinetic properties of intramuscular versus oral syrup paracetamol in Plasmodium falciparum malaria.

PubMed

Wattanakul, Thanaporn; Teerapong, Pramote; Plewes, Katherine; Newton, Paul N; Chierakul, Wirongrong; Silamut, Kamolrat; Chotivanich, Kesinee; Ruengweerayut, Ronnatrai; White, Nicholas J; Dondorp, Arjen M; Tarning, Joel

2016-04-27

Fever is an inherent symptom of malaria in both adults and children. Paracetamol (acetaminophen) is the recommended antipyretic as it is inexpensive, widely available and has a good safety profile, but patients may not be able to take the oral drug reliably. A comparison between the pharmacokinetics of oral syrup and intramuscular paracetamol given to patients with acute falciparum malaria and high body temperature was performed. A randomized, open-label, two-treatment, crossover, pharmacokinetic study of paracetamol dosed orally and intramuscularly was conducted. Twenty-one adult patients with uncomplicated falciparum malaria were randomized to receive a single 600 mg dose of paracetamol either as syrup or intramuscular injection on day 0 followed by a single dose administered by the alternative route on day 1. Paracetamol plasma concentrations were quantified frequently and modelled simultaneously using nonlinear mixed-effects modelling. The final population pharmacokinetic model was used for dose optimization simulations. Relationships between paracetamol concentrations with temperature and parasite half-life were investigated using linear and non-linear regression analyses. The population pharmacokinetic properties of paracetamol were best described by a two-compartment disposition model, with zero-order and first-order absorption for intramuscular and oral syrup administration, respectively. The relative bioavailability of oral syrup was 84.4 % (95 % CI 68.2-95.1 %) compared to intramuscular administration. Dosing simulations showed that 1000 mg of intramuscular or oral syrup administered six-hourly reached therapeutic steady state concentrations for antipyresis, but more favourable concentration-time profiles were achieved with a loading dose of 1500 mg, followed by a 1000 mg maintenance dose. This ensured that maximum therapeutic concentrations were reached rapidly during the first 6 h. No significant relationships between paracetamol concentrations and temperature or parasite half-life were found. Paracetamol plasma concentrations after oral syrup and intramuscular administration in patients with acute falciparum malaria were described successfully by a two-compartment disposition model. Relative oral bioavailability compared to intramuscular dosing was estimated as 84.4 % (95 % CI 68.2-95.1 %). Dosing simulations showed that a loading dose followed by six-hourly dosing intervals reduced the time delay to reach therapeutic drug levels after both routes of administration. The safety and efficacy of loading dose paracetamol antipyretic regimens now needs to be established in larger studies.

Design of experiments confirms optimization of lithium administration parameters for enhanced fracture healing.

PubMed

Vachhani, Kathak; Pagotto, Andrea; Wang, Yufa; Whyne, Cari; Nam, Diane

2018-01-03

Fracture healing is a lengthy process which fails in 5-10% of cases. Lithium, a low-cost therapeutic used in psychiatric medicine, up-regulates the canonical Wingless pathway crucial for osteoblastic mineralization in fracture healing. A design-of-experiments (DOE) methodology was used to optimize lithium administration parameters (dose, onset time and treatment duration) to enhance healing in a rat femoral fracture model. In the previously completed first stage (screening), onset time was found to significantly impact healing, with later (day 7 vs. day 3 post-fracture) treatment yielding improved maximum yield torque. The greatest strength was found in healing femurs treated at day 7 post fracture, with a low lithium dose (20 mg/kg) for 2 weeks duration. This paper describes the findings of the second (optimization) and third (verification) stages of the DOE investigation. Closed traumatic diaphyseal femur fractures were induced in 3-month old rats. Healing was evaluated on day 28 post fracture by CT-based morphometry and torsional loading. In optimization, later onset times of day 10 and 14 did not perform as well as day 7 onset. As such, efficacy of the best regimen (20 mg/kg dose given at day 7 onset for 2 weeks duration) was reassessed in a distinct cohort of animals to complete the DOE verification. A significant 44% higher maximum yield torque (primary outcome) was seen with optimized lithium treatment vs. controls, which paralleled the 46% improvement seen in the screening stage. Successful completion of this robustly designed preclinical DOE study delineates the optimal lithium regimen for enhancing preclinical long-bone fracture healing. Copyright © 2017 Elsevier Ltd. All rights reserved.

Onset and extent of platelet inhibition by clopidogrel loading in patients undergoing elective coronary stenting: the Plavix Reduction Of New Thrombus Occurrence (PRONTO) trial.

PubMed

Gurbel, Paul A; Cummings, Charles C; Bell, Christopher R; Alford, Amanda B; Meister, Andrew F; Serebruany, Victor L

2003-02-01

Despite the common practice of clopidogrel loading for coronary stenting, the time dependence and degree of platelet inhibition after this therapy are not well defined. We sought to establish an optimal clopidogrel dosing regimen for sustained platelet inhibition in stented patients. Platelets were assessed by conventional aggregation with 5 micromol/L adenosine diphosphate (ADP), 1 microg/mL collagen (COLL), and 750 micromol/L arachidonic acid; whole blood aggregation by 1 microg/mL collagen (WBA); shear-induced closure time (CT); contractile force (CF); and expression of 9 surface receptors by flow cytometry in 100 patients undergoing elective stent placement without glycoprotein (GP) IIb/IIIa receptor antagonists. Blood was obtained at baseline and serially over 5 days poststenting after different clopidogrel loading regimens: 300 mg 24 hours before (Group A), 12 hours before (Group B), 3 to 6 hours before (Group C), and 75 mg at the time of intervention (Group D). Before stenting, ADP, COLL, CT, and WBA were reduced by clopidogrel loading (P <.05). CF was not affected by clopidogrel. Before stenting, GP IIb/IIIa expression increased in groups A through C (P <.05), whereas PECAM-1 and CD107a were reduced (P <.05). At 2 hours and 2 days poststenting, platelets, in general, exhibited an increase in activity that was most inhibited by clopidogrel loading. Clopidogrel inhibited GP Ib, platelet/endothelial cell adhesion molecule-1, CD 107a, CD 151, and GP IIb/IIIa expression at day 5 poststenting. A 300 mg clopidogrel load given 3 to 24 hours before stenting inhibits platelets at the time of the procedure and reduces poststent activity more than a 75 mg dose given at the time of the procedure. The inhibition of adhesive molecule expression may also contribute an antithrombotic effect. Poststent activation of platelets may warrant higher periprocedural dosing.

Association between peak neutrophil count, clopidogrel loading dose, and left ventricular systolic function in patients with primary percutaneous coronary intervention.

PubMed

Wang, Xinyu; Yu, Haiyi; Li, Zhaoping; Li, Liuning; Zhang, Youyi; Gao, Wei

2014-01-01

Inflammation plays an important role in plaque development and left ventricular remodeling during acute myocardial infarction (AMI). Clopidogrel may exhibit some anti-inflammatory properties and high loading dose of clopidogrel results in improved clinical outcomes in patients with AMI. 357 patients who received successful primary percutaneous coronary intervention from January 2008 to March 2011 in Peking University Third Hospital were included in this study. Different loading dose of clopidogrel (300 mg, 450 mg, or 600 mg) was given at the discretion of the clinician. Neutrophils reached their peak values on the first day after AMI. Higher levels of peak neutrophil and lower left ventricular ejection fraction (LVEF) were found in patients of low clopidogrel loading dose group (300 mg or 450 mg). After adjusting for the related confounders, a logistic regression model showed that low clopidogrel loading dose remained an independent predictor of low LVEF (LVEF ≤ 50%) [OR: 1.97, 95% CI: 1.03-3.79, P = 0.04]. Low clopidogrel loading dose was associated with higher peak neutrophil count and poor left ventricular systolic function, suggesting an important role of clopidogrel loading dose in the improvement of left ventricular function and high loading dose may exhibit better anti-inflammatory properties.

Continuous intensity map optimization (CIMO): A novel approach to leaf sequencing in step and shoot IMRT

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

Cao Daliang; Earl, Matthew A.; Luan, Shuang

2006-04-15

A new leaf-sequencing approach has been developed that is designed to reduce the number of required beam segments for step-and-shoot intensity modulated radiation therapy (IMRT). This approach to leaf sequencing is called continuous-intensity-map-optimization (CIMO). Using a simulated annealing algorithm, CIMO seeks to minimize differences between the optimized and sequenced intensity maps. Two distinguishing features of the CIMO algorithm are (1) CIMO does not require that each optimized intensity map be clustered into discrete levels and (2) CIMO is not rule-based but rather simultaneously optimizes both the aperture shapes and weights. To test the CIMO algorithm, ten IMRT patient cases weremore » selected (four head-and-neck, two pancreas, two prostate, one brain, and one pelvis). For each case, the optimized intensity maps were extracted from the Pinnacle{sup 3} treatment planning system. The CIMO algorithm was applied, and the optimized aperture shapes and weights were loaded back into Pinnacle. A final dose calculation was performed using Pinnacle's convolution/superposition based dose calculation. On average, the CIMO algorithm provided a 54% reduction in the number of beam segments as compared with Pinnacle's leaf sequencer. The plans sequenced using the CIMO algorithm also provided improved target dose uniformity and a reduced discrepancy between the optimized and sequenced intensity maps. For ten clinical intensity maps, comparisons were performed between the CIMO algorithm and the power-of-two reduction algorithm of Xia and Verhey [Med. Phys. 25(8), 1424-1434 (1998)]. When the constraints of a Varian Millennium multileaf collimator were applied, the CIMO algorithm resulted in a 26% reduction in the number of segments. For an Elekta multileaf collimator, the CIMO algorithm resulted in a 67% reduction in the number of segments. An average leaf sequencing time of less than one minute per beam was observed.« less

Dosing of Milrinone in Preterm Neonates to Prevent Postligation Cardiac Syndrome: Simulation Study Suggests Need for Bolus Infusion.

PubMed

Hallik, Maarja; Tasa, Tõnis; Starkopf, Joel; Metsvaht, Tuuli

2017-01-01

Milrinone has been suggested as a possible first-line therapy for preterm neonates to prevent postligation cardiac syndrome (PLCS) through decreasing systemic vascular resistance and increasing cardiac contractility. The optimal dosing regimen, however, is not known. To model the dosing of milrinone in preterm infants for prevention of PLCS after surgical closure of patent ductus arteriosus (PDA). Milrinone time-concentration profiles were simulated for 1,000 subjects using the volume of distribution and clearance estimates based on one compartmental population pharmacokinetic model by Paradisis et al. [Arch Dis Child Fetal Neonatal Ed 2007;92:F204-F209]. Dose optimization was based on retrospectively collected demographic data from neonates undergoing PDA ligation in Estonian PICUs between 2012 and 2014 and existing pharmacodynamic data. The target plasma concentration was set at 150-200 ng/ml. The simulation study used demographic data from 31 neonates who underwent PDA ligation. The median postnatal age was 13 days (range: 3-29) and weight was 760 g (range: 500-2,351). With continuous infusion of milrinone 0.33 μg/kg/min, the proportion of subjects within the desired concentration range was 0% by 3 h, 36% by 6 h, and 61% by 8 h; 99% of subjects exceeded the range by 18 h. The maximum proportion of total simulated concentrations in the target range was attained with a bolus infusion of 0.73 μg/kg/min for 3 h followed by a 0.16-μg/kg/min maintenance infusion. Mathematical simulations suggest that in preterm neonates the plasma time-concentration profile of milrinone can be optimized with a slow loading dose followed by maintenance infusion. © 2016 S. Karger AG, Basel.

Population pharmacokinetics and dosing regimen design of milrinone in preterm infants

PubMed Central

Paradisis, Mary; Jiang, Xuemin; McLachlan, Andrew J; Evans, Nick; Kluckow, Martin; Osborn, David

2007-01-01

Aims To define the pharmacokinetics of milrinone in very preterm infants and determine an optimal dose regimen to prevent low systemic blood flow in the first 12 h after birth. Methods A prospective open‐labelled, dose‐escalation pharmacokinetic study was undertaken in two stages. In stage one, infants received milrinone at 0.25 μg/kg/min (n = 8) and 0.5 μg/kg/min (n = 11) infused from 3 to 24 h of age. Infants contributed 4–5 blood samples for concentration–time data which were analysed using a population modelling approach. A simulation study was used to explore the optimal dosing regimen to achieve target milrinone concentrations (180–300 ng/ml). This milrinone regimen was evaluated in stage two (n = 10). Results Infants (n = 29) born before 29 weeks gestation were enrolled. Milrinone pharmacokinetics were described using a one‐compartment model with first‐order elimination rate, with a population mean clearance (CV%) of 35 ml/h (24%) and volume of distribution of 512 ml (21%) and estimated half‐life of 10 h. The 0.25 and 0.5 μg/kg/min dosage regimens did not achieve optimal milrinone concentration‐time profiles to prevent early low systemic blood flow. Simulation studies predicted a loading infusion (0.75 μg/kg/min for 3 h) followed by maintenance infusion (0.2 μg/kg/min until 18 h of age) would provide an optimal milrinone concentration profile. This was confirmed in stage two of the study. Conclusion Population pharmacokinetic modelling in the preterm infant has established an optimal dose regimen for milrinone that increases the likelihood of achieving therapeutic aims and highlights the importance of pharmacokinetic studies in neonatal clinical pharmacology. PMID:16690639

Optimization of liposomal topotecan for use in treating neuroblastoma.

PubMed

Chernov, Lina; Deyell, Rebecca J; Anantha, Malathi; Dos Santos, Nancy; Gilabert-Oriol, Roger; Bally, Marcel B

2017-06-01

The purpose of this work was to develop an optimized liposomal formulation of topotecan for use in the treatment of patients with neuroblastoma. Drug exposure time studies were used to determine that topotecan (Hycamtin) exhibited great cytotoxic activity against SK-N-SH, IMR-32 and LAN-1 neuroblastoma human cell lines. Sphingomyelin (SM)/cholesterol (Chol) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/Chol liposomes were prepared using extrusion methods and then loaded with topotecan by pH gradient and copper-drug complexation. In vitro studies showed that SM/Chol liposomes retained topotecan significantly better than DSPC/Chol liposomes. Decreasing the drug-to-lipid ratio engendered significant increases in drug retention. Dose-range finding studies on NRG mice indicated that an optimized SM/Chol liposomal formulation of topotecan prepared with a final drug-to-lipid ratio of 0.025 (mol: mol) was better tolerated than the previously described DSPC/Chol topotecan formulation. Pharmacokinetic studies showed that the optimized SM/Chol liposomal topotecan exhibited a 10-fold increase in plasma half-life and a 1000-fold increase in AUC 0-24 h when compared with Hycamtin administered at equivalent doses (5 mg/kg). In contrast to the great extension in exposure time, SM/Chol liposomal topotecan increased the life span of mice with established LAN-1 neuroblastoma tumors only modestly in a subcutaneous and systemic model. The extension in exposure time may still not be sufficient and the formulation may require further optimization. In the future, liposomal topotecan will be assessed in combination with high-dose radiotherapy such as 131 I-metaiodobenzylguanidine, and immunotherapy treatment modalities currently used in neuroblastoma therapy. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Optimization of novel pentablock copolymer based composite formulation for sustained delivery of peptide/protein in the treatment of ocular diseases

PubMed Central

Patel, Sulabh P.; Vaishya, Ravi; Patel, Ashaben; Agrahari, Vibhuti; Pal, Dhananjay; Mitra, Ashim K.

2016-01-01

This manuscript is focused on the development of pentablock (PB) copolymer based sustained release formulation for the treatment of posterior segment ocular diseases. We have successfully synthesized biodegradable and biocompatible PB copolymers for the preparation of nanoparticles (NPs) and thermosensitive gel. Achieving high drug loading with hydrophilic biotherapeutics (peptides /proteins) is a challenging task. Moreover, small intravitreal injection volume (≤100 μL) requires high loading to develop a long term (6 months) sustained release formulation. We have successfully investigated various formulation parameters to achieve maximum peptide/protein (octreotide, insulin, lysozyme, IgG-Fab, IgG, and catalase) loading in PB NPs. Improvement in drug loading can facilitate delivery of larger doses of therapeutic proteins via limited injection volume. A composite formulation comprised of NPs in gel system exhibited sustained release (without burst effect) of peptides and proteins, may serve as a platform technology for the treatment of posterior segment ocular diseases. PMID:26964498

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

Paclitaxel-loaded polymeric microparticles: Quantitative relationships between in vitro drug release rate and in vivo pharmacodynamics

PubMed Central

Tsai, Max; Lu, Ze; Wientjes, M. Guillaume; Au, Jessie L.-S.

2013-01-01

Intraperitoneal therapy (IP) has demonstrated survival advantages in patients with peritoneal cancers, but has not become a widely practiced standard-of-care in part due to local toxicity and sub-optimal drug delivery. Paclitaxel-loaded, polymeric microparticles were developed to overcome these limitations. The present study evaluated the effects of microparticle properties on paclitaxel release (extent and rate) and in vivo pharmacodynamics. In vitro paclitaxel release from microparticles with varying physical characteristics (i.e., particle size, copolymer viscosity and composition) was evaluated. A method was developed to simulate the dosing rate and cumulative dose released in the peritoneal cavity based on the in vitro release data. The relationship between the simulated drug delivery and treatment outcomes of seven microparticle compositions was studied in mice bearing IP human pancreatic tumors, and compared to that of the intravenous Cremophor micellar paclitaxel solution used off-label in previous IP studies. Paclitaxel release from polymeric microparticles in vitro was multi-phasic; release was greater and more rapid from microparticles with lower polymer viscosities and smaller diameters (e.g., viscosity of 0.17 vs. 0.67 dl/g and diameter of 5–6 vs. 50–60 μm). The simulated drug release in the peritoneal cavity linearly correlated with treatment efficacy in mice (r2>0.8, p<0.001). The smaller microparticles, which distribute more evenly in the peritoneal cavity compared to the large microparticles, showed greater dose efficiency. For single treatment, the microparticles demonstrated up to 2-times longer survival extension and 4-times higher dose efficiency, relative to the paclitaxel/Cremophor micellar solution. Upon repeated dosing, the paclitaxel/Cremophor micellar solution showed cumulative toxicity whereas the microparticle that yielded 2-times longer survival did not display cumulative toxicity. The efficacy of IP therapy depended on both temporal and spatial factors that were determined by the characteristics of the drug delivery system. A combination of fast- and slow-releasing microparticles with 5–6 μm diameter provided favorable spatial distribution and optimal drug release for IP therapy. PMID:24056144

Early and late benefits of prasugrel in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction) analysis.

PubMed

Antman, Elliott M; Wiviott, Stephen D; Murphy, Sabina A; Voitk, Juri; Hasin, Yonathan; Widimsky, Petr; Chandna, Harish; Macias, William; McCabe, Carolyn H; Braunwald, Eugene

2008-05-27

We evaluated the relative contributions of the loading and maintenance doses of prasugrel on events in a TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction) analysis. Prasugrel is superior to clopidogrel in preventing ischemic events in patients with an acute coronary syndrome who are undergoing percutaneous coronary intervention, but it is associated with an increased risk of major bleeding. Landmark analyses for efficacy, safety, and net clinical benefit were performed from randomization to day 3 and from day 3 to the end of the trial. Significant reductions in ischemic events, including myocardial infarction, stent thrombosis, and urgent target vessel revascularization, were observed with the use of prasugrel both during the first 3 days and from 3 days to the end of the trial. Thrombolysis In Myocardial Infarction major non-coronary artery bypass graft bleeding was similar to clopidogrel during the first 3 days but was significantly greater with the use of prasugrel from 3 days to the end of the study. Net clinical benefit significantly favored prasugrel both early and late in the trial. Both the loading dose and maintenance dose of prasugrel were superior to clopidogrel for the reduction of ischemic events. This result emphasizes the importance of maintaining high levels of inhibition of platelet aggregation via P2Y(12) receptor inhibition, not only for the prevention of periprocedural ischemic events but also during long-term follow-up. The excess major bleeding observed with the use of prasugrel occurred predominantly during the maintenance phase. Approaches to reduce the relative excess of bleeding with prasugrel should focus on the maintenance dose (e.g., reduction in maintenance dose in previously reported high-risk subgroups, such as the elderly and those patients with low body weight). (A Comparison of CS-747 and Clopidogrel in Acute Coronary Syndrome Subjects Who Are to Undergo Percutaneous Coronary Intervention; NCT00097591).

Optimization of a Nanomedicine-based Pc 4-PDT Strategy for Targeted Treatment of EGFR-Overexpressing Cancers

PubMed Central

Master, Alyssa M.; Livingston, Megan; Oleinick, Nancy L.; Gupta, Anirban Sen

2012-01-01

The current clinical mainstays for cancer treatment, namely, surgical resection, chemotherapy and radiotherapy, can cause significant trauma, systemic toxicity, and functional/cosmetic debilitation of tissue, especially if repetitive treatment becomes necessary due to tumor recurrence. Hence there is significant clinical interest in alternate treatment strategies like photodynamic therapy (PDT) which can effectively and selectively eradicate tumors and can be safely repeated if needed. We have previously demonstrated that the second-generation photosensitizer Pc 4 can be formulated within polymeric micelles, and these micelles can be specifically targeted to EGFR-overexpressing cancer cells using GE11 peptide ligands, to enhance cell-specific Pc 4 delivery and internalization. In the current study, we report on the in vitro optimization of the EGFR-targeting, Pc 4 loading of the micellar nanoformulation, along with optimization of the corresponding photoirradiation conditions to maximize Pc 4 delivery, internalization and subsequent PDT-induced cytotoxicity in EGFR-overexpressing cells in vitro. In our studies, absorption and fluorescence spectroscopy were used to monitor the cell-specific uptake of the GE11-decorated Pc 4-loaded micelles and the cytotoxic singlet oxygen production from the micelle-encapsulated Pc 4, to determine the optimum ligand density and Pc 4 loading. It was found that the micelle formulations bearing 10 mole% of GE11-modified polymer component resulted in the highest cellular uptake in EGFR-overexpressing A431 cells within the shortest incubation periods. Also, the loading of ~50 μg Pc 4 per mg of polymer in these micellar formulations resulted in the highest levels of singlet oxygen production. When formulations bearing these optimized parameters were tested in vitro on A431 cells for PDT effect, a formulation dose containing 400 nM Pc 4 and photoirradiation duration of 400 seconds at a fluence of 200 mJ/cm2 yielded close to 100% cell death. PMID:22775587

Single oral dose of cannabinoid derivate loaded PLGA nanocarriers relieves neuropathic pain for eleven days.

PubMed

Berrocoso, Esther; Rey-Brea, Raquel; Fernández-Arévalo, Mercedes; Micó, Juan Antonio; Martín-Banderas, Lucía

2017-11-01

Neuropathic pain, resistant to opiates and other drugs, is a chronic/persistent state with a complex treatment and often poor efficacy. In this scenario, cannabinoids are increasingly regarded as a genuine alternative. In this paper, and in an experimental animal model of neuropathic pain, we studied the efficacy of three kinds of PLGA nanoparticles containing synthetic cannabinoid CB13: (i) plain nanoparticles (PLGA); (ii) particles coated with PEG chains (PLGA+PEG) and (iii) particles possessing hydrophilic surfaces obtained by covalently binding PEG chains (PLGA-PEG). The optimized formulation, CB13-PLGA-PEG, showed high drug loading (13%) and small size (<300nm) with a narrow distribution and controlled surface properties (near-neutral zeta potential and stable PEG corona). Animal nociceptive behavioral studies were conducted by paw pressure and acetone tests. Versus the free CB13, CB13-PLGA-PEG nanoparticles showed a very noticeable analgesic efficacy with the longest sustained pain-relieving effect, lasting up to eleven days after one oral dose. Copyright © 2017 Elsevier Inc. All rights reserved.

Neutron dose equivalent meter

DOEpatents

Olsher, Richard H.; Hsu, Hsiao-Hua; Casson, William H.; Vasilik, Dennis G.; Kleck, Jeffrey H.; Beverding, Anthony

1996-01-01

A neutron dose equivalent detector for measuring neutron dose capable of accurately responding to neutron energies according to published fluence to dose curves. The neutron dose equivalent meter has an inner sphere of polyethylene, with a middle shell overlying the inner sphere, the middle shell comprising RTV.RTM. silicone (organosiloxane) loaded with boron. An outer shell overlies the middle shell and comprises polyethylene loaded with tungsten. The neutron dose equivalent meter defines a channel through the outer shell, the middle shell, and the inner sphere for accepting a neutron counter tube. The outer shell is loaded with tungsten to provide neutron generation, increasing the neutron dose equivalent meter's response sensitivity above 8 MeV.

SU-F-J-133: Adaptive Radiation Therapy with a Four-Dimensional Dose Calculation Algorithm That Optimizes Dose Distribution Considering Breathing Motion

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

Gamma irradiation of sun-dried apricots ( Prunus armeniaca L.) for quality maintenance and quarantine purposes

NASA Astrophysics Data System (ADS)

Hussain, Peerzada R.; Meena, Raghuveer S.; Dar, Mohd A.; Wani, Ali M.

2011-07-01

The study is aimed at the optimization of gamma irradiation treatment of sun-dried apricots for quality maintenance and quarantine purposes. Sun-dried apricots pre-treated with potassium meta-bisulphite (KMS) at 2.5% w/v were procured from progressive apricot grower of district Kargil, Ladakh region of Jammu and Kashmir state. The sun-dried apricots were packed in 250 gauge polyethylene packs and gamma irradiated in the dose range 1.0-3.0 kGy. The gamma irradiated fruit including control was stored under ambient (15±2-25±2 °C, RH 70-80%) conditions and periodically evaluated for physico-chemical, sensory and microbial quality parameters. Radiation treatment at dose levels of 2.5 and 3.0 kGy proved significantly ( p≤0.05) beneficial in retention of higher levels of β-carotene, ascorbic acid, total sugars and color values without impairing the taste as perceived by the sensory panel analysists. The above optimized doses retained the β-carotene content of sun-dried apricots to the extent of 71.2% and 72.6% compared to 63.9% in control samples after 18 months of storage. Irradiation treatment facilitated the release of residual sulfur dioxide in KMS pre-treated sun-dried apricots significantly ( p≤0.05) below the prescribed limit for dried products. During storage, two-fold decrease in sulfur dioxide content was recorded in irradiated samples (3.0 kGy) as compared to 16.9% in control. The above optimized doses besides maintaining the higher overall acceptability of sun-dried apricots resulted in 5 log reductions in microbial load just after irradiation and 1.0 and 1.3 log reductions in yeast and mold and bacterial count after 18 months of ambient storage.

Dose rate in brachytherapy using after-loading machine: pulsed or high-dose rate?

PubMed

Hannoun-Lévi, J-M; Peiffert, D

2014-10-01

Since February 2014, it is no longer possible to use low-dose rate 192 iridium wires due to the end of industrial production of IRF1 and IRF2 sources. The Brachytherapy Group of the French society of radiation oncology (GC-SFRO) has recommended switching from iridium wires to after-loading machines. Two types of after-loading machines are currently available, based on the dose rate used: pulsed-dose rate or high-dose rate. In this article, we propose a comparative analysis between pulsed-dose rate and high-dose rate brachytherapy, based on biological, technological, organizational and financial considerations. Copyright © 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Alginate coated chitosan nanogel for the controlled topical delivery of Silver sulfadiazine.

PubMed

El-Feky, Gina S; El-Banna, Sally T; El-Bahy, G S; Abdelrazek, E M; Kamal, Mustafa

2017-12-01

Burn wounds environment favors the growth of micro-organisms causing delay in wound healing. The traditional treatment with antimicrobial creams offer inaccurate doses. The aim of the present study is to formulate and evaluate different silver sulfadiazine loaded nanogel formulations. A factorial design experiment was used for the identification of critical process parameters and for the optimization of the respective process conditions. The prepared drug loaded nanogels were characterized for their particle size, zeta potential, entrapment efficiency and swelling index in order to demonstrate their physicochemical properties, in addition, FTIR, TEM, SEM and in vitro release were used for characterization. The release profile of all tested nanogels showed an initial burst followed by a slow and continuous release rate. An optimum nanogel formulation was predicted by the JMP ® software according to the stated prediction expressions and was composed of 0.4% sodium alginate (ALG) and 0.414% Silver sulfadiazine (SSD). The optimized formulation showed higher therapeutic efficacy in vivo when compared to market product. Copyright © 2017 Elsevier Ltd. All rights reserved.

Optimal load scheduling in commercial and residential microgrids

NASA Astrophysics Data System (ADS)

Ganji Tanha, Mohammad Mahdi

Residential and commercial electricity customers use more than two third of the total energy consumed in the United States, representing a significant resource of demand response. Price-based demand response, which is in response to changes in electricity prices, represents the adjustments in load through optimal load scheduling (OLS). In this study, an efficient model for OLS is developed for residential and commercial microgrids which include aggregated loads in single-units and communal loads. Single unit loads which include fixed, adjustable and shiftable loads are controllable by the unit occupants. Communal loads which include pool pumps, elevators and central heating/cooling systems are shared among the units. In order to optimally schedule residential and commercial loads, a community-based optimal load scheduling (CBOLS) is proposed in this thesis. The CBOLS schedule considers hourly market prices, occupants' comfort level, and microgrid operation constraints. The CBOLS' objective in residential and commercial microgrids is the constrained minimization of the total cost of supplying the aggregator load, defined as the microgrid load minus the microgrid generation. This problem is represented by a large-scale mixed-integer optimization for supplying single-unit and communal loads. The Lagrangian relaxation methodology is used to relax the linking communal load constraint and decompose the independent single-unit functions into subproblems which can be solved in parallel. The optimal solution is acceptable if the aggregator load limit and the duality gap are within the bounds. If any of the proposed criteria is not satisfied, the Lagrangian multiplier will be updated and a new optimal load schedule will be regenerated until both constraints are satisfied. The proposed method is applied to several case studies and the results are presented for the Galvin Center load on the 16th floor of the IIT Tower in Chicago.

Optimization of Nanowire-Resistance Load Logic Inverter.

PubMed

Hashim, Yasir; Sidek, Othman

2015-09-01

This study is the first to demonstrate characteristics optimization of nanowire resistance load inverter. Noise margins and inflection voltage of transfer characteristics are used as limiting factors in this optimization. Results indicate that optimization depends on resistance value. Increasing of load resistor tends to increasing in noise margins until saturation point, increasing load resistor after this point will not improve noise margins significantly.

An implementation of particle swarm optimization to evaluate optimal under-voltage load shedding in competitive electricity markets

NASA Astrophysics Data System (ADS)

Hosseini-Bioki, M. M.; Rashidinejad, M.; Abdollahi, A.

2013-11-01

Load shedding is a crucial issue in power systems especially under restructured electricity environment. Market-driven load shedding in reregulated power systems associated with security as well as reliability is investigated in this paper. A technoeconomic multi-objective function is introduced to reveal an optimal load shedding scheme considering maximum social welfare. The proposed optimization problem includes maximum GENCOs and loads' profits as well as maximum loadability limit under normal and contingency conditions. Particle swarm optimization (PSO) as a heuristic optimization technique, is utilized to find an optimal load shedding scheme. In a market-driven structure, generators offer their bidding blocks while the dispatchable loads will bid their price-responsive demands. An independent system operator (ISO) derives a market clearing price (MCP) while rescheduling the amount of generating power in both pre-contingency and post-contingency conditions. The proposed methodology is developed on a 3-bus system and then is applied to a modified IEEE 30-bus test system. The obtained results show the effectiveness of the proposed methodology in implementing the optimal load shedding satisfying social welfare by maintaining voltage stability margin (VSM) through technoeconomic analyses.

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

PubMed Central

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

1994-01-01

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

Topical ketoprofen nanogel: artificial neural network optimization, clustered bootstrap validation, and in vivo activity evaluation based on longitudinal dose response modeling.

PubMed

Elkomy, Mohammed H; Elmenshawe, Shahira F; Eid, Hussein M; Ali, Ahmed M A

2016-11-01

This work aimed at investigating the potential of solid lipid nanoparticles (SLN) as carriers for topical delivery of Ketoprofen (KP); evaluating a novel technique incorporating Artificial Neural Network (ANN) and clustered bootstrap for optimization of KP-loaded SLN (KP-SLN); and demonstrating a longitudinal dose response (LDR) modeling-based approach to compare the activity of topical non-steroidal anti-inflammatory drug formulations. KP-SLN was fabricated by a modified emulsion/solvent evaporation method. Box-Behnken design was implemented to study the influence of glycerylpalmitostearate-to-KP ratio, Tween 80, and lecithin concentrations on particle size, entrapment efficiency, and amount of drug permeated through rat skin in 24 hours. Following clustered bootstrap ANN optimization, the optimized KP-SLN was incorporated into an aqueous gel and evaluated for rheology, in vitro release, permeability, skin irritation and in vivo activity using carrageenan-induced rat paw edema model and LDR mathematical model to analyze the time course of anti-inflammatory effect at various application durations. Lipid-to-drug ratio of 7.85 [bootstrap 95%CI: 7.63-8.51], Tween 80 of 1.27% [bootstrap 95%CI: 0.601-2.40%], and Lecithin of 0.263% [bootstrap 95%CI: 0.263-0.328%] were predicted to produce optimal characteristics. Compared with profenid® gel, the optimized KP-SLN gel exhibited slower release, faster permeability, better texture properties, greater efficacy, and similar potency. SLNs are safe and effective permeation enhancers. ANN coupled with clustered bootstrap is a useful method for finding optimal solutions and estimating uncertainty associated with them. LDR models allow mechanistic understanding of comparative in vivo performances of different topical formulations, and help design efficient dermatological bioequivalence assessment methods.

Microspheres for the oral delivery of insulin: preparation, evaluation and hypoglycaemic effect in streptozotocin-induced diabetic rats.

PubMed

Zhang, Huan; Wang, Weimei; Li, Haoran; Peng, Yi; Zhang, Zhiqing

2018-01-01

Insulin-loaded microspheres were prepared by alternating deposition film layers that were composed of insulin and poly(vinyl sulfate) potassium on the surface of poly(lactic acid) (PLA) microspheres. The preparation of the insulin-loaded microspheres was optimized by an orthogonal test design, and the relationship between drug loading (DL) and film layers was studied. The particle size, DL and encapsulation efficiency of the obtained insulin-loaded microspheres with 10 films were 5.25 ± 0.15 µm, 111.33 ± 1.15 mg/g and 33.7 ± 0.19%, respectively. Following this, the physical characteristics of the insulin-loaded microspheres were investigated. The results from scanning electron microscopy and a laser particle size analyzer (LPSA) indicated the spherical morphology, rough surface and increasing particle sizes of the insulin-loaded microspheres, which were compared to those of PLA microspheres. An in vitro release study showed that the insulin-loaded microspheres were stable in HCl solution (pH 1.0) and released insulin slowly in phosphate-buffered solution (pH 6.8). Finally, the drug efficacy of the prepared insulin-loaded microspheres via oral administration was evaluated in rats with diabetes induced by streptozotocin, and an obvious dose-dependent hypoglycemic effect was observed. This preliminary data could illustrate the prospect of using microspheres for the oral delivery of insulin.

A Dose-Response Study of Inactivated Low Pathogenic Avian Influenza H9N2 Virus in Specific-Pathogen-Free and Commercial Broiler Chickens.

PubMed

Kilany, Walid H; Ali, Ahmed; Bazid, Abdel-Hamid I; El-Deeb, Ayman H; El-Abideen, Mohamed A Zain; Sayed, Magdy El; El-Kady, Magdy F

2016-05-01

Since the first report of low pathogenic avian influenza (LPAI) H9N2 virus in Egypt in 2011, the Egyptian poultry industry has suffered from unexpected economic losses as a result of the wide spread of LPAI H9N2. Hence, inactivated H9N2 vaccines have been included in the vaccination programs of different poultry production sectors. The optimal antigen content of avian influenza virus vaccines is essential to reach protective antibody titers. In this study, the correlation between antigen content (based on hemagglutinating units [HAU]) and postvaccination (PV) antibody response of H9N2 inactivated vaccine was studied. Five different vaccine antigen loads (128, 200, 250, 300, and 350 HAU formulas/dose) were investigated in commercial broiler and specific-pathogen-free (SPF) chickens. Vaccine safety and PV antibody responses were monitored. At the fourth week PV only SPF vaccinated groups (128, 200, 250, and 300 HAU/dose) were challenged using LPAI H9N2 (A/Ck/EG/114940v/NLQP/11) virus with 10(6) EID50/bird. Oropharyngeal swabs were used to monitor virus shedding at 2, 4, 6, and 10 days postchallenge. Results showed that all vaccine formulations were well tolerated, and the highest antibody titers were observed in birds vaccinated with higher HAU. Vaccines containing 128 and 200 HAU/dose did not induce the required protective HI titers by 3 wk PV. Meanwhile, the challenge experiment in SPF chickens showed that 250 and 300 HAU vaccine doses were required to reduce the level and duration of virus shedding. Study results thus suggest that inactivated H9N2 vaccines containing at least 250 HAU/dose will induce the optimal protective titers and minimize virus shedding in SPF chickens.

SU-E-T-750: Three Dimensional in Silico Study of Brachytherapy Application with In-Situ Dose-Painting Administered Via Gold-Nanoparticle Eluters

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

Sinha, N; Cifter, G; Ngwa, W

Purpose: Brachytherapy Application with in-situ Dose-painting Administered via Gold-Nanoparticle Eluters (BANDAGE) has been proposed as a new therapeutic strategy for radiation boosting of high-risk prostate tumor subvolume while minimizing dose to neighboring organs-at-risk. In a previous study the one-dimensional dose-painting with gold nanoparticles (GNP) released from GNP-loaded brachytherapy spacers was investigated. The current study investigates BANDAGE in three-dimensions. Methods: To simulate GNPs transport in prostrate tumors, a three dimensional, cylindrically symmetric transport model was generated using a finite element method (FEM). A mathematical model of Gold nanoparticle (GNPs) transport provides a useful strategy to optimize potential treatment planning for BANDAGE.more » Here, treatment of tumors with a radius of 2.5 cm was simulated in 3-D. This simulation phase considered one gold based cylindrical spacer (GBS of size 5mm × 0.8 mm) introduced at the center of the spherical tumor with initial concentration of 100 mg/g or 508 mol/m3 of GNP. Finite element mesh is used to stimulate the GNP transport. Gold concentrations within the tumor were obtained using a 3-D FEM solution implemented by COMSOL. Results: The analysis shows the spread of the GNPs through-out the tumor with the increase of concentration towards the periphery with time. The analysis also shows the concentration profiles and corresponding dose enhancement factors (dose boost factor) as a function of GNP size. Conclusion: This study demonstrates the use of computational modeling and optimal parameter estimation to predict local GNPs from central implant as a function of x, y and z axis . Such a study provides a useful reference for ongoing translational studies for the BANDAGE approach.« less

Effect of Low-Dose MDCT and Iterative Reconstruction on Trabecular Bone Microstructure Assessment.

PubMed

Kopp, Felix K; Holzapfel, Konstantin; Baum, Thomas; Nasirudin, Radin A; Mei, Kai; Garcia, Eduardo G; Burgkart, Rainer; Rummeny, Ernst J; Kirschke, Jan S; Noël, Peter B

2016-01-01

We investigated the effects of low-dose multi detector computed tomography (MDCT) in combination with statistical iterative reconstruction algorithms on trabecular bone microstructure parameters. Twelve donated vertebrae were scanned with the routine radiation exposure used in our department (standard-dose) and a low-dose protocol. Reconstructions were performed with filtered backprojection (FBP) and maximum-likelihood based statistical iterative reconstruction (SIR). Trabecular bone microstructure parameters were assessed and statistically compared for each reconstruction. Moreover, fracture loads of the vertebrae were biomechanically determined and correlated to the assessed microstructure parameters. Trabecular bone microstructure parameters based on low-dose MDCT and SIR significantly correlated with vertebral bone strength. There was no significant difference between microstructure parameters calculated on low-dose SIR and standard-dose FBP images. However, the results revealed a strong dependency on the regularization strength applied during SIR. It was observed that stronger regularization might corrupt the microstructure analysis, because the trabecular structure is a very small detail that might get lost during the regularization process. As a consequence, the introduction of SIR for trabecular bone microstructure analysis requires a specific optimization of the regularization parameters. Moreover, in comparison to other approaches, superior noise-resolution trade-offs can be found with the proposed methods.

Positively charged biopolymeric nanoparticles for the inhibition of Pseudomonas aeruginosa biofilms

NASA Astrophysics Data System (ADS)

Chronopoulou, Laura; Di Domenico, Enea Gino; Ascenzioni, Fiorentina; Palocci, Cleofe

2016-10-01

Currently, many microbial infections have the potential to become lethal owing to the development of antimicrobial resistance by means of different mechanisms and mainly on the basis of the fact that many drugs are unable to reach therapeutic levels in the target sites. This requires the use of high doses and frequent administrations, causing adverse side effects or in some cases toxicity. The use of nanoparticle systems could help overcome such problems and increase drug efficacy. In the present study, we developed a new drug delivery system based on the use of biopolymeric nanovectors loaded with tobramycin (Tb), which is the standard antibiotic for the treatment of Cystic Fibrosis-associated P. aeruginosa lung infections. Tb-loaded biopolymeric nanoparticles composed by dextran sulfate (DS) and chitosan (CS) were prepared by ionotropic gelation. We optimized drug entrapment in DS/CS nanoparticles, obtaining particles of 170 nm and with a drug loading of 400 µg Tb/mg of nanoparticles. In accord with in vitro release experiments, such preparations were able to release approximately 25 % of their cargo in 60 h. In vitro, the antimicrobial efficacy of the drug delivery system on P. aeruginosa biofilm was tested and compared to the effects of free drug revealing that this formulation can reduce the viability of P. aeruginosa biofilms for 48 h with a single-dose administration.

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

Ferreira, C; Ahmad, S; Firestone, B

Purpose: To compare dosimetrically three plan calculation systems (Plato, Varian Brachytherapy, and in-house-made Excel) available for I-125 COMS eye plaque treatment with measurement. Methods: All systems assume homogeneous media and calculations are based on a three-dimensional Cartesian coordinates, Plato and Brachytherapy Planning are based on AAPM TG-43 and the in-house Excel program only on inverse square corrections. Doses at specific depths were measured with EBT3 Gafchromic film from a fully loaded and a partially loaded 16 mm plaque (13 and 8 seeds respectively, I-125, model 6711 GE, Oncura). Measurements took place in a water tank, utilizing solid water blocks andmore » a 3D-printed plaque holder. Taking advantage that gafchromic film has low energy dependence, a dose step wedge was delivered with 6 MV photon beam from a Varian 2100 EX linac for calibration. The gray-scale to dose in cGy was obtained with an Epson Expression 10000 XL scanner in the green channel. Treatment plans were generated for doses of 2200 cGy to a depth of 7 mm, and measurements were taken on a sagittal plane. Results: The calculated dose at the prescription point was 2242, 2344, and 2211 cGy with Excel, Brachyvision and Plato respectively for a fully loaded plaque, for the partially loaded plaque the doses were 2266, 2477, and 2193 cGy respectively. At 5 mm depth the doses for Brachyvision and Plato were comparable (3399 and 3267 cGy respectively), however, the measured dose in film was 3180 cGy which was lower by as much as 6.4% in the fully loaded plaque and 7.6% in the partially loaded plaque. Conclusion: Careful methodology and calibration are essential when measuring doses at specific depth due to the sensitivity and rapid dose fall off of I-125.« less

In Vivo Biomarker Analysis of the Effects of Intranasally Dosed PC945, a Novel Antifungal Triazole, on Aspergillus fumigatus Infection in Immunocompromised Mice

PubMed Central

Kimura, Genki; Nakaoki, Takahiro; Colley, Thomas; Rapeport, Garth; Strong, Pete; Kizawa, Yasuo

2017-01-01

ABSTRACT PC945 is a novel triazole optimized for lung delivery, and the objective of this study is to determine the effects of intranasally dosed PC945 on Aspergillus fumigatus infection and associated biomarkers in immunocompromised mice. PC945, posaconazole, or voriconazole was administered intranasally once daily on days 0 to 3 (early intervention) or days 1 to 3 (late intervention) postinfection in temporarily neutropenic A/J mice infected intranasally with A. fumigatus, and bronchoalveolar lavage fluid (BALF) and serum were collected on day 3. The effects of extended prophylaxis treatment (daily from days −7 to +3 or days −7 to 0) were also compared with those of the shorter treatment regimens (days −1 to +3 or days −1 and 0). Early and late interventions with PC945 (2.8 to 350 μg/mouse; approximately 0.11 to ∼14 mg/kg of body weight) were found to inhibit lung fungal loads and to decrease the concentrations of galactomannan (GM) in both BALF and serum as well as several biomarkers in BALF (interferon gamma [IFN-γ], interleukin-17 [IL-17], and malondialdehyde) and serum (tumor necrosis factor alpha [TNF-α] and IL-6) in a dose-dependent manner and were >3- and >47-fold more potent than intranasally dosed posaconazole and voriconazole, respectively. Furthermore, extended prophylaxis with low-dose PC945 (0.56 μg/mouse; 0.022 mg/kg) was found to inhibit fungal loads and to decrease the concentrations biomarkers more potently than did the shorter treatment regimens. Thus, PC945 dosed intranasally once daily showed potent antifungal effects, and the effects of PC945 accumulated upon repeat dosing and were persistent. Therefore, PC945 has the potential to be a novel inhaled therapy for the treatment of A. fumigatus infection in humans. PMID:28630185

Dose to mass for evaluation and optimization of lung cancer radiation therapy.

PubMed

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.

Numerical optimization of composite hip endoprostheses under different loading conditions

NASA Technical Reports Server (NTRS)

Blake, T. A.; Davy, D. T.; Saravanos, D. A.; Hopkins, D. A.

1992-01-01

The optimization of composite hip implants was investigated. Emphasis was placed on the effect of shape and material tailoring of the implant to improve the implant-bone interaction. A variety of loading conditions were investigated to better understand the relationship between loading and optimization outcome. Comparisons of the initial and optimal models with more complex 3D finite element models were performed. The results indicate that design improvements made using this method result in similar improvements in the 3D models. Although the optimization outcomes were significantly affected by the choice of loading conditions, certain trends were observed that were independent of the applied loading.

Metal-free virucidal effects induced by g-C3N4 under visible light irradiation: Statistical analysis and parameter optimization.

PubMed

Zhang, Chi; Li, Yi; Zhang, Wenlong; Wang, Peifang; Wang, Chao

2018-03-01

Waterborne viruses with a low infectious dose and a high pathogenic potential pose a serious risk for humans all over the world, calling for a cost-effective and environmentally-friendly inactivation method. Optimizing operational parameters during the disinfection process is a facile and efficient way to achieve the satisfactory viral inactivation efficiency. Here, the antiviral effects of a metal-free visible-light-driven graphitic carbon nitride (g-C 3 N 4 ) photocatalyst were optimized by varying operating parameters with response surface methodology (RSM). Twenty sets of viral inactivation experiments were performed by changing three operating parameters, namely light intensity, photocatalyst loading and reaction temperature, at five levels. According to the experimental data, a semi-empirical model was developed with a high accuracy (determination coefficient R 2  = 0.9908) and then applied to predict the final inactivation efficiency of MS2 (a model virus) after 180 min exposure to the photocatalyst and visible light illumination. The corresponding optimal values were found to be 199.80 mW/cm 2 , 135.40 mg/L and 24.05 °C for light intensity, photocatalyst loading and reaction temperature, respectively. Under the optimized conditions, 8 log PFU/mL of viruses could be completely inactivated by g-C 3 N 4 without regrowth within 240 min visible light irradiation. Our study provides not only an extended application of RSM in photocatalytic viral inactivation but also a green and effective method for water disinfection. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effect of statistical noise on IMRT plan quality and convergence for MC-based and MC-correction-based optimized treatment plans.

PubMed

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.

Optimization of Methylphenidate Extended-Release Chewable Tablet Dose in Children with ADHD: Open-Label Dose Optimization in a Laboratory Classroom Study.

PubMed

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.

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

PubMed Central

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

2017-01-01

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

Risk Assessment Integrated QbD Approach for Development of Optimized Bicontinuous Mucoadhesive Limicubes for Oral Delivery of Rosuvastatin.

PubMed

Javed, Md Noushad; Kohli, Kanchan; Amin, Saima

2018-04-01

Statins are widely prescribed for hyperlipidemia, cancer, and Alzheimer's disease but are facing some inherent challenges such as low solubility and drug loading, higher hepatic metabolism, as well as instability at gastric pH. So, relatively higher circulating dose, required for exerting the therapeutic benefits, leads to dose-mediated severe toxicity. Furthermore, due to low biocompatibility, high toxicity, and other regulatory caveats such as product conformity, reproducibility, and stability of conventional formulations as well as preferentially higher bioabsorption of lipids in their favorable cuboidal geometry, enhancement in in vivo biopharmaceutical performance of Rosuvastatin could be well manifested in Quality by Design (QbD) integrated cuboidal-shaped mucoadhesive microcrystalline delivery systems (Limicubes). Here, quality-target-product-profile (QTPPs), critical quality attributes (CQAs), Ishikawa fishbone diagram, and integration of risk management through risk assessment matrix for failure mode and effects analysis (FMEA) followed by processing of Plackett-Burman design matrix using different statistical test for the first time established an approach to substantiate the claims that controlling levels of only these three screened out independent process variables, i.e., Monoolein (B = 800-1100 μL), Poloxamer (C = 150-200 mg), and stirring speed (F = 700-1000 rpm) were statistically significant to modulate and improve the biopharmaceutical performance affecting key attributes, viz., average particle size (Y 1  = 1.40-2.70 μ), entrapment efficiency (Y 2  = 62.60-88.80%), and drug loading (Y 3  = 0.817-1.15%), in QbD-enabled process. The optimal performance of developed Limicubes exhibited an average particle size of 1.8 ± 0.2 μ, entrapment efficiency 80.32 ± 2.88%, and drug loading 0.93 ± 0.08% at the level of 1100 μL (+ 1), 200 mg (+ 1), and 700 rpm (- 1) for Monoolein, Poloxamer, and stirring speed, respectively.

Safety and tolerability of adjunctive lacosamide intravenous loading dose in lacosamide-naive patients with partial-onset seizures.

PubMed

Fountain, Nathan B; Krauss, Gregory; Isojarvi, Jouko; Dilley, Deanne; Doty, Pamela; Rudd, G David

2013-01-01

To examine the safety and tolerability of rapidly initiating adjunctive lacosamide via a single intravenous loading dose followed by twice-daily oral lacosamide in lacosamide-naive adults with partial-onset seizures. This open-label, multicenter trial, enrolled patients with epilepsy who were taking 1-2 antiepileptic drugs (AEDs) in one of four sequential cohorts containing 25 subjects each. An intravenous lacosamide loading dose (200, 300, or 400 mg) was administered over 15 min followed 12 h later by initiation of oral dosing consisting of one-half of the loading dose administered twice daily for 6.5 days. The first cohort was administered lacosamide 200 mg/day, followed by a cohort at 300 mg/day, and then a cohort at 400 mg/day. The results from each cohort were evaluated before enrolling the next highest dose level. The fourth cohort enrolled patients at the highest dose with clinically acceptable safety and tolerability results. Safety evaluations included treatment-emergent adverse events (TEAEs), patient withdrawals due to TEAEs, and changes in vital signs, 12-lead electrocardiography (ECG) studies, laboratory parameters, and clinical examinations. Postinfusion lacosamide plasma concentrations were also evaluated. A total of 100 patients were enrolled, 25 in each cohort. The loading dose for the repeat cohort was 300 mg; therefore, 25 patients were enrolled at 200 mg/day, 50 at 300 mg/day, and 25 at 400 mg/day. Most TEAEs occurred within the first 4 h following infusion; dose-related TEAEs (incidence ≥10%) during this timeframe included dizziness, somnolence, and nausea. Seven patients withdrew, all due to TEAEs: three (6%) from the combined 300 mg group and four (16%) from the 400 mg group; four of these patients discontinued within 4 h following infusion. The most common TEAEs leading to discontinuation (overall incidence >1%) were dizziness (6%), nausea (5%), and vomiting (3%). No clinically relevant pattern of changes from baseline ECG, clinical laboratory parameters, or vital signs were observed. Trough plasma concentrations suggested that near steady-state lacosamide concentrations were achieved with a single intravenous loading dose. Intravenous loading doses of 200 and 300 mg lacosamide administered over 15 min followed by oral lacosamide were well tolerated in lacosamide-naive patients. The 400-mg loading dose was less well tolerated due to a higher frequency of dose-related TEAEs. These results support the feasibility of rapid initiation of adjunctive lacosamide treatment. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Short-Term Load Forecasting Based Automatic Distribution Network Reconfiguration

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

Jiang, Huaiguang; Ding, Fei; Zhang, Yingchen

In a traditional dynamic network reconfiguration study, the optimal topology is determined at every scheduled time point by using the real load data measured at that time. The development of the load forecasting technique can provide an accurate prediction of the load power that will happen in a future time and provide more information about load changes. With the inclusion of load forecasting, the optimal topology can be determined based on the predicted load conditions during a longer time period instead of using a snapshot of the load at the time when the reconfiguration happens; thus, the distribution system operatormore » can use this information to better operate the system reconfiguration and achieve optimal solutions. This paper proposes a short-term load forecasting approach to automatically reconfigure distribution systems in a dynamic and pre-event manner. Specifically, a short-term and high-resolution distribution system load forecasting approach is proposed with a forecaster based on support vector regression and parallel parameters optimization. The network reconfiguration problem is solved by using the forecasted load continuously to determine the optimal network topology with the minimum amount of loss at the future time. The simulation results validate and evaluate the proposed approach.« less

Short-Term Load Forecasting Based Automatic Distribution Network Reconfiguration: Preprint

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

Jiang, Huaiguang; Ding, Fei; Zhang, Yingchen

In the traditional dynamic network reconfiguration study, the optimal topology is determined at every scheduled time point by using the real load data measured at that time. The development of load forecasting technique can provide accurate prediction of load power that will happen in future time and provide more information about load changes. With the inclusion of load forecasting, the optimal topology can be determined based on the predicted load conditions during the longer time period instead of using the snapshot of load at the time when the reconfiguration happens, and thus it can provide information to the distribution systemmore » operator (DSO) to better operate the system reconfiguration to achieve optimal solutions. Thus, this paper proposes a short-term load forecasting based approach for automatically reconfiguring distribution systems in a dynamic and pre-event manner. Specifically, a short-term and high-resolution distribution system load forecasting approach is proposed with support vector regression (SVR) based forecaster and parallel parameters optimization. And the network reconfiguration problem is solved by using the forecasted load continuously to determine the optimal network topology with the minimum loss at the future time. The simulation results validate and evaluate the proposed approach.« less

Short-Term Load Forecasting-Based Automatic Distribution Network Reconfiguration

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

Jiang, Huaiguang; Ding, Fei; Zhang, Yingchen

In a traditional dynamic network reconfiguration study, the optimal topology is determined at every scheduled time point by using the real load data measured at that time. The development of the load forecasting technique can provide an accurate prediction of the load power that will happen in a future time and provide more information about load changes. With the inclusion of load forecasting, the optimal topology can be determined based on the predicted load conditions during a longer time period instead of using a snapshot of the load at the time when the reconfiguration happens; thus, the distribution system operatormore » can use this information to better operate the system reconfiguration and achieve optimal solutions. This paper proposes a short-term load forecasting approach to automatically reconfigure distribution systems in a dynamic and pre-event manner. Specifically, a short-term and high-resolution distribution system load forecasting approach is proposed with a forecaster based on support vector regression and parallel parameters optimization. The network reconfiguration problem is solved by using the forecasted load continuously to determine the optimal network topology with the minimum amount of loss at the future time. The simulation results validate and evaluate the proposed approach.« less

The optimization of fermentation conditions for producing cellulase of Bacillus amyloliquefaciens and its application to goose feed

PubMed Central

Ye, Miao; Sun, Linghong; Yang, Ru; Qi, KeZong

2017-01-01

The proper culture conditions for producing cellulase of Bacillus amyloliquefaciens S1, isolated from the cecum of goose was optimized by single-factor experiment combined with orthogonal test. The properties of the cellulase were investigated by DNS method. The appropriate doses of B. amyloliquefaciens S1 were obtained by adding them to goose feed. It indicated that the suitable culture conditions of producing cellulase were the culture temperature of 37°C, the initial pH of 7.0, the incubation time of 72 h and the loaded liquid volume of 75 ml per 250 ml. The effects of each factor on producing cellulase by B. amyloliquefaciens S1 were as follows: initial pH > incubation time = culture temperature > loaded liquid volume. The optimum reaction temperature and pH were 50°C and 7.0, respectively. This enzyme is a kind of neutral cellulase that possesses resistance to heat and acidity. It showed high activity to absorbent cotton, soya bean meal and filter paper. By adding different doses of B. amyloliquefaciens S1 to the goose feed, it was found that the egg production, average egg weight, fertilization rate and the hatching rate were promoted both in experiment 1 (1.5 g kg−1) and experiment 2 (3 g kg−1). Also the difference of egg production, fertilization rate and hatching rate between experiment 1 and control group was obvious (p < 0.05), and the average egg weight was significantly increased in experiment 2 (p < 0.05). PMID:29134097

Ultra-fast fluence optimization for beam angle selection algorithms

NASA Astrophysics Data System (ADS)

Bangert, M.; Ziegenhein, P.; Oelfke, U.

2014-03-01

Beam angle selection (BAS) including fluence optimization (FO) is among the most extensive computational tasks in radiotherapy. Precomputed dose influence data (DID) of all considered beam orientations (up to 100 GB for complex cases) has to be handled in the main memory and repeated FOs are required for different beam ensembles. In this paper, the authors describe concepts accelerating FO for BAS algorithms using off-the-shelf multiprocessor workstations. The FO runtime is not dominated by the arithmetic load of the CPUs but by the transportation of DID from the RAM to the CPUs. On multiprocessor workstations, however, the speed of data transportation from the main memory to the CPUs is non-uniform across the RAM; every CPU has a dedicated memory location (node) with minimum access time. We apply a thread node binding strategy to ensure that CPUs only access DID from their preferred node. Ideal load balancing for arbitrary beam ensembles is guaranteed by distributing the DID of every candidate beam equally to all nodes. Furthermore we use a custom sorting scheme of the DID to minimize the overall data transportation. The framework is implemented on an AMD Opteron workstation. One FO iteration comprising dose, objective function, and gradient calculation takes between 0.010 s (9 beams, skull, 0.23 GB DID) and 0.070 s (9 beams, abdomen, 1.50 GB DID). Our overall FO time is < 1 s for small cases, larger cases take ~ 4 s. BAS runs including FOs for 1000 different beam ensembles take ~ 15-70 min, depending on the treatment site. This enables an efficient clinical evaluation of different BAS algorithms.

Total body irradiation, toward optimal individual delivery: dose evaluation with metal oxide field effect transistors, thermoluminescence detectors, and a treatment planning system.

PubMed

Bloemen-van Gurp, Esther J; Mijnheer, Ben J; Verschueren, Tom A M; Lambin, Philippe

2007-11-15

To predict the three-dimensional dose distribution of our total body irradiation technique, using a commercial treatment planning system (TPS). In vivo dosimetry, using metal oxide field effect transistors (MOSFETs) and thermoluminescence detectors (TLDs), was used to verify the calculated dose distributions. A total body computed tomography scan was performed and loaded into our TPS, and a three-dimensional-dose distribution was generated. In vivo dosimetry was performed at five locations on the patient. Entrance and exit dose values were converted to midline doses using conversion factors, previously determined with phantom measurements. The TPS-predicted dose values were compared with the MOSFET and TLD in vivo dose values. The MOSFET and TLD dose values agreed within 3.0% and the MOSFET and TPS data within 0.5%. The convolution algorithm of the TPS, which is routinely applied in the clinic, overestimated the dose in the lung region. Using a superposition algorithm reduced the calculated lung dose by approximately 3%. The dose inhomogeneity, as predicted by the TPS, can be reduced using a simple intensity-modulated radiotherapy technique. The use of a TPS to calculate the dose distributions in individual patients during total body irradiation is strongly recommended. Using a TPS gives good insight of the over- and underdosage in a patient and the influence of patient positioning on dose homogeneity. MOSFETs are suitable for in vivo dosimetry purposes during total body irradiation, when using appropriate conversion factors. The MOSFET, TLD, and TPS results agreed within acceptable margins.

Effects of particle size, helium gas pressure and microparticle dose on the plasma concentration of indomethacin after bombardment of indomethacin-loaded poly-L-lactic acid microspheres using a Helios gun system.

PubMed

Uchida, Masaki; Natsume, Hideshi; Kobayashi, Daisuke; Sugibayashi, Kenji; Morimoto, Yasunori

2002-05-01

We investigated the effects of the particle size of indomethacin-loaded poly-L-lactic acid microspheres (IDM-loaded PLA MS), the helium pressure used to accelerate the particles, and the bombardment dose of PLA MS on the plasma concentration of IDM after bombarding with IDM-loaded PLA MS of different particle size ranges, 20-38, 44-53 and 75-100 microm, the abdomen of hairless rats using the Helios gene gun system (Helios gun system). Using larger particles and a higher helium pressure, produced an increase in the plasma IDM concentration and the area under the plasma concentration-time curve (AUC) and resultant F (relative bioavailability with respect to intracutaneous injection) of IDM increased by an amount depending on the particle size and helium pressure. Although a reduction in the bombardment dose led to a decrease in C(max) and AUC, F increased on decreasing the bombardment dose. In addition, a more efficient F was obtained after bombarding with IDM-loaded PLA MS of 75-100 microm in diameter at each low dose in different sites of the abdomen compared with that after bolus bombardment with a high dose (dose equivalent). These results suggest that the bombardment injection of drug-loaded microspheres by the Helios gun system is a very useful tool for delivering a variety of drugs in powder form into the skin and systemic circulation.

Capsaicin-loaded nanolipoidal carriers for topical application: design, characterization, and in vitro/in vivo evaluation.

PubMed

Wang, Xia-Rong; Gao, Si-Qian; Niu, Xiao-Qian; Li, Long-Jian; Ying, Xiao-Ying; Hu, Zhong-Jie; Gao, Jian-Qing

2017-01-01

Capsaicin has been used in clinical applications for the treatment of pain disorders and inflammatory diseases. Given the strong pungency and high oil/water partition coefficient of capsaicin, capsaicin-loaded nanolipoidal carriers (NLCs) were designed to increase permeation and achieve the analgesic, anti-inflammatory effect with lower skin irritation. Capsaicin-loaded NLCs were prepared and later optimized by the Box-Behnken design. The physicochemical characterizations, morphology, and encapsulation of the capsaicin-loaded NLCs were subsequently confirmed. Capsaicin-loaded NLCs and capsaicin-loaded NLCs gel exhibited sustained release and no cytotoxicity properties. Also, they could significantly enhance the penetration amount, permeation flux, and skin retention amounts of capsaicin due to the application of NLCs. To study the topical permeation mechanism of capsaicin, 3,3'-dioctadecyloxacarbocyanine perchlorate (Dio) was used as a fluorescent dye. Dio-loaded NLCs and Dio-loaded NLCs gel could effectively deliver Dio up to a skin depth of 260 and 210 μm, respectively, primarily through the appendage route on the basis of version skin sections compared with Dio solution, which only delivered Dio up to 150 μm. In vivo therapeutic experiments demonstrated that capsaicin-loaded NLCs and capsaicin-loaded NLCs gel could improve the pain threshold in a dose-dependent manner and inhibit inflammation, primarily by reducing the prostaglandin E2 levels in the tissue compared with capsaicin cream and capsaicin solution. Meanwhile, skin irritation was reduced, indicating that application of NLCs could decrease the irritation caused by capsaicin. Overall, NLCs may be a potential carrier for topical delivery of capsaicin for useful pain and inflammation therapy.

Quantifying the importance of pMHC valency, total pMHC dose and frequency on nanoparticle therapeutic efficacy.

PubMed

Sugarman, Jordan; Tsai, Sue; Santamaria, Pere; Khadra, Anmar

2013-05-01

Nanoparticles (NPs) coated with β-cell-specific peptide major histocompatibility complex (pMHC) class I molecules can effectively restore normoglycemia in spontaneously diabetic nonobese diabetic mice. They do so by expanding pools of cognate memory autoreactive regulatory CD8+ T cells that arise from naive low-avidity T-cell precursors to therapeutic levels. Here we develop our previously constructed mathematical model to explore the effects of compound design parameters (NP dose and pMHC valency) on therapeutic efficacy with the underlying hypothesis that the functional correlates of the therapeutic response (expansion of autoregulatory T cells and deletion of autoantigen-loaded antigen-presenting cells by these T cells) are biphasic. We show, using bifurcation analysis, that the model exhibits a 'resonance'-like behavior for a given range of NP dose in which bistability between the healthy state (possessing zero level of effector T-cell population) and autoimmune state (possessing elevated level of the same population) disappears. A heterogeneous population of model mice subjected to several treatment protocols under these new conditions is conducted to quantify both the average percentage of autoregulatory T cells in responsive and nonresponsive model mice, and the average valency-dependent minimal optimal dose needed for effective therapy. Our results reveal that a moderate increase (≥1.6-fold) in the NP-dependent expansion rate of autoregulatory T-cell population leads to a significant increase in the efficacy and the area corresponding to the effective treatment regimen, provided that NP dose ≥8 μg. We expect the model developed here to generalize to other autoimmune diseases and serve as a computational tool to understand and optimize pMHC-NP-based therapies.

A comparative study of the effects of Escherichia coli and Clostridium perfringens upon boar semen preserved in liquid storage.

PubMed

Pinart, Elisabeth; Domènech, Esther; Bussalleu, Eva; Yeste, Marc; Bonet, Sergi

2017-02-01

The present study compares the sperm quality of boar seminal doses artificially inoculated with Escherichia coli and Clostridium perfringens, and maintained in liquid storage at 15°C for a 9-day period. Seminal doses from 10 sexually mature Piétrain boars were diluted in a Beltsville Thawing Solution (BTS)-based extender and infected either with E. coli or C. perfringens, with bacterial loads ranging from 10 1 to 10 7 cfumL -1 . During storage, the changes in sperm quality were determined by assessing pH, sperm viability, sperm motiliy, sperm morphology, sperm agglutination degree, and sperm-bacteria interaction. The infection of seminal doses led to an alkalinization of the medium, which was of higher extend in doses infected with C. perfringens. The effect of contamination on sperm viability and motility relied on bacterial type and load. Therefore, while E. coli was more harmful than C. perfringens in bacterial loads ranging from 10 1 to 10 6 cfumL -1 , the detrimental impact of C. perfringens was more apparent than that of E. coli at a bacterial load of 10 7 cfumL -1 . Despite sperm morphology not being affected by either bacterial type or load, sperm agglutination and sperm-bacteria interaction were characteristic of doses infected with E. coli, and increased concomintantly with bacterial load and along storage period. In conclusion, the effects of infection by E. coli on sperm quality were dependent of both bacterial load and storage period, whereas the effects of C. perfringens were mainly dependent on the bacterial load, with a threshold at 10 7 cfumL -1 from which the sperm quality of seminal doses was greatly impaired. Copyright © 2016 Elsevier B.V. All rights reserved.

A new Monte Carlo-based treatment plan optimization approach for intensity modulated radiation therapy.

PubMed

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.

A Short-Term and High-Resolution System Load Forecasting Approach Using Support Vector Regression with Hybrid Parameters Optimization

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

Jiang, Huaiguang

This work proposes an approach for distribution system load forecasting, which aims to provide highly accurate short-term load forecasting with high resolution utilizing a support vector regression (SVR) based forecaster and a two-step hybrid parameters optimization method. Specifically, because the load profiles in distribution systems contain abrupt deviations, a data normalization is designed as the pretreatment for the collected historical load data. Then an SVR model is trained by the load data to forecast the future load. For better performance of SVR, a two-step hybrid optimization algorithm is proposed to determine the best parameters. In the first step of themore » hybrid optimization algorithm, a designed grid traverse algorithm (GTA) is used to narrow the parameters searching area from a global to local space. In the second step, based on the result of the GTA, particle swarm optimization (PSO) is used to determine the best parameters in the local parameter space. After the best parameters are determined, the SVR model is used to forecast the short-term load deviation in the distribution system.« less

Reliability Constrained Priority Load Shedding for Aerospace Power System Automation

NASA Technical Reports Server (NTRS)

Momoh, James A.; Zhu, Jizhong; Kaddah, Sahar S.; Dolce, James L. (Technical Monitor)

2000-01-01

The need for improving load shedding on board the space station is one of the goals of aerospace power system automation. To accelerate the optimum load-shedding functions, several constraints must be involved. These constraints include congestion margin determined by weighted probability contingency, component/system reliability index, generation rescheduling. The impact of different faults and indices for computing reliability were defined before optimization. The optimum load schedule is done based on priority, value and location of loads. An optimization strategy capable of handling discrete decision making, such as Everett optimization, is proposed. We extended Everett method to handle expected congestion margin and reliability index as constraints. To make it effective for real time load dispatch process, a rule-based scheme is presented in the optimization method. It assists in selecting which feeder load to be shed, the location of the load, the value, priority of the load and cost benefit analysis of the load profile is included in the scheme. The scheme is tested using a benchmark NASA system consisting of generators, loads and network.

Implementation of a dose gradient method into optimization of dose distribution in prostate cancer 3D-CRT plans

PubMed Central

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

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

PubMed

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

2013-07-08

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

Complete recovery after severe myxoedema coma complicated by status epilepticus

PubMed Central

Fjølner, Jesper; Søndergaard, Esben; Kampmann, Ulla; Nielsen, Søren

2015-01-01

We report a case of life-threatening myxoedema presenting with hypothermia, hypotension, bradycardia, pericardial effusion and deep coma. The condition was complicated by prolonged status epilepticus. The optimal treatment strategy has been debated over the years and the literature is briefly reviewed. Treatment with l-thyroxine (LT4) monotherapy without initial loading dose and with no l-triiodothyronine (LT3) treatment was successful with full recovery after hospitalisation for more than a month. Myxoedema coma is a rare, reversible condition with a high mortality and should be considered as a differential diagnosis in medical emergencies. PMID:25809434

Complete recovery after severe myxoedema coma complicated by status epilepticus.

PubMed

Fjølner, Jesper; Søndergaard, Esben; Kampmann, Ulla; Nielsen, Søren

2015-03-25

We report a case of life-threatening myxoedema presenting with hypothermia, hypotension, bradycardia, pericardial effusion and deep coma. The condition was complicated by prolonged status epilepticus. The optimal treatment strategy has been debated over the years and the literature is briefly reviewed. Treatment with l-thyroxine (LT4) monotherapy without initial loading dose and with no l-triiodothyronine (LT3) treatment was successful with full recovery after hospitalisation for more than a month. Myxoedema coma is a rare, reversible condition with a high mortality and should be considered as a differential diagnosis in medical emergencies. 2015 BMJ Publishing Group Ltd.

The effectiveness of low-dose and high-dose tranexamic acid in posterior lumbar interbody fusion: a double-blinded, placebo-controlled randomized study.

PubMed

Kim, Ki-Tack; Kim, Cheung-Kue; Kim, Yong-Chan; Juh, Hyung-Suk; Kim, Hyo-Jong; Kim, Hyeon-Soo; Hong, Se Jung; Hey, Hwee Weng Dennis

2017-11-01

Tranexamic acid is a proven drug used for reduction of intraoperative blood loss in spinal surgery. However, optimal dosing considering risk/benefits is not well established owing to the heterogeneity in patient selection and surgical procedures of previous studies. This study aimed to evaluate the effectiveness and safety of various tranexamic acid regimens in reducing perioperative blood loss in single-level posterior lumbar interbody fusion (PLIF). Patients were randomly grouped into three different interventions: low-dose tranexamic acid (LD), high-dose tranexamic acid (HD), and placebo-controlled (PC) groups. The HD and LD groups received 10 and 5 mg/kg of bolus loading dose and 2 and 1 mg/kg of continuous infusion until 5 h after surgery, respectively. Data on patient demographics and preoperative and 24-h postoperative laboratory values were collected. Outcome parameters include intraoperative blood loss, 24-h postoperative blood loss, and blood loss during removal of the last drain. Seventy-two patients (mean age 63.3 ± 7.6 years) showed similar baseline characteristics. Intraoperatively, blood loss was reduced by the administration of tranexamic acid (P = 0.04), contributed predominantly by a difference between the LD and HD groups (123 mL; P < 0.01). The 24-h postoperative blood loss was reduced (P < 0.01), contributed predominantly by a difference between the PC and LD groups (144 mL; P = 0.02). During the removal of the last drain, statistical difference was found between the PC and HD groups (125 mL; P = 0.00). No complications or side effects from tranexamic acid use were noted. Tranexamic acid administration for single-level PLIF was effective and safe in reducing perioperative blood loss in a dose-dependent manner. An HD regimen comprising 10 mg/kg of bolus loading dose and 2 mg/kg/h of continuous infusion is recommended. Level 1 study according to Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence.

Optimizing Preseason Training Loads in Australian Football.

PubMed

Carey, David L; Crow, Justin; Ong, Kok-Leong; Blanch, Peter; Morris, Meg E; Dascombe, Ben J; Crossley, Kay M

2018-02-01

To investigate whether preseason training plans for Australian football can be computer generated using current training-load guidelines to optimize injury-risk reduction and performance improvement. A constrained optimization problem was defined for daily total and sprint distance, using the preseason schedule of an elite Australian football team as a template. Maximizing total training volume and maximizing Banister-model-projected performance were both considered optimization objectives. Cumulative workload and acute:chronic workload-ratio constraints were placed on training programs to reflect current guidelines on relative and absolute training loads for injury-risk reduction. Optimization software was then used to generate preseason training plans. The optimization framework was able to generate training plans that satisfied relative and absolute workload constraints. Increasing the off-season chronic training loads enabled the optimization algorithm to prescribe higher amounts of "safe" training and attain higher projected performance levels. Simulations showed that using a Banister-model objective led to plans that included a taper in training load prior to competition to minimize fatigue and maximize projected performance. In contrast, when the objective was to maximize total training volume, more frequent training was prescribed to accumulate as much load as possible. Feasible training plans that maximize projected performance and satisfy injury-risk constraints can be automatically generated by an optimization problem for Australian football. The optimization methods allow for individualized training-plan design and the ability to adapt to changing training objectives and different training-load metrics.

[Oral loading dose of phenytoin in the treatment of serial seizures, prevention of seizure recurrence and rapid drug substitution].

PubMed

Sokić, D; Janković, S M

1994-01-01

Over a period of nine months twenty-five epileptic patients were treated with the oral loading dose of phenytoin. The dose ranged from 12 to 23 mg/kg body weight during 1 to 12 hours. In 20 patients with serial seizures or intolerance to other antiepileptic drugs this treatment was effective. Seizures also stopped in 2 of 4 patients with serial partial motor seizures. These 2 patients required both higher loading dose and faster rate of administration than the other patients. A patient with epilepsia partialis continua failed to respond to the treatment. Patients that received phenytoin through the naso-gastric tube, in respect to oral administration, required higher doses to obtain therapeutic plasma levels of phenytoin. One patient had mild nausea, 3 mild dizziness, and 1 tinitus on the first day of the treatment. There was no correlation between a given dose and the achieved phenytoin plasma levels. In our opinion the therapy with oral loading dose of phenytoin is highly effective in the treatment of serial generalized seizures and rapid antiepileptic drug substitution, and partially effective in the prevention of partial motor seizures. It produces only mild and transient side-effects.

Fabrication and in vivo evaluation of Nelfinavir loaded PLGA nanoparticles for enhancing oral bioavailability and therapeutic effect

PubMed Central

Venkatesh, D. Nagasamy; Baskaran, Mahendran; Karri, Veera Venkata Satyanarayana Reddy; Mannemala, Sai Sandeep; Radhakrishna, Kollipara; Goti, Sandip

2015-01-01

Nelfinavir mesylate (NFV) is an anti-viral drug, used in the treatment of Acquired Immunodeficiency Syndrome (AIDS). Poor oral bioavailability and shorter half-life (3.5–5 h) remain a major clinical limitation of NFV leading to unpredictable drug bioavailability and frequent dosing. In this context, the objective of the present study was to formulate NFV loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), which can increase the solubility and oral bioavailability along with sustained release of the drug. NFV loaded PLGA-NPs were prepared by nanoprecipitation method using PLGA and Poloxomer 407. The prepared NPs were evaluated for particle size, zeta potential, morphology, drug content, entrapment efficiency (EE) and in vitro dissolution studies. Oral bioavailability studies were carried out in New Zealand rabbits by administering developed NFV PLGA-NPs and pure drug suspension. PLGA-NPs prepared by using 1:4 ratio of drug and PLGA, with a stirring rate of 1500 rpm for 4 h. The prepared NPs were in the size of 185 ± 0.83 nm with a zeta potential of 28.7 ± 0.09 mV. The developed NPs were found to be spherical with uniform size distribution. The drug content and EE of the optimized formulation were found to be 36 ± 0.19% and 72 ± 0.47% respectively. After oral administration of NFV PLGA-NPs, the relative bioavailability was enhanced about 4.94 fold compared to NFV suspension as a control. The results describe an effective strategy for oral delivery of NFV loaded PLGA NPs that helps in enhancing bioavailability and reduce the frequency of dosing. PMID:26702262

Role of optimization criterion in static asymmetric analysis of lumbar spine load.

PubMed

Daniel, Matej

2011-10-01

A common method for load estimation in biomechanics is the inverse dynamics optimization, where the muscle activation pattern is found by minimizing or maximizing the optimization criterion. It has been shown that various optimization criteria predict remarkably similar muscle activation pattern and intra-articular contact forces during leg motion. The aim of this paper is to study the effect of the choice of optimization criterion on L4/L5 loading during static asymmetric loading. Upright standing with weight in one stretched arm was taken as a representative position. Musculoskeletal model of lumbar spine model was created from CT images of Visible Human Project. Several criteria were tested based on the minimization of muscle forces, muscle stresses, and spinal load. All criteria provide the same level of lumbar spine loading (difference is below 25%), except the criterion of minimum lumbar shear force which predicts unrealistically high spinal load and should not be considered further. Estimated spinal load and predicted muscle force activation pattern are in accordance with the intradiscal pressure measurements and EMG measurements. The L4/L5 spine loads 1312 N, 1674 N, and 1993 N were predicted for mass of weight in hand 2, 5, and 8 kg, respectively using criterion of mininum muscle stress cubed. As the optimization criteria do not considerably affect the spinal load, their choice is not critical in further clinical or ergonomic studies and computationally simpler criterion can be used.

New dosing strategies for an old antibiotic: pharmacodynamics of front-loaded regimens of colistin at simulated pharmacokinetics in patients with kidney or liver disease.

PubMed

Rao, Gauri G; Ly, Neang S; Haas, Curtis E; Garonzik, Samira; Forrest, Alan; Bulitta, Jurgen B; Kelchlin, Pamela A; Holden, Patricia N; Nation, Roger L; Li, Jian; Tsuji, Brian T

2014-01-01

Increasing evidence suggests that colistin monotherapy is suboptimal at currently recommended doses. We hypothesized that front-loading provides an improved dosing strategy for polymyxin antibiotics to maximize killing and minimize total exposure. Here, we utilized an in vitro pharmacodynamic model to examine the impact of front-loaded colistin regimens against a high bacterial density (10(8) CFU/ml) of Pseudomonas aeruginosa. The pharmacokinetics were simulated for patients with hepatic (half-life [t1/2] of 3.2 h) or renal (t1/2 of 14.8 h) disease. Front-loaded regimens (n=5) demonstrated improvement in bacterial killing, with reduced overall free drug areas under the concentration-time curve (fAUC) compared to those with traditional dosing regimens (n=14) with various dosing frequencies (every 12 h [q12h] and q24h). In the renal failure simulations, front-loaded regimens at lower exposures (fAUC of 143 mg · h/liter) obtained killing activity similar to that of traditional regimens (fAUC of 268 mg · h/liter), with an ∼97% reduction in the area under the viable count curve over 48 h. In hepatic failure simulations, front-loaded regimens yielded rapid initial killing by up to 7 log10 within 2 h, but considerable regrowth occurred for both front-loaded and traditional regimens. No regimen eradicated the high bacterial inoculum of P. aeruginosa. The current study, which utilizes an in vitro pharmacodynamic infection model, demonstrates the potential benefits of front-loading strategies for polymyxins simulating differential pharmacokinetics in patients with hepatic and renal failure at a range of doses. Our findings may have important clinical implications, as front-loading polymyxins as a part of a combination regimen may be a viable strategy for aggressive treatment of high-bacterial-burden infections.

SU-E-T-109: An Investigation of Including Variable Relative Biological Effectiveness in Intensity Modulated Proton Therapy Planning Optimization for Head and Neck Cancer Patients

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

Activity of Oral ALS-008176 in a Respiratory Syncytial Virus Challenge Study.

PubMed

DeVincenzo, John P; McClure, Matthew W; Symons, Julian A; Fathi, Hosnieh; Westland, Christopher; Chanda, Sushmita; Lambkin-Williams, Rob; Smith, Patrick; Zhang, Qingling; Beigelman, Leo; Blatt, Lawrence M; Fry, John

2015-11-19

BACKGROUND Respiratory syncytial virus (RSV) infection is a cause of substantial morbidity and mortality. There is no known effective therapy. METHODS We conducted a randomized, double-blind, clinical trial in healthy adults inoculated with RSV. Participants received the oral nucleoside analogue ALS-008176 or placebo 12 hours after confirmation of RSV infection or 6 days after inoculation. Treatment was administered every 12 hours for 5 days. Viral load, disease severity, resistance, and safety were measured throughout the 28-day study period, with measurement beginning before inoculation. The primary end point was the area under the curve (AUC) for viral load, which was assessed immediately before administration of the first dose through the 12th day after inoculation in participants infected with RSV. RESULTS A total of 62 participants received placebo or one of three ALS-008176 dosing regimens: 1 loading dose of 750 mg followed by 9 maintenance doses of 500 mg (group 1), 1 loading dose of 750 mg followed by 9 maintenance doses of 150 mg (group 2), or 10 doses of 375 mg (group 3). In the 35 infected participants (23 of whom were treated with ALS-008176), the AUCs for viral load for groups 1, 2, and 3 and the placebo group were 59.9, 73.7, 133.4, and 500.9 log10 plaque-forming-unit equivalents × hours per milliliter, respectively (P≤0.001). The time to nondetectability on polymerase-chain-reaction assay (P<0.001), the peak viral load (P≤0.001), the AUC for symptom score (P<0.05), and the AUC for mucus weight were lower in all groups receiving ALS-008176 than in the placebo group. Antiviral activity was greatest in the two groups that received a loading dose--viral clearance was accelerated (P≤0.05), and the AUC for viral load decreased by 85 to 88% as compared with the placebo group. Within this small trial, no viral rebound or resistance was identified. There were no serious adverse events, and there was no need for premature discontinuation of the study drug. CONCLUSIONS In this RSV challenge study, more rapid RSV clearance and a greater reduction of viral load, with accompanying improvements in the severity of clinical disease, were observed in the groups treated with ALS-008176 than in the placebo group. (Funded by Alios BioPharma; ClinicalTrials.gov number, NCT02094365.).

Compact D-D Neutron Source-Driven Subcritical Multiplier and Beam-Shaping Assembly for Boron Neutron Capture Therapy

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

Evaluation of dose-response relationship between smoking load and cardiopulmonary fitness in adult smokers: A cross-sectional study.

PubMed

Lauria, V T; Sperandio, E F; de Sousa, T L W; de Oliveira Vieira, W; Romiti, M; de Toledo Gagliardi, A R; Arantes, R L; Dourado, V Z

To evaluate the dose-response relationship between smoking load and cardiopulmonary fitness, as measured with cardiopulmonary exercise testing (CPET), in adult smokers free of respiratory diseases. After a complete clinical evaluation and spirometry, 95 adult smokers (35 men and 60 women) underwent CPET on a treadmill. The physiological responses during CPET showed lower cardiorespiratory fitness levels, regardless of smoking load, with a peak [Formula: see text] lower than 100% of the expected value and a lower maximum heart rate. We observed a significant moderate negative correlation between smoking load and peak [Formula: see text] . The smoking load also presented a significant negative correlation with maximum heart rate(r=-0.36; p<0.05), lactate threshold(r=-0.45; p<0.05), and peak ventilation(r=-0.43; p<0.05). However, a dose-response relationship between smoking load quartiles and cardiopulmonary fitness was not found comparing quartiles of smoking loads after adjustment for age, sex and cardiovascular risk. There appears to be no dose-response relationship between SL and cardiopulmonary fitness in adult smokers with preserved pulmonary function, after adjusting the analysis for age and cardiovascular risk. Our results suggest that smoking cessation might be useful as the primary strategy to prevent cardiopulmonary fitness decline in smokers, regardless of smoking load. Thus, even a very low dose of tobacco use must be avoided in preventive strategies focusing on becoming people more physically active and fit. Copyright © 2016 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.

A Study on a Centralized Under-Voltage Load Shedding Scheme Considering the Load Characteristics

NASA Astrophysics Data System (ADS)

Deng, Jiyu; Liu, Junyong

Under-voltage load shedding is an important measure for maintaining voltage stability.Aiming at the optimal load shedding problem considering the load characteristics,firstly,the traditional under-voltage load shedding scheme based on a static load model may cause the analysis inaccurate is pointed out on the equivalent Thevenin circuit.Then,the dynamic voltage stability margin indicator is derived through local measurement.The derived indicator can reflect the voltage change of the key area in a myopia linear way.Dimensions of the optimal problem will be greatly simplified using this indicator.In the end,mathematical model of the centralized load shedding scheme is built with the indicator considering load characteristics.HSPPSO is introduced to slove the optimal problem.Simulation results on IEEE-39 system show that the proposed scheme display a good adaptability in solving the under-voltage load shedding considering dynamic load characteristics.

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.

Assessing the system value of optimal load shifting

DOE PAGES

Merrick, James; Ye, Yinyu; Entriken, Bob

2017-04-30

We analyze a competitive electricity market, where consumers exhibit optimal load shifting behavior to maximize utility and producers/suppliers maximize their profit under supply capacity constraints. The associated computationally tractable formulation can be used to inform market design or policy analysis in the context of increasing availability of the smart grid technologies that enable optimal load shifting. Through analytic and numeric assessment of the model, we assess the equilibrium value of optimal electricity load shifting, including how the value changes as more electricity consumers adopt associated technologies. For our illustrative numerical case, derived from the Current Trends scenario of the ERCOTmore » Long Term System Assessment, the average energy arbitrage value per ERCOT customer of optimal load shifting technologies is estimated to be $3 for the 2031 scenario year. We assess the sensitivity of this result to the flexibility of load, along with its relationship to the deployment of renewables. Finally, the model presented can also be a starting point for designing system operation infrastructure that communicates with the devices that schedule loads in response to price signals.« less

Assessing the system value of optimal load shifting

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

Merrick, James; Ye, Yinyu; Entriken, Bob

We analyze a competitive electricity market, where consumers exhibit optimal load shifting behavior to maximize utility and producers/suppliers maximize their profit under supply capacity constraints. The associated computationally tractable formulation can be used to inform market design or policy analysis in the context of increasing availability of the smart grid technologies that enable optimal load shifting. Through analytic and numeric assessment of the model, we assess the equilibrium value of optimal electricity load shifting, including how the value changes as more electricity consumers adopt associated technologies. For our illustrative numerical case, derived from the Current Trends scenario of the ERCOTmore » Long Term System Assessment, the average energy arbitrage value per ERCOT customer of optimal load shifting technologies is estimated to be $3 for the 2031 scenario year. We assess the sensitivity of this result to the flexibility of load, along with its relationship to the deployment of renewables. Finally, the model presented can also be a starting point for designing system operation infrastructure that communicates with the devices that schedule loads in response to price signals.« less

Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials

PubMed Central

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.

PubMed

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.

Methylphenidate dose optimization for ADHD treatment: review of safety, efficacy, and clinical necessity

PubMed Central

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

Methylphenidate dose optimization for ADHD treatment: review of safety, efficacy, and clinical necessity.

PubMed

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.

Pediatric Obesity: Pharmacokinetic Alterations and Effects on Antimicrobial Dosing.

PubMed

Natale, Stephanie; Bradley, John; Nguyen, William Huy; Tran, Tri; Ny, Pamela; La, Kirsten; Vivian, Eva; Le, Jennifer

2017-03-01

Limited data exist for appropriate drug dosing in obese children. This comprehensive review summarizes pharmacokinetic (PK) alterations that occur with age and obesity, and these effects on antimicrobial dosing. A thorough comparison of different measures of body weight and specific antimicrobial agents including cefazolin, cefepime, ceftazidime, daptomycin, doripenem, gentamicin, linezolid, meropenem, piperacillin-tazobactam, tobramycin, vancomycin, and voriconazole is presented. PubMed (1966-July 2015) and Cochrane Library searches were performed using these key terms: children, pharmacokinetic, obesity, overweight, body mass index, ideal body weight, lean body weight, body composition, and specific antimicrobial drugs. PK studies in obese children and, if necessary, data from adult studies were summarized. Knowledge of PK alterations stemming from physiologic changes that occur with age from the neonate to adolescent, as well as those that result from increased body fat, become an essential first step toward optimizing drug dosing in obese children. Excessive amounts of adipose tissue contribute significantly to body size, total body water content, and organ size and function that may modify drug distribution and clearance. PK studies that evaluated antimicrobial dosing primarily used total (or actual) body weight (TBW) for loading doses and TBW or adjusted body weight for maintenance doses, depending on the drugs' properties and dosing units. PK studies in obese children are imperative to elucidate drug distribution, clearance, and, consequently, the dose required for effective therapy in these children. Future studies should evaluate the effects of both age and obesity on drug dosing because the incidence of obesity is increasing in pediatric patients. © 2017 Pharmacotherapy Publications, Inc.

Use and optimization of a dual-flowrate loading strategy to maximize throughput in protein-a affinity chromatography.

PubMed

Ghose, Sanchayita; Nagrath, Deepak; Hubbard, Brian; Brooks, Clayton; Cramer, Steven M

2004-01-01

The effect of an alternate strategy employing two different flowrates during loading was explored as a means of increasing system productivity in Protein-A chromatography. The effect of such a loading strategy was evaluated using a chromatographic model that was able to accurately predict experimental breakthrough curves for this Protein-A system. A gradient-based optimization routine is carried out to establish the optimal loading conditions (initial and final flowrates and switching time). The two-step loading strategy (using a higher flowrate during the initial stages followed by a lower flowrate) was evaluated for an Fc-fusion protein and was found to result in significant improvements in process throughput. In an extension of this optimization routine, dynamic loading capacity and productivity were simultaneously optimized using a weighted objective function, and this result was compared to that obtained with the single flowrate. Again, the dual-flowrate strategy was found to be superior.

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.

SU-F-T-670: From the OR to the Radiobiology Lab: The Journey of a Small X-Ray Source

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

Lehmann, J; The University of Sydney, Sydney, NSW; The University of Newcastle, Newcastle, NSW

Purpose: Irradiation of small animal tumor models within laboratories is vital to radiobiological experiments. Often the animals are not able to be brought back into the lab after being taken out for irradiation. Cell biology laboratories benefit from irradiation capability available around the clock without regard to patient load in an associated radiotherapy clinic. Commercial systems are available, but bulky and expensive. Methods: An intraoperative kV irradiation system (IntraBeam™) designed to deliver spherical dose distributions to surgical cavities has been repurposed for the irradiation of cell plates and small laboratory animals. An applicator has been altered to allow for simple,more » open fields. Special collimators are being developed. BEAMnrc Monte Carlo simulations with the “NRC swept BEAM” source model have been performed to characterize the dose distributions, to develop optimal collimators and as basis for dose prescription. Measurements with radiochromic film and with an ionization chamber were performed to characterize the beam and to validate the simulations. Results: Using its highest setting (50 kV and 40 µA) the x-ray unit is capable of delivering dose rates over 1 Gy/min homogeneously to standard cell plates even without an optimized collimator. Smaller areas (tumors in animals) can be irradiated with significantly higher dose rates (> 20 Gy/min) depending on distance of the source to the tumor. The HVL was found to be 0.21 mm Al which means the shielding requirements for the device are easily achievable in the lab. Conclusion: A mobile irradiation facility is feasible. It will allow easier access to radiation for radiobiology experiments. The modified system is versatile in that for cell plates homogenous irradiations can be achieved through distance from the source, while for high dose rate small field irradiations the source can be brought in close proximity to the target.« less

Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study.

PubMed

Gurbel, Paul A; Bliden, Kevin P; Butler, Kathleen; Tantry, Udaya S; Gesheff, Tania; Wei, Cheryl; Teng, Renli; Antonino, Mark J; Patil, Shankar B; Karunakaran, Arun; Kereiakes, Dean J; Parris, Cordel; Purdy, Drew; Wilson, Vance; Ledley, Gary S; Storey, Robert F

2009-12-22

Ticagrelor is the first reversibly binding oral P2Y(12) receptor antagonist. This is the first study to compare the onset and offset of platelet inhibition (IPA) with ticagrelor using the PLATO (PLATelet inhibition and patient Outcomes) trial loading dose (180 mg) with a high loading dose (600 mg) of clopidogrel. In a multicenter, randomized, double-blind study, 123 patients with stable coronary artery disease who were taking aspirin therapy (75 to 100 mg/d) received ticagrelor (180-mg load, 90-mg BID maintenance dose [n=57]), clopidogrel (600-mg load, 75-mg/d maintenance dose [n=54]), or placebo (n=12) for 6 weeks. Greater IPA (20 micromol/L ADP, final extent) occurred with ticagrelor than with clopidogrel at 0.5, 1, 2, 4, 8, and 24 hours after loading and at 6 weeks (P<0.0001 for all); by 2 hours after loading, a greater proportion of patients achieved >50% IPA (98% versus 31%, P<0.0001) and >70% IPA (90% versus 16%, P<0.0001) in the ticagrelor group than in the clopidogrel group, respectively. A faster offset occurred with ticagrelor than with clopidogrel (4-to-72-hour slope [% IPA/h] -1.04 versus -0.48, P<0.0001). At 24 hours after the last dose, mean IPA was 58% for ticagrelor versus 52% for clopidogrel (P=NS). IPA for ticagrelor on day 3 after the last dose was comparable to clopidogrel at day 5; IPA on day 5 for ticagrelor was similar to clopidogrel on day 7 and did not differ from placebo (P=NS). Ticagrelor achieved more rapid and greater platelet inhibition than high-loading-dose clopidogrel; this was sustained during the maintenance phase and was faster in offset after drug discontinuation.

Optimal methotrexate dose is associated with better clinical outcomes than non-optimal dose in daily practice: results from the ESPOIR early arthritis cohort.

PubMed

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.

Dynamic Hydrostatic Pressure Regulates Nucleus Pulposus Phenotypic Expression and Metabolism in a Cell Density-Dependent Manner.

PubMed

Shah, Bhranti S; Chahine, Nadeen O

2018-02-01

Dynamic hydrostatic pressure (HP) loading can modulate nucleus pulposus (NP) cell metabolism, extracellular matrix (ECM) composition, and induce transformation of notochordal NP cells into mature phenotype. However, the effects of varying cell density and dynamic HP magnitude on NP phenotype and metabolism are unknown. This study examined the effects of physiological magnitudes of HP loading applied to bovine NP cells encapsulated within three-dimensional (3D) alginate beads. Study 1: seeding density (1 M/mL versus 4 M/mL) was evaluated in unloaded and loaded (0.1 MPa, 0.1 Hz) conditions. Study 2: loading magnitude (0, 0.1, and 0.6 MPa) applied at 0.1 Hz to 1 M/mL for 7 days was evaluated. Study 1: 4 M/mL cell density had significantly lower adenosine triphosphate (ATP), glycosaminoglycan (GAG) and collagen content, and increased lactate dehydrogenase (LDH). HP loading significantly increased ATP levels, and expression of aggrecan, collagen I, keratin-19, and N-cadherin in HP loaded versus unloaded groups. Study 2: aggrecan expression increased in a dose dependent manner with HP magnitude, whereas N-cadherin and keratin-19 expression were greatest in low HP loading compared to unloaded. Overall, the findings of the current study indicate that cell seeding density within a 3D construct is a critical variable influencing the mechanobiological response of NP cells to HP loading. NP mechanobiology and phenotypic expression was also found to be dependent on the magnitude of HP loading. These findings suggest that HP loading and culture conditions of NP cells may require complex optimization for engineering an NP replacement tissue.

Coordinated Optimization of Distributed Energy Resources and Smart Loads in Distribution Systems: Preprint

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

Yang, Rui; Zhang, Yingchen

2016-08-01

Distributed energy resources (DERs) and smart loads have the potential to provide flexibility to the distribution system operation. A coordinated optimization approach is proposed in this paper to actively manage DERs and smart loads in distribution systems to achieve the optimal operation status. A three-phase unbalanced Optimal Power Flow (OPF) problem is developed to determine the output from DERs and smart loads with respect to the system operator's control objective. This paper focuses on coordinating PV systems and smart loads to improve the overall voltage profile in distribution systems. Simulations have been carried out in a 12-bus distribution feeder andmore » results illustrate the superior control performance of the proposed approach.« less

Coordinated Optimization of Distributed Energy Resources and Smart Loads in Distribution Systems

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

Yang, Rui; Zhang, Yingchen

2016-11-14

Distributed energy resources (DERs) and smart loads have the potential to provide flexibility to the distribution system operation. A coordinated optimization approach is proposed in this paper to actively manage DERs and smart loads in distribution systems to achieve the optimal operation status. A three-phase unbalanced Optimal Power Flow (OPF) problem is developed to determine the output from DERs and smart loads with respect to the system operator's control objective. This paper focuses on coordinating PV systems and smart loads to improve the overall voltage profile in distribution systems. Simulations have been carried out in a 12-bus distribution feeder andmore » results illustrate the superior control performance of the proposed approach.« less

A temperature match based optimization method for daily load prediction considering DLC effect

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

Yu, Z.

This paper presents a unique optimization method for short term load forecasting. The new method is based on the optimal template temperature match between the future and past temperatures. The optimal error reduction technique is a new concept introduced in this paper. Two case studies show that for hourly load forecasting, this method can yield results as good as the rather complicated Box-Jenkins Transfer Function method, and better than the Box-Jenkins method; for peak load prediction, this method is comparable in accuracy to the neural network method with back propagation, and can produce more accurate results than the multi-linear regressionmore » method. The DLC effect on system load is also considered in this method.« less

Comparing paediatric intravenous phenytoin doses using physiologically based pharmacokinetic (PBPK) modelling software.

PubMed

Batchelor, Hannah; Appleton, Richard; Hawcutt, Daniel B

2015-12-01

To use a physiologically based pharmacokinetic (PBPK) modelling system to predict the serum levels achieved by two different intravenous loading doses of phenytoin. A phenytoin pharmacokinetic model was used in the Simcyp population-based ADME simulator, simulating 100 children age 2-10 years receiving intravenous phenytoin (18 and 20mg/kg). Visual checks were used to evaluate the predictive performance of the candidate model. Loading with doses of 18 mg/kg, blood levels were sub-therapeutic in 22/100 (concentration at 2h post infusion (C2h) <10 μg/mL), therapeutic in 62/100 (C2h 10-20 μg/mL), and supra-therapeutic in 16/100 (C2h>20 μg/mL). Loading with 20mg/kg, the percentages were 15, 59, and 26, respectively. Increasing from 18 to 20 mg/kg increased the mean C2h from 16.0 to 17.9 μg/mL, and the mean AUC from 145 to 162 μg/mL/h. A C2h>30 μg/mL was predicted in 4% and 8% of children in the 18 and 20 mg/kg doses, with 3% predicted to have a C2h>40 μg/mL following either dose. For maintenance doses, a 1st dose of 2.5 or 5mg/kg (intravenous) given at 12h (after either 18 or 20 mg/kg loading) gives the highest percentages of 10-20 μg/mL serum concentrations. For sub-therapeutic concentrations following intravenous loading (20 mg/kg), a 1st maintenance dose (intravenous) of 10mg/kg will achieve therapeutic concentrations in 93%. Use of PBPK modelling suggests that children receiving the 20 mg/kg intravenous loading dose are at slightly increased risk of supra-therapeutic blood levels. Ideally, therapeutic drug monitoring is required to monitor serum concentrations, although the dose regime suggested by the BNFc appear appropriate. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

SU-E-T-280: Reconstructed Rectal Wall Dose Map-Based Verification of Rectal Dose Sparing Effect According to Rectum Definition Methods and Dose Perturbation by Air Cavity in Endo-Rectal Balloon

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

Normalization of doxorubicin release from graphene oxide: New approach for optimization of effective parameters on drug loading.

PubMed

Hashemi, Mohadeseh; Yadegari, Amir; Yazdanpanah, Ghasem; Omidi, Meisam; Jabbehdari, Sayena; Haghiralsadat, Fatemeh; Yazdian, Fatemeh; Tayebi, Lobat

2017-05-01

Graphene oxide (GO) has been recently introduced as a suitable anticancer drug carrier, which could be loaded with doxorubicin (DOX) as a general chemotherapy agent. Herein, the attempts were made to optimize the effective parameters on both loading and release of DOX on GO. GO and GO-DOX were characterized using transition electron microscopy , zeta potential, Raman spectroscopy, UV-visible spectroscopy, and Fourier transform infrared spectroscopy. In addition, loading and releasing behaviors of DOX on GO were studied in terms of different temperature and pH values. The primary optimized values of pH and temperature for best-loaded amount of DOX were 8.9 and 309 K, respectively. Moreover, we found that the smallest amount of released DOX, in pH of cancer microenvironment (5.4), occurs when DOX had been previously loaded in pH 7.8 and 310 K. Although the highest amount of loaded DOX was in basic pH, the results of efficient release of DOX from the GO-DOX complex and also cellular toxicity assay revealed that the best pH for loading of DOX on GO was 7.8. Therefore, in addition to optimization of parameters for efficient loading of DOX on GO, this study suggested that normalization of a released drug compared with the amount of a loaded drug could be a new approach for optimization of drug loading on nanocarriers. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

Open-label dose optimization of methylphenidate modified release long acting (MPH-LA): a post hoc analysis of real-life titration from a 40-week randomized trial.

PubMed

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.

Association of Depressive Symptoms with Lapses in Antiretroviral Medication Adherence Among People Living with HIV: A Test of an Indirect Pathway.

PubMed

Babowitch, Jacklyn D; Sheinfil, Alan Z; Woolf-King, Sarah E; Vanable, Peter A; Sweeney, Shannon M

2018-03-23

Viral suppression, a critical component of HIV care, is more likely when individuals initiate antiretroviral therapy (ART) early in disease progression and maintain optimal levels of adherence to ART regimens. Although several studies have documented the negative association of depressive symptoms with ART adherence, less is known about how depressed mood relates to intentional versus unintentional lapses in adherence as well as the mechanisms underlying this association. The purpose of the current study was to examine the association of depressive symptoms with ART adherence, assessed as a multidimensional construct. Secondarily, this study conducted preliminary indirect path models to determine if medication self-efficacy could explain the depressed mood-adherence relationship. Depressive symptoms were not associated with 95% ART taken, self-reported viral load, deliberate adjustments to ART regimens or skipped ART doses. However, the indirect association of depressive symptoms via decrements in medication self-efficacy was significant for 95% ART taken, self-reported viral load and skipped ART doses, but not deliberate changes to ART regimens. In this sample of HIV-positive outpatients, there is evidence to support medication self-efficacy as a potential mechanism underlying the association between depressive symptoms and ART adherence. Additional longitudinal studies are needed to formally examine medication taking self-efficacy as a mediator.

Targeted Intracellular Delivery of Antituberculosis Drugs to Mycobacterium tuberculosis-Infected Macrophages via Functionalized Mesoporous Silica Nanoparticles

PubMed Central

Lee, Bai-Yu; Xue, Min; Thomas, Courtney R.; Meng, Huan; Ferris, Daniel; Nel, Andre E.; Zink, Jeffrey I.

2012-01-01

Delivery of antituberculosis drugs by nanoparticles offers potential advantages over free drug, including the potential to target specifically the tissues and cells that are infected by Mycobacterium tuberculosis, thereby simultaneously increasing therapeutic efficacy and decreasing systemic toxicity, and the capacity for prolonged release of drug, thereby allowing less-frequent dosing. We have employed mesoporous silica nanoparticle (MSNP) drug delivery systems either equipped with a polyethyleneimine (PEI) coating to release rifampin or equipped with cyclodextrin-based pH-operated valves that open only at acidic pH to release isoniazid (INH) into M. tuberculosis-infected macrophages. The MSNP are internalized efficiently by human macrophages, traffic to acidified endosomes, and release high concentrations of antituberculosis drugs intracellularly. PEI-coated MSNP show much greater loading of rifampin than uncoated MSNP and much greater efficacy against M. tuberculosis-infected macrophages. MSNP were devoid of cytotoxicity at the particle doses employed for drug delivery. Similarly, we have demonstrated that the isoniazid delivered by MSNP equipped with pH-operated nanovalves kill M. tuberculosis within macrophages significantly more effectively than an equivalent amount of free drug. These data demonstrate that MSNP provide a versatile platform that can be functionalized to optimize the loading and intracellular release of specific drugs for the treatment of tuberculosis. PMID:22354311

Effect of caffeine on superior mesenteric artery blood flow velocities in preterm neonates.

PubMed

Abdel Wahed, Mohamed A; Issa, Hanan M; Khafagy, Soha M; Abdel Raouf, Shaimaa M

2017-09-22

To investigate the effect of caffeine infusion on superior mesenteric artery (SMA) blood flow velocities (BFV) in preterm infants. Prospective observational study on 38 preterm neonates 28-33 +6 weeks gestation, who developed apnea on their first day of life, and caffeine citrate infusion was initiated at a loading dose of 20 mg/kg, followed by a maintenance dose of 5-10 mg/kg/day. Duplex ultrasound measurements of SMA BFV were recorded: peak systolic velocity (PSV), end diastolic velocity (EDV) and resistive index (RI), at 15 min before, 1-, 2- and 6-h after caffeine loading dose, and 2 h after two maintenance doses. There was a significant reduction in PSV 1-h (p = .008), a significant decrease in EDV 1- and 2-h (p = .000 and p = .005, respectively) and a significant increase in RI 1- and 2-h (p = .003 and p = .005, respectively) following caffeine loading dose, as compared to values before caffeine infusion. No significant effect of caffeine maintenance doses on SMA BFV was observed (p > .05). Blood flow in SMA is significantly reduced after caffeine citrate infusion at a loading dose of 20 mg/kg. This effect continues for at least 2 h. Meanwhile, SMA BFV seems not affected by maintenance doses.

Spatial optimization of watershed management practices for nitrogen load reduction using a modeling-optimization framework.

PubMed

Yang, Guoxiang; Best, Elly P H

2015-09-15

Best management practices (BMPs) can be used effectively to reduce nutrient loads transported from non-point sources to receiving water bodies. However, methodologies of BMP selection and placement in a cost-effective way are needed to assist watershed management planners and stakeholders. We developed a novel modeling-optimization framework that can be used to find cost-effective solutions of BMP placement to attain nutrient load reduction targets. This was accomplished by integrating a GIS-based BMP siting method, a WQM-TMDL-N modeling approach to estimate total nitrogen (TN) loading, and a multi-objective optimization algorithm. Wetland restoration and buffer strip implementation were the two BMP categories used to explore the performance of this framework, both differing greatly in complexity of spatial analysis for site identification. Minimizing TN load and BMP cost were the two objective functions for the optimization process. The performance of this framework was demonstrated in the Tippecanoe River watershed, Indiana, USA. Optimized scenario-based load reduction indicated that the wetland subset selected by the minimum scenario had the greatest N removal efficiency. Buffer strips were more effective for load removal than wetlands. The optimized solutions provided a range of trade-offs between the two objective functions for both BMPs. This framework can be expanded conveniently to a regional scale because the NHDPlus catchment serves as its spatial computational unit. The present study demonstrated the potential of this framework to find cost-effective solutions to meet a water quality target, such as a 20% TN load reduction, under different conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Use of tailored loading-dose clopidogrel in patients undergoing selected percutaneous coronary intervention based on adenosine diphosphate-mediated platelet aggregation.

PubMed

Meng, Kang; Lü, Shu-Zheng; Zhu, Hua-Gang; Chen, Xin; Ge, Chang-Jiang; Song, Xian-Tao

2010-12-01

Adenosine phosphate-mediated platelet aggregation is a prognostic factor for major adverse cardiac events in patients who have undergone selective percutaneous coronary interventions. This study aimed to assess whether an adjusted loading dose of clopidogrel could more effectively inhibit platelet aggregation in patients undergoing selected percutaneous coronary intervention. A total of 205 patients undergoing selected percutaneous coronary intervention were enrolled in this multicenter, prospective, randomized study. Patients receiving domestic clopidogrel (n = 104) served as the Talcom (Taijia) group; others (n = 101) received Plavix, the Plavix group. Patients received up to 3 additional 300-mg loading doses of clopidogrel to decrease the adenosine phosphate-mediated platelet aggregation index by more than 50% (the primary endpoint) compared with the baseline. The secondary endpoint was major adverse cardiovascular events at 12 months. Compared with the rational loading dosage, the tailored loading dosage better inhibited platelet aggregation based on a > 50% decrease in adenosine phosphate-mediated platelet aggregation (rational loading dosage vs. tailored loading dosage, 48% vs. 73%, P = 0.028). There was no significant difference in the eligible index between the Talcom and Plavix groups (47% vs. 49% at 300 mg; 62% vs. 59% at 600 mg; 74% vs. 72% at 900 mg; P > 0.05) based on a standard adenosine diphosphate-mediated platelet aggregation decrease of > 50%. After 12 months of follow-up, there were no significant differences in major adverse cardiac events (2.5% vs. 2.9%, P = 5.43). No acute or subacute stent thrombosis events occurred. An adjusted loading dose of clopidogrel could have significant effects on antiplatelet aggregation compared with a rational dose, decreasing 1-year major adverse cardiac events in patients undergoing percutaneous coronary interventions based on adenosine phosphate-mediated platelet aggregation with no increase in bleeding.

Intermediate-dose cidofovir without probenecid in the treatment of BK virus allograft nephropathy.

PubMed

Araya, Carlos E; Lew, Judy F; Fennell, Robert S; Neiberger, Richard E; Dharnidharka, Vikas R

2006-02-01

BK virus allograft nephropathy (BKVAN) is a rising complication in kidney transplant recipients. Reducing immunosuppression has been the initial form of therapy in most cases, but is not always associated with improvement in graft function. Anti-viral therapy with low-dose cidofovir (0.25-0.42 mg/kg/dose) has been used successfully in some patients, but dose-related nephrotoxicity has limited its use. We present our experience with 3 kidney transplant recipients diagnosed with BKVAN who received intermediate-dose cidofovir (0.75-1.0 mg/kg/dose) without probenecid, and without concomitant nephrotoxicity. Three female patients, ages 8, 19 and 20 yr, presented with elevated serum creatinine (SCr) values, BK virus stain positive on renal biopsy and high plasma BK viral loads. As a result of viral loads being >2 million copies/ml in two patients and a lack of response to reduction in immunosuppression in the third, we initiated therapy with low-dose cidofovir. Because of persistent positive BK stain and positive plasma viral load, we then administered intermediate-dose cidofovir, without probenecid, for several subsequent doses (seven to 15 infusions till date). All patients tolerated the intermediate-dose cidofovir with no significant rise in SCr during the course of the infusions. The most recent SCr values in all three patients were improved from those at the initial diagnosis of BKVAN. All three patients showed a marked drop in BK viral loads when on intermediate-dose cidofovir, with complete clearing of viremia in two patients. In our experience, intermediate-dose cidofovir without probenecid, used judiciously, is not associated with additional nephrotoxicity and may provide an additional alternative for treatment.

Anti-buckling design of variable stiffness composite cylinder under combined loading based on the multi-objective optimization method

NASA Astrophysics Data System (ADS)

Zheng, Y.; Chen, J.

2018-06-01

Variable stiffness composite structures take full advantages of composite’s design ability. An enlarged design space will make the structure’s performance more excellent. Through an optimal design of a variable stiffness cylinder, the buckling capacity of the cylinder will be increased as compared with its constant stiffness counterpart. In this paper, variable stiffness composite cylinders sustaining combined loadings are considered, and the optimization is conducted based on the multi-objective optimization method. The results indicate that variable stiffness cylinder’s loading capacity is increased significantly as compared with the constant stiffness, especially when an inhomogeneous loading is considered.

Optimal design of clinical trials with biologics using dose-time-response models.

PubMed

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.

Stress-Constrained Structural Topology Optimization with Design-Dependent Loads

NASA Astrophysics Data System (ADS)

Lee, Edmund

Topology optimization is commonly used to distribute a given amount of material to obtain the stiffest structure, with predefined fixed loads. The present work investigates the result of applying stress constraints to topology optimization, for problems with design-depending loading, such as self-weight and pressure. In order to apply pressure loading, a material boundary identification scheme is proposed, iteratively connecting points of equal density. In previous research, design-dependent loading problems have been limited to compliance minimization. The present study employs a more practical approach by minimizing mass subject to failure constraints, and uses a stress relaxation technique to avoid stress constraint singularities. The results show that these design dependent loading problems may converge to a local minimum when stress constraints are enforced. Comparisons between compliance minimization solutions and stress-constrained solutions are also given. The resulting topologies of these two solutions are usually vastly different, demonstrating the need for stress-constrained topology optimization.

Determining the optimal load for jump squats: a review of methods and calculations.

PubMed

Dugan, Eric L; Doyle, Tim L A; Humphries, Brendan; Hasson, Christopher J; Newton, Robert U

2004-08-01

There has been an increasing volume of research focused on the load that elicits maximum power output during jump squats. Because of a lack of standardization for data collection and analysis protocols, results of much of this research are contradictory. The purpose of this paper is to examine why differing methods of data collection and analysis can lead to conflicting results for maximum power and associated optimal load. Six topics relevant to measurement and reporting of maximum power and optimal load are addressed: (a) data collection equipment, (b) inclusion or exclusion of body weight force in calculations of power, (c) free weight versus Smith machine jump squats, (d) reporting of average versus peak power, (e) reporting of load intensity, and (f) instructions given to athletes/ participants. Based on this information, a standardized protocol for data collection and reporting of jump squat power and optimal load is presented.

Application of Hybrid Optimization-Expert System for Optimal Power Management on Board Space Power Station

NASA Technical Reports Server (NTRS)

Momoh, James; Chattopadhyay, Deb; Basheer, Omar Ali AL

1996-01-01

The space power system has two sources of energy: photo-voltaic blankets and batteries. The optimal power management problem on-board has two broad operations: off-line power scheduling to determine the load allocation schedule of the next several hours based on the forecast of load and solar power availability. The nature of this study puts less emphasis on speed requirement for computation and more importance on the optimality of the solution. The second category problem, on-line power rescheduling, is needed in the event of occurrence of a contingency to optimally reschedule the loads to minimize the 'unused' or 'wasted' energy while keeping the priority on certain type of load and minimum disturbance of the original optimal schedule determined in the first-stage off-line study. The computational performance of the on-line 'rescheduler' is an important criterion and plays a critical role in the selection of the appropriate tool. The Howard University Center for Energy Systems and Control has developed a hybrid optimization-expert systems based power management program. The pre-scheduler has been developed using a non-linear multi-objective optimization technique called the Outer Approximation method and implemented using the General Algebraic Modeling System (GAMS). The optimization model has the capability of dealing with multiple conflicting objectives viz. maximizing energy utilization, minimizing the variation of load over a day, etc. and incorporates several complex interaction between the loads in a space system. The rescheduling is performed using an expert system developed in PROLOG which utilizes a rule-base for reallocation of the loads in an emergency condition viz. shortage of power due to solar array failure, increase of base load, addition of new activity, repetition of old activity etc. Both the modules handle decision making on battery charging and discharging and allocation of loads over a time-horizon of a day divided into intervals of 10 minutes. The models have been extensively tested using a case study for the Space Station Freedom and the results for the case study will be presented. Several future enhancements of the pre-scheduler and the 'rescheduler' have been outlined which include graphic analyzer for the on-line module, incorporating probabilistic considerations, including spatial location of the loads and the connectivity using a direct current (DC) load flow model.

A short-term and high-resolution distribution system load forecasting approach using support vector regression with hybrid parameters optimization

DOE PAGES

Jiang, Huaiguang; Zhang, Yingchen; Muljadi, Eduard; ...

2016-01-01

This paper proposes an approach for distribution system load forecasting, which aims to provide highly accurate short-term load forecasting with high resolution utilizing a support vector regression (SVR) based forecaster and a two-step hybrid parameters optimization method. Specifically, because the load profiles in distribution systems contain abrupt deviations, a data normalization is designed as the pretreatment for the collected historical load data. Then an SVR model is trained by the load data to forecast the future load. For better performance of SVR, a two-step hybrid optimization algorithm is proposed to determine the best parameters. In the first step of themore » hybrid optimization algorithm, a designed grid traverse algorithm (GTA) is used to narrow the parameters searching area from a global to local space. In the second step, based on the result of the GTA, particle swarm optimization (PSO) is used to determine the best parameters in the local parameter space. After the best parameters are determined, the SVR model is used to forecast the short-term load deviation in the distribution system. The performance of the proposed approach is compared to some classic methods in later sections of the paper.« less

Structural topology optimization with fuzzy constraint

NASA Astrophysics Data System (ADS)

Rosko, Peter

2011-12-01

The paper deals with the structural topology optimization with fuzzy constraint. The optimal topology of structure is defined as a material distribution problem. The objective is the weight of the structure. The multifrequency dynamic loading is considered. The optimal topology design of the structure has to eliminate the danger of the resonance vibration. The uncertainty of the loading is defined with help of fuzzy loading. Special fuzzy constraint is created from exciting frequencies. Presented study is applicable in engineering and civil engineering. Example demonstrates the presented theory.

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

PubMed Central

Hyun, Seung Won; Wong, Weng Kee

2016-01-01

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

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

PubMed

Hyun, Seung Won; Wong, Weng Kee

2015-11-01

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

WE-AB-303-06: Combining DAO with MV + KV Optimization to Improve Skin Dose Sparing with Real-Time Fluoroscopy

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

Investigation of progressive failure robustness and alternate load paths for damage tolerant structures

NASA Astrophysics Data System (ADS)

Marhadi, Kun Saptohartyadi

Structural optimization for damage tolerance under various unforeseen damage scenarios is computationally challenging. It couples non-linear progressive failure analysis with sampling-based stochastic analysis of random damage. The goal of this research was to understand the relationship between alternate load paths available in a structure and its damage tolerance, and to use this information to develop computationally efficient methods for designing damage tolerant structures. Progressive failure of a redundant truss structure subjected to small random variability was investigated to identify features that correlate with robustness and predictability of the structure's progressive failure. The identified features were used to develop numerical surrogate measures that permit computationally efficient deterministic optimization to achieve robustness and predictability of progressive failure. Analysis of damage tolerance on designs with robust progressive failure indicated that robustness and predictability of progressive failure do not guarantee damage tolerance. Damage tolerance requires a structure to redistribute its load to alternate load paths. In order to investigate the load distribution characteristics that lead to damage tolerance in structures, designs with varying degrees of damage tolerance were generated using brute force stochastic optimization. A method based on principal component analysis was used to describe load distributions (alternate load paths) in the structures. Results indicate that a structure that can develop alternate paths is not necessarily damage tolerant. The alternate load paths must have a required minimum load capability. Robustness analysis of damage tolerant optimum designs indicates that designs are tailored to specified damage. A design Optimized under one damage specification can be sensitive to other damages not considered. Effectiveness of existing load path definitions and characterizations were investigated for continuum structures. A load path definition using a relative compliance change measure (U* field) was demonstrated to be the most useful measure of load path. This measure provides quantitative information on load path trajectories and qualitative information on the effectiveness of the load path. The use of the U* description of load paths in optimizing structures for effective load paths was investigated.

Inverse optimal design of the radiant heating in materials processing and manufacturing

NASA Astrophysics Data System (ADS)

Fedorov, A. G.; Lee, K. H.; Viskanta, R.

1998-12-01

Combined convective, conductive, and radiative heat transfer is analyzed during heating of a continuously moving load in the industrial radiant oven. A transient, quasi-three-dimensional model of heat transfer between a continuous load of parts moving inside an oven on a conveyor belt at a constant speed and an array of radiant heaters/burners placed inside the furnace enclosure is developed. The model accounts for radiative exchange between the heaters and the load, heat conduction in the load, and convective heat transfer between the moving load and oven environment. The thermal model developed has been used to construct a general framework for an inverse optimal design of an industrial oven as an example. In particular, the procedure based on the Levenberg-Marquardt nonlinear least squares optimization algorithm has been developed to obtain the optimal temperatures of the heaters/burners that need to be specified to achieve a prescribed temperature distribution of the surface of a load. The results of calculations for several sample cases are reported to illustrate the capabilities of the procedure developed for the optimal inverse design of an industrial radiant oven.

Optimization for high-dose-rate brachytherapy of cervical cancer with adaptive simulated annealing and gradient descent.

PubMed

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.

TU-EF-204-09: A Preliminary Method of Risk-Informed Optimization of Tube Current Modulation for Dose Reduction in CT

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

Evidence-Based Design of Fixed-Dose Combinations: Principles and Application to Pediatric Anti-Tuberculosis Therapy.

PubMed

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.

Fabrication of solar light induced Fe-TiO{sub 2} immobilized on glass-fiber and application for phenol photocatalytic degradation

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

Lin, Shaohua, E-mail: linsh75@163.com; Zhang, Xiwang; Sun, Qinju

2013-11-15

Graphical abstract: - Highlights: • Fe-doped TiO{sub 2} immobilized on glass-fiber net were prepared by sol–gel method. • Fe inhibited the phase transition of TiO{sub 2} from anatase to rutile. • The optimal Fe doping dose was around 0.005 wt%. • The optimal calcination temperature was around 600 °C. - Abstract: Iron-doped anatase titanium dioxide catalysts coated on glass-fiber were successfully synthesized by a dip-coating sol–gel method. The prepared catalysts were characterized by scanning electron microscopy (SEM) with energy dispersive X-ray (EDX) analysis, X-ray diffraction (XRD), UV-Vis diffuse reflectance spectroscopy to understand the synthesis mechanism, and their photocatalytic activities weremore » evaluated by photodegradation of phenol under simulated solar irradiation. EDX analysis confirmed the existence of iron in the immobilized catalysts. XRD suggested that the phase transition of the catalysts from anatase to rutile were restrained, and almost pure anatase TiO{sub 2} could retain even the calcination temperature reached 800 °C. The UV-Vis diffuse reflectance spectroscopy of the catalysts showed a red shift and increased photoabsorbance in the visible range for all the doped samples. Iron loading and calcination temperature have obvious influences on photocatalytic activity. In this study, the optimal doping dose and calcination temperature were around 0.005 wt% and 600 °C, respectively.« less

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

Nuclear fuel management optimization using genetic algorithms

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

DeChaine, M.D.; Feltus, M.A.

1995-07-01

The code independent genetic algorithm reactor optimization (CIGARO) system has been developed to optimize nuclear reactor loading patterns. It uses genetic algorithms (GAs) and a code-independent interface, so any reactor physics code (e.g., CASMO-3/SIMULATE-3) can be used to evaluate the loading patterns. The system is compared to other GA-based loading pattern optimizers. Tests were carried out to maximize the beginning of cycle k{sub eff} for a pressurized water reactor core loading with a penalty function to limit power peaking. The CIGARO system performed well, increasing the k{sub eff} after lowering the peak power. Tests of a prototype parallel evaluation methodmore » showed the potential for a significant speedup.« less

Voice amplification as a means of reducing vocal load for elementary music teachers.

PubMed

Morrow, Sharon L; Connor, Nadine P

2011-07-01

Music teachers are over four times more likely than classroom teachers to develop voice disorders and greater than eight times more likely to have voice-related problems than the general public. Research has shown that individual voice-use parameters of phonation time, fundamental frequency and vocal intensity, as well as vocal load as calculated by cycle dose and distance dose are significantly higher for music teachers than their classroom teacher counterparts. Finding effective and inexpensive prophylactic measures to decrease vocal load for music teachers is an important aspect for voice preservation for this group of professional voice users. The purpose of this study was to determine the effects of voice amplification on vocal intensity and vocal load in the workplace as measured using a KayPENTAX Ambulatory Phonation Monitor (APM) (KayPENTAX, Lincoln Park, NJ). Seven music teachers were monitored for 1 workweek using an APM to determine average vocal intensity (dB sound pressure level [SPL]) and vocal load as calculated by cycle dose and distance dose. Participants were monitored a second week while using a voice amplification unit (Asyst ChatterVox; Asyst Communications Company, Inc., Indian Creek, IL). Significant decreases in mean vocal intensity of 7.00-dB SPL (P<0.001) were found using amplification, along with significant decreases (P=0.001) in cycle dose and distance dose. In addition, mean phonation time was found to decrease using amplification (P=0.023). These data suggest that voice amplification may be an effective intervention to decrease the potentially damaging vocal loads experienced by elementary music teachers in the classroom. Copyright © 2011 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

In vitro validation of a shape-optimized fiber-reinforced dental bridge.

PubMed

Chen, YungChung; Li, Haiyan; Fok, Alex

2011-12-01

To improve its mechanical performance, structural optimization had been used in a previous study to obtain an alternative design for a 3-unit inlay-retained fiber-reinforced composite (FRC) dental bridge. In that study, an optimized layout of the FRC substructure had been proposed to minimize stresses in the veneering composite and interfacial stresses between the composite and substructure. The current work aimed to validate in vitro the improved fracture resistance of the optimized design. All samples for the 3-unit inlay-retained FRC dental bridge were made with glass-fibers (FibreKor) as the substructure, surrounded by a veneering composite (GC Gradia). Two different FRC substructure designs were prepared: a conventional (n=20) and an optimized design (n=21). The conventional design was a straight beam linking one proximal box to the other, while the optimized design was a curved beam following the lower outline of the pontic. All samples were loaded to 400N on a universal test machine (MTS 810) with a loading speed of 0.2mm/min. During loading, the force and displacement were recorded. Meanwhile, a two-channel acoustic emission (AE) system was used to monitor the development of cracks during loading. The load-displacement curves of the two groups displayed significant differences. For the conventional design, there were numerous drops in load corresponding to local damage of the sample. For the optimized design, the load curves were much smoother. Cracks were clearly visible on the surface of the conventional group only, and the directions of those cracks were perpendicular to those of the most tensile stresses. Results from the more sensitive AE measurement also showed that the optimized design had, on average, fewer cracking events: 38 versus 2969 in the conventional design. The much lower number of AE events and smoother load-displacement curves indicated that the optimized FRC bridge design had a higher fracture resistance. It is expected that the optimized design will significantly improve the clinical performance of FRC bridges. Copyright © 2011 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Pharmaceutical optimization of lipid-based dosage forms for the improvement of taste-masking, chemical stability and solubilizing capacity of phenobarbital.

PubMed

Monteagudo, Ezequiel; Langenheim, Mariana; Salerno, Claudia; Buontempo, Fabián; Bregni, Carlos; Carlucci, Adriana

2014-06-01

Microemulsions (MEs) and self-emulsifying drug delivery systems (SEEDS) containing phenobarbital (Phe) were developed to improve its chemical stability, solubilizing capacity and taste-masking in oral liquid dosage forms. Cremophor® RH40 and Labrasol® were used as surfactants for the screening of ME regions, Capmul® MCM L, Captex® 355, Imwitor® 408, Myglyol® 840 and Isopropyl myristate were the oil phases assayed; Transcutol® P, Polyethylene-glycol 400, glycerol, Propylene-glycol and ethanol the cosurfactants. Phe stability assay was carried out (20:4:20:56% and 20:4:35:41% (w/w); surfactant:oily phase:cosurfactant:water) for both surfactants; only one containing ethanol showed significant dismissing in its drug content. Solubility capacity for these selected formulations were also evaluated, an amount between 17 and 58 mg/mL of Phe could be loaded. At last, an optimized ME formulation with Cremophor® RH40 20%, Capmul® MCM L 4%, PEG 400 35% and sucralose 2% (w/w) was chosen in order to optimize taste-masking using an electronic tongue. Strawberry along with banana and tutti-frutti flavors plus mint flavor proved to be the best ones. Labrasol-based pre-concentrates were tested for (micro)emulsifying properties; all of them resulted to behave as SEDDS. In summary, a rationale experimental design conducted to an optimized ME for Phe oral pediatric administration which was able to load 5-fold times the currently used dose (4 mg/mL), with no sign of physical or chemical instability and with improved taste; SEDDS for capsule filling were also obtained. The biopharmaceutical advantages described for these dosage forms encourage furthering in vivo evaluation.

Optimizing the design and in vitro evaluation of bioreactive glucose oxidase-microspheres for enhanced cytotoxicity against multidrug resistant breast cancer cells.

PubMed

Cheng, Ji; Liu, Qun; Shuhendler, Adam J; Rauth, Andrew M; Wu, Xiao Yu

2015-06-01

Glucose oxidase (GOX) encapsulated in alginate-chitosan microspheres (GOX-MS) was shown in our previous work to produce reactive oxygen species (ROS) in situ and exhibit anticancer effects in vitro and in vivo. The purpose of present work was to optimize the design and thus enhance the efficacy of GOX-MS against multidrug resistant (MDR) cancer cells. GOX-MS with different mean diameters of 4, 20 or 140 μm were prepared using an emulsification-internal gelation-adsorption-chitosan coating method with varying compositions and conditions. The GOX loading efficiency, loading level, relative bioactivity of GOX-MS, and GOX leakage were determined and optimal chitosan concentrations in the coating solution were identified. The influence of particle size on cellular uptake, ROS generation, cytotoxicity and their underlying mechanisms was investigated. At the same GOX dose and incubation time, smaller sized GOX-MS produced larger amounts of H2O2 in cell culture medium and greater cytotoxicity toward murine breast cancer MDR (EMT6/AR1.0) and wild type (EMT6/WT) cells. Fluorescence and confocal laser scanning microscopy revealed significant uptake of small sized (4 μm) GOX-MS by both MDR and WT cells, but no cellular uptake of large (140 μm) GOX-MS. The GOX-MS were equally effective in killing both MDR cells and WT cells. The cytotoxicity of the GOX formulations was positively correlated with membrane damage and lipid peroxidation. GOX-MS induced greater membrane damage and lipid peroxidation in MDR cells than the WT cells. These results suggest that the optimized, small micron-sized GOX-MS are highly effective against MDR breast cancer cells. Copyright © 2015 Elsevier B.V. All rights reserved.

Single Enteral Loading Dose of Phenobarbital for Achieving Its Therapeutic Serum Levels in Neonates

PubMed Central

Turhan, Ali H.; Atici, Aytug; Okuyaz, Cetin; Uysal, Sercan

2010-01-01

Aim To investigate whether therapeutic serum drug levels may be achieved with a single enteral loading dose of phenobarbital. Methods The study was performed at the Mersin University Hospital in Turkey between April 2004 and August 2006, and included 29 newborn babies with seizure. After the acute treatment of the seizure with midazolam at a dose of 0.1 mg/kg, phenobarbital was administered by orogastric route at a loading dose of 20 mg/kg. Serum phenobarbital concentrations were measured at 0.5, 3, 6, and 12 hours after the loading. Serum phenobarbital levels between 10-30 μg/mL were considered as the therapeutic range. Results The serum phenobarbital levels reached therapeutic values in 9 (31%), 19 (66%), 21 (72%), and 23 (79%) patients at 0.5, 3, 6, and 12 hours after loading, respectively, while they did not reach therapeutic values in 6 patients (21%) after 12 hours. Four of the patients in whom there was no increase in serum phenobarbital levels had hypoxic-ischemic encephalopathy. Conclusion Enteral loading of phenobarbital can achieve therapeutic serum levels in the large majority of newborn babies with seizure and may be safely used in babies with the intact gastrointestinal tract. PMID:20564764

Dose Dependent Side Effect of Superparamagnetic Iron Oxide Nanoparticle Labeling on Cell Motility in Two Fetal Stem Cell Populations

PubMed Central

Diana, Valentina; Bossolasco, Patrizia; Moscatelli, Davide; Silani, Vincenzo; Cova, Lidia

2013-01-01

Multipotent stem cells (SCs) could substitute damaged cells and also rescue degeneration through the secretion of trophic factors able to activate the endogenous SC compartment. Therefore, fetal SCs, characterized by high proliferation rate and devoid of ethical concern, appear promising candidate, particularly for the treatment of neurodegenerative diseases. Super Paramagnetic Iron Oxide nanoparticles (SPIOn), routinely used for pre-clinical cell imaging and already approved for clinical practice, allow tracking of transplanted SCs and characterization of their fate within the host tissue, when combined with Magnetic Resonance Imaging (MRI). In this work we investigated how SPIOn could influence cell migration after internalization in two fetal SC populations: human amniotic fluid and chorial villi SCs were labeled with SPIOn and their motility was evaluated. We found that SPIOn loading significantly reduced SC movements without increasing production of Reactive Oxygen Species (ROS). Moreover, motility impairment was directly proportional to the amount of loaded SPIOn while a chemoattractant-induced recovery was obtained by increasing serum levels. Interestingly, the migration rate of SPIOn labeled cells was also significantly influenced by a degenerative surrounding. In conclusion, this work highlights how SPIOn labeling affects SC motility in vitro in a dose-dependent manner, shedding the light on an important parameter for the creation of clinical protocols. Establishment of an optimal SPIOn dose that enables both a good visualization of grafted cells by MRI and the physiological migration rate is a main step in order to maximize the effects of SC therapy in both animal models of neurodegeneration and clinical studies. PMID:24244310

Nanovaccine for leishmaniasis: preparation of chitosan nanoparticles containing Leishmania superoxide dismutase and evaluation of its immunogenicity in BALB/c mice

PubMed Central

Danesh-Bahreini, Mohammad Ali; Shokri, Javad; Samiei, Afshin; Kamali-Sarvestani, Eskandar; Barzegar-Jalali, Mohammad; Mohammadi-Samani, Soliman

2011-01-01

Background: Leishmaniasis is a protozoan disease, affecting 12 million people in different regions of the world with a wide spectrum of diseases. Although several chemotherapeutic agents have been used for treating the disease, long-term therapy, limited efficacy and the development of drug-resistant parasites remain the major limitations. Methods: To develop a new nanovaccine for leishmaniasis, recombinant Leishmania superoxide dismutase (SODB1) was loaded onto chitosan nanoparticles by the ionotropic gelation method. Size and loading efficiency of the nanoparticles were evaluated and optimized, and an immunization study was undertaken on BALB/c mice. The mice received phosphate buffer saline (PBS), superoxide dismutase B1 (SODB1) in PBS and nanoparticles via subcutaneous injection. Soluble Leishmania Antigens (SLA) and complete Freund’s adjuvant (CFA) were also injected subcutaneously three times every three weeks (some groups received only a single dose). Three weeks after the last injection, blood samples were collected and assessed with ELISA to detect IgG2a and IgG1. Results: Immunological analysis showed that in single and triple doses of SODB1 nanoparticles, IgG2a and IgG2a/IgG1 were significantly higher than the other groups (P<0.05). Conclusion: The results revealed that formulations of SODB1 in biodegradable and stable chitosan nanoparticles can increase the immunogenicity toward cell-mediated immunity (TH1 cells producing IgG2a in mice) that is effective in Leishmania eradication and could be presented as a single dose nanovaccine for leishmaniasis. PMID:21589651

SU-E-T-175: Clinical Evaluations of Monte Carlo-Based Inverse Treatment Plan Optimization for Intensity Modulated Radiotherapy

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.

PubMed

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.

Single Event Effects and Total Dose Testing of the Intersil ISL 70003SEH Integrated Point of Load Converter

NASA Astrophysics Data System (ADS)

van Vonno, N. W.; White, J. D.; Pearce, L. G.; Thomson, E. J.; Gill, J. S.; Mansilla, O. E.

2014-08-01

Single-event transient (SET) phenomena in power management applications has evolved into a key issue, particularly in point of load (POL) buck regulators, as the loads driven by these devices are sensitive to even short-term overvoltage conditions. We preface this paper by a discussion of earlier destructive and nondestructive SEE testing of Intersil integrated point of load regulators, with emphasis on SET phenomena and some of the lessons learned in this work. We then report recent results of SET and destructive SEE testing of the ISL70003SEH POL converter, together with a brief discussion of the part's electrical and radiation hardness specifications. We conclude with a brief overview of low and high dose rate total dose testing of the part.

Dual Inhibition of the Epidermal Growth Factor Receptor Pathway with Cetuximab and Erlotinib: A Phase I Study in Patients with Advanced Solid Malignancies

PubMed Central

Guarino, Michael J.; Schneider, Charles J.; Hosford, Martha A.; Brahmer, Julie R.; Rudin, Charles M.; Finckenstein, Friedrich Graf; Philip-Norton, Robyn E.; Lu, Haolan; Weber, Martin R.; Ettinger, David S.

2017-01-01

Purpose To determine the optimal dose of the antiepidermal growth factor receptor (EGFR) monoclonal antibody cetuximab that can be safely administered in combination with a standard daily dose of erlotinib in patients with advanced solid malignancies. Patients and Methods Patients with advanced solid malignancies who had failed standard chemotherapies received escalating doses of cetuximab without a loading dose (100, 200, 250 mg/m2 i.v. weekly) in combination with a fixed dose of erlotinib (150 mg daily orally) until disease progression or unacceptable toxicity. Results Twenty-two patients were treated, including 14 patients (64%) with non-small cell lung cancer. Twenty patients received combination treatment at the highest dose level for a median of 5.5 weeks (range, 1–31 weeks). One dose-limiting toxicity was observed: grade 3 skin rash. Overall, the most common adverse events (any grade, grade 3/4) were consistent with the safety profiles of the individual drugs: acneform rash (100%, 9%), diarrhea (77%, 5%), and hypomagnesemia (59%, 12%). Seven of 18 evaluable patients (38.9%) had stable disease lasting for a median of 16.6 weeks (range, 6.1–25.1 weeks). Conclusion Dual EGFR inhibition with cetuximab and erlotinib is feasible; the observed toxicities were manageable and consistent with the safety profiles of the individual drugs. The recommended doses for phase II studies are 250 mg/m2 i.v. weekly for cetuximab and 150 mg daily orally for erlotinib. PMID:19182243

Optimal Scheduling of Time-Shiftable Electric Loads in Expeditionary Power Grids

DTIC Science & Technology

2015-09-01

NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS OPTIMAL SCHEDULING OF TIME-SHIFTABLE ELECTRIC LOADS IN EXPEDITIONARY POWER GRIDS by John G...to 09-25-2015 4. TITLE AND SUBTITLE OPTIMAL SCHEDULING OF TIME-SHIFTABLE ELECTRIC LOADS IN EXPEDI- TIONARY POWER GRIDS 5. FUNDING NUMBERS 6. AUTHOR(S...eliminate unmanaged peak demand, reduce generator peak-to-average power ratios, and facilitate a persistent shift to higher fuel efficiency. Using

4D Optimization of Scanned Ion Beam Tracking Therapy for Moving Tumors

PubMed Central

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.

PubMed

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.

PubMed

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.

SU-F-BRD-07: Fast Monte Carlo-Based Biological Optimization of Proton Therapy Treatment Plans for Thyroid Tumors

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

Study protocol for a phase II dose evaluation randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study).

PubMed

McNally, Dayre; Amrein, Karin; O'Hearn, Katharine; Fergusson, Dean; Geier, Pavel; Henderson, Matt; Khamessan, Ali; Lawson, Margaret L; McIntyre, Lauralyn; Redpath, Stephanie; Weiler, Hope A; Menon, Kusum

2017-01-01

Clinical research has recently demonstrated that vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (PICU) and associated with worse clinical course. Multiple adult ICU trials have suggested that optimization of vitamin D status through high-dose supplementation may reduce mortality and improve other clinically relevant outcomes; however, there have been no trials of rapid normalization in the PICU setting. The objective of this study is to evaluate the safety and efficacy of an enteral weight-based cholecalciferol loading dose regimen in critically ill children with VDD. The VITdAL-PICU pilot study is designed as a multicenter placebo-controlled phase II dose evaluation pilot randomized controlled trial. We aim to randomize 67 VDD critically ill children using a 2:1 randomization schema to receive loading dose enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or a placebo solution. Participants, caregivers and outcome assessors will be blinded to allocation. Eligibility criteria include ICU patient, aged 37 weeks to 18 years, expected ICU length of stay more than 48 h, anticipated access to bloodwork at 7 days, and VDD (blood total 25 hydroxyvitamin D < 50 nmol/L). The primary objective is to determine whether the dosing protocol normalizes vitamin D status, defined as a blood total 25(OH)D concentration above 75 nmol/L. Secondary objectives include an examination of the safety of the dosing regimen (e.g. hypercalcemia, hypercalciuria, nephrocalcinosis), measures of vitamin D axis function (e.g. calcitriol levels, immune function), and protocol feasibility (eligibility criteria, protocol deviations, blinding). Despite significant observational literature suggesting VDD to be a modifiable risk factor in the PICU setting, there is no robust clinical trial evidence evaluating the benefits of rapid normalization. This phase II clinical trial will evaluate an innovative weight-based dosing regimen intended to rapidly and safely normalize vitamin D levels in critically ill children. Study findings will be used to inform the design of a multicenter phase III trial evaluating the clinical and economic benefits to rapid normalization. Recruitment for this trial was initiated in January 2016 and is expected to continue until November 30, 2017. Clinicaltrials.gov NCT02452762.

Testing Dose-Dependent Effects of the Nectar Alkaloid Anabasine on Trypanosome Parasite Loads in Adult Bumble Bees.

PubMed

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.

A heuristic approach to optimization of structural topology including self-weight

NASA Astrophysics Data System (ADS)

Tajs-Zielińska, Katarzyna; Bochenek, Bogdan

2018-01-01

Topology optimization of structures under a design-dependent self-weight load is investigated in this paper. The problem deserves attention because of its significant importance in the engineering practice, especially nowadays as topology optimization is more often applied when designing large engineering structures, for example, bridges or carrying systems of tall buildings. It is worth noting that well-known approaches of topology optimization which have been successfully applied to structures under fixed loads cannot be directly adapted to the case of design-dependent loads, so that topology generation can be a challenge also for numerical algorithms. The paper presents the application of a simple but efficient non-gradient method to topology optimization of elastic structures under self-weight loading. The algorithm is based on the Cellular Automata concept, the application of which can produce effective solutions with low computational cost.

Using spatial information about recurrence risk for robust optimization of dose-painting prescription functions

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

Investigation of Optimal Control Allocation for Gust Load Alleviation in Flight Control

NASA Technical Reports Server (NTRS)

Frost, Susan A.; Taylor, Brian R.; Bodson, Marc

2012-01-01

Advances in sensors and avionics computation power suggest real-time structural load measurements could be used in flight control systems for improved safety and performance. A conventional transport flight control system determines the moments necessary to meet the pilot's command, while rejecting disturbances and maintaining stability of the aircraft. Control allocation is the problem of converting these desired moments into control effector commands. In this paper, a framework is proposed to incorporate real-time structural load feedback and structural load constraints in the control allocator. Constrained optimal control allocation can be used to achieve desired moments without exceeding specified limits on monitored load points. Minimization of structural loads by the control allocator is used to alleviate gust loads. The framework to incorporate structural loads in the flight control system and an optimal control allocation algorithm will be described and then demonstrated on a nonlinear simulation of a generic transport aircraft with flight dynamics and static structural loads.

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.

PubMed

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.

Effect of high-dose rosuvastatin loading before percutaneous coronary intervention in Chinese patients with acute coronary syndrome: A systematic review and meta-analysis

PubMed Central

Su, Qiang; Guo, Wenqin; Dai, Weiran; Li, Hongqing; Yang, Huafeng; Li, Lang

2017-01-01

Background Acute coronary syndrome (ACS) is an important disease threatening human life and health. Many studies have shown that the loading dose of atorvastatin can significantly improve the prognosis of patients with ACS, and reduce the mortality. However, this conclusion is not consistent. Thus, we aimed to evaluate the effect of high-dose rosuvastatin loading before percutaneous coronary intervention (PCI) in Chinese patients with ACS using a meta-analysis based on a systematic review of published articles. Methods We systematically reviewed published studies, evaluating the effect of high-dose rosuvastatin loading before percutaneous coronary intervention in Chinese patients with ACS. The retrieval time is limited from inception to 2 November 2016, and the retrieved databases included PubMed, Embase, the Cochrane Library, Web of Science, CBM, CNKI, the VIP database and the Wang Fang database. Two researchers independently assessed the quality of the included studies and then extracted the data. Stata 11.0 was used for data analysis. Results In total, 11 articles, which included 802 patients, were included in our meta-analysis. Among these patients, 398 patients were in the high-dose group (20 mg/day) and 404 patients were in the conventional dose group (10 mg/day). Meta-analysis results showed that compared with the conventional dose group: 1) The loading dose of rosuvastatin can significantly reduce the hs-CRP level after PCI, including at 24 hours (SMD = -0.65, 95%CI -0.84 ~ -0.47, P = 0.000), 48 hours (SMD = -0.40, 95%CI -0.68 ~ -0.11, P = 0.006), and four weeks (SMD = -1.64, 95%CI -2.01 ~ -1.26, P = 0.000). 2) The loading dose of rosuvastatin can significantly reduce the levels of LDL-C and cTnT, including the level of LDL-C at 30 d after PCI (SMD = -0.89, 95%CI -1.10 ~ -0.69, P = 0.000), and the level of cTnT at 24 h after PCI (SMD = -1.93, 95%CI -2.28 ~ -1.59, P = 0.000), and increase the level of HDL-C at 48 h after PCI (SMD = 0.61, 95%CI 0.34 ~ 0.88, P = 0.000). 3) The loading dose of rosuvastatin can significantly reduce the levels of TG and TC, including the level of TG at 30 d after PCI (SMD = -0.94, 95%CI -1.17 ~ -0.71, P = 0.000), the level of TC at 48 h after PCI (SMD = -0.35, 95%CI -0.68 ~ -0.01, P = 0.043), and the level of TC at 30 d after PCI (SMD = -0.77, 95%CI -0.98 ~ -0.56, P = 0.000). Conclusions Our systematic review and meta-analysis showed that, compared with the conventional dose, the loading dose of rosuvastatin was more beneficial to patients with ACS in China and is suitable for clinical application. Due to the limitations of the quality and quantity of included articles, this conclusion still needs to be confirmed by multicenter clinical trials. PMID:28231287

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

PubMed

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

2018-04-01

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

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

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

Yan Di; Liang Jian

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

Evaluation in vitro and in vivo of curcumin-loaded mPEG-PLA/TPGS mixed micelles for oral administration.

PubMed

Duan, Yuwei; Zhang, Baomei; Chu, Lianjun; Tong, Henry Hy; Liu, Weidong; Zhai, Guangxi

2016-05-01

The aim of this work is to prepare and characterize curcumin-loaded methoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA)/D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) mixed micelles (CUR-MPP-TPGS-MMs), analyze the influence of formulation on enhancing the solubility of curcumin in water, and evaluate the improvement of intestinal absorption after oral administration. CUR-MPP-TPGS-MMs were prepared using the thin film diffusion method and optimized with the uniform design. The optimal CUR-MPP-TPGS-MMs were provided with high drug-loading (16.1%), small size (46.0 nm) and spherical shape. Low critical micelle concentration (CMC) and superior dilution stability showed that CUR-MPP-TPGS-MMs could keep integrity during the dilution of gastrointestinal fluid. In vitro drug release study indicated a sustained release of curcumin from CUR-MPP-TPGS-MMs in simulated gastrointestinal solution. The absorption mechanism of passive diffusion was obtained by measuring in situ intestinal absorption of CUR-MPP-TPGS-MMs in rats, and the best absorption segment was found to be the duodenum. The pharmacokinetics was evaluated in rats at the dose of 75 mg/kg by intragastric administration. The Cmax and mean retention time (MRT0-24) for CUR-MPP-TPGS-MMs were both increased, and the relative bioavailability of micelle formulation to curcumin suspension was 927.3%. These results suggested that mPEG-PLA/TPGS mixed micelle system (MPP-TPGS-MMs) showed great potential in improving oral bioavailability of curcumin. Copyright © 2016 Elsevier B.V. All rights reserved.

Thiolated alginate-based multiple layer mucoadhesive films of metformin forintra-pocket local delivery: in vitro characterization and clinical assessment.

PubMed

Kassem, Abeer Ahmed; Issa, Doaa Ahmed Elsayed; Kotry, Gehan Sherif; Farid, Ragwa Mohamed

2017-01-01

Periodontal disease broadly defines group of conditions in which the supportive structure of the tooth (periodontium) is destroyed. Recent studies suggested that the anti-diabetic drug metformin hydrochloride (MF) has an osteogenic effect and is beneficial for the management of periodontitis. Development of strong mucoadhesive multiple layer film loading small dose of MF for intra-pocket application. Multiple layer film was developed by double casting followed by compression method. Either 6% carboxy methyl cellulose sodium (CMC) or sodium alginate (ALG) constituted the inner drug (0.6%) loaded layer. Thiolated sodium alginate (TSA; 2 or 4%) constituted the outer drug free layers to enhance mucoadhesion and achieve controlled drug release. Optimized formulation was assessed clinically on 20 subjects. Films were uniform, thin and hard enough for easy insertion into periodontal pockets. Based on water uptake and in vitro drug release, CMC based film with 4% TSA as an outer layer was the optimized formulation with enhanced mucoadhesion and controlled drug release (83.73% over 12 h). SEM showed the effective fabrication of the triple layer film in which connective lines between the layers could be observed. FTIR examination suggests possibility of hydrogen bonding between the -NH groups of metformin and -OH groups of CMC. DSC revealed the presence of MF mainly in the amorphous form. Clinical results indicated improvement of all clinical parameters six months post treatment. The results suggested that local application of the mucoadhesive multiple layer films loaded with metformin hydrochloride was able to manage moderate chronic periodontitis.

[Example of product development by industry and research solidarity].

PubMed

Seki, Masayoshi

2014-01-01

When the industrial firms develop the product, the research result from research institutions is used or to reflect the ideas from users on the developed product would be significant in order to improve the product. To state the software product which developed jointly as an example to describe the adopted development technique and its result, and to consider the modality of the industry solidarity seen from the company side and joint development. The software development methods have the merit and demerit and necessary to choose the optimal development technique by the system which develops. We have been jointly developed the dose distribution browsing software. As the software development method, we adopted the prototype model. In order to display the dose distribution information, it is necessary to load four objects which are CT-Image, Structure Set, RT-Plan, and RT-Dose, are displayed in a composite manner. The prototype model which is the development technique was adopted by this joint development was optimal especially to develop the dose distribution browsing software. In a prototype model, since the detail design was created based on the program source code after the program was finally completed, there was merit on the period shortening of document written and consist in design and implementation. This software eventually opened to the public as an open source. Based on this developed prototype software, the release version of the dose distribution browsing software was developed. Developing this type of novelty software, it normally takes two to three years, but since the joint development was adopted, it shortens the development period to one year. Shortening the development period was able to hold down to the minimum development cost for a company and thus, this will be reflected to the product price. The specialists make requests on the product from user's point of view are important, but increase in specialists as professionals for product development will increase the expectations to develop a product to meet the users demand.

Optimization and performance comparison for galloping-based piezoelectric energy harvesters with alternating-current and direct-current interface circuits

NASA Astrophysics Data System (ADS)

Tan, Ting; Yan, Zhimiao; Lei, Hong

2017-07-01

Galloping-based piezoelectric energy harvesters scavenge small-scale wind energy and convert it into electrical energy. For piezoelectric energy harvesting with the same vibrational source (galloping) but different (alternating-current (AC) and direct-current (DC)) interfaces, general analytical solutions of the electromechanical coupled distributed parameter model are proposed. Galloping is theoretically proven to appear when the linear aerodynamic negative damping overcomes the electrical damping and mechanical damping. The harvested power is demonstrated as being done by the electrical damping force. Via tuning the load resistance to its optimal value for optimal or maximal electrical damping, the harvested power of the given structure with the AC/DC interface is maximized. The optimal load resistances and the corresponding performances of such two systems are compared. The optimal electrical damping are the same but with different optimal load resistances for the systems with the AC and DC interfaces. At small wind speeds where the optimal electrical damping can be realized by only tuning the load resistance, the performances of such two energy harvesting systems, including the minimal onset speeds to galloping, maximal harvested powers and corresponding tip displacements are almost the same. Smaller maximal electrical damping with larger optimal load resistance is found for the harvester with the DC interface when compared to those for the harvester with the AC interface. At large wind speeds when the maximal electrical damping rather than the optimal electrical damping can be reached by tuning the load resistance alone, the harvester with the AC interface circuit is recommended for a higher maximal harvested power with a smaller tip displacement. This study provides a method using the general electrical damping to connect and compare the performances of piezoelectric energy harvesters with same excitation source but different interfaces.

Date seed oil loaded niosomes: development, optimization and anti-inflammatory effect evaluation on rats.

PubMed

Soliman, Mahmoud S; Abd-Allah, Fathy I; Hussain, Talib; Saeed, Noha M; El-Sawy, Hossam S

2018-07-01

An optimized date seed oil (DSO) loaded niosomes was formulated. Maximize the extract anti-inflammatory efficacy and govern its release characteristics from nanoparticles for osteoarthritis prevention and treatment purposes. By using Box-Behnken Design, the effect of three formulation factors on the entrapment efficiency percentage (Y 1 ), initial DSO release percentage after 2 h (Y 2 ), and cumulative DSO release percentage of DSO after 12 h (Y 3 ), were optimized and studied. The optimized DSO formulation was specified, elaborated, particle size and zeta potential assessed, examined morphologically under electron and light microscope, and in vivo evaluated via carrageenan-induced rat paw edema study. 65.89%, 18.39%, and 58.27% were the measured responses of the optimized niosomes for Y 1 , Y 2 , and Y 3 , respectively. The vesicular structure of the optimized DSO loaded nano-vesicles with nano-size range and good stability features were confirmed. Furthermore, a distinguished anti-inflammatory activity in both prompt and sustained effectiveness were exhibited via the optimized DSO niosomes. Interestingly, the delayed efficacy outcomes of the extract loaded nanoparticles showed a similarity profile as well as the negative control group outcomes. To emphasize, DSO loading in niosomes revealed a significant enhancement toward inflammation alleviation, which offers a promising implement in osteoarthritis remediation and prohibition.

An Optimized Control for LLC Resonant Converter with Wide Load Range

NASA Astrophysics Data System (ADS)

Xi, Xia; Qian, Qinsong

2017-05-01

This paper presents an optimized control which makes LLC resonant converters operate with a wider load range and provides good closed-loop performance. The proposed control employs two paralleled digital compensations to guarantee the good closed-loop performance in a wide load range during the steady state, an optimized trajectory control will take over to change the gate-driving signals immediately at the load transients. Finally, the proposed control has been implemented and tested on a 150W 200kHz 400V/24V LLC resonant converter and the result validates the proposed method.

Numerical verification of two-component dental implant in the context of fatigue life for various load cases.

PubMed

Szajek, Krzysztof; Wierszycki, Marcin

2016-01-01

Dental implant designing is a complex process which considers many limitations both biological and mechanical in nature. In earlier studies, a complete procedure for improvement of two-component dental implant was proposed. However, the optimization tasks carried out required assumption on representative load case, which raised doubts on optimality for the other load cases. This paper deals with verification of the optimal design in context of fatigue life and its main goal is to answer the question if the assumed load scenario (solely horizontal occlusal load) leads to the design which is also "safe" for oblique occlussal loads regardless the angle from an implant axis. The verification is carried out with series of finite element analyses for wide spectrum of physiologically justified loads. The design of experiment methodology with full factorial technique is utilized. All computations are done in Abaqus suite. The maximal Mises stress and normalized effective stress amplitude for various load cases are discussed and compared with the assumed "safe" limit (equivalent of fatigue life for 5e6 cycles). The obtained results proof that coronial-appical load component should be taken into consideration in the two component dental implant when fatigue life is optimized. However, its influence in the analyzed case is small and does not change the fact that the fatigue life improvement is observed for all components within whole range of analyzed loads.

SU-E-T-368: Evaluating Dosimetric Outcome of Modulated Photon Radiotherapy (XMRT) Optimization for Head and Neck Patients

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

Optimization of structures undergoing harmonic or stochastic excitation. Ph.D. Thesis; [atmospheric turbulence and white noise

NASA Technical Reports Server (NTRS)

Johnson, E. H.

1975-01-01

The optimal design was investigated of simple structures subjected to dynamic loads, with constraints on the structures' responses. Optimal designs were examined for one dimensional structures excited by harmonically oscillating loads, similar structures excited by white noise, and a wing in the presence of continuous atmospheric turbulence. The first has constraints on the maximum allowable stress while the last two place bounds on the probability of failure of the structure. Approximations were made to replace the time parameter with a frequency parameter. For the first problem, this involved the steady state response, and in the remaining cases, power spectral techniques were employed to find the root mean square values of the responses. Optimal solutions were found by using computer algorithms which combined finite elements methods with optimization techniques based on mathematical programming. It was found that the inertial loads for these dynamic problems result in optimal structures that are radically different from those obtained for structures loaded statically by forces of comparable magnitude.

Implications of improved diagnostic imaging of small nodal metastases in head and neck cancer: Radiotherapy target volume transformation and dose de-escalation.

PubMed

van den Bosch, Sven; Vogel, Wouter V; Raaijmakers, Cornelis P; Dijkema, Tim; Terhaard, Chris H J; Al-Mamgani, Abrahim; Kaanders, Johannes H A M

2018-05-03

Diagnostic imaging continues to evolve, and now has unprecedented accuracy for detecting small nodal metastasis. This influences the tumor load in elective target volumes and subsequently has consequences for the radiotherapy dose required to control disease in these volumes. Small metastases that used to remain subclinical and were included in elective volumes, will nowadays be detected and included in high-dose volumes. Consequentially, high-dose volumes will more often contain low-volume disease. These target volume transformations lead to changes in the tumor burden in elective and "gross" tumor volumes with implications for the radiotherapy dose prescribed to these volumes. For head and neck tumors, nodal staging has evolved from mere palpation to combinations of high-resolution imaging modalities. A traditional nodal gross tumor volume in the neck typically had a minimum diameter of 10-15 mm, while nowadays much smaller tumor deposits are detected in lymph nodes. However, the current dose levels for elective nodal irradiation were empirically determined in the 1950s, and have not changed since. In this report the radiobiological consequences of target volume transformation caused by modern imaging of the neck are evaluated, and theoretically derived reductions of dose in radiotherapy for head and neck cancer are proposed. The concept of target volume transformation and subsequent strategies for dose adaptation applies to many other tumor types as well. Awareness of this concept may result in new strategies for target definition and selection of dose levels with the aim to provide optimal tumor control with less toxicity. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

SU-E-T-549: A Combinatorial Optimization Approach to Treatment Planning with Non-Uniform Fractions in Intensity Modulated Proton Therapy

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

PubMed Central

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

2012-01-01

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

[Optimization on trehalose loading technique as protective conditioning for lyophilization of human platelets].

PubMed

Liu, Jing-Han; Zhou, Jun; Ouyang, Xi-Lin; Li, Xi-Jin; Lu, Fa-Qiang

2005-08-01

This study was aimed to further optimize trehalose loading technique including loading temperature, loading time, loading solution and loading concentration of trehalose, based on the established parameters. Loading efficiency in plasma was compared with that in buffer at 37 degrees C; the curves of intracellular trehalose concentration versus loading time at 37 degrees C and 16 degrees C were measured; curves of mean platelet volume (MPV) versus loading time and loading concentration were investigated and compared. According to results obtained, the loaing time, loading temperature, loading solution and trehalose concentration were ascertained for high loading efficiency of trehalose into human platelet. The results showed that the loading efficiency in plasma was markedly higher than that in buffer at 37 degrees C, the loading efficiency in plasma at 37 degrees C was significantly higher than that at 16 degrees C and reached 19.51% after loading for 4 hours, but 6.16% at 16 degrees C. MPV at 16 degrees C was increased by 43.2% than that at 37 degrees C, but had no distinct changes with loading time and loading concentration. In loading at 37 degrees C, MPV increased with loading time and loading concentration positively. Loading time and loading concentration displayed synergetic effect on MPV. MPV increased with loading time and concentration while trehalose loading concentration was above 50 mmol/L. It is concluded that the optimization parameters of trehalose loading technique are 37 degrees C (temperature), 4 hours (leading time), plasma (loading solution), 50 mmol/L (feasible trehalose concentration). The trehalose concentration can be adjusted to meet the requirement of lyophilization.

Effect of Impaction Sequence on Osteochondral Graft Damage: The Role of Repeated and Varying Loads

PubMed Central

Kang, Richard W.; Friel, Nicole A.; Williams, James M.; Cole, Brian J.; Wimmer, Markus A.

2013-01-01

Background Osteochondral autografts and allografts require mechanical force for proper graft placement into the defect site; however, impaction compromises the tissue. This study aimed to determine the effect of impaction force and number of hits to seat the graft on cartilage integrity. Hypothesis Under constant impulse conditions, higher impaction load magnitudes are more detrimental to cell viability, matrix integrity and collagen network organization and will result in proteoglycan loss and nitric oxide release. Study Design Controlled laboratory study Methods Osteochondral explants, harvested from fresh bovine trochleas, were exposed to a series of consistent impact loads delivered by a pneumatically driven device. Each plug received the same overall impulse of 7 Ns, reflecting the mean of 23 clinically inserted plugs. Impaction loads of 37.5N, 75N, 150N, and 300N were matched with 74, 37, 21, and 11 hits respectively. Following impaction, the plugs were harvested and cartilage was analyzed for cell viability, histology by safranin-o and picosirius red, and release of sulfated glycosaminoglycans and nitric oxide. Data were compared with non-impacted control. Results Impacted plugs had significantly lower cell viability than non-impacted plugs. A dose response relationship in loss of cell viability with respect to load magnitude was seen immediately and after 4 days but lost after 8 days. Histologic analysis revealed intact cartilage surface in all samples (loaded or control), with loaded samples showing alterations in birefringence. While the sulfated GAG release was similar across varying impaction loads, release of nitric oxide increased with increasing impaction magnitudes and time. Conclusions Impaction loading parameters have a direct effect on the time course of the viability of the cartilage in the graft tissue. Clinical Relevance Optimal loading parameters for surgical impaction of osteochondral grafts are those with lower load magnitudes and a greater number of hits to ensure proper fit. PMID:19915099

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

PubMed

Ozbaş, Z Y; Vural, H; Aytaç, S A

1996-01-01

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

Near infrared radio-luminescence of O{sub 2} loaded radiation hardened silica optical fibers: A candidate dosimeter for harsh environments

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

Di Francesca, D., E-mail: diego.di.francesca@univ-st-etienne.fr; Dipartimento di Fisica e Chimica, Università degli Studi di Palermo, I-90123 Palermo; Girard, S.

2014-11-03

We report on an experimental investigation of the infrared Radio-Luminescence (iRL) emission of interstitial O{sub 2} molecules loaded in radiation hardened pure-silica-core and fluorine-doped silica-based optical fibers (OFs). The O{sub 2} loading treatment successfully dissolved high concentrations of oxygen molecules into the silica matrix. A sharp luminescence at 1272 nm was detected when 2.5 cm of the treated OFs were irradiated with 10 keV X-rays. This emission originates from the radiative decay of the first excited singlet state of the embedded O{sub 2} molecules. The dose, dose-rate, and temperature dependencies of the infrared emission are studied through in situ optical measurements. The resultsmore » show that the iRL is quite stable in doses of up to 1 MGy(SiO{sub 2}) and is linearly dependent on the dose-rate up to the maximum investigated dose-rate of ∼200 kGy(SiO{sub 2})/h. The temperature dependency of the iRL shows a decrease in efficiency above 200 °C, which is attributed to the non-radiative decay of the excited O{sub 2} molecules. The results obtained and the long-term stability of the O{sub 2}-loading treatment (no out-gassing effect) strongly suggest the applicability of these components to real-time remote dosimetry in environments characterized by high radiation doses and dose-rates.« less

Optimization of cryoprotectant loading into murine and human oocytes.

PubMed

Karlsson, Jens O M; Szurek, Edyta A; Higgins, Adam Z; Lee, Sang R; Eroglu, Ali

2014-02-01

Loading of cryoprotectants into oocytes is an important step of the cryopreservation process, in which the cells are exposed to potentially damaging osmotic stresses and chemical toxicity. Thus, we investigated the use of physics-based mathematical optimization to guide design of cryoprotectant loading methods for mouse and human oocytes. We first examined loading of 1.5 M dimethyl sulfoxide (Me(2)SO) into mouse oocytes at 23°C. Conventional one-step loading resulted in rates of fertilization (34%) and embryonic development (60%) that were significantly lower than those of untreated controls (95% and 94%, respectively). In contrast, the mathematically optimized two-step method yielded much higher rates of fertilization (85%) and development (87%). To examine the causes for oocyte damage, we performed experiments to separate the effects of cell shrinkage and Me(2)SO exposure time, revealing that neither shrinkage nor Me(2)SO exposure single-handedly impairs the fertilization and development rates. Thus, damage during one-step Me(2)SO addition appears to result from interactions between the effects of Me(2)SO toxicity and osmotic stress. We also investigated Me(2)SO loading into mouse oocytes at 30°C. At this temperature, fertilization rates were again lower after one-step loading (8%) in comparison to mathematically optimized two-step loading (86%) and untreated controls (96%). Furthermore, our computer algorithm generated an effective strategy for reducing Me(2)SO exposure time, using hypotonic diluents for cryoprotectant solutions. With this technique, 1.5 M Me(2)SO was successfully loaded in only 2.5 min, with 92% fertilizability. Based on these promising results, we propose new methods to load cryoprotectants into human oocytes, designed using our mathematical optimization approach. Copyright © 2013 Elsevier Inc. All rights reserved.

Optimization of Cryoprotectant Loading into Murine and Human Oocytes

PubMed Central

Karlsson, Jens O.M.; Szurek, Edyta A.; Higgins, Adam Z.; Lee, Sang R.; Eroglu, Ali

2014-01-01

Loading of cryoprotectants into oocytes is an important step of the cryopreservation process, in which the cells are exposed to potentially damaging osmotic stresses and chemical toxicity. Thus, we investigated the use of physics-based mathematical optimization to guide design of cryoprotectant loading methods for mouse and human oocytes. We first examined loading of 1.5 M dimethylsulfoxide (Me2SO) into mouse oocytes at 23°C. Conventional one-step loading resulted in rates of fertilization (34%) and embryonic development (60%) that were significantly lower than those of untreated controls (95% and 94%, respectively). In contrast, the mathematically optimized two-step method yielded much higher rates of fertilization (85%) and development (87%). To examine the causes for oocyte damage, we performed experiments to separate the effects of cell shrinkage and Me2SO exposure time, revealing that neither shrinkage nor Me2SO exposure single-handedly impairs the fertilization and development rates. Thus, damage during one-step Me2SO addition appears to result from interactions between the effects of Me2SO toxicity and osmotic stress. We also investigated Me2SO loading into mouse oocytes at 30°C. At this temperature, fertilization rates were again lower after one-step loading (8%) in comparison to mathematically optimized two-step loading (86%) and untreated controls (96%). Furthermore, our computer algorithm generated an effective strategy for reducing Me2SO exposure time, using hypotonic diluents for cryoprotectant solutions. With this technique, 1.5 M Me2SO was successfully loaded in only 2.5 min, with 92% fertilizability. Based on these promising results, we propose new methods to load cryoprotectants into human oocytes, designed using our mathematical optimization approach. PMID:24246951

A Method to Analyze and Optimize the Load Sharing of Split Path Transmissions

NASA Technical Reports Server (NTRS)

Krantz, Timothy L.

1996-01-01

Split-path transmissions are promising alternatives to the common planetary transmissions for rotorcraft. Heretofore, split-path designs proposed for or used in rotorcraft have featured load-sharing devices that add undesirable weight and complexity to the designs. A method was developed to analyze and optimize the load sharing in split-path transmissions without load-sharing devices. The method uses the clocking angle as a design parameter to optimize for equal load sharing. In addition, the clocking angle tolerance necessary to maintain acceptable load sharing can be calculated. The method evaluates the effects of gear-shaft twisting and bending, tooth bending, Hertzian deformations within bearings, and movement of bearing supports on load sharing. It was used to study the NASA split-path test gearbox and the U.S. Army's Comanche helicopter main rotor gearbox. Acceptable load sharing was found to be achievable and maintainable by using proven manufacturing processes. The analytical results compare favorably to available experimental data.

Design and Performance of Lift-Offset Rotorcraft for Short-Haul Missions

DTIC Science & Technology

2012-01-01

loading and blade loading were varied to optimize the designs, based on gross weight and fuel burn. The influence of technology is shown, in terms of...loading were varied to optimize the designs, based on gross weight and fuel burn. The influence of technology is shown, in terms of rotor hub drag and...distributions were optimized for these conditions (Fig. 4), and the rotor and aircraft cruise performance was calculated (Fig. 5). Based on comprehensive

General shape optimization capability

NASA Technical Reports Server (NTRS)

Chargin, Mladen K.; Raasch, Ingo; Bruns, Rudolf; Deuermeyer, Dawson

1991-01-01

A method is described for calculating shape sensitivities, within MSC/NASTRAN, in a simple manner without resort to external programs. The method uses natural design variables to define the shape changes in a given structure. Once the shape sensitivities are obtained, the shape optimization process is carried out in a manner similar to property optimization processes. The capability of this method is illustrated by two examples: the shape optimization of a cantilever beam with holes, loaded by a point load at the free end (with the shape of the holes and the thickness of the beam selected as the design variables), and the shape optimization of a connecting rod subjected to several different loading and boundary conditions.

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

Anatomical robust optimization to account for nasal cavity filling variation during intensity-modulated proton therapy: a comparison with conventional and adaptive planning strategies

NASA Astrophysics Data System (ADS)

van de Water, Steven; Albertini, Francesca; Weber, Damien C.; Heijmen, Ben J. M.; Hoogeman, Mischa S.; Lomax, Antony J.

2018-01-01

The aim of this study is to develop an anatomical robust optimization method for intensity-modulated proton therapy (IMPT) that accounts for interfraction variations in nasal cavity filling, and to compare it with conventional single-field uniform dose (SFUD) optimization and online plan adaptation. We included CT data of five patients with tumors in the sinonasal region. Using the planning CT, we generated for each patient 25 ‘synthetic’ CTs with varying nasal cavity filling. The robust optimization method available in our treatment planning system ‘Erasmus-iCycle’ was extended to also account for anatomical uncertainties by including (synthetic) CTs with varying patient anatomy as error scenarios in the inverse optimization. For each patient, we generated treatment plans using anatomical robust optimization and, for benchmarking, using SFUD optimization and online plan adaptation. Clinical target volume (CTV) and organ-at-risk (OAR) doses were assessed by recalculating the treatment plans on the synthetic CTs, evaluating dose distributions individually and accumulated over an entire fractionated 50 GyRBE treatment, assuming each synthetic CT to correspond to a 2 GyRBE fraction. Treatment plans were also evaluated using actual repeat CTs. Anatomical robust optimization resulted in adequate CTV doses (V95%  ⩾  98% and V107%  ⩽  2%) if at least three synthetic CTs were included in addition to the planning CT. These CTV requirements were also fulfilled for online plan adaptation, but not for the SFUD approach, even when applying a margin of 5 mm. Compared with anatomical robust optimization, OAR dose parameters for the accumulated dose distributions were on average 5.9 GyRBE (20%) higher when using SFUD optimization and on average 3.6 GyRBE (18%) lower for online plan adaptation. In conclusion, anatomical robust optimization effectively accounted for changes in nasal cavity filling during IMPT, providing substantially improved CTV and OAR doses compared with conventional SFUD optimization. OAR doses can be further reduced by using online plan adaptation.

A 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

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

Single point estimation of phenytoin dosing: a reappraisal.

PubMed

Koup, J R; Gibaldi, M; Godolphin, W

1981-11-01

A previously proposed method for estimation of phenytoin dosing requirement using a single serum sample obtained 24 hours after intravenous loading dose (18 mg/Kg) has been re-evaluated. Using more realistic values for the volume of distribution of phenytoin (0.4 to 1.2 L/Kg), simulations indicate that the proposed method will fail to consistently predict dosage requirements. Additional simulations indicate that two samples obtained during the 24 hour interval following the iv loading dose could be used to more reliably predict phenytoin dose requirement. Because of the nonlinear relationship which exists between phenytoin dose administration rate (RO) and the mean steady state serum concentration (CSS), small errors in prediction of the required RO result in much larger errors in CSS.

Data Report on Post-Irradiation Dimensional Change of AGC-1 Samples

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

William Windes

This report summarizes the initial dimensional changes for loaded and unloaded AGC-1 samples. The dimensional change for all samples is presented as a function of dose. The data is further presented by graphite type and applied load levels to illustrate the differences between graphite forming processes and stress levels within the graphite components. While the three different loads placed on the samples have been verified [ ref: Larry Hull’s report] verification of the AGC-1 sample temperatures and dose levels are expected in the summer of 2012. Only estimated dose and temperature values for the samples are presented in this reportmore » to allow a partial analysis of the results.« less

Dual-layer DECT for multiphasic hepatic CT with 50 percent iodine load: a matched-pair comparison with a 120 kVp protocol.

PubMed

Nagayama, Yasunori; Nakaura, Takeshi; Oda, Seitaro; Utsunomiya, Daisuke; Funama, Yoshinori; Iyama, Yuji; Taguchi, Narumi; Namimoto, Tomohiro; Yuki, Hideaki; Kidoh, Masafumi; Hirata, Kenichiro; Nakagawa, Masataka; Yamashita, Yasuyuki

2018-04-01

To evaluate the image quality and lesion conspicuity of virtual-monochromatic-imaging (VMI) with dual-layer DECT (DL-DECT) for reduced-iodine-load multiphasic-hepatic CT. Forty-five adults with renal dysfunction who had undergone hepatic DL-DECT with 300-mgI/kg were included. VMI (40-70-keV, DL-DECT-VMI) was generated at each enhancement phase. As controls, 45 matched patients undergoing standard 120-kVp protocol (120-kVp, 600-mgI/kg, and iterative reconstruction) were included. We compared the size-specific dose estimate (SSDE), image noise, CT attenuation, and contrast-to-noise ratio (CNR) between protocols. Two radiologists scored the image quality and lesion conspicuity. SSDE was significantly lower in DL-DECT group (p < 0.01). Image noise of DL-DECT-VMI was almost constant at each keV (differences of ≤15%) and equivalent to or lower than of 120-kVp. As the energy decreased, CT attenuation and CNR gradually increased; the values of 55-60 keV images were almost equivalent to those of standard 120-kVp. The highest scores for overall quality and lesion conspicuity were assigned at 40-keV followed by 45 to 55-keV, all of which were similar to or better than of 120-kVp. For multiphasic-hepatic CT with 50% iodine-load, DL-DECT-VMI at 40- to 55-keV provides equivalent or better image quality and lesion conspicuity without increasing radiation dose compared with standard 120-kVp protocol. • 40-55-keV yields optimal image quality for half-iodine-load multiphasic-hepatic CT with DL-DECT. • DL-DECT protocol decreases radiation exposure compared with 120-kVp scans with iterative reconstruction. • 40-keV images maximise conspicuity of hepatocellular carcinoma especially at hepatic-arterial phase.

Spatial optimization of watershed management practices for nitrogen load reduction using a modeling-optimization framework

EPA Science Inventory

Best management practices (BMPs) are perceived as being effective in reducing nutrient loads transported from non-point sources (NPS) to receiving water bodies. The objective of this study was to develop a modeling-optimization framework that can be used by watershed management p...

Real - time Optimization of Distributed Energy Storage System Operation Strategy Based on Peak Load Shifting

NASA Astrophysics Data System (ADS)

Wang, Qian; Lu, Guangqi; Li, Xiaoyu; Zhang, Yichi; Yun, Zejian; Bian, Di

2018-01-01

To take advantage of the energy storage system (ESS) sufficiently, the factors that the service life of the distributed energy storage system (DESS) and the load should be considered when establishing optimization model. To reduce the complexity of the load shifting of DESS in the solution procedure, the loss coefficient and the equal capacity ratio distribution principle were adopted in this paper. Firstly, the model was established considering the constraint conditions of the cycles, depth, power of the charge-discharge of the ESS, the typical daily load curves, as well. Then, dynamic programming method was used to real-time solve the model in which the difference of power Δs, the real-time revised energy storage capacity Sk and the permission error of depth of charge-discharge were introduced to optimize the solution process. The simulation results show that the optimized results was achieved when the load shifting in the load variance was not considered which means the charge-discharge of the energy storage system was not executed. In the meantime, the service life of the ESS would increase.

Universal field matching in craniospinal irradiation by a background-dose gradient-optimized method.

PubMed

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.

Efficacy of robust optimization plan with partial-arc VMAT for photon volumetric-modulated arc therapy: A phantom study.

PubMed

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.

Synthesis, Characterization, and In Vivo Efficacy of Shell Cross-Linked Nanoparticle Formulations Carrying Silver Antimicrobials as Aerosolized Therapeutics

PubMed Central

2014-01-01

The use of nebulizable, nanoparticle-based antimicrobial delivery systems can improve efficacy and reduce toxicity for treatment of multi-drug-resistant bacteria in the chronically infected lungs of cystic fibrosis patients. Nanoparticle vehicles are particularly useful for applying broad-spectrum silver-based antimicrobials, for instance, to improve the residence time of small-molecule silver carbene complexes (SCCs) within the lung. Therefore, we have synthesized multifunctional, shell cross-linked knedel-like polymeric nanoparticles (SCK NPs) and capitalized on the ability to independently load the shell and core with silver-based antimicrobial agents. We formulated three silver-loaded variants of SCK NPs: shell-loaded with silver cations, core-loaded with SCC10, and combined loading of shell silver cations and core SCC10. All three formulations provided a sustained delivery of silver over the course of at least 2–4 days. The two SCK NP formulations with SCC10 loaded in the core each exhibited excellent antimicrobial activity and efficacy in vivo in a mouse model of Pseudomonas aeruginosa pneumonia. SCK NPs with shell silver cation-load only, while efficacious in vitro, failed to demonstrate efficacy in vivo. However, a single dose of core SCC10-loaded SCK NPs (0.74 ± 0.16 mg Ag) provided a 28% survival advantage over sham treatment, and administration of two doses (0.88 mg Ag) improved survival to 60%. In contrast, a total of 14.5 mg of Ag+ delivered over 5 doses at 12 h intervals was necessary to achieve a 60% survival advantage with a free-drug (SCC1) formulation. Thus, SCK NPs show promise for clinical impact by greatly reducing antimicrobial dosage and dosing frequency, which could minimize toxicity and improve patient adherence. PMID:23718195

Simultaneous optimization of loading pattern and burnable poison placement for PWRs

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

Alim, F.; Ivanov, K.; Yilmaz, S.

2006-07-01

To solve in-core fuel management optimization problem, GARCO-PSU (Genetic Algorithm Reactor Core Optimization - Pennsylvania State Univ.) is developed. This code is applicable for all types and geometry of PWR core structures with unlimited number of fuel assembly (FA) types in the inventory. For this reason an innovative genetic algorithm is developed with modifying the classical representation of the genotype. In-core fuel management heuristic rules are introduced into GARCO. The core re-load design optimization has two parts, loading pattern (LP) optimization and burnable poison (BP) placement optimization. These parts depend on each other, but it is difficult to solve themore » combined problem due to its large size. Separating the problem into two parts provides a practical way to solve the problem. However, the result of this method does not reflect the real optimal solution. GARCO-PSU achieves to solve LP optimization and BP placement optimization simultaneously in an efficient manner. (authors)« less

TU-EF-304-07: Monte Carlo-Based Inverse Treatment Plan Optimization for Intensity Modulated Proton Therapy

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

Pseudo-spectral control of a novel oscillating surge wave energy converter in regular waves for power optimization including load reduction

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

Tom, Nathan M.; Yu, Yi -Hsiang; Wright, Alan D.

The aim of this study is to describe a procedure to maximize the power-to-load ratio of a novel wave energy converter (WEC) that combines an oscillating surge wave energy converter with variable structural components. The control of the power-take-off torque will be on a wave-to-wave timescale, whereas the structure will be controlled statically such that the geometry remains the same throughout the wave period. Linear hydrodynamic theory is used to calculate the upper and lower bounds for the time-averaged absorbed power and surge foundation loads while assuming that the WEC motion remains sinusoidal. Previous work using pseudo-spectral techniques to solvemore » the optimal control problem focused solely on maximizing absorbed energy. This work extends the optimal control problem to include a measure of the surge foundation force in the optimization. The objective function includes two competing terms that force the optimizer to maximize power capture while minimizing structural loads. A penalty weight was included with the surge foundation force that allows control of the optimizer performance based on whether emphasis should be placed on power absorption or load shedding. Results from pseudo-spectral optimal control indicate that a unit reduction in time-averaged power can be accompanied by a greater reduction in surge-foundation force.« less

Pseudo-spectral control of a novel oscillating surge wave energy converter in regular waves for power optimization including load reduction

DOE PAGES

Tom, Nathan M.; Yu, Yi -Hsiang; Wright, Alan D.; ...

2017-04-18

The aim of this study is to describe a procedure to maximize the power-to-load ratio of a novel wave energy converter (WEC) that combines an oscillating surge wave energy converter with variable structural components. The control of the power-take-off torque will be on a wave-to-wave timescale, whereas the structure will be controlled statically such that the geometry remains the same throughout the wave period. Linear hydrodynamic theory is used to calculate the upper and lower bounds for the time-averaged absorbed power and surge foundation loads while assuming that the WEC motion remains sinusoidal. Previous work using pseudo-spectral techniques to solvemore » the optimal control problem focused solely on maximizing absorbed energy. This work extends the optimal control problem to include a measure of the surge foundation force in the optimization. The objective function includes two competing terms that force the optimizer to maximize power capture while minimizing structural loads. A penalty weight was included with the surge foundation force that allows control of the optimizer performance based on whether emphasis should be placed on power absorption or load shedding. Results from pseudo-spectral optimal control indicate that a unit reduction in time-averaged power can be accompanied by a greater reduction in surge-foundation force.« 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

Quality assurance for high dose rate brachytherapy treatment planning optimization: using a simple optimization to verify a complex optimization

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.

Novel Pharmacological Approaches for Treatment of Neurotoxicity Induced by Chronic Exposure to Depleted Uranium

DTIC Science & Technology

2010-09-01

control group and low (300 mg load) and high dose (600 mg load) DU exposure conditions, but utilized a vehicle and three drug-treated groups ( memantine ...applied long after exposure was initiated. The minipumps were filled with drug solutions of 30 mg/ml memantine (3.6 mg/kg/day dose) and/or 10 mg/ml...riluzole (1.2 mg/kg/day dose). Besides its potential usefulness as an uncompetitive NMDA receptor antagonist, memantine also has been reported to have

General equations for optimal selection of diagnostic image acquisition parameters in clinical X-ray imaging.

PubMed

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.

PubMed

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

Effect of Loading Dose of Atorvastatin Prior to Planned Percutaneous Coronary Intervention on Major Adverse Cardiovascular Events in Acute Coronary Syndrome: The SECURE-PCI Randomized Clinical Trial.

PubMed

Berwanger, Otavio; Santucci, Eliana Vieira; de Barros E Silva, Pedro Gabriel Melo; Jesuíno, Isabella de Andrade; Damiani, Lucas Petri; Barbosa, Lilian Mazza; Santos, Renato Hideo Nakagawa; Laranjeira, Ligia Nasi; Egydio, Flávia de Mattos; Borges de Oliveira, Juliana Aparecida; Dall Orto, Frederico Toledo Campo; Beraldo de Andrade, Pedro; Bienert, Igor Ribeiro de Castro; Bosso, Carlos Eduardo; Mangione, José Armando; Polanczyk, Carisi Anne; Sousa, Amanda Guerra de Moraes Rego; Kalil, Renato Abdala Karam; Santos, Luciano de Moura; Sposito, Andrei Carvalho; Rech, Rafael Luiz; Sousa, Antônio Carlos Sobral; Baldissera, Felipe; Nascimento, Bruno Ramos; Giraldez, Roberto Rocha Corrêa Veiga; Cavalcanti, Alexandre Biasi; Pereira, Sabrina Bernardez; Mattos, Luiz Alberto; Armaganijan, Luciana Vidal; Guimarães, Hélio Penna; Sousa, José Eduardo Moraes Rego; Alexander, John Hunter; Granger, Christopher Bull; Lopes, Renato Delascio

2018-04-03

The effects of loading doses of statins on clinical outcomes in patients with acute coronary syndrome (ACS) and planned invasive management remain uncertain. To determine if periprocedural loading doses of atorvastatin decrease 30-day major adverse cardiovascular events (MACE) in patients with ACS and planned invasive management. Multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 53 sites in Brazil among 4191 patients with ACS evaluated with coronary angiography to proceed with a percutaneous coronary intervention (PCI) if anatomically feasible. Enrollment occurred between April 18, 2012, and October 6, 2017. Final follow-up for 30-day outcomes was on November 6, 2017. Patients were randomized to receive 2 loading doses of 80 mg of atorvastatin (n = 2087) or matching placebo (n = 2104) before and 24 hours after a planned PCI. All patients received 40 mg of atorvastatin for 30 days starting 24 hours after the second dose of study medication. The primary outcome was MACE, defined as a composite of all-cause mortality, myocardial infarction, stroke, and unplanned coronary revascularization through 30 days. Among the 4191 patients (mean age, 61.8 [SD, 11.5] years; 1085 women [25.9%]) enrolled, 4163 (99.3%) completed 30-day follow-up. A total of 2710 (64.7%) underwent PCI, 333 (8%) underwent coronary artery bypass graft surgery, and 1144 (27.3%) had exclusively medical management. At 30 days, 130 patients in the atorvastatin group (6.2%) and 149 in the placebo group (7.1%) had a MACE (absolute difference, 0.85% [95% CI, -0.70% to 2.41%]; hazard ratio, 0.88; 95% CI, 0.69-1.11; P = .27). No cases of hepatic failure were reported; 3 cases of rhabdomyolysis were reported in the placebo group (0.1%) and 0 in the atorvastatin group. Among patients with ACS and planned invasive management with PCI, periprocedural loading doses of atorvastatin did not reduce the rate of MACE at 30 days. These findings do not support the routine use of loading doses of atorvastatin among unselected patients with ACS and intended invasive management. clinicaltrials.gov Identifier: NCT01448642.

Use of a channelized Hotelling observer to assess CT image quality and optimize dose reduction for iteratively reconstructed images.

PubMed

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.

Application of a loading dose of colistin methanesulfonate in critically ill patients: population pharmacokinetics, protein binding, and prediction of bacterial kill.

PubMed

Mohamed, Ami F; Karaiskos, Ilias; Plachouras, Diamantis; Karvanen, Matti; Pontikis, Konstantinos; Jansson, Britt; Papadomichelakis, Evangelos; Antoniadou, Anastasia; Giamarellou, Helen; Armaganidis, Apostolos; Cars, Otto; Friberg, Lena E

2012-08-01

A previous pharmacokinetic study on dosing of colistin methanesulfonate (CMS) at 240 mg (3 million units [MU]) every 8 h indicated that colistin has a long half-life, resulting in insufficient concentrations for the first 12 to 48 h after initiation of treatment. A loading dose would therefore be beneficial. The aim of this study was to evaluate CMS and colistin pharmacokinetics following a 480-mg (6-MU) loading dose in critically ill patients and to explore the bacterial kill following the use of different dosing regimens obtained by predictions from a pharmacokinetic-pharmacodynamic model developed from an in vitro study on Pseudomonas aeruginosa. The unbound fractions of colistin A and colistin B were determined using equilibrium dialysis and considered in the predictions. Ten critically ill patients (6 males; mean age, 54 years; mean creatinine clearance, 82 ml/min) with infections caused by multidrug-resistant Gram-negative bacteria were enrolled in the study. The pharmacokinetic data collected after the first and eighth doses were analyzed simultaneously with the data from the previous study (total, 28 patients) in the NONMEM program. For CMS, a two-compartment model best described the pharmacokinetics, and the half-lives of the two phases were estimated to be 0.026 and 2.2 h, respectively. For colistin, a one-compartment model was sufficient and the estimated half-life was 18.5 h. The unbound fractions of colistin in the patients were 26 to 41% at clinical concentrations. Colistin A, but not colistin B, had a concentration-dependent binding. The predictions suggested that the time to 3-log-unit bacterial kill for a 480-mg loading dose was reduced to half of that for the dose of 240 mg.

Application of a Loading Dose of Colistin Methanesulfonate in Critically Ill Patients: Population Pharmacokinetics, Protein Binding, and Prediction of Bacterial Kill

PubMed Central

Karaiskos, Ilias; Plachouras, Diamantis; Karvanen, Matti; Pontikis, Konstantinos; Jansson, Britt; Papadomichelakis, Evangelos; Antoniadou, Anastasia; Giamarellou, Helen; Armaganidis, Apostolos; Cars, Otto; Friberg, Lena E.

2012-01-01

A previous pharmacokinetic study on dosing of colistin methanesulfonate (CMS) at 240 mg (3 million units [MU]) every 8 h indicated that colistin has a long half-life, resulting in insufficient concentrations for the first 12 to 48 h after initiation of treatment. A loading dose would therefore be beneficial. The aim of this study was to evaluate CMS and colistin pharmacokinetics following a 480-mg (6-MU) loading dose in critically ill patients and to explore the bacterial kill following the use of different dosing regimens obtained by predictions from a pharmacokinetic-pharmacodynamic model developed from an in vitro study on Pseudomonas aeruginosa. The unbound fractions of colistin A and colistin B were determined using equilibrium dialysis and considered in the predictions. Ten critically ill patients (6 males; mean age, 54 years; mean creatinine clearance, 82 ml/min) with infections caused by multidrug-resistant Gram-negative bacteria were enrolled in the study. The pharmacokinetic data collected after the first and eighth doses were analyzed simultaneously with the data from the previous study (total, 28 patients) in the NONMEM program. For CMS, a two-compartment model best described the pharmacokinetics, and the half-lives of the two phases were estimated to be 0.026 and 2.2 h, respectively. For colistin, a one-compartment model was sufficient and the estimated half-life was 18.5 h. The unbound fractions of colistin in the patients were 26 to 41% at clinical concentrations. Colistin A, but not colistin B, had a concentration-dependent binding. The predictions suggested that the time to 3-log-unit bacterial kill for a 480-mg loading dose was reduced to half of that for the dose of 240 mg. PMID:22615285

Fluence map optimization (FMO) with dose-volume constraints in IMRT using the geometric distance sorting method.

PubMed

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.

SU-E-T-618: Dosimetric Comparison of Manual and Beam Angle Optimization of Gantry Angles in IMRT for Cervical Cancer

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

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.

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

Biomechanical evaluation of an innovative spring-loaded axillary crutch design.

PubMed

Zhang, Yanxin; Liu, Guangyu; Xie, Shengquan; Liger, Aurélien

2011-01-01

We evaluated an innovative spring-loaded crutch design by comparing its performance with standard crutches through a biomechanical approach. Gait analysis was conducted for 7 male subjects under two conditions: walking with standard crutches and with spring-loaded crutches. Three-dimensional kinematic data and ground reaction force were recorded. Spatiotemporal variables, external mechanical work, and elastic energy (for spring crutches) were calculated based on recorded data. The trajectories of vertical ground reaction forces with standard crutches had two main peaks before and after mid-stance, and those with optimized spring-loaded crutches had only one main peak. The magnitude of external mechanical work was significantly higher with spring-loaded crutches than with standard crutches for all subjects, and the transferred elastic energy made an important contribution to the total external work for spring-loaded crutches. No significant differences in the spatiotemporal parameters were observed. Optimized spring-loaded crutches can efficiently propel crutch walkers and could reduce the total energy expenditure in crutch walking. Further research using optimized spring-loaded crutches with respect to energy efficiency is recommended.

Analytic model for ultrasound energy receivers and their optimal electric loads II: Experimental validation

NASA Astrophysics Data System (ADS)

Gorostiaga, M.; Wapler, M. C.; Wallrabe, U.

2017-10-01

In this paper, we verify the two optimal electric load concepts based on the zero reflection condition and on the power maximization approach for ultrasound energy receivers. We test a high loss 1-3 composite transducer, and find that the measurements agree very well with the predictions of the analytic model for plate transducers that we have developed previously. Additionally, we also confirm that the power maximization and zero reflection loads are very different when the losses in the receiver are high. Finally, we compare the optimal load predictions by the KLM and the analytic models with frequency dependent attenuation to evaluate the influence of the viscosity.

Research Based on AMESim of Electro-hydraulic Servo Loading System

NASA Astrophysics Data System (ADS)

Li, Jinlong; Hu, Zhiyong

2017-09-01

Electro-hydraulic servo loading system is a subject studied by many scholars in the field of simulation and control at home and abroad. The electro-hydraulic servo loading system is a loading device simulation of stress objects by aerodynamic moment and other force in the process of movement, its function is all kinds of gas in the lab condition to analyze stress under dynamic load of objects. The purpose of this paper is the design of AMESim electro-hydraulic servo system, PID control technology is used to configure the parameters of the control system, complete the loading process under different conditions, the optimal design parameters, optimization of dynamic performance of the loading system.

Comparison of linear and nonlinear programming approaches for "worst case dose" and "minmax" robust optimization of intensity-modulated proton therapy dose distributions.

PubMed

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.

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

Viner, Brian J.; Jannik, Tim; Stone, Daniel

Firefighters responding to wildland fires where surface litter and vegetation contain radiological contamination will receive a radiological dose by inhaling resuspended radioactive material in the smoke. This may increase their lifetime risk of contracting certain types of cancer. Using published data, we modelled hypothetical radionuclide emissions, dispersion and dose for 70th and 97th percentile environmental conditions and for average and high fuel loads at the Savannah River Site. We predicted downwind concentration and potential dose to firefighters for radionuclides of interest ( 137Cs, 238Pu, 90Sr and 210Po). Predicted concentrations exceeded dose guidelines in the base case scenario emissions of 1.0more » × 10 7 Bq ha –1 for 238Pu at 70th percentile environmental conditions and average fuel load levels for both 4- and 14-h shifts. Under 97th percentile environmental conditions and high fuel loads, dose guidelines were exceeded for several reported cases for 90Sr, 238Pu and 210Po. Potential for exceeding dose guidelines was mitigated by including plume rise (>2 m s –1) or moving a small distance from the fire owing to large concentration gradients near the edge of the fire. As a result, our approach can quickly estimate potential dose from airborne radionuclides in wildland fire and assist decision-making to reduce firefighter exposure.« less

Assessment of hemodynamic load components affecting optimization of cardiac resynchronization therapy by lumped parameter mode.

PubMed

Xu, Ke; Butlin, Mark; Avolio, Alberto P

2012-01-01

Timing of biventricular pacing devices employed in cardiac resynchronization therapy (CRT) is a critical determinant of efficacy of the procedure. Optimization is done by maximizing function in terms of arterial pressure (BP) or cardiac output (CO). However, BP and CO are also determined by the hemodynamic load of the pulmonary and systemic vasculature. This study aims to use a lumped parameter circulatory model to assess the influence of the arterial load on the atrio-ventricular (AV) and inter-ventricular (VV) delay for optimal CRT performance.

SCCT guidelines on radiation dose and dose-optimization strategies in cardiovascular CT

PubMed Central

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

Modelling and mitigating dose to firefighters from inhalation of radionuclides in wildland fire smoke

DOE PAGES

Viner, Brian J.; Jannik, Tim; Stone, Daniel; ...

2015-06-12

Firefighters responding to wildland fires where surface litter and vegetation contain radiological contamination will receive a radiological dose by inhaling resuspended radioactive material in the smoke. This may increase their lifetime risk of contracting certain types of cancer. Using published data, we modelled hypothetical radionuclide emissions, dispersion and dose for 70th and 97th percentile environmental conditions and for average and high fuel loads at the Savannah River Site. We predicted downwind concentration and potential dose to firefighters for radionuclides of interest ( 137Cs, 238Pu, 90Sr and 210Po). Predicted concentrations exceeded dose guidelines in the base case scenario emissions of 1.0more » × 10 7 Bq ha –1 for 238Pu at 70th percentile environmental conditions and average fuel load levels for both 4- and 14-h shifts. Under 97th percentile environmental conditions and high fuel loads, dose guidelines were exceeded for several reported cases for 90Sr, 238Pu and 210Po. Potential for exceeding dose guidelines was mitigated by including plume rise (>2 m s –1) or moving a small distance from the fire owing to large concentration gradients near the edge of the fire. As a result, our approach can quickly estimate potential dose from airborne radionuclides in wildland fire and assist decision-making to reduce firefighter exposure.« less

Curcumin loaded pH-sensitive nanoparticles for the treatment of colon cancer.

PubMed

Prajakta, Dandekar; Ratnesh, Jain; Chandan, Kumar; Suresh, Subramanian; Grace, Samuel; Meera, Venkatesh; Vandana, Patravale

2009-10-01

The investigation was aimed at designing pH-sensitive, polymeric nanoparticles of curcumin, a natural anti-cancer agent, for the treatment of colon cancer. The objective was to enhance the bioavailability of curcumin, simultaneously reducing the required dose through selective targeting to colon. Eudragit S100 was chosen to aid targeting since the polymer dissolves at colonic pH to result in selective colonic release of the entrapped drug. Solvent emulsion-evaporation technique was employed to formulate the nanoparticles. Various process parameters were optimized and the optimized formulation was evaluated for particle size distribution and encapsulation efficiency before subjecting to freeze-drying. The freeze dried product was characterized for particle size, drug content, DSC studies, particle morphology. Anti-cancer potential of the formulation was demonstrated by MTT assay in HT-29 cell line. Nanometric, homogeneous, spherical particles were obtained with encapsulation efficiency of 72%. Freeze-dried nanoparticles exhibited a negative surface charge, drug content of > 99% and presence of drug in amorphous form which may result in possible enhanced absorption. MTT assay demonstrated almost double inhibition of the cancerous cells by nanoparticles, as compared to curcumin alone, at the concentrations tested. Enhanced action may be attributed to size influenced improved cellular uptake, and may result in reduction of overall dose requirement. Results indicate the potential for in vivo studies to establish the clinical application of the formulation.

Optimization of vitamins A and D3 loading in re-assembled casein micelles and effect of loading on stability of vitamin D3 during storage.

PubMed

Loewen, Anisa; Chan, Benny; Li-Chan, Eunice C Y

2018-02-01

The objectives of this study were to apply response surface methodology to optimize fat-soluble vitamin loading in re-assembled casein micelles, and to evaluate vitamin D stability of dry formulations during ambient or accelerated storage and in fortified fluid skim milk stored under refrigeration. Optimal loading of vitamin A (1.46-1.48mg/100mgcasein) was found at 9.7mM phosphate, 5.5mM citrate and 30.0mM calcium, while optimal loading of vitamin D (1.38-1.46mg/100mg casein) was found at 4.9mM phosphate, 4.0mM citrate and 26.1mM calcium. In general, more vitamin D was retained in vitamin D-re-assembled casein micelles than control powders during storage, while vitamin D loss was not different for vitamin D-re-assembled casein micelles and control fortified milks after 21days of refrigerated storage with light exposure. In conclusion, re-assembled casein micelles with high loading efficiency show promise for improving vitamin D stability during dry storage. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

A VVWBO-BVO-based GM (1,1) and its parameter optimization by GRA-IGSA integration algorithm for annual power load forecasting

PubMed Central

Wang, Hongguang

2018-01-01

Annual power load forecasting is not only the premise of formulating reasonable macro power planning, but also an important guarantee for the safety and economic operation of power system. In view of the characteristics of annual power load forecasting, the grey model of GM (1,1) are widely applied. Introducing buffer operator into GM (1,1) to pre-process the historical annual power load data is an approach to improve the forecasting accuracy. To solve the problem of nonadjustable action intensity of traditional weakening buffer operator, variable-weight weakening buffer operator (VWWBO) and background value optimization (BVO) are used to dynamically pre-process the historical annual power load data and a VWWBO-BVO-based GM (1,1) is proposed. To find the optimal value of variable-weight buffer coefficient and background value weight generating coefficient of the proposed model, grey relational analysis (GRA) and improved gravitational search algorithm (IGSA) are integrated and a GRA-IGSA integration algorithm is constructed aiming to maximize the grey relativity between simulating value sequence and actual value sequence. By the adjustable action intensity of buffer operator, the proposed model optimized by GRA-IGSA integration algorithm can obtain a better forecasting accuracy which is demonstrated by the case studies and can provide an optimized solution for annual power load forecasting. PMID:29768450

SU-E-T-488: An Iso-Dose Curve Based Interactive IMRT Optimization System for Physician-Driven Plan Tuning

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

SU-F-P-61: Does It Matter Not to Use Optimization Points at the Apex for Vaginal Cylinder HDR Brachytherapy Planning?

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

Performance tradeoffs in static and dynamic load balancing strategies

NASA Technical Reports Server (NTRS)

Iqbal, M. A.; Saltz, J. H.; Bokhart, S. H.

1986-01-01

The problem of uniformly distributing the load of a parallel program over a multiprocessor system was considered. A program was analyzed whose structure permits the computation of the optimal static solution. Then four strategies for load balancing were described and their performance compared. The strategies are: (1) the optimal static assignment algorithm which is guaranteed to yield the best static solution, (2) the static binary dissection method which is very fast but sub-optimal, (3) the greedy algorithm, a static fully polynomial time approximation scheme, which estimates the optimal solution to arbitrary accuracy, and (4) the predictive dynamic load balancing heuristic which uses information on the precedence relationships within the program and outperforms any of the static methods. It is also shown that the overhead incurred by the dynamic heuristic is reduced considerably if it is started off with a static assignment provided by either of the other three strategies.

A Framework for Optimal Control Allocation with Structural Load Constraints

NASA Technical Reports Server (NTRS)

Frost, Susan A.; Taylor, Brian R.; Jutte, Christine V.; Burken, John J.; Trinh, Khanh V.; Bodson, Marc

2010-01-01

Conventional aircraft generally employ mixing algorithms or lookup tables to determine control surface deflections needed to achieve moments commanded by the flight control system. Control allocation is the problem of converting desired moments into control effector commands. Next generation aircraft may have many multipurpose, redundant control surfaces, adding considerable complexity to the control allocation problem. These issues can be addressed with optimal control allocation. Most optimal control allocation algorithms have control surface position and rate constraints. However, these constraints are insufficient to ensure that the aircraft's structural load limits will not be exceeded by commanded surface deflections. In this paper, a framework is proposed to enable a flight control system with optimal control allocation to incorporate real-time structural load feedback and structural load constraints. A proof of concept simulation that demonstrates the framework in a simulation of a generic transport aircraft is presented.

TU-EF-204-03: Task-Based KV and MAs Optimization for Radiation Dose Reduction in CT: From FBP to Statistical Model-Based Iterative Reconstruction (MBIR)

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

Usefulness of oral loading of oxcarbazepine suspension in selected patients with epilepsy.

PubMed

Kim, Dong Wook; Gu, Namyi; Lee, Howard; Jang, In-Jin; Chu, Kon; Yu, Kyung-Sang; Cho, Joo-Youn; Yoon, Seo Hyun; Na, Hyun Jeong; Lee, Sang Kun

2013-10-01

Oral loading of oxcarbazepine tablet is effective and well tolerated to adequately achieve the therapeutic levels of its active metabolite, 10,11-dihydro-10-hydroxy-carbazepine (monohydroxy derivative, MHD) in epilepsy patients. The present study was performed to investigate the safety, tolerability, and pharmacokinetic profiles of oral loading of oxcarbazepine suspension in epilepsy patients with a high risk of recurrent seizures. Oxcarbazepine suspension was administered orally at a single loading dose of 30 mg/kg to 38 adult patients with recurrent seizures, who required rapid seizure control or temporarily discontinued antiepileptic drugs for diagnostic or pre-surgical evaluation. Plasma concentrations of oxcarbazepine and MHD were determined, and adverse events were assessed at 2, 4, 6, 8, 10, 12, 14, 16, and 24 hours after oral loading of oxcarbazepine suspension. 30 patients experienced ≥ 1 adverse event during the first 24 hours after oral loading of oxcarbazepine (e.g., dizziness, transient diplopia, nausea or vomiting), most of which occurred within 4 hours after loading, suggesting no temporal association with MHD plasma levels. 35 (92.1%) patients were still compliant with a maintenance dose of oxcarbazepine after discharge from hospital. 34 (89.4%) patients reached the lower therapeutic level of MHD (12 mg/l) at 4 hours after oral loading of oxcarbazepine suspension, which lasted up to 24 hours in most patients. No patient reached the supratherapeutic levels of MHD (> 35 mg/l) during the study. The mean plasma concentration-time curves and pharmacokinetic profiles of oral loading of oxcarbazepine suspension were similar to those of oral loading of oxcarbazepine tablet. Oral loading of oxcarbazepine suspension followed by maintenance dosing is well tolerated and effective in steadily achieving the therapeutic level of MHD in selected patients with epilepsy.

Optimal bladder filling during high-dose-rate intracavitary brachytherapy for cervical cancer: a dosimetric study

PubMed Central

Shetty, Saurabha; Majumder, Dipanjan; Adurkar, Pranjal; Swamidas, Jamema; Engineer, Reena; Chopra, Supriya; Shrivastava, Shyamkishore

2017-01-01

Purpose The aim of this study is to compare 3D dose volume histogram (DVH) parameters of bladder and other organs at risk with different bladder filling protocol during high-dose-rate intracavitary brachytherapy (HDR-ICBT) in cervical cancer, and to find optimized bladder volume. Material and methods This dosimetric study was completed with 21 patients who underwent HDR-ICBT with computed tomography/magnetic resonance compatible applicator as a routine treatment. Computed tomography planning was done for each patient with bladder emptied (series 1), after 50 ml (series 2), and 100 ml (series 3) bladder filling with a saline infusion through the bladder catheter. Contouring was done on the Eclipse Planning System. 7 Gy to point A was prescribed with the standard loading patterns. Various 3D DVH parameters including 0.1 cc, 1 cc, 2 cc doses and mean doses to the OAR’s were noted. Paired t-test was performed. Results The mean (± SD) bladder volume was 64.5 (± 25) cc, 116.2 (± 28) cc, and 172.9 (± 29) cc, for series 1, 2, and 3, respectively. The 0.1 cm3,1 cm3, 2 cm3 mean bladder doses for series 1, series 2, and series 3 were 9.28 ± 2.27 Gy, 7.38 ± 1.72 Gy, 6.58 ± 1.58 Gy; 9.39 ± 2.28 Gy, 7.85 ± 1.85 Gy, 7.05 ± 1.59 Gy, and 10.09 ± 2.46 Gy, 8.33 ± 1.75 Gy, 7.6 ± 1.55 Gy, respectively. However, there was a trend towards higher bladder doses in series 3. Similarly, for small bowel dose 0.1 cm3, 1 cm3, and 2 cm3 in series 1, 2, and 3 were 5.44 ± 2.2 Gy, 4.41 ± 1.84 Gy, 4 ± 1.69 Gy; 4.57 ± 2.89 Gy, 3.78 ± 2.21 Gy, 3.35 ± 2.02 Gy, and 4.09 ± 2.38 Gy, 3.26 ± 1.8 Gy, 3.05 ± 1.58 Gy. Significant increase in small bowel dose in empty bladder (series 1) compared to full bladder (series 3) (p = 0.03) was noted. However, the rectal and sigmoid doses were not significantly affected with either series. Conclusions Bladder filling protocol with 50 ml and 100 ml was well tolerated and achieved a reasonably reproducible bladder volume during cervical brachytherapy. In our analysis so far, there is no significant impact of bladder filling on DVH parameters, although larger bladders tend to have higher doses. Small bowel doses are lesser with higher bladder volumes. Further evaluation and validation are necessary. PMID:28533798

TH-AB-202-09: Direct-Aperture Optimization for Combined MV+kV Dose Planning in Fluoroscopic Real-Time Tumor-Tracking Radiation Therapy

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

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

Statistical model based iterative reconstruction in clinical CT systems. Part III. Task-based kV/mAs optimization for radiation dose reduction

PubMed Central

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

Optimal policies for simultaneous energy consumption and ancillary service provision for flexible loads under stochastic prices and no capacity reservation constraint

NASA Astrophysics Data System (ADS)

Kefayati, Mahdi; Baldick, Ross

2015-07-01

Flexible loads, i.e. the loads whose power trajectory is not bound to a specific one, constitute a sizable portion of current and future electric demand. This flexibility can be used to improve the performance of the grid, should the right incentives be in place. In this paper, we consider the optimal decision making problem faced by a flexible load, demanding a certain amount of energy over its availability period, subject to rate constraints. The load is also capable of providing ancillary services (AS) by decreasing or increasing its consumption in response to signals from the independent system operator (ISO). Under arbitrarily distributed and correlated Markovian energy and AS prices, we obtain the optimal policy for minimising expected total cost, which includes cost of energy and benefits from AS provision, assuming no capacity reservation requirement for AS provision. We also prove that the optimal policy has a multi-threshold form and can be computed, stored and operated efficiently. We further study the effectiveness of our proposed optimal policy and its impact on the grid. We show that, while optimal simultaneous consumption and AS provision under real-time stochastic prices are achievable with acceptable computational burden, the impact of adopting such real-time pricing schemes on the network might not be as good as suggested by the majority of the existing literature. In fact, we show that such price responsive loads are likely to induce peak-to-average ratios much more than what is observed in the current distribution networks and adversely affect the grid.

Assessment of Optimal Flexibility in Ensemble of Frequency Responsive Loads

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

Kundu, Soumya; Hansen, Jacob; Lian, Jianming

2018-04-19

Potential of electrical loads in providing grid ancillary services is often limited due to the uncertainties associated with the load behavior. A knowledge of the expected uncertainties with a load control program would invariably yield to better informed control policies, opening up the possibility of extracting the maximal load control potential without affecting grid operations. In the context of frequency responsive load control, a probabilistic uncertainty analysis framework is presented to quantify the expected error between the target and actual load response, under uncertainties in the load dynamics. A closed-form expression of an optimal demand flexibility, minimizing the expected errormore » in actual and committed flexibility, is provided. Analytical results are validated through Monte Carlo simulations of ensembles of electric water heaters.« less

Cost optimization of reinforced concrete cantilever retaining walls under seismic loading using a biogeography-based optimization algorithm with Levy flights

NASA Astrophysics Data System (ADS)

Aydogdu, Ibrahim

2017-03-01

In this article, a new version of a biogeography-based optimization algorithm with Levy flight distribution (LFBBO) is introduced and used for the optimum design of reinforced concrete cantilever retaining walls under seismic loading. The cost of the wall is taken as an objective function, which is minimized under the constraints implemented by the American Concrete Institute (ACI 318-05) design code and geometric limitations. The influence of peak ground acceleration (PGA) on optimal cost is also investigated. The solution of the problem is attained by the LFBBO algorithm, which is developed by adding Levy flight distribution to the mutation part of the biogeography-based optimization (BBO) algorithm. Five design examples, of which two are used in literature studies, are optimized in the study. The results are compared to test the performance of the LFBBO and BBO algorithms, to determine the influence of the seismic load and PGA on the optimal cost of the wall.

SU-E-T-625: Robustness Evaluation and Robust Optimization of IMPT Plans Based on Per-Voxel Standard Deviation of Dose Distributions.

PubMed

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.

Development of implants composed of bioactive materials for bone repair

NASA Astrophysics Data System (ADS)

Xiao, Wei

The purpose of this Ph.D. research was to address the clinical need for synthetic bioactive materials to heal defects in non-loaded and loaded bone. Hollow hydroxyapatite (HA) microspheres created in a previous study were evaluated as a carrier for controlled release of bone morphogenetic protein-2 (BMP2) in bone regeneration. New bone formation in rat calvarial defects implanted with BMP2-loaded microspheres (43%) was significantly higher than microspheres without BMP2 (17%) at 6 weeks postimplantation. Then hollow HA microspheres with a carbonate-substituted composition were prepared to improve their resorption rate. Hollow HA microspheres with 12 wt. % of carbonate showed significantly higher new bone formation (73 +/- 8%) and lower residual HA (7 +/- 2%) than stoichiometric HA microspheres (59 +/- 2% new bone formation; 21 +/- 3% residual HA). The combination of carbonate-substituted hollow HA microspheres and clinically-safe doses of BMP2 could provide promising implants for healing non-loaded bone defects. Strong porous scaffolds of bioactive silicate (13-93) glass were designed with the aid of finite-element modeling, created by robocasting and evaluated for loaded bone repair. Scaffolds with a porosity gradient to mimic human cortical bone showed a compressive strength of 88 +/- 20 MPa, a flexural strength of 34 +/- 5 MPa and the ability to support bone infiltration in vivo. The addition of a biodegradable polylactic acid (PLA) layer to the external surface of these scaffolds increased their load-bearing capacity in four-point bending by 50% and dramatically enhanced their work of fracture, resulting in a "ductile" mechanical response. These bioactive glass-PLA composites, combining bioactivity, high strength, high work of fracture and an internal architecture conducive to bone infiltration, could provide optimal implants for structural bone repair.

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

Load management as a smart grid concept for sizing and designing of hybrid renewable energy systems

NASA Astrophysics Data System (ADS)

Eltamaly, Ali M.; Mohamed, Mohamed A.; Al-Saud, M. S.; Alolah, Abdulrahman I.

2017-10-01

Optimal sizing of hybrid renewable energy systems (HRES) to satisfy load requirements with the highest reliability and lowest cost is a crucial step in building HRESs to supply electricity to remote areas. Applying smart grid concepts such as load management can reduce the size of HRES components and reduce the cost of generated energy considerably. In this article, sizing of HRES is carried out by dividing the load into high- and low-priority parts. The proposed system is formed by a photovoltaic array, wind turbines, batteries, fuel cells and a diesel generator as a back-up energy source. A smart particle swarm optimization (PSO) algorithm using MATLAB is introduced to determine the optimal size of the HRES. The simulation was carried out with and without division of the load to compare these concepts. HOMER software was also used to simulate the proposed system without dividing the loads to verify the results obtained from the proposed PSO algorithm. The results show that the percentage of division of the load is inversely proportional to the cost of the generated energy.

Tafenoquine for the treatment of recurrent Plasmodium vivax malaria.

PubMed

Kitchener, Scott; Nasveld, Peter; Edstein, Michael D

2007-03-01

Tafenoquine was used to treat Plasmodium vivax malaria cases who had previously failed treatment with chloroquine and primaquine. Chloroquine was followed by a loading dose of tafenoquine (200 mg base/day for 3 days) and 200 mg a week was given for 8 weeks. One of 27 treated patients relapsed after 6 months of observation. A standard course of chloroquine administered with 8 weeks of tafenoquine may be more effective than chloroquine with primaquine (22.5 mg/day for 14 days) in preventing additional P. vivax relapses. Larger studies are required to optimize the combination, but our findings suggest that an extended use of tafenoquine may be required to prevent relapses of primaquine-tolerant strains of P. vivax malaria.

Discovery and Delivery of Synergistic Chemotherapy Drug Combinations to Tumors

NASA Astrophysics Data System (ADS)

Camacho, Kathryn Militar

Chemotherapy combinations for cancer treatments harbor immense therapeutic potentials which have largely been untapped. Of all diseases, clinical studies of drug combinations are the most prevalent in oncology, yet their effectiveness is disputable, as complete tumor regressions are rare. Our research has been devoted towards developing delivery vehicles for combinations of chemotherapy drugs which elicit significant tumor reduction yet limit toxicity in healthy tissue. Current administration methods assume that chemotherapy combinations at maximum tolerable doses will provide the greatest therapeutic effect -- a presumption which often leads to unprecedented side effects. Contrary to traditional administration, we have found that drug ratios rather than total cumulative doses govern combination therapeutic efficacy. In this thesis, we have developed nanoparticles to incorporate synergistic ratios of chemotherapy combinations which significantly inhibit cancer cell growth at lower doses than would be required for their single drug counterparts. The advantages of multi-drug incorporation in nano-vehicles are many: improved accumulation in tumor tissue via the enhanced permeation and retention effect, limited uptake in healthy tissue, and controlled exposure of tumor tissue to optimal synergistic drug ratios. To exploit these advantages for polychemotherapy delivery, two prominent nanoparticles were investigated: liposomes and polymer-drug conjugates. Liposomes represent the oldest class of nanoparticles, with high drug loading capacities and excellent biocompatibility. Polymer-drug conjugates offer controlled drug incorporations through reaction stoichiometry, and potentially allow for delivery of precise ratios. Here, we show that both vehicles, when armed with synergistic ratios of chemotherapy drugs, significantly inhibit tumor growth in an aggressive mouse breast carcinoma model. Furthermore, versatile drug incorporation methods investigated here can be broadly applied to various agents. Findings from our research can potentially widen the therapeutic window of chemotherapy combinations by emphasizing investigations of optimal drug ratios rather than maximum drug doses and by identifying appropriate nanoparticles for their delivery. Application of these concepts can ultimately help capture the full therapeutic potential of combination regimens.

Algorithms for the optimization of RBE-weighted dose in particle therapy.

PubMed

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.

Study on Pyroelectric Harvesters with Various Geometry

PubMed Central

Siao, An-Shen; Chao, Ching-Kong; Hsiao, Chun-Ching

2015-01-01

Pyroelectric harvesters convert time-dependent temperature variations into electric current. The appropriate geometry of the pyroelectric cells, coupled with the optimal period of temperature fluctuations, is key to driving the optimal load resistance, which enhances the performance of pyroelectric harvesters. The induced charge increases when the thickness of the pyroelectric cells decreases. Moreover, the induced charge is extremely reduced for the thinner pyroelectric cell when not used for the optimal period. The maximum harvested power is achieved when a 100 μm-thick PZT (Lead zirconate titanate) cell is used to drive the optimal load resistance of about 40 MΩ. Moreover, the harvested power is greatly reduced when the working resistance diverges even slightly from the optimal load resistance. The stored voltage generated from the 75 μm-thick PZT cell is less than that from the 400 μm-thick PZT cell for a period longer than 64 s. Although the thinner PZT cell is advantageous in that it enhances the efficiency of the pyroelectric harvester, the much thinner 75 μm-thick PZT cell and the divergence from the optimal period further diminish the performance of the pyroelectric cell. Therefore, the designers of pyroelectric harvesters need to consider the coupling effect between the geometry of the pyroelectric cells and the optimal period of temperature fluctuations to drive the optimal load resistance. PMID:26270666

Minihepcidins prevent iron overload in a hepcidin-deficient mouse model of severe hemochromatosis

PubMed Central

Ramos, Emilio; Ruchala, Piotr; Goodnough, Julia B.; Kautz, Léon; Preza, Gloria C.; Nemeth, Elizabeta

2012-01-01

The deficiency of hepcidin, the hormone that controls iron absorption and its tissue distribution, is the cause of iron overload in nearly all forms of hereditary hemochromatosis and in untransfused iron-loading anemias. In a recent study, we reported the development of minihepcidins, small drug-like hepcidin agonists. Here we explore the feasibility of using minihepcidins for the prevention and treatment of iron overload in hepcidin-deficient mice. An optimized minihepcidin (PR65) was developed that had superior potency and duration of action compared with natural hepcidin or other minihepcidins, and favorable cost of synthesis. PR65 was administered by subcutaneous injection daily for 2 weeks to iron-depleted or iron-loaded hepcidin knockout mice. PR65 administration to iron-depleted mice prevented liver iron loading, decreased heart iron levels, and caused the expected iron retention in the spleen and duodenum. At high doses, PR65 treatment also caused anemia because of profound iron restriction. PR65 administration to hepcidin knockout mice with pre-existing iron overload had a more moderate effect and caused partial redistribution of iron from the liver to the spleen. Our study demonstrates that minihepcidins could be beneficial in iron overload disorders either used alone for prevention or possibly as adjunctive therapy with phlebotomy or chelation. PMID:22990014

Adherence to Anti-Retroviral Therapy in North Central Nigeria.

PubMed

Avong, Yohanna Kambai; van Wyk, Brian; Njab, Jean; Abimiku, Alash'le G; Ndembi, Nicaise; Okuma, James; Ogbanufe, Obinna; Ekong, Ernest; Dakum, Patrick; Blattner, William A

2015-01-01

Nigeria bears nearly 10% of the global burden of HIV/AIDS. Most of the AIDS patients dwell in the part of Nigeria known as the "North Central" geopolitical region. Sustaining HIV patients in this high risk region is critical for the overall success of the ART program in Nigeria. We assessed the level of adherence to ART and adherence determinants among participants who had been on ART for an average of three and half years. Eligible study participants initiated HAART between 2004 and 2010. HAART regimens contained AZT/3TC +NVP or EFV; AZT/3TC/NVP; 3TC/NVP/d4T; TDF/FTC +EFV or NVP and TDF+3TC+LPV/r. A composite adherence measure defined as not missing a dose and taking the correct dose and adhering to the correct frequency and correct schedule of drug administration was used to assess self-reported adherence over a period of three days. Selfreported adherence was validated with viral load test. Base line adherence was fixed at ≥95% adherence level. Significant test was fixed at p<0.05. We included 502 participants in the analysis. Median age for men was 42 years (IQR: 38 - 44 years) and women, 36 years (IQR: 30-40 years). Mean duration of therapy was 43 (16-70) months. Effective self-reported adherence was 97.3%. Only age and virologic suppression were significantly associated with adherence to ART. Forgetfullness (43%) was the major reason for non-adherence, while improvement in health condition (40%) was the main facilitator of adherence to the medications. Most participants achieved optimal adherence (≥95%) with high virologic suppression. Strategies to sustain optimal adherence, e.g., the use of fixed dose combinations (FDCs) and comprehensive adherence counselling should be maintained.

Immunomodulatory effect of ganoderma lucidum polysaccharides (GLP) on long-term heavy-load exercising mice.

PubMed

Shi, Yali; Cai, Dehua; Wang, Xiaojie; Liu, Xinshen

2012-12-01

Long-term heavy-load exercise can lead to a decrease in the organism's immune response. In this study, we used 100 Kunming (KM) mice to investigate the immune-regulatory effects of Ganoderma lucidum polysaccharides (GLP) on long-term heavy-load exercising mice. Peripheral white blood cells (WBC), the absolute value of neutrophils (NEUT), the phagocytic function of macrophages, serum agglutination valence, and the number of plaque-forming cells (PFC) were evaluated 4 weeks after gavaging long-term heavy-load exercising mice with GLP. After exercise, the WBC count in peripheral blood, absolute neutrophil count, macrophage phagocytic index, serum agglutination valence, and the number of plaque-forming cells were significantly reduced in the mice not fed GLP. Both medium and high doses of GLP drastically increased peripheral WBC, absolute neutrophil count, macrophage phagocytic index, serum agglutination valence, and the number of plaque-forming cells in long-term heavy-load exercising mice. High doses of GLP increased peritoneal macrophage phagocytic rate considerably. With this study, we demonstrate that 4 weeks of heavy-load exercise can lead to exercise-induced immunosuppression in mice. A supplement of GLP fed to these mice improves both non-specific and specific immune responses among these mice. The effect for the high-dose GLP treatment is especially significant.

Vitamin C-driven epirubicin loading into liposomes.

PubMed

Lipka, Dominik; Gubernator, Jerzy; Filipczak, Nina; Barnert, Sabine; Süss, Regine; Legut, Mateusz; Kozubek, Arkadiusz

2013-01-01

The encapsulation of anticancer drugs in a liposome structure protects the drug during circulation and increases drug accumulation in the cancer tissue and antitumor activity while decreasing drug toxicity. This paper presents a new method of active drug loading based on a vitamin C pH/ion gradient. Formulations were characterized in terms of the following parameters: optimal external pH, time and drug-to-lipid ratio for the purpose of remote loading, and in vitro stability. In the case of the selected drug, epirubicin (EPI), its coencapsulation increases its anticancer activity through a possibly synergistic effect previously reported by other groups for a free nonencapsulated drug/vitamin C cocktail. The method also has another advantage over other remote-loading methods: it allows faster drug release through liposome destabilization at the tumor site, thanks to the very good solubility of the EPI vitamin C salt, as seen on cryogenic transmission electron microscopy images. This influences the drug-release process and increases the anticancer activity of the liposome formulation. The liposomes are characterized as stable, with very good pharmacokinetics (half-life 18.6 hours). The antitumor activity toward MCF-7 and 4T-1 breast cancer cells was higher in the case of EPI loaded via our gradient than via an ammonium sulfate gradient. Finally, the EPI liposomal formulation and the free drug were tested using the murine 4T-1 breast cancer model. The antitumor activity of the encapsulated drug was confirmed (tumor-growth inhibition over 40% from day 16 until the end of the experiment), and the free drug was shown to have no anticancer activity at the tested dose.

The Effectiveness of Low-Level Light Therapy in Attenuating Vocal Fatigue.

PubMed

Kagan, Loraine Sydney; Heaton, James T

2017-05-01

Low-level light therapy (LLLT) is effective in reducing inflammation, promoting wound healing, and preventing tissue damage, but has not yet been studied in the treatment of voice disorders. The objective of this study was to investigate the possible effectiveness of LLLT in attenuating symptoms of vocal fatigue created by a vocal loading task as measured by acoustic, aerodynamic, and self-reported vocal effort. In a randomized, prospective study, 16 vocally healthy adults divided into four groups underwent a 1-hour vocal loading procedure, followed by infrared wavelength LLLT (828 nm), red wavelength LLLT (628 nm), heat, or no heat-light (control) treatment targeting the laryngeal region of the ventral neck surface. Phonation threshold pressure (PTP), relative fundamental frequency (RFF), and the inability to produce soft voice (IPSV) self-perceptual rating scale were recorded (1) at baseline, (2) immediately after vocal loading, (3) after treatment, and (4) 1 hour after treatment. Vocal loading significantly increased PTP and IPSV and decreased onset and offset RFFs, consistent with a shift toward vocal dysfunction. Red light significantly normalized the combination of PTP, IPSV, and RFF measures compared to other conditions. RFF is sensitive to a vocal loading task in conjunction with PTP and IPSV, and red LLLT may have a normalizing effect on objective and subjective measures of vocal fatigue. The results of this study lay the groundwork and rationale for future research to optimize LLLT wavelength combinations and overall dose. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Low Doses of Imatinib Induce Myelopoiesis and Enhance Host Anti-microbial Immunity

PubMed Central

Swimm, Alyson; Giver, Cynthia R.; Harris, Wayne A. C.; Laval, Julie; Napier, Brooke A.; Patel, Gopi; Crump, Ryan; Peng, Zhenghong; Bornmann, William; Pulendran, Bali; Buller, R. Mark; Weiss, David S.; Tirouvanziam, Rabindra; Waller, Edmund K.; Kalman, Daniel

2015-01-01

Imatinib mesylate (Gleevec) inhibits Abl1, c-Kit, and related protein tyrosine kinases (PTKs) and serves as a therapeutic for chronic myelogenous leukemia and gastrointestinal stromal tumors. Imatinib also has efficacy against various pathogens, including pathogenic mycobacteria, where it decreases bacterial load in mice, albeit at doses below those used for treating cancer. We report that imatinib at such low doses unexpectedly induces differentiation of hematopoietic stem cells and progenitors in the bone marrow, augments myelopoiesis but not lymphopoiesis, and increases numbers of myeloid cells in blood and spleen. Whereas progenitor differentiation relies on partial inhibition of c-Kit by imatinib, lineage commitment depends upon inhibition of other PTKs. Thus, imatinib mimics “emergency hematopoiesis,” a physiological innate immune response to infection. Increasing neutrophil numbers by adoptive transfer sufficed to reduce mycobacterial load, and imatinib reduced bacterial load of Franciscella spp., which do not utilize imatinib-sensitive PTKs for pathogenesis. Thus, potentiation of the immune response by imatinib at low doses may facilitate clearance of diverse microbial pathogens. PMID:25822986

Low doses of imatinib induce myelopoiesis and enhance host anti-microbial immunity.

PubMed

Napier, Ruth J; Norris, Brian A; Swimm, Alyson; Giver, Cynthia R; Harris, Wayne A C; Laval, Julie; Napier, Brooke A; Patel, Gopi; Crump, Ryan; Peng, Zhenghong; Bornmann, William; Pulendran, Bali; Buller, R Mark; Weiss, David S; Tirouvanziam, Rabindra; Waller, Edmund K; Kalman, Daniel

2015-03-01

Imatinib mesylate (Gleevec) inhibits Abl1, c-Kit, and related protein tyrosine kinases (PTKs) and serves as a therapeutic for chronic myelogenous leukemia and gastrointestinal stromal tumors. Imatinib also has efficacy against various pathogens, including pathogenic mycobacteria, where it decreases bacterial load in mice, albeit at doses below those used for treating cancer. We report that imatinib at such low doses unexpectedly induces differentiation of hematopoietic stem cells and progenitors in the bone marrow, augments myelopoiesis but not lymphopoiesis, and increases numbers of myeloid cells in blood and spleen. Whereas progenitor differentiation relies on partial inhibition of c-Kit by imatinib, lineage commitment depends upon inhibition of other PTKs. Thus, imatinib mimics "emergency hematopoiesis," a physiological innate immune response to infection. Increasing neutrophil numbers by adoptive transfer sufficed to reduce mycobacterial load, and imatinib reduced bacterial load of Franciscella spp., which do not utilize imatinib-sensitive PTKs for pathogenesis. Thus, potentiation of the immune response by imatinib at low doses may facilitate clearance of diverse microbial pathogens.

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

Augmented bioavailability of felodipine through an α-linolenic acid-based microemulsion.

PubMed

Singh, Mahendra; Kanoujia, Jovita; Parashar, Poonam; Arya, Malti; Tripathi, Chandra B; Sinha, V R; Saraf, Shailendra K; Saraf, Shubhini A

2018-02-01

The oral bioavailability of felodipine, a dihydropyridine calcium channel antagonist, is about 15%. This may be due to poor water solubility, and a lower intestinal permeability than a BCS class I drug, and hepatic first-pass metabolism of the drug. Many drugs are unpopular due to solubility issues. The goal of this study was to develop and optimize a felodipine-containing microemulsion to improve the intestinal permeability and bioavailability of the drug. The felodipine microemulsions were developed with the selected components, i.e., α-linolenic acid as the oil phase, Tween 80 as a surfactant, and isopropyl alcohol as co-surfactant using Box-Behnken design and characterized for in vitro release and particle size. The optimized felodipine-loaded microemulsion was investigated for physicochemical interaction, surface morphology, intestinal permeability, rheology, cytotoxicity, cellular uptake, pharmacodynamic (electrocardiogram and heart rate variability), and pharmacokinetic studies to explore its suitability as a promising oral drug delivery system for the treatment of hypertension. The optimized felodipine-loaded microemulsion showed significantly higher (P < 0.05) apparent permeability coefficients (Papp) at 7.918 × 10 -5  cm/s after 1 h, when compared with conventional formulations that are marketed tablet, drug oily solution, and drug emulsion, which showed a maximum Papp of 3.013, 4.428, and 5.335 × 10 -5  cm/s, respectively. The optimized felodipine-loaded microemulsion showed biocompatibility and no cytotoxicity. Cellular uptake studies confirmed payload delivery to a cellular site on the J774.A1 cell line. The rheology study of the optimized felodipine-loaded microemulsion revealed Newtonian-type flow behavior and discontinuous microemulsion formation. In pharmacodynamic studies, significant differences in parameters were observed between the optimized felodipine-loaded microemulsion and marketed formulation. The optimized felodipine-loaded microemulsion showed significantly higher (p < 0.01) C max (7.12 ± 1.04 μg/ml) than marketed tablets (2.44 ± 1.03 μg/ml). It was found that AUC last obtained from the optimized felodipine-loaded microemulsion (84.53 ± 10.73 μg h/ml) was significantly higher (p < 0.01) than the marketed tablet (27.41 ± 5.54 μg h/ml). The relative bioavailability (Fr) of the optimized felodipine-loaded microemulsion was about 308.3% higher than that of the marketed formulation. The results demonstrate that the prepared microemulsion is an advanced and efficient oral delivery system of felodipine for the management of hypertension.

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.

PubMed

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.

SN-38 loading capacity of hydrophobic polymer blend nanoparticles: formulation, optimization and efficacy evaluation.

PubMed

Dimchevska, Simona; Geskovski, Nikola; Petruševski, Gjorgji; Chacorovska, Marina; Popeski-Dimovski, Riste; Ugarkovic, Sonja; Goracinova, Katerina

2017-03-01

One of the most important problems in nanoencapsulation of extremely hydrophobic drugs is poor drug loading due to rapid drug crystallization outside the polymer core. The effort to use nanoprecipitation, as a simple one-step procedure with good reproducibility and FDA approved polymers like Poly(lactic-co-glycolic acid) (PLGA) and Polycaprolactone (PCL), will only potentiate this issue. Considering that drug loading is one of the key defining characteristics, in this study we attempted to examine whether the nanoparticle (NP) core composed of two hydrophobic polymers will provide increased drug loading for 7-Ethyl-10-hydroxy-camptothecin (SN-38), relative to NPs prepared using individual polymers. D-optimal design was applied to optimize PLGA/PCL ratio in the polymer blend and the mode of addition of the amphiphilic copolymer Lutrol ® F127 in order to maximize SN-38 loading and obtain NPs with acceptable size for passive tumor targeting. Drug/polymer and polymer/polymer interaction analysis pointed to high degree of compatibility and miscibility among both hydrophobic polymers, providing core configuration with higher drug loading capacity. Toxicity studies outlined the biocompatibility of the blank NPs. Increased in vitro efficacy of drug-loaded NPs compared to the free drug was confirmed by growth inhibition studies using SW-480 cell line. Additionally, the optimized NP formulation showed very promising blood circulation profile with elimination half-time of 7.4 h.

Optimization of laminated stacking sequence for buckling load maximization by genetic algorithm

NASA Technical Reports Server (NTRS)

Le Riche, Rodolphe; Haftka, Raphael T.

1992-01-01

The use of a genetic algorithm to optimize the stacking sequence of a composite laminate for buckling load maximization is studied. Various genetic parameters including the population size, the probability of mutation, and the probability of crossover are optimized by numerical experiments. A new genetic operator - permutation - is proposed and shown to be effective in reducing the cost of the genetic search. Results are obtained for a graphite-epoxy plate, first when only the buckling load is considered, and then when constraints on ply contiguity and strain failure are added. The influence on the genetic search of the penalty parameter enforcing the contiguity constraint is studied. The advantage of the genetic algorithm in producing several near-optimal designs is discussed.

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.)

Leaching of pesticides from biobeds: effect of biobed depth and water loading.

PubMed

Fogg, Paul; Boxall, Alistair B A; Walker, Allan; Jukes, Andrew

2004-10-06

Pesticides may be released to farmyard surfaces as a result of spillages, leakages, and the decontamination of tractors and sprayers. Biobeds can be used to intercept and treat contaminated runoff, thus minimizing losses to the environment. Previous studies using lined and unlined biobeds showed that water management was the limiting factor for both systems. While lined biobeds effectively retained pesticides, the system rapidly became water logged and degradation was slow. Studies using unlined biobeds showed that >99% of the applied pesticides were removed by the system, with a significant proportion degraded within 9 months. However, peak concentrations of certain pesticides (Koc < 125) were unacceptable to the regulatory authorities. These experiments were designed to optimize the design and management of unlined biobeds. Experiments performed to investigate the relationship between biobed depth and water loading showed that biobeds need to have a minimum depth of 1-1.5 m. The surface area dimension of the biobed depends on the water loading, which is controlled by the nature and frequency of pesticide handling activities on the farm. Leaching losses of all but the most mobile (Koc < 15) pesticides were <0.32% of the applied dose from 1.5 m deep biobeds subject to a water loading of 1175 L m(-2). These were reduced to <0.06% when a water loading of 688 L m(-2) was applied and down to <0.0001% for a water loading of 202 L m(-2). On the basis of these data, a 1.5 m deep biobed, subject to a maximum water loading of 1121 L m(-2) and with a surface area of 40 m(2) should be able to treat < or =44000 L of pesticide waste and washings such that the average concentration of all pesticides, other than those classified as very mobile, does not exceed 5 microg L(-1). This level of treatment can be improved by further reduction in the hydraulic loading.

[Research on land use structure optimization based on nonpoint source dissolved nitrogen load estimation in Shuaishui watershed].

PubMed

Lu, Yu-Chao; Bi, Meng-Fei; Li, Ze-Li; Sha, Jian; Wang, Yu-Qiu; Qian, Li-Ping

2014-06-01

Regional Nutrient Management (ReNuMa) was applied to estimate dissolved nitrogen (DN) load and perform source apportionment in Shuaishui watershed during 2000-2010. Satisfactory performance of ReNuMa was revealed by the E(ns) and R2 of greater than 0.9 in calibrating and validating streamflow and DN. The average nonpoint DN load in this watershed was 1.11 x 10(3) t x a(-1), with the load intensity of (0.75 +/- 0.22) t x km(-2). Among all the land uses, paddy field had the largest DN load intensity [28.60 kg x (hm2 x a)(-1)], while forest had the least [2.71 kg x (hm2 x a)(-1)]. Agricultural land (including paddy, grain, cash crop, tea plant and orchard) contributed most to DN load in Shuaishui watershed, indicating that the human dominated agricultural activities was the major contributor of nonpoint source pollution. Land use structure optimization for Shuaishui watershed in 2015 was conducted under the rule of reducing pollutants loads and maximizing the agricultural output value. The results demonstrated that agricultural monetary growth was accompanied with the increasing DN load at the optimal level, although output increment was higher than that of DN load.

The role of gut microbiota in the regulation of standard metabolic rate in female Periplaneta americana.

PubMed

Ayayee, Paul A; Ondrejech, Andrew; Keeney, George; Muñoz-Garcia, Agustí

2018-01-01

Insect gut microbiota contribute significantly to host nutritional ecology. Disrupting insect gut microbial assemblages impacts nutrient provisioning functions, and can potentially affect host standard metabolic rate (SMR), a measure of host energy balance. In this study, we evaluated the effect of disrupting gut microbial assemblages on the SMR of female Periplaneta americana cockroaches fed dog food (DF, high protein/carbohydrate (p/c) ratio), and cellulose-amended dog food (CADF, 30% dog food, 70% cellulose, low p/c ratio) diets, supplemented with none, low, or high antibiotic doses. Bacterial loads decreased significantly between diet types ( P = 0.04) and across antibiotic doses ( P = 0.04). There was a significant diet type x antibiotic dose interaction on SMR of females on both diets ( P = 0.05) by the end of the seven-day experimental period. In CADF-fed females, SMR decreased linearly with decreasing bacterial load. However, SMR of DF-fed females on the low dose was significantly higher than those in the control and high dose groups. This is interpreted as a diet-dependent response by low dose DF-fed females to the loss of nutritional services provided by gut bacteria. Severe reductions in bacterial load at high doses reduced SMR of females on both diet types. This study provides insights into the potential role of gut bacteria as modulators of host energy expenditure under varying dietary conditions.

Exploratory Study of 4D Versus 3D Robust Optimization in Intensity-Modulated Proton Therapy for Lung Cancer

PubMed Central

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

Generation of uniformly distributed dose points for anatomy-based three-dimensional dose optimization methods in brachytherapy.

PubMed

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.

Dosimetric comparison of helical tomotherapy treatment plans for total marrow irradiation created using GPU and CPU dose calculation engines.

PubMed

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.

Optimal allocation of industrial PV-storage micro-grid considering important load

NASA Astrophysics Data System (ADS)

He, Shaohua; Ju, Rong; Yang, Yang; Xu, Shuai; Liang, Lei

2018-03-01

At present, the industrial PV-storage micro-grid has been widely used. This paper presents an optimal allocation model of PV-storage micro-grid capacity considering the important load of industrial users. A multi-objective optimization model is established to promote the local extinction of PV power generation and the maximum investment income of the enterprise as the objective function. Particle swarm optimization (PSO) is used to solve the case of a city in Jiangsu Province, the results are analyzed economically.

Evaluation of material heterogeneity dosimetric effects using radiochromic film for COMS eye plaques loaded with {sup 125}I seeds (model I25.S16)

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

Acar, Hilal; Chiu-Tsao, Sou-Tung; Oezbay, Ismail

Purpose: (1) To measure absolute dose distributions in eye phantom for COMS eye plaques with {sup 125}I seeds (model I25.S16) using radiochromic EBT film dosimetry. (2) To determine the dose correction function for calculations involving the TG-43 formalism to account for the presence of the COMS eye plaque using Monte Carlo (MC) method specific to this seed model. (3) To test the heterogeneous dose calculation accuracy of the new version of Plaque Simulator (v5.3.9) against the EBT film data for this seed model. Methods: Using EBT film, absolute doses were measured for {sup 125}I seeds (model I25.S16) in COMS eyemore » plaques (1) along the plaque's central axis for (a) uniformly loaded plaques (14-20 mm in diameter) and (b) a 20 mm plaque with single seed, and (2) in off-axis direction at depths of 5 and 12 mm for all four plaque sizes. The EBT film calibration was performed at {sup 125}I photon energy. MC calculations using MCNP5 code for a single seed at the center of a 20 mm plaque in homogeneous water and polystyrene medium were performed. The heterogeneity dose correction function was determined from the MC calculations. These function values at various depths were entered into PS software (v5.3.9) to calculate the heterogeneous dose distributions for the uniformly loaded plaques (of all four sizes). The dose distributions with homogeneous water assumptions were also calculated using PS for comparison. The EBT film measured absolute dose rate values (film) were compared with those calculated using PS with homogeneous assumption (PS Homo) and heterogeneity correction (PS Hetero). The values of dose ratio (film/PS Homo) and (film/PS Hetero) were obtained. Results: The central axis depth dose rate values for a single seed in 20 mm plaque measured using EBT film and calculated with MCNP5 code (both in ploystyrene phantom) were compared, and agreement within 9% was found. The dose ratio (film/PS Homo) values were substantially lower than unity (mostly between 0.8 and 0.9) for all four plaque sizes, indicating dose reduction by COMS plaque compared with homogeneous assumption. The dose ratio (film/PS Hetero) values were close to unity, indicating the PS Hetero calculations agree with those from the film study. Conclusions: Substantial heterogeneity effect on the {sup 125}I dose distributions in an eye phantom for COMS plaques was verified using radiochromic EBT film dosimetry. The calculated doses for uniformly loaded plaques using PS with heterogeneity correction option enabled were corroborated by the EBT film measurement data. Radiochromic EBT film dosimetry is feasible in measuring absolute dose distributions in eye phantom for COMS eye plaques loaded with single or multiple {sup 125}I seeds. Plaque Simulator is a viable tool for the calculation of dose distributions if one understands its limitations and uses the proper heterogeneity correction feature.« less

L∞-Optimal feedforward gust load alleviation design for a large blended wing body airliner

NASA Astrophysics Data System (ADS)

Wildschek, A.; Haniš, T.; Stroscher, F.

2013-12-01

The potential advantages of Blended Wing Body (BWB) aircraft in terms of fuel efficiency are opposed by technical challenges such as the alleviation of gust loads. Due to the low wing, loading gusts, generally, have a more severe impact on BWB aircraft than on conventional aircraft. This paper presents the design and optimization of a Gust Load Alleviation System (GLAS) for a large BWB airliner. Numerical simulations are performed with an aeroelastic model of the aircraft including GLAS in order to compute time series of modal displacements for deriving equivalent static load cases which are used for the resizing of the aircraft structure.

A novel load balanced energy conservation approach in WSN using biogeography based optimization

NASA Astrophysics Data System (ADS)

Kaushik, Ajay; Indu, S.; Gupta, Daya

2017-09-01

Clustering sensor nodes is an effective technique to reduce energy consumption of the sensor nodes and maximize the lifetime of Wireless sensor networks. Balancing load of the cluster head is an important factor in long run operation of WSNs. In this paper we propose a novel load balancing approach using biogeography based optimization (LB-BBO). LB-BBO uses two separate fitness functions to perform load balancing of equal and unequal load respectively. The proposed method is simulated using matlab and compared with existing methods. The proposed method shows better performance than all the previous works implemented for energy conservation in WSN

Preparation and characterization of oxybenzone-loaded gelatin microspheres for enhancement of sunscreening efficacy.

PubMed

Patel, M; Jain, Sunil K; Yadav, Awesh K; Gogna, D; Agrawal, G P

2006-01-01

The objective of our present study was to prepare and evaluate gelatin microspheres of oxybenzone to enhance its sunscreening efficacy. The gelatin microspheres of oxybenzone were prepared by emulsion method. Process parameters were analyzed to optimize the formulation. The in vitro drug release study was performed in pH 7.4 using cellulose acetate membrane. Microspheres prepared using oxybenzone:gelatin ratio of 1:6 showed slowest drug release and those prepared with oxybenzone:gelatin ratio of 1:2 showed fastest drug release. The gelatin microspheres of oxybenzone were incorporated in aloe vera gel. Sun exposure method using sodium nitroprusside solution was used for in vitro sunscreen efficacy testing. The formulation C5 containing oxybenzone-bearing gelatin microspheres in aloe vera gel showed best sunscreen efficacy. The formulations were evaluated for skin irritation test in human volunteers, sun protection factor, and minimum erythema dose in albino rats. These studies revealed that the incorporation of sunscreening agent-loaded microspheres into aloe vera gel greatly increased the efficacy of sunscreen formulation more than four times.

Optimal Loading for Maximizing Power During Sled-Resisted Sprinting.

PubMed

Cross, Matt R; Brughelli, Matt; Samozino, Pierre; Brown, Scott R; Morin, Jean-Benoit

2017-09-01

To ascertain whether force-velocity-power relationships could be compiled from a battery of sled-resisted overground sprints and to clarify and compare the optimal loading conditions for maximizing power production for different athlete cohorts. Recreational mixed-sport athletes (n = 12) and sprinters (n = 15) performed multiple trials of maximal sprints unloaded and towing a selection of sled masses (20-120% body mass [BM]). Velocity data were collected by sports radar, and kinetics at peak velocity were quantified using friction coefficients and aerodynamic drag. Individual force-velocity and power-velocity relationships were generated using linear and quadratic relationships, respectively. Mechanical and optimal loading variables were subsequently calculated and test-retest reliability assessed. Individual force-velocity and power-velocity relationships were accurately fitted with regression models (R 2 > .977, P < .001) and were reliable (ES = 0.05-0.50, ICC = .73-.97, CV = 1.0-5.4%). The normal loading that maximized peak power was 78% ± 6% and 82% ± 8% of BM, representing a resistance of 3.37 and 3.62 N/kg at 4.19 ± 0.19 and 4.90 ± 0.18 m/s (recreational athletes and sprinters, respectively). Optimal force and normal load did not clearly differentiate between cohorts, although sprinters developed greater maximal power (17.2-26.5%, ES = 0.97-2.13, P < .02) at much greater velocities (16.9%, ES = 3.73, P < .001). Mechanical relationships can be accurately profiled using common sled-training equipment. Notably, the optimal loading conditions determined in this study (69-96% of BM, dependent on friction conditions) represent much greater resistance than current guidelines (~7-20% of BM). This method has potential value in quantifying individualized training parameters for optimized development of horizontal power.

Vitamin D3 Loading Is Superior to Conventional Supplementation After Weight Loss Surgery in Vitamin D-Deficient Morbidly Obese Patients: a Double-Blind Randomized Placebo-Controlled Trial.

PubMed

Luger, Maria; Kruschitz, Renate; Kienbacher, Christian; Traussnigg, Stefan; Langer, Felix B; Prager, Gerhard; Schindler, Karin; Kallay, Enikö; Hoppichler, Friedrich; Trauner, Michael; Krebs, Michael; Marculescu, Rodrig; Ludvik, Bernhard

2017-05-01

Bariatric patients often suffer from vitamin D deficiency (VDD), and both, morbid obesity and VDD, are related to non-alcoholic fatty liver disease. However, limited data are available regarding best strategies for treating VDD, particularly, in bariatric patients undergoing omega-loop gastric bypass (OLGB). Therefore, we examined the efficacy and safety of a forced vitamin D dosing regimen and intervention effects in liver fibrotic patients. In this double-blind, randomized, placebo-controlled trial, 50 vitamin D-deficient patients undergoing OLGB were randomly assigned to receive, in the first month postoperatively, oral vitamin D 3 (≤3 doses of 100,000 IU; intervention group) or placebo as loading dose (control group) with subsequent maintenance dose (3420 IU/day) in both groups until 6-month visit. Compared with control group, higher increase of 25(OH)D (67.9 (21.1) vs. 55.7 nmol/L (21.1); p = 0.049) with lower prevalence of secondary hyperparathyroidism (10 vs. 24 %; p = 0.045) was observed in intervention group. No (serious) adverse events related to study medication were found. The loading dose regimen was more effective in increasing 25(OH)D in patients with significant liver fibrosis while this was not the case for conventional supplementation (placebo with maintenance dose) (71.5 (20.5) vs. 22.5 nmol/L (13.8); p = 0.022; n = 14). Our findings indicate that a high vitamin D 3 loading dose, in the first month postoperatively, with subsequent maintenance dose is effective and safe in achieving higher vitamin D concentrations in OLGB patients. Unexpectedly, it is more effective in patients with significant liver fibrosis which is of potentially high clinical relevance and requires further investigation.

The antiplatelet effect of higher loading and maintenance dose regimens of clopidogrel: the PRINC (Plavix Response in Coronary Intervention) trial.

PubMed

Gladding, Patrick; Webster, Mark; Zeng, Irene; Farrell, Helen; Stewart, Jim; Ruygrok, Peter; Ormiston, John; El-Jack, Seif; Armstrong, Guy; Kay, Patrick; Scott, Douglas; Gunes, Arzu; Dahl, Marja-Liisa

2008-12-01

This study evaluated the antiplatelet effect of a higher loading and maintenance dose regimen of clopidogrel and a possible drug interaction with verapamil. Clopidogrel loading doses above 600 mg have not resulted in more rapid or complete platelet inhibition. Higher maintenance dosages may be more effective than 75 mg/day. A double-blind, randomized, placebo-controlled trial was undertaken in 60 patients undergoing percutaneous coronary intervention. All patients received clopidogrel 600 mg at the start of the procedure. Using a 2 x 2 design, patients were allocated to clopidogrel 600 mg given 2 h later or matching placebo, and to verapamil 5 mg intra-arterial or placebo. Platelet function was measured using the VerifyNow P2Y12 analyzer (Accumetrics Ltd., San Diego, California) at 2, 4, and 7 h. Patients were further randomized to receive a clopidogrel 75 or 150 mg once daily, with platelet function assessed after 1 week. Two hours after the second dose of clopidogrel or placebo, platelet inhibition was 42 +/- 27% with clopidogrel, compared with 24 +/- 22% with placebo (p = 0.0006). By 5 h after the second dose, platelet inhibition was 49 +/- 30% with clopidogrel, compared with 29 +/- 22% with placebo (p = 0.01). No drug interaction was seen with verapamil. A clopidogrel maintenance dosage of 150 mg daily for 1 week resulted in greater platelet inhibition than 75 mg daily (50 +/- 28% vs. 29 +/- 19%, p = 0.01). In an unselected population undergoing percutaneous coronary intervention a clopidogrel 1,200-mg loading dose, given as two 600-mg doses 2 h apart, results in more rapid and complete platelet inhibition than a single 600-mg dose. A maintenance dosage of 150 mg daily produces greater platelet inhibition than 75 mg daily. (The PRINC trial; ACTRN12606000129583).

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

NASA Astrophysics Data System (ADS)

Yarmand, Hamed; Winey, Brian; Craft, David

2013-09-01

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

A GPU-accelerated and Monte Carlo-based intensity modulated proton therapy optimization system.

PubMed

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.

Load Forecasting Based Distribution System Network Reconfiguration -- A Distributed Data-Driven Approach

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

Jiang, Huaiguang; Zhang, Yingchen; Muljadi, Eduard

In this paper, a short-term load forecasting approach based network reconfiguration is proposed in a parallel manner. Specifically, a support vector regression (SVR) based short-term load forecasting approach is designed to provide an accurate load prediction and benefit the network reconfiguration. Because of the nonconvexity of the three-phase balanced optimal power flow, a second-order cone program (SOCP) based approach is used to relax the optimal power flow problem. Then, the alternating direction method of multipliers (ADMM) is used to compute the optimal power flow in distributed manner. Considering the limited number of the switches and the increasing computation capability, themore » proposed network reconfiguration is solved in a parallel way. The numerical results demonstrate the feasible and effectiveness of the proposed approach.« less

Load Frequency Control of AC Microgrid Interconnected Thermal Power System

NASA Astrophysics Data System (ADS)

Lal, Deepak Kumar; Barisal, Ajit Kumar

2017-08-01

In this paper, a microgrid (MG) power generation system is interconnected with a single area reheat thermal power system for load frequency control study. A new meta-heuristic optimization algorithm i.e. Moth-Flame Optimization (MFO) algorithm is applied to evaluate optimal gains of the fuzzy based proportional, integral and derivative (PID) controllers. The system dynamic performance is studied by comparing the results with MFO optimized classical PI/PID controllers. Also the system performance is investigated with fuzzy PID controller optimized by recently developed grey wolf optimizer (GWO) algorithm, which has proven its superiority over other previously developed algorithm in many interconnected power systems.

Preoperative single fraction partial breast radiotherapy for early-stage breast cancer.

PubMed

Palta, Manisha; Yoo, Sua; Adamson, Justus D; Prosnitz, Leonard R; Horton, Janet K

2012-01-01

Several recent series evaluating external beam accelerated partial breast irradiation (PBI) have reported adverse cosmetic outcomes, possibly related to large volumes of normal tissue receiving near-prescription doses. We hypothesized that delivery of external beam PBI in a single fraction to the preoperative tumor volume would be feasible and result in a decreased dose to the uninvolved breast compared with institutional postoperative PBI historical controls. A total of 17 patients with unifocal Stage T1 breast cancer were identified. Contrast-enhanced subtraction magnetic resonance images were loaded into an Eclipse treatment planning system and used to define the target volumes. A "virtual plan" was created using four photon beams in a noncoplanar beam arrangement and optimized to deliver 15 Gy to the planning target volume. The median breast volume was 1,713 cm(3) (range: 1,014-2,140), and the median clinical target volume was 44 cm(3) (range: 26-73). In all cases, 100% of the prescription dose covered 95% of the clinical target volume. The median conformity index was 0.86 (range: 0.70-1.12). The median percentage of the ipsilateral breast volume receiving 100% and 50% of the prescribed dose was 3.8% (range: 2.2-6.9) and 13.3% (range: 7.5-20.8) compared with 18% (range: 3-42) and 53% (range: 24-65) in the institutional historical controls treated with postoperative external beam PBI (p = .002). The median maximum skin dose was 9 Gy. The median dose to 1 and 10 cm(3) of skin was 6.7 and 4.9 Gy. The doses to the heart and ipsilateral lung were negligible. Preoperative PBI resulted in a substantial reduction in ipsilateral breast tissue dose compared with postoperative PBI. The skin dose appeared reasonable, given the small volumes. A prospective Phase I trial evaluating this technique is ongoing. Copyright © 2012 Elsevier Inc. All rights reserved.

Enhanced electrochemical performance of manganese dioxide spheres deposited on a titanium dioxide nanotube arrays substrate

NASA Astrophysics Data System (ADS)

Zhou, He; Zhang, Yanrong

2014-12-01

The deposition of MnO2 spheres on a TiO2 nanotube arrays substrate are achieved via a sequential chemical bath deposition (SCBD) method for an application of anode materials in supercapacitors. The electrochemical performance of the MnO2-TiO2 composite electrode is observed to show a strong dependence on the MnO2 loading mass, which could be adjusted by repeating the SCBD treatment for several cycles. The optimized doses of MnO2 loaded MnO2-TiO2 and MnO2-Ti samples are compared in terms of their areal capacitance studies and the former is of 175 and 101 mF cm-2 at a scan rate of 10 and 100 mV s-1, respectively, which are 1.52-fold and 1.51-fold of that of the latter sample at corresponding scan rates. The enhancement in areal capacitance has been accounted to the progressive effect of the TiO2 tubular substrate on the capacitive behavior of the loaded MnO2 rather than the different MnO2 loading mass on these two substrates. Impedance analysis reveals this enhanced electrochemical activity is owing to the tubular structure of the TiO2 substrate provides an increased reaction area and facilitates the contact of electrolyte with the active MnO2 material. This work justified the suitability of using the TiO2 nanotube arrays for constructing high-performance supercapacitors.

Optimized Controller Design for a 12-Pulse Voltage Source Converter Based HVDC System

NASA Astrophysics Data System (ADS)

Agarwal, Ruchi; Singh, Sanjeev

2017-12-01

The paper proposes an optimized controller design scheme for power quality improvement in 12-pulse voltage source converter based high voltage direct current system. The proposed scheme is hybrid combination of golden section search and successive linear search method. The paper aims at reduction of current sensor and optimization of controller. The voltage and current controller parameters are selected for optimization due to its impact on power quality. The proposed algorithm for controller optimizes the objective function which is composed of current harmonic distortion, power factor, and DC voltage ripples. The detailed designs and modeling of the complete system are discussed and its simulation is carried out in MATLAB-Simulink environment. The obtained results are presented to demonstrate the effectiveness of the proposed scheme under different transient conditions such as load perturbation, non-linear load condition, voltage sag condition, and tapped load fault under one phase open condition at both points-of-common coupling.

Role of the parameters involved in the plan optimization based on the generalized equivalent uniform dose and radiobiological implications

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.

An optimized computational method for determining the beta dose distribution using a multiple-element thermoluminescent dosimeter system.

PubMed

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.

Weight optimization of large span steel truss structures with genetic algorithm

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

Mojolic, Cristian; Hulea, Radu; Pârv, Bianca Roxana

2015-03-10

The paper presents the weight optimization process of the main steel truss that supports the Slatina Sport Hall roof. The structure was loaded with self-weight, dead loads, live loads, snow, wind and temperature, grouped in eleven load cases. The optimization of the structure was made using genetic algorithms implemented in a Matlab code. A total number of four different cases were taken into consideration when trying to determine the lowest weight of the structure, depending on the types of connections with the concrete structure ( types of supports, bearing modes), and the possibility of the lower truss chord nodes tomore » change their vertical position. A number of restrictions for tension, maximum displacement and buckling were enforced on the elements, and the cross sections are chosen by the program from a user data base. The results in each of the four cases were analyzed in terms of weight, element tension, element section and displacement. The paper presents the optimization process and the conclusions drawn.« less

Solar plus: Optimization of distributed solar PV through battery storage and dispatchable load in residential buildings

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

O'Shaughnessy, Eric; Cutler, Dylan; Ardani, Kristen

As utility electricity rates evolve, pairing solar photovoltaic (PV) systems with battery storage has potential to ensure the value proposition of residential solar by mitigating economic uncertainty. In addition to batteries, load control technologies can reshape customer load profiles to optimize PV system use. The combination of PV, energy storage, and load control provides an integrated approach to PV deployment, which we call 'solar plus'. The U.S. National Renewable Energy Laboratory's Renewable Energy Optimization (REopt) model is utilized to evaluate cost-optimal technology selection, sizing, and dispatch in residential buildings under a variety of rate structures and locations. The REopt modelmore » is extended to include a controllable or 'smart' domestic hot water heater model and smart air conditioner model. We find that the solar plus approach improves end user economics across a variety of rate structures - especially those that are challenging for PV - including lower grid export rates, non-coincident time-of-use structures, and demand charges.« less

Solar plus: Optimization of distributed solar PV through battery storage and dispatchable load in residential buildings

DOE PAGES

O'Shaughnessy, Eric; Cutler, Dylan; Ardani, Kristen; ...

2018-01-11

As utility electricity rates evolve, pairing solar photovoltaic (PV) systems with battery storage has potential to ensure the value proposition of residential solar by mitigating economic uncertainty. In addition to batteries, load control technologies can reshape customer load profiles to optimize PV system use. The combination of PV, energy storage, and load control provides an integrated approach to PV deployment, which we call 'solar plus'. The U.S. National Renewable Energy Laboratory's Renewable Energy Optimization (REopt) model is utilized to evaluate cost-optimal technology selection, sizing, and dispatch in residential buildings under a variety of rate structures and locations. The REopt modelmore » is extended to include a controllable or 'smart' domestic hot water heater model and smart air conditioner model. We find that the solar plus approach improves end user economics across a variety of rate structures - especially those that are challenging for PV - including lower grid export rates, non-coincident time-of-use structures, and demand charges.« less

PSO-Based Smart Grid Application for Sizing and Optimization of Hybrid Renewable Energy Systems

PubMed Central

Mohamed, Mohamed A.; Eltamaly, Ali M.; Alolah, Abdulrahman I.

2016-01-01

This paper introduces an optimal sizing algorithm for a hybrid renewable energy system using smart grid load management application based on the available generation. This algorithm aims to maximize the system energy production and meet the load demand with minimum cost and highest reliability. This system is formed by photovoltaic array, wind turbines, storage batteries, and diesel generator as a backup source of energy. Demand profile shaping as one of the smart grid applications is introduced in this paper using load shifting-based load priority. Particle swarm optimization is used in this algorithm to determine the optimum size of the system components. The results obtained from this algorithm are compared with those from the iterative optimization technique to assess the adequacy of the proposed algorithm. The study in this paper is performed in some of the remote areas in Saudi Arabia and can be expanded to any similar regions around the world. Numerous valuable results are extracted from this study that could help researchers and decision makers. PMID:27513000

PSO-Based Smart Grid Application for Sizing and Optimization of Hybrid Renewable Energy Systems.

PubMed

Mohamed, Mohamed A; Eltamaly, Ali M; Alolah, Abdulrahman I

2016-01-01

This paper introduces an optimal sizing algorithm for a hybrid renewable energy system using smart grid load management application based on the available generation. This algorithm aims to maximize the system energy production and meet the load demand with minimum cost and highest reliability. This system is formed by photovoltaic array, wind turbines, storage batteries, and diesel generator as a backup source of energy. Demand profile shaping as one of the smart grid applications is introduced in this paper using load shifting-based load priority. Particle swarm optimization is used in this algorithm to determine the optimum size of the system components. The results obtained from this algorithm are compared with those from the iterative optimization technique to assess the adequacy of the proposed algorithm. The study in this paper is performed in some of the remote areas in Saudi Arabia and can be expanded to any similar regions around the world. Numerous valuable results are extracted from this study that could help researchers and decision makers.

Data centers as dispatchable loads to harness stranded power

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

Kim, Kibaek; Yang, Fan; Zavala, Victor M.

Here, we analyze how traditional data center placement and optimal placement of dispatchable data centers affect power grid efficiency. We use detailed network models, stochastic optimization formulations, and diverse renewable generation scenarios to perform our analysis. Our results reveal that significant spillage and stranded power will persist in power grids as wind power levels are increased. A counter-intuitive finding is that collocating data centers with inflexible loads next to wind farms has limited impacts on renewable portfolio standard (RPS) goals because it provides limited system-level flexibility. Such an approach can, in fact, increase stranded power and fossil-fueled generation. In contrast,more » optimally placing data centers that are dispatchable provides system-wide flexibility, reduces stranded power, and improves efficiency. In short, optimally placed dispatchable computing loads can enable better scaling to high RPS. In our case study, we find that these dispatchable computing loads are powered to 60-80% of their requested capacity, indicating that there are significant economic incentives provided by stranded power.« less

Data centers as dispatchable loads to harness stranded power

DOE PAGES

Kim, Kibaek; Yang, Fan; Zavala, Victor M.; ...

2016-07-20

Here, we analyze how traditional data center placement and optimal placement of dispatchable data centers affect power grid efficiency. We use detailed network models, stochastic optimization formulations, and diverse renewable generation scenarios to perform our analysis. Our results reveal that significant spillage and stranded power will persist in power grids as wind power levels are increased. A counter-intuitive finding is that collocating data centers with inflexible loads next to wind farms has limited impacts on renewable portfolio standard (RPS) goals because it provides limited system-level flexibility. Such an approach can, in fact, increase stranded power and fossil-fueled generation. In contrast,more » optimally placing data centers that are dispatchable provides system-wide flexibility, reduces stranded power, and improves efficiency. In short, optimally placed dispatchable computing loads can enable better scaling to high RPS. In our case study, we find that these dispatchable computing loads are powered to 60-80% of their requested capacity, indicating that there are significant economic incentives provided by stranded power.« less

Docetaxel-loaded thermosensitive liquid suppository: optimization of rheological properties.

PubMed

Yeo, Woo Hyun; Ramasamy, Thiruganesh; Kim, Dong-Wuk; Cho, Hyuk Jun; Kim, Yong-Il; Cho, Kwan Hyung; Yong, Chul Soon; Kim, Jong Oh; Choi, Han-Gon

2013-12-01

The main purpose of this work was to optimize the rheological properties of docetaxel (DCT)-loaded thermosensitive liquid suppositories for rectal administration. DCT-loaded liquid suppositories were prepared by a cold method and characterized in terms of physicochemical and viscoelastic properties. Major formulation parameters including poloxamer (P407) and Tween 80 were optimized to adjust the thermogelling and mucoadhesive properties for rectal administration. Notably, the gel strength and mucoadhesive force significantly increased with the increase in these variables. Furthermore, DCT incorporation did not alter the viscoelastic behavior, and the mean particle size of nanomicelles in it was approximately 16 nm with a distinct spherical shape. The formulation existed as liquid at room temperature and transformed into gel at physiological temperature through the reverse gelation phenomenon. Thus, DCT-loaded thermosensitive liquid suppositories [DCT/P407/P188/Tween 80 (0.25/11/15/10 %)] with optimal gel properties were easy to prepare and administer rectally, and might enable the gel to stay in the rectum without getting out from rectum.

Mathematical optimization of high dose-rate brachytherapy—derivation of a linear penalty model from a dose-volume model

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.

Optimization of the RF cavity heat load and trip rates for CEBAF at 12 GeV

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

Zhang, He; Roblin, Yves R.; Freyberger, Arne P.

2017-05-01

The Continuous Electron Beam Accelerator Facility at JLab has 200 RF cavities in the north linac and the south linac respectively after the 12 GeV upgrade. The purpose of this work is to simultaneously optimize the heat load and the trip rate for the cavities and to reconstruct the pareto-optimal front in a timely manner when some of the cavities are turned down. By choosing an efficient optimizer and strategically creating the initial gradients, the pareto-optimal front for no more than 15 cavities down can be re-established within 20 seconds.

Operational load estimation of a smart wind turbine rotor blade

NASA Astrophysics Data System (ADS)

White, Jonathan R.; Adams, Douglas E.; Rumsey, Mark A.

2009-03-01

Rising energy prices and carbon emission standards are driving a fundamental shift from fossil fuels to alternative sources of energy such as biofuel, solar, wind, clean coal and nuclear. In 2008, the U.S. installed 8,358 MW of new wind capacity increasing the total installed wind power by 50% to 25,170 MW. A key technology to improve the efficiency of wind turbines is smart rotor blades that can monitor the physical loads being applied by the wind and then adapt the airfoil for increased energy capture. For extreme wind and gust events, the airfoil could be changed to reduce the loads to prevent excessive fatigue or catastrophic failure. Knowledge of the actual loading to the turbine is also useful for maintenance planning and design improvements. In this work, an array of uniaxial and triaxial accelerometers was integrally manufactured into a 9m smart rotor blade. DC type accelerometers were utilized in order to estimate the loading and deflection from both quasi-steady-state and dynamic events. A method is presented that designs an estimator of the rotor blade static deflection and loading and then optimizes the placement of the sensor(s). Example results show that the method can identify the optimal location for the sensor for both simple example cases and realistic complex loading. The optimal location of a single sensor shifts towards the tip as the curvature of the blade deflection increases with increasingly complex wind loading. The framework developed is practical for the expansion of sensor optimization in more complex blade models and for higher numbers of sensors.

Characterization and Performance Optimization of a Cementitious Composite for Quasi-Static and Dynamic Loads

DTIC Science & Technology

2011-01-01

blast and weapon fragmentation. A particular cementitious composite of interest is an inorganic polymer cement or “ geopolymer ” cement. The term...www.sciencedirect.com ICM11 Characterization and performance optimization of a cementitious composite for quasi-static and dynamic loads W.F. Hearda,b, P.K. Basub...rapid-set, high-strength geopolymer cement under quasi-static and dynamic loads. Four unique tensile experiments were conducted to characterize and

Using the Enhanced Daily Load Stimulus Model to Quantify the Mechanical Load and Bone Mineral Density Changes Experienced by Crew Members on the International Space Station

NASA Technical Reports Server (NTRS)

Genc, K. O.; Gopalakrishnan, R.; Kuklis, M. M.; Maender, C. C.; Rice, A. J.; Cavanagh, P. R.

2009-01-01

Despite the use of exercise countermeasures during long-duration space missions, bone mineral density (BMD) and predicted bone strength of astronauts continue to show decreases in the lower extremities and spine. This site-specific bone adaptation is most likely caused by the effects of microgravity on the mechanical loading environment of the crew member. There is, therefore, a need to quantify the mechanical loading experienced on Earth and on-orbit to define the effect of a given "dose" of loading on bone homeostasis. Gene et al. recently proposed an enhanced DLS (EDLS) model that, when used with entire days of in-shoe forces, takes into account recently developed theories on the importance of factors such as saturation, recovery, and standing and their effects on the osteogenic response of bone to daily physical activity. This algorithm can also quantify the tinting and type of activity (sit/unload, stand, walk, run or other loaded activity) performed throughout the day. The purpose of the current study was to use in-shoe force measurements from entire typical work days on Earth and on-orbit in order to quantify the type and amount of loading experienced by crew members. The specific aim was to use these measurements as inputs into the EDLS model to determine activity timing/type and the mechanical "dose" imparted on the musculoskeletal system of crew members and relate this dose to changes in bone homeostasis.

FLORIS 2017

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

2017-08-04

This code is an enhancement to the existing FLORIS code, SWR 14-20. In particular, this enhancement computes overall thrust and turbulence intensity throughout a wind plant. This information is used to form a description of the fatigue loads experienced throughtout the wind plant. FLORIS has been updated to include an optimization routine that optimizes FLORIS to minimize thrust and turbulence intensity (and therefore loads) across the wind plant. Previously, FLORIS had been designed to optimize power out of a wind plant. However, as turbines age, more wind plant owner/operators are looking for ways to reduce their fatigue loads without sacrificingmore » too much power.« less

Feasibility study for the treatment of municipal wastewater by using a hybrid bio-solar process.

PubMed

Barwal, Anjali; Chaudhary, Rubina

2016-07-15

A moving bed biofilm reactor (MBBR) coupled with solar parabolic structured system has been designed and developed to get the maximum organic load removal and microbial disinfection from the wastewater. The effluent was first subjected to organic degradation in MBBR (with optimized carrier filling rate of 30%) followed by the bacterial degradation using solar energy in parabolic trough and the changes in values of parameters like pH, turbidity, chemical oxygen demand (COD), bio-chemical oxygen demand (BOD) and microbial count were monitored. The titanium dioxide (TiO2) was used as a photocatalyst for the removal of organic load from the wastewater but in optimized conditions. At optimum dose of 1.0 g/L of TiO2 and pH value of 7.6, maximum COD removal of 69% and 13% was achieved at sunny days (solar irradiation 400-700 W m(-2)) and cloudy days (solar irradiation 170-250 W m(-2)) respectively within 5-6 h solar irradiation time. The results obtained showed that it is possible to decrease in six logarithms (log) the concentration of TC and FC within only 240 min of solar exposure. Moreover, this process can offer economically reasonable, chemical free and practical solution to the processing of municipal wastewater where solar intensity is readily available and can be used for making zero liquid discharge (ZLD) an effective reality. Copyright © 2016 Elsevier Ltd. All rights reserved.

Advanced Intelligent System Application to Load Forecasting and Control for Hybrid Electric Bus

NASA Technical Reports Server (NTRS)

Momoh, James; Chattopadhyay, Deb; Elfayoumy, Mahmoud

1996-01-01

The primary motivation for this research emanates from providing a decision support system to the electric bus operators in the municipal and urban localities which will guide the operators to maintain an optimal compromise among the noise level, pollution level, fuel usage etc. This study is backed up by our previous studies on study of battery characteristics, permanent magnet DC motor studies and electric traction motor size studies completed in the first year. The operator of the Hybrid Electric Car must determine optimal power management schedule to meet a given load demand for different weather and road conditions. The decision support system for the bus operator comprises three sub-tasks viz. forecast of the electrical load for the route to be traversed divided into specified time periods (few minutes); deriving an optimal 'plan' or 'preschedule' based on the load forecast for the entire time-horizon (i.e., for all time periods) ahead of time; and finally employing corrective control action to monitor and modify the optimal plan in real-time. A fully connected artificial neural network (ANN) model is developed for forecasting the kW requirement for hybrid electric bus based on inputs like climatic conditions, passenger load, road inclination, etc. The ANN model is trained using back-propagation algorithm employing improved optimization techniques like projected Lagrangian technique. The pre-scheduler is based on a Goal-Programming (GP) optimization model with noise, pollution and fuel usage as the three objectives. GP has the capability of analyzing the trade-off among the conflicting objectives and arriving at the optimal activity levels, e.g., throttle settings. The corrective control action or the third sub-task is formulated as an optimal control model with inputs from the real-time data base as well as the GP model to minimize the error (or deviation) from the optimal plan. These three activities linked with the ANN forecaster proving the output to the GP model which in turn produces the pre-schedule of the optimal control model. Some preliminary results based on a hypothetical test case will be presented for the load forecasting module. The computer codes for the three modules will be made available fe adoption by bus operating agencies. Sample results will be provided using these models. The software will be a useful tool for supporting the control systems for the Electric Bus project of NASA.

Humoral and cell-mediated immune responses after a booster dose of HBV vaccine in HIV-infected children, adolescents and young adults.

PubMed

Giacomet, Vania; Masetti, Michela; Nannini, Pilar; Forlanini, Federica; Clerici, Mario; Zuccotti, Gian Vincenzo; Trabattoni, Daria

2018-01-01

HBV vaccine induces protective antibodies only in 23-56% of HIV-infected children. The aim of our study is to evaluate the immunologic effects of a booster dose of HBV vaccine in HIV-infected youth. 53 young HIV-infected patients in whom HBV vaccination did not elicit protective Ab titers were enrolled. All patients were on ART with optimal immunological and viral response. All patients received a booster dose of HBV vaccine (HBVAXPRO 10 μg i.m.). HBV-specific Ab titer, viral load and CD4+ T cells were measured at baseline (T0), T1, T6 and T12 months. In a subgroup of 16 patients HBV-specific cell mediated immune responses were evaluated at baseline, at T1 and T6. The booster dose induced seroconversion in 51% of patients at T1, 57% at T6, and49% at T12; seroconversion rate was significantly correlated with CD4+T cells at T0 and to the CD4 nadir. The booster dose induced HBV-specific cell mediated immunity at T6 mainly in Responders (Rs): Effector Memory CD8+T cells, HBV-specific TNFα-, IFNγ-, granzyme secreting CD8+ T cells and IL2-secreting CD4+ T cells were significantly increased in Rs compared to T0. In Non Responders (NRs), HBV-specific IL2-secreting CD4+ T cells, Central and Effector Memory CD8+ T cells were the only parameters modified at T6. Seroconversion induced by a booster dose of vaccine correlates with the development of T cell immunological memory in HIV-infected patients who did not respond to the standard immunization. Alternate immunization schedules need to be considered in NRs.

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

Brachytherapy optimization using radiobiological-based planning for high dose rate and permanent implants for prostate cancer treatment

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.

Polyurethane foam loaded with SDS for the adsorption of cationic dyes from aqueous medium: Multivariate optimization of the loading process.

PubMed

Robaina, Nicolle F; Soriano, Silvio; Cassella, Ricardo J

2009-08-15

This paper reports the development of a new procedure for the adsorption of four cationic dyes (Rhodamine B, Methylene Blue, Crystal Violet and Malachite Green) from aqueous medium employing polyurethane foam (PUF) loaded with sodium dodecylsulfate (SDS) as solid phase. PUF loading process was based on the stirring of 200mg PUF cylinders with acidic solutions containing SDS. The conditions for loading were optimized by response surface methodology (RSM) using a Doehlert design with three variables that were SDS and HCl concentrations and stirring time. Results obtained in the optimization process showed that the stirring time is not a relevant parameter in the PUF loading, evidencing that the transport of SDS from solution to PUF surface is fast. On the other hand, both SDS and HCl concentrations were important parameters causing significant variation in the efficiency of the resulting solid phase for the removal of dyes from solution. At optimized conditions, SDS and HCl concentrations were 4.0 x 10(-4) and 0.90 mol L(-1), respectively. The influence of stirring time was evaluated by univariate methodology. A 20 min stirring time was established in order to make the PUF loading process fast and robust without losing efficiency. The procedure was tested for the removal of the four cationic dyes from aqueous solutions and removal efficiencies always better than 90% were achieved for the two concentrations tested (2.0 x 10(-5) and 1.0 x 10(-4)mol L(-1)).

Automatic CT simulation optimization for radiation therapy: A general strategy.

PubMed

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.

Characterization of low-dose doxorubicin-loaded silica-based nanocomposites

NASA Astrophysics Data System (ADS)

Prokopowicz, Magdalena

2018-01-01

In this study, we synthesized multicomponent solid films of low-dose doxorubicin (DOX)-loaded polydimethylsiloxane (PDMS)-SiO2/CaP nanocomposites via sol-gel process combined with the method of evaporation-induced self-assembly (EISA) at low temperature. Nanomechanical properties (elasticity and adhesion) of the synthesized multicomponent films were determined by using atomic force microscopy with a PeakForce™ quantitative nanomechanical mapping imaging technique. Solid state of DOX in the synthesized films was studied by using UV-vis and fluorescence spectroscopy. The release profile of different concentrations of DOX loaded (1, 3, and 5 wt%) on the multicomponent films was assessed using USP Apparatus 4 and via UV-vis end analysis. Results indicate drug-component interactions on the overall morphology of domains (size and shape), nanomechanical properties, and release behavior of the DOX-loaded nanocomposites. We observed a progressive increase in surface roughness and mean adhesive value with increasing concentration of DOX loaded (0-5 wt%). In addition, for all the different concentrations of DOX-loaded, we observed a diffusion-controlled drug release.

SU-F-T-201: Acceleration of Dose Optimization Process Using Dual-Loop Optimization Technique for Spot Scanning Proton Therapy

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

Hirayama, S; Fujimoto, R

Purpose: The purpose was to demonstrate a developed acceleration technique of dose optimization and to investigate its applicability to the optimization process in a treatment planning system (TPS) for proton therapy. Methods: In the developed technique, the dose matrix is divided into two parts, main and halo, based on beam sizes. The boundary of the two parts is varied depending on the beam energy and water equivalent depth by utilizing the beam size as a singular threshold parameter. The optimization is executed with two levels of iterations. In the inner loop, doses from the main part are updated, whereas dosesmore » from the halo part remain constant. In the outer loop, the doses from the halo part are recalculated. We implemented this technique to the optimization process in the TPS and investigated the dependence on the target volume of the speedup effect and applicability to the worst-case optimization (WCO) in benchmarks. Results: We created irradiation plans for various cubic targets and measured the optimization time varying the target volume. The speedup effect was improved as the target volume increased, and the calculation speed increased by a factor of six for a 1000 cm3 target. An IMPT plan for the RTOG benchmark phantom was created in consideration of ±3.5% range uncertainties using the WCO. Beams were irradiated at 0, 45, and 315 degrees. The target’s prescribed dose and OAR’s Dmax were set to 3 Gy and 1.5 Gy, respectively. Using the developed technique, the calculation speed increased by a factor of 1.5. Meanwhile, no significant difference in the calculated DVHs was found before and after incorporating the technique into the WCO. Conclusion: The developed technique could be adapted to the TPS’s optimization. The technique was effective particularly for large target cases.« less

Optimization of the Mu2e Production Solenoid Heat and Radiation Shield

NASA Astrophysics Data System (ADS)

Pronskikh, V. S.; Coleman, R.; Glenzinski, D.; Kashikhin, V. V.; Mokhov, N. V.

2014-03-01

The Mu2e experiment at Fermilab is designed to study the conversion of a negative muon to electron in the field of a nucleus without emission of neutrinos. Observation of this process would provide unambiguous evidence for physics beyond the Standard Model, and can point to new physics beyond the reach of the LHC. The main parts of the Mu2e apparatus are its superconducting solenoids: Production Solenoid (PS), Transport Solenoid (TS), and Detector Solenoid (DS). Being in the vicinity of the beam, PS magnets are most subjected to the radiation damage. In order for the PS superconducting magnet to operate reliably, the peak neutron flux in the PS coils must be reduced by 3 orders of magnitude by means of sophisticatedly designed massive Heat and Radiation Shield (HRS), optimized for the performance and cost. An issue with radiation damage is related to large residual electrical resistivity degradation in the superconducting coils, especially its Al stabilizer. A detailed MARS15 analysis and optimization of the HRS has been carried out both to satisfy the Mu2e requirements to the radiation quantities (such as displacements per atom, peak temperature and power density in the coils, absorbed dose in the insulation, and dynamic heat load) and cost. Results of MARS15 simulations of these radiation quantities are reported and optimized HRS models are presented; it is shown that design levels satisfy all requirements.

Toxicity assessment of tannery effluent treated by an optimized photo-Fenton process.

PubMed

Borba, Fernando Henrique; Módenes, Aparecido Nivaldo; Espinoza-Quiñones, Fernando Rodolfo; Manenti, Diego Ricieri; Bergamasco, Rosangela; Mora, Nora Diaz

2013-01-01

In this work, an optimized photo-Fenton process was applied to remove pollutants from tannery industrial effluent (TIE) with its final toxicity level being assessed by a lettuce-seed-based bioassay test. A full 33 factorial design was applied for the optimization of long-term photo-Fenton experiments. The oPtimum conditions of the photo-Fenton process were attained at concentration values of 0.3 g Fe(2+) L(-1) and 20 g H2O2 L(-1) and pH3, for 120 min UV irradiation time. Reactor operating parameter (ROP) effects on the removal of chemical oxygen demand, colour, turbidity, total suspended solids and total volatile solids were evaluated, suggesting that a broad range of ROP values are also suitable to give results very near to those of the photo-Fenton experiments under optimal conditions. Based on the low calculated median lethal dose (LD50) values from a lettuce-seed-based bioassay test, we suggest that recalcitrant substances are present in treated TIE samples. A possible cause of the high toxicity level could partly be attributed to the nitrate concentration, which was not completely abated by the photo-Fenton process. Apart from this, the photo-Fenton process can be used as a part of an industrial effluent treatment system in order to abate high organic pollutant loads.

Advanced optimal design concepts for composite material aircraft repair

NASA Astrophysics Data System (ADS)

Renaud, Guillaume

The application of an automated optimization approach for bonded composite patch design is investigated. To do so, a finite element computer analysis tool to evaluate patch design quality was developed. This tool examines both the mechanical and the thermal issues of the problem. The optimized shape is obtained with a bi-quadratic B-spline surface that represents the top surface of the patch. Additional design variables corresponding to the ply angles are also used. Furthermore, a multi-objective optimization approach was developed to treat multiple and uncertain loads. This formulation aims at designing according to the most unfavorable mechanical and thermal loads. The problem of finding the optimal patch shape for several situations is addressed. The objective is to minimize a stress component at a specific point in the host structure (plate) while ensuring acceptable stress levels in the adhesive. A parametric study is performed in order to identify the effects of various shape parameters on the quality of the repair and its optimal configuration. The effects of mechanical loads and service temperature are also investigated. Two bonding methods are considered, as they imply different thermal histories. It is shown that the proposed techniques are effective and inexpensive for analyzing and optimizing composite patch repairs. It is also shown that thermal effects should not only be present in the analysis, but that they play a paramount role on the resulting quality of the optimized design. In all cases, the optimized configuration results in a significant reduction of the desired stress level by deflecting the loads away from rather than over the damage zone, as is the case with standard designs. Furthermore, the automated optimization ensures the safety of the patch design for all considered operating conditions.

Reduced Design Load Basis for Ultimate Blade Loads Estimation in Multidisciplinary Design Optimization Frameworks

NASA Astrophysics Data System (ADS)

Pavese, Christian; Tibaldi, Carlo; Larsen, Torben J.; Kim, Taeseong; Thomsen, Kenneth

2016-09-01

The aim is to provide a fast and reliable approach to estimate ultimate blade loads for a multidisciplinary design optimization (MDO) framework. For blade design purposes, the standards require a large amount of computationally expensive simulations, which cannot be efficiently run each cost function evaluation of an MDO process. This work describes a method that allows integrating the calculation of the blade load envelopes inside an MDO loop. Ultimate blade load envelopes are calculated for a baseline design and a design obtained after an iteration of an MDO. These envelopes are computed for a full standard design load basis (DLB) and a deterministic reduced DLB. Ultimate loads extracted from the two DLBs with the two blade designs each are compared and analyzed. Although the reduced DLB supplies ultimate loads of different magnitude, the shape of the estimated envelopes are similar to the one computed using the full DLB. This observation is used to propose a scheme that is computationally cheap, and that can be integrated inside an MDO framework, providing a sufficiently reliable estimation of the blade ultimate loading. The latter aspect is of key importance when design variables implementing passive control methodologies are included in the formulation of the optimization problem. An MDO of a 10 MW wind turbine blade is presented as an applied case study to show the efficacy of the reduced DLB concept.

Optimal Topology of Aircraft Rib and Spar Structures under Aeroelastic Loads

NASA Technical Reports Server (NTRS)

Stanford, Bret K.; Dunning, Peter D.

2014-01-01

Several topology optimization problems are conducted within the ribs and spars of a wing box. It is desired to locate the best position of lightening holes, truss/cross-bracing, etc. A variety of aeroelastic metrics are isolated for each of these problems: elastic wing compliance under trim loads and taxi loads, stress distribution, and crushing loads. Aileron effectiveness under a constant roll rate is considered, as are dynamic metrics: natural vibration frequency and flutter. This approach helps uncover the relationship between topology and aeroelasticity in subsonic transport wings, and can therefore aid in understanding the complex aircraft design process which must eventually consider all these metrics and load cases simultaneously.

Optimal design of high-speed loading spindle based on ABAQUS

NASA Astrophysics Data System (ADS)

Yang, Xudong; Dong, Yu; Ge, Qingkuan; Yang, Hai

2017-12-01

The three-dimensional model of high-speed loading spindle is established by using ABAQUS’s modeling module. A finite element analysis model of high-speed loading spindle was established by using spring element to simulate bearing boundary condition. The static and dynamic performance of the spindle structure with different specifications of the rectangular spline and the different diameter neck of axle are studied in depth, and the influence of different spindle span on the static and dynamic performance of the high-speed loading spindle is studied. Finally, the optimal structure of the high-speed loading spindle is obtained. The results provide a theoretical basis for improving the overall performance of the test-bed

Optimization of self-acting step thrust bearings for load capacity and stiffness.

NASA Technical Reports Server (NTRS)

Hamrock, B. J.

1972-01-01

Linearized analysis of a finite-width rectangular step thrust bearing. Dimensionless load capacity and stiffness are expressed in terms of a Fourier cosine series. The dimensionless load capacity and stiffness were found to be a function of the dimensionless bearing number, the pad length-to-width ratio, the film thickness ratio, the step location parameter, and the feed groove parameter. The equations obtained in the analysis were verified. The assumptions imposed were substantiated by comparing the results with an existing exact solution for the infinite width bearing. A digital computer program was developed which determines optimal bearing configuration for maximum load capacity or stiffness. Simple design curves are presented. Results are shown for both compressible and incompressible lubrication. Through a parameter transformation the results are directly usable in designing optimal step sector thrust bearings.

Co-optimization of Energy and Demand-Side Reserves in Day-Ahead Electricity Markets

NASA Astrophysics Data System (ADS)

Surender Reddy, S.; Abhyankar, A. R.; Bijwe, P. R.

2015-04-01

This paper presents a new multi-objective day-ahead market clearing (DAMC) mechanism with demand-side reserves/demand response (DR) offers, considering realistic voltage-dependent load modeling. The paper proposes objectives such as social welfare maximization (SWM) including demand-side reserves, and load served error (LSE) minimization. In this paper, energy and demand-side reserves are cleared simultaneously through co-optimization process. The paper clearly brings out the unsuitability of conventional SWM for DAMC in the presence of voltage-dependent loads, due to reduction of load served (LS). Under such circumstances multi-objective DAMC with DR offers is essential. Multi-objective Strength Pareto Evolutionary Algorithm 2+ (SPEA 2+) has been used to solve the optimization problem. The effectiveness of the proposed scheme is confirmed with results obtained from IEEE 30 bus system.

Current and efficiency optimization under oscillating forces in entropic barriers

NASA Astrophysics Data System (ADS)

Nutku, Ferhat; Aydıner, Ekrem

2016-09-01

The transport of externally overdriven particles confined in entropic barriers is investigated under various types of oscillating and temporal forces. Temperature, load, and amplitude dependence of the particle current and energy conversion efficiency are investigated in three dimensions. For oscillating forces, the optimized temperature-load, amplitude-temperature, and amplitude-load intervals are determined when fixing the amplitude, load, and temperature, respectively. By using three-dimensional plots rather than two-dimensional ones, it is clearly shown that oscillating forces provide more efficiency compared with a temporal one in specified optimized parameter regions. Furthermore, the dependency of efficiency to the angle between the unbiased driving force and a constant force is investigated and an asymmetric angular dependence is found for all types of forces. Finally, it is shown that oscillating forces with a high amplitude and under a moderate load lead to higher efficiencies than a temporal force at both low and high temperatures for the entire range of contact angle. Project supported by the Istanbul University, Turkey (Grant No. 55383).

Optimal Control Allocation with Load Sensor Feedback for Active Load Suppression, Experiment Development

NASA Technical Reports Server (NTRS)

Miller, Christopher J.; Goodrick, Dan

2017-01-01

The problem of control command and maneuver induced structural loads is an important aspect of any control system design. The aircraft structure and the control architecture must be designed to achieve desired piloted control responses while limiting the imparted structural loads. The classical approach is to utilize high structural margins, restrict control surface commands to a limited set of analyzed combinations, and train pilots to follow procedural maneuvering limitations. With recent advances in structural sensing and the continued desire to improve safety and vehicle fuel efficiency, it is both possible and desirable to develop control architectures that enable lighter vehicle weights while maintaining and improving protection against structural damage. An optimal control technique has been explored and shown to achieve desirable vehicle control performance while limiting sensed structural loads. The subject of this paper is the design of the optimal control architecture, and provides the reader with some techniques for tailoring the architecture, along with detailed simulation results.

Impact of respiratory motion on worst-case scenario optimized intensity modulated proton therapy for lung cancers.

PubMed

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.

SU-E-T-452: Impact of Respiratory Motion On Robustly-Optimized Intensity-Modulated Proton Therapy to Treat Lung Cancers

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

Can we safely administer the recommended dose of phenobarbital in very low birth weight infants?

PubMed

Oztekin, Osman; Kalay, Salih; Tezel, Gonul; Akcakus, Mustafa; Oygur, Nihal

2013-08-01

We investigated whether the recommended phenobarbital loading dose of 15-20 mg/kg with maintenance of 3-4 mg/kg/day can safely be administered to very low birth weight preterm newborns with seizures. Twenty-four convulsive preterms of <1,500 g were enrolled in the study. Phenobarbital was administered intravenously with a loading dose of 15 mg/kg in approximately 10-15 min. After 24 h, the maintenance dose of 3 mg/kg/day was administered as a single injection. Blood samples were obtained 2, 24, 48, 72, and 96 h after the phenobarbital loading dose was administered, immediately before the next phenobarbital dose was injected. None of the cases had plasma phenobarbital concentrations above the therapeutic upper limit of 40 μg/mL on the 2nd hour; one case (4.7%), on the 24th; 11 cases (45.8%), on the 48th; 15 cases (62.5%), on the 72nd; and 17 cases (70.8%), on the 96th hour. A negative correlation was detected between the serum concentrations of phenobarbital and gestational age on the 72th (p, 0.036; r, -0.608) and 96th hour (p, 0.043; r, -0.769). We suggest that particular attention should be done while administering phenobarbital in preterms, as blood levels of phenobarbital are higher than the reference ranges that those are often reached with the recommended doses in these groups of babies.

[CALCULATION OF RADIATION LOADS ON THE ANTHROPOMORPHIC PHANTOM ONBOARD THE SPACE STATION IN THE CASE OF ADDITIONAL SHIELDING].

PubMed

Kartashov, D A; Shurshakov, V A

2015-01-01

The paper presents the results of calculating doses from space ionizing radiation for a modeled orbital station cabin outfitted with an additional shield aimed to reduce radiation loads on cosmonaut. The shield is a layer with the mass thickness of -6 g/cm2 (mean density = 0.62 g/cm3) that covers the outer cabin wall and consists of wet tissues and towels used by cosmonauts for hygienic purposes. A tissue-equivalent anthropomorphic phantom imitates human body. Doses were calculated for the standard orbit of the International space station (ISS) with consideration of the longitudinal and transverse phantom orientation relative to the wall with or without the additional shield. Calculation of dose distribution in the human body improves prediction of radiation loads. The additional shield reduces radiation exposure of human critical organs by -20% depending on their depth and body spatial orientation in the ISS compartment.

Impact of Spot Size and Spacing on the Quality of Robustly Optimized Intensity Modulated Proton Therapy Plans for Lung Cancer.

PubMed

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.

Feasibility and robustness of dose painting by numbers in proton therapy with contour-driven plan optimization

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

Dose Calibration of the ISS-RAD Fast Neutron Detector

NASA Technical Reports Server (NTRS)

Zeitlin, C.

2015-01-01

The ISS-RAD instrument has been fabricated by Southwest Research Institute and delivered to NASA for flight to the ISS in late 2015 or early 2016. ISS-RAD is essentially two instruments that share a common interface to ISS. The two instruments are the Charged Particle Detector (CPD), which is very similar to the MSL-RAD detector on Mars, and the Fast Neutron Detector (FND), which is a boron-loaded plastic scintillator with readout optimized for the 0.5 to 10 MeV energy range. As the FND is completely new, it has been necessary to develop methodology to allow it to be used to measure the neutron dose and dose equivalent. This talk will focus on the methods developed and their implementation using calibration data obtained in quasi-monoenergetic (QMN) neutron fields at the PTB facility in Braunschweig, Germany. The QMN data allow us to determine an approximate response function, from which we estimate dose and dose equivalent contributions per detected neutron as a function of the pulse height. We refer to these as the "pSv per count" curves for dose equivalent and the "pGy per count" curves for dose. The FND is required to provide a dose equivalent measurement with an accuracy of ?10% of the known value in a calibrated AmBe field. Four variants of the analysis method were developed, corresponding to two different approximations of the pSv per count curve, and two different implementations, one for real-time analysis onboard ISS and one for ground analysis. We will show that the preferred method, when applied in either real-time or ground analysis, yields good accuracy for the AmBe field. We find that the real-time algorithm is more susceptible to chance-coincidence background than is the algorithm used in ground analysis, so that the best estimates will come from the latter.

Exploratory Study of 4D versus 3D Robust Optimization in Intensity Modulated Proton Therapy for Lung Cancer

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.

PubMed

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.

Special features of total knee replacement in hemophilia.

PubMed

Rodriguez-Merchan, Emerito Carlos

2013-12-01

Total knee replacement is an operation frequently needed by hemophilia patients, which greatly improves their quality of life. This operation, however, carries a higher risk of bleeding and infection for hemophiliacs than it does for osteoarthritis sufferers. It is advisable to implant prosthetic components using antibiotic-loaded cement. It is essential to maintain a level of 100% of the replacement clotting factor for 2 weeks. Hematological treatment must be established, depending on the patient's factor levels and other pharmacokinetic parameters such as recovery and half-life, optimal doses and treatment time. It is preferable to use general anesthesia due to the risk of spinal bleeding. The lifespan of total knee replacement in hemophilic patients is shorter than in patients with osteoarthritis because of the increased risk of infection.

Tailoring the Employment of Offshore Wind Turbine Support Structure Load Mitigation Controllers

NASA Astrophysics Data System (ADS)

Shrestha, Binita; Kühn, Martin

2016-09-01

The currently available control concepts to mitigate aerodynamic and hydrodynamic induced support structure loads reduce either fore-aft or side-to-side damage under certain operational conditions. The load reduction is achieved together with an increase in loads in other components of the turbine e.g. pitch actuators or drive train, increasing the risk of unscheduled maintenance. The main objective of this paper is to demonstrate a methodology for reduction of support structure damage equivalent loads (DEL) in fore-aft and side-to-side directions using already available control concepts. A multi-objective optimization problem is formulated to minimize the DELs, while limiting the collateral effects of the control algorithms for load reduction. The optimization gives trigger values of sea state condition for the activation or deactivation of certain control concepts. As a result, by accepting the consumption of a small fraction of the load reserve in the design load envelope of other turbine components, a considerable reduction of the support structure loads is facilitated.

Rail Mounted Gantry Crane Scheduling Optimization in Railway Container Terminal Based on Hybrid Handling Mode

PubMed Central

Zhu, Xiaoning

2014-01-01

Rail mounted gantry crane (RMGC) scheduling is important in reducing makespan of handling operation and improving container handling efficiency. In this paper, we present an RMGC scheduling optimization model, whose objective is to determine an optimization handling sequence in order to minimize RMGC idle load time in handling tasks. An ant colony optimization is proposed to obtain near optimal solutions. Computational experiments on a specific railway container terminal are conducted to illustrate the proposed model and solution algorithm. The results show that the proposed method is effective in reducing the idle load time of RMGC. PMID:25538768

Effect of rosuvastatin dose-loading on serum sLox-1, hs-CRP, and postoperative prognosis in diabetic patients with acute coronary syndromes undergoing selected percutaneous coronary intervention (PCI).

PubMed

Jiao, Yungen; Hu, Feng; Zhang, Zhengang; Gong, Kaizheng; Sun, Xiaoning; Li, Aihua; Liu, Naifeng

2015-01-01

To investigate the effect of rosuvastatin dose-loading on serum levels of lectin-like oxidized low-density lipoprotein receptor-1 (Lox-1) and high-sensitivity c-reactive protein (hs-CRP) and postoperative prognosis in patients with diabetes and non-ST segment elevation acute coronary syndromes (NSTEACS) undergoing selected percutaneous coronary intervention (PCI). A total of 72 patients with diabetes and NSTEACS were randomized to either the group treated with 20 mg rosuvastatin 12 hours prior to PCI with a second dose administered just before PCI (n = 33), or a control group treated with standard method according guideline (n = 39). Serum levels of sLox-1, hs-CRP, CK-MB, and cTnI were measured prior to PCI, and at 24 hours and 30 days after PCI. The 30-day incidence of major adverse cardiac events (MACE) was recorded in both groups. Compared to pre-PCI, serum levels of sLox-1 and hs-CRP of the two groups were increased at 24 hours after PCI (P < 0.05); the levels of CK-MB and cTnI were also improved (P < 0.01); however, the ascended values of sLox-1, hs-CRP, CK-MB, and cTnI were significantly lower in the loading-dose rosuvastatin-treated group than in the control-treated group. Serum levels of sLox-1 and hs-CRP were higher in the loading-dose rosuvastatin-treated group than in the control-treated group at 30 days after PCI (P < 0.05); compared to pre-PCI, the levels of TC and LDL-C were not changed at 24 hours after PCI (P > 0.05) until 30 days after PCI (P < 0.05), but there were no difference between the two groups. The levels of ALT and Scr had no significant difference between the two groups before and after PCI; the 30-day incidence of MACE occurred in 6.06% of patients in the loading-dose rosuvastatin-treated group and in 23.08% of patients in the control-treated group (P < 0.05). The therapy of dose-loading rosuvastatin for patients with diabetes and non-ST segment elevation acute coronary syndromes undergoing selected percutaneous coronary intervention can attenuate the increase of serum levels of sLox-1, reduce myocardial injury and inflammatory reaction caused by PCI, and also reduce the occurrence of MACE 30 days after PCI.

Optimization of spatiotemporally fractionated radiotherapy treatments with bounds on the achievable benefit

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.

SU-E-T-295: Simultaneous Beam Sampling and Aperture Shape Optimization for Station Parameter Optimized Radiation Therapy (SPORT)

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

Nano-encapsulation of Dietary Phytoconstituent Capsaicin on Emulsome: Evaluation of Anticancer Activity Through the Measurement of Liver Oxidative Stress in Rats.

PubMed

Giri, Tapan K; Pramanik, Kaustav; Barman, Tapan K; Maity, Subhasis

2017-01-01

Excessive reactive species derived from oxygen and nitrogen leads to oxidative damage to tissue and organs. Capsaicin (CAP), a pungent component found in red pepper can prevent oxidative stress. The aim of the present work was to evaluate the protective effects of CAP loaded nano-emulsomes (EML) against the oxidative stress of rat livers induced through sodium fluoride (NaF). EML was prepared by thin film hydration method that is development of thin lipid film followed by hydration and sonication. EML was characterized by Fourier transform infrared (FT-IR) spectroscopy and X-ray diffraction (XRD) techniques. EML was evaluated for drug entrapment, in vitro drug release, and in vivo study. In vitro drug release study of optimized formulation showed that 50% of CAP was released within 50.21 min while 85% CAP was released in 227.4 min. Single oral dose of free CAP and CAP loaded EML were given to rats 2 hour after NaF administration. Membrane of hepatic cells was damaged by NaF and it was judged by the estimation of lipid peroxidation, reactive oxygen species (ROS), and catalase activity. The administration of CAP loaded EML 2 hr after NAF consumption showed significant decrease in ROS level compared to free CAP. EML containing CAP was more effective in comparison to free CAP in controlling the lipid peroxidation that is thiobarbituric acid substance augmentation in liver by the treatment of NaF. The administration of CAP loaded EML showed significant increase in catalase activity compared to free CAP administration. The results clearly demonstrated that CAP loaded EML may be accepted as an effective therapeutic formulation in preventing oxidative damage. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Vitamin C-driven epirubicin loading into liposomes

PubMed Central

Lipka, Dominik; Gubernator, Jerzy; Filipczak, Nina; Barnert, Sabine; Süss, Regine; Legut, Mateusz; Kozubek, Arkadiusz

2013-01-01

The encapsulation of anticancer drugs in a liposome structure protects the drug during circulation and increases drug accumulation in the cancer tissue and antitumor activity while decreasing drug toxicity. This paper presents a new method of active drug loading based on a vitamin C pH/ion gradient. Formulations were characterized in terms of the following parameters: optimal external pH, time and drug-to-lipid ratio for the purpose of remote loading, and in vitro stability. In the case of the selected drug, epirubicin (EPI), its coencapsulation increases its anticancer activity through a possibly synergistic effect previously reported by other groups for a free nonencapsulated drug/vitamin C cocktail. The method also has another advantage over other remote-loading methods: it allows faster drug release through liposome destabilization at the tumor site, thanks to the very good solubility of the EPI vitamin C salt, as seen on cryogenic transmission electron microscopy images. This influences the drug-release process and increases the anticancer activity of the liposome formulation. The liposomes are characterized as stable, with very good pharmacokinetics (half-life 18.6 hours). The antitumor activity toward MCF-7 and 4T-1 breast cancer cells was higher in the case of EPI loaded via our gradient than via an ammonium sulfate gradient. Finally, the EPI liposomal formulation and the free drug were tested using the murine 4T-1 breast cancer model. The antitumor activity of the encapsulated drug was confirmed (tumor-growth inhibition over 40% from day 16 until the end of the experiment), and the free drug was shown to have no anticancer activity at the tested dose. PMID:24101870

Cloud computing task scheduling strategy based on differential evolution and ant colony optimization

NASA Astrophysics Data System (ADS)

Ge, Junwei; Cai, Yu; Fang, Yiqiu

2018-05-01

This paper proposes a task scheduling strategy DEACO based on the combination of Differential Evolution (DE) and Ant Colony Optimization (ACO), aiming at the single problem of optimization objective in cloud computing task scheduling, this paper combines the shortest task completion time, cost and load balancing. DEACO uses the solution of the DE to initialize the initial pheromone of ACO, reduces the time of collecting the pheromone in ACO in the early, and improves the pheromone updating rule through the load factor. The proposed algorithm is simulated on cloudsim, and compared with the min-min and ACO. The experimental results show that DEACO is more superior in terms of time, cost, and load.

Analytic model for ultrasound energy receivers and their optimal electric loads

NASA Astrophysics Data System (ADS)

Gorostiaga, M.; Wapler, M. C.; Wallrabe, U.

2017-08-01

In this paper, we present an analytic model for thickness resonating plate ultrasound energy receivers, which we have derived from the piezoelectric and the wave equations and, in which we have included dielectric, viscosity and acoustic attenuation losses. Afterwards, we explore the optimal electric load predictions by the zero reflection and power maximization approaches present in the literature with different acoustic boundary conditions, and discuss their limitations. To validate our model, we compared our expressions with the KLM model solved numerically with very good agreement. Finally, we discuss the differences between the zero reflection and power maximization optimal electric loads, which start to differ as losses in the receiver increase.

High drug loading self-microemulsifying/micelle formulation: design by high-throughput formulation screening system and in vivo evaluation.

PubMed

Sakai, Kenichi; Obata, Kouki; Yoshikawa, Mayumi; Takano, Ryusuke; Shibata, Masaki; Maeda, Hiroyuki; Mizutani, Akihiko; Terada, Katsuhide

2012-10-01

To design a high drug loading formulation of self-microemulsifying/micelle system. A poorly-soluble model drug (CH5137291), 8 hydrophilic surfactants (HS), 10 lipophilic surfactants (LS), 5 oils, and PEG400 were used. A high loading formulation was designed by a following stepwise approach using a high-throughput formulation screening (HTFS) system: (1) an oil/solvent was selected by solubility of the drug; (2) a suitable HS for highly loading was selected by the screenings of emulsion/micelle size and phase stability in binary systems (HS, oil/solvent) with increasing loading levels; (3) a LS that formed a broad SMEDDS/micelle area on a phase diagram containing the HS and oil/solvent was selected by the same screenings; (4) an optimized formulation was selected by evaluating the loading capacity of the crystalline drug. Aqueous solubility behavior and oral absorption (Beagle dog) of the optimized formulation were compared with conventional formulations (jet-milled, PEG400). As an optimized formulation, d-α-tocopheryl polyoxyethylene 1000 succinic ester: PEG400 = 8:2 was selected, and achieved the target loading level (200 mg/mL). The formulation formed fine emulsion/micelle (49.1 nm), and generated and maintained a supersaturated state at a higher level compared with the conventional formulations. In the oral absorption test, the area under the plasma concentration-time curve of the optimized formulation was 16.5-fold higher than that of the jet-milled formulation. The high loading formulation designed by the stepwise approach using the HTFS system improved the oral absorption of the poorly-soluble model drug.

[Optimization of trehalose loading in red blood cells before freeze-drying].

PubMed

Zhuang, Yuan; Liu, Jing-Han; Ouyang, Xi-Lin; Chen, Lin-Feng; Che, Ji

2007-04-01

The key points for better protection of trehalose in freeze-drying red blood cells (RBCs) are to resolve non-osmosis of trehalose to red blood cells and to make cytoplasmic trehalose to reach effective concentration. This study was aimed to investigate the regularity of loading RBCs with trehalose, screen out optimal loading condition and evaluate the effect of trehalose on physico-chemical parameters of RBCs during the period of loading. The cytoplasmic trehalose concentration in red blood cells, free hemoglobin and ATP level were determined at different incubation temperatures (4, 22 and 37 degrees C), different trehaolse concentrations (0, 200, 400, 600, 800 and 1000 mmol/L) and different incubation times (2, 4, 6, 8 and 10 hours), the cytoplasmic trehalose, free hemoglobin (FHb), hemoglobin (Hb) and mean corpuscular volume (MCV) in fresh RBCs and RBCs stored for 72 hours at 4 degrees C were compared, when loading condition was ensured. The results showed that with increase of incubation temperature, time and extracellular trehalose concentration, the loading of trehalose in RBCs also increased. Under the optimal loading condition, cytoplasmic trehalose concentration and free hemoglobin level of fresh RBCs and RBCs stored for 72 hours at 4 degrees C were 65.505 +/- 6.314 mmol/L, 66.2 +/- 5.002 mmol/L and 6.567 +/- 2.568 g/L, 16.168 +/- 3.922 g/L respectively. It is concluded that the most optimal condition of loading trehalose is that fresh RBCs incubate in 800 mmol/L trehalose solution for 8 hours at 37 degrees C. This condition can result in a efficient cytoplasmic trehalose concentration. The study provides an important basis for long-term preservation of RBCs.

Optimal acetabular component orientation estimated using edge-loading and impingement risk in patients with metal-on-metal hip resurfacing arthroplasty.

PubMed

Mellon, Stephen J; Grammatopoulos, George; Andersen, Michael S; Pandit, Hemant G; Gill, Harinderjit S; Murray, David W

2015-01-21

Edge-loading in patients with metal-on-metal resurfaced hips can cause high serum metal ion levels, the development of soft-tissue reactions local to the joint called pseudotumours and ultimately, failure of the implant. Primary edge-loading is where contact between the femoral and acetabular components occurs at the edge/rim of the acetabular component whereas impingement of the femoral neck on the acetabular component's edge causes secondary or contrecoup edge-loading. Although the relationship between the orientation of the acetabular component and primary edge-loading has been identified, the contribution of acetabular component orientation to impingement and secondary edge-loading is less clear. Our aim was to estimate the optimal acetabular component orientation for 16 metal-on-metal hip resurfacing arthroplasty (MoMHRA) subjects with known serum metal ion levels. Data from motion analysis, subject-specific musculoskeletal modelling and Computed Tomography (CT) measurements were used to calculate the dynamic contact patch to rim (CPR) distance and impingement risk for 3416 different acetabular component orientations during gait, sit-to-stand, stair descent and static standing. For each subject, safe zones free from impingement and edge-loading (CPR <10%) were defined and, consequently, an optimal acetabular component orientation was determined (mean inclination 39.7° (SD 6.6°) mean anteversion 14.9° (SD 9.0°)). The results of this study suggest that the optimal acetabular component orientation can be determined from a patient's motion and anatomy. However, 'safe' zones of acetabular component orientation associated with reduced risk of dislocation and pseudotumour are also associated with a reduced risk of edge-loading and impingement. Copyright © 2014 Elsevier Ltd. All rights reserved.

MO-DE-204-01: Radiation Doses in Over 50 Developing Countries of Asia, Africa, Eastern European and Latin America

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

Case Study: Ticagrelor in PLATO and Prasugrel in TRITON-TIMI 38 and TRILOGY-ACS Trials in Patients With Acute Coronary Syndromes

PubMed Central

Husted, Steen; Boersma, Eric

2016-01-01

Cross-trial comparisons are typically inappropriate as there are often numerous differences in study designs, populations, end points, and loading doses of the study drugs. These differences are clearly reflected in the most recent updates to the European Society of Cardiology (ESC) non-ST elevation acute coronary syndrome (NSTE-ACS) and ST elevation myocardial infarction (STEMI) guidelines, which include recommendations for the use of the antiplatelet agents ticagrelor, prasugrel, and clopidogrel, based in part on results from the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet inhibitioN with prasugrel–Thrombolysis In Myocardial Infarction (TRITON-TIMI) 38, TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medicallY manage Acute Coronary Syndromes (TRILOGY-ACS) and PLATelet inhibition and patient Outcomes (PLATO) trials. Here, we describe each of these trials in detail and explain the differences between them that make direct comparisons difficult. In conclusion, this information, along with the current guidelines and recommendations, will assist clinicians in deciding the most appropriate treatment pathway for their patients with NSTE-ACS and STEMI. PMID:25830867

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.

Study on loading coefficient in steam explosion process of corn stalk.

PubMed

Sui, Wenjie; Chen, Hongzhang

2015-03-01

The object of this work was to evaluate the effect of loading coefficient on steam explosion process and efficacy of corn stalk. Loading coefficient's relation with loading pattern and material property was first revealed, then its effect on transfer process and pretreatment efficacy of steam explosion was assessed by established models and enzymatic hydrolysis tests, respectively, in order to propose its optimization strategy for improving the process economy. Results showed that loading coefficient was mainly determined by loading pattern, moisture content and chip size. Both compact loading pattern and low moisture content improved the energy efficiency of steam explosion pretreatment and overall sugar yield of pretreated materials, indicating that they are desirable to improve the process economy. Pretreatment of small chip size showed opposite effects in pretreatment energy efficiency and enzymatic hydrolysis performance, thus its optimization should be balanced in investigated aspects according to further techno-economical evaluation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Contrast Dose and Radiation Dose Reduction in Abdominal Enhanced Computerized Tomography Scans with Single-phase Dual-energy Spectral Computerized Tomography Mode for Children with Solid Tumors

PubMed Central

Yu, Tong; Gao, Jun; Liu, Zhi-Min; Zhang, Qi-Feng; Liu, Yong; Jiang, Ling; Peng, Yun

2017-01-01

Background: Contrast dose and radiation dose reduction in computerized tomography (CT) scan for adult has been explored successfully, but there have been few studies on the application of low-concentration contrast in pediatric abdominal CT examinations. This was a feasibility study on the use of dual-energy spectral imaging and adaptive statistical iterative reconstruction (ASiR) for the reduction of radiation dose and iodine contrast dose in pediatric abdominal CT patients with solid tumors. Methods: Forty-five patients with solid tumors who had initial CT (Group B) and follow-up CT (Group A) after chemotherapy were enrolled. The initial diagnostic CT scan (Group B) was performed using the standard two-phase enhanced CT with 320 mgI/ml concentration contrast, and the follow-up scan (Group A) was performed using a single-phase enhanced CT at 45 s after the beginning of the 270 mgI/ml contrast injection using spectral mode. Forty percent ASiR was used for the images in Group B and monochromatic images with energy levels ≥60 keV in Group A. In addition, filtered back-projection (FBP) reconstruction was used for monochromatic images <60 keV in Group A. The total radiation dose, total iodine load, contrast injection speed, and maximum injection pressure were compared between the two groups. The 40 keV and 60 keV spectral CT images of Group A were compared with the images of Group B to evaluate overall image quality. Results: The total radiation dose, total iodine load, injection speed, and maximum injection pressure for Group A were decreased by 19%, 15%, 34.4%, and 18.3%, respectively. The optimal energy level in spectral CT for displaying the abdominal vessels was 40 keV. At this level, the CT values in the abdominal aorta and its three branches, the portal vein and its two branches, and the inferior vena cava were all greater than 340 hounsfield unit (HU). The abdominal organs of Groups A and B had similar degrees of absolute and relative enhancement (t = 0.36 and −1.716 for liver, −0.153 and −1.546 for pancreas, and 2.427 and 0.866 for renal cortex, all P > 0.05). Signal-to-noise ratio of the abdominal organs was significantly lower in Group A than in Group B (t = −8.11 for liver, −7.83 for pancreas, and −5.38 for renal cortex, all P < 0.05). However, the subjective scores for the 40 keV (FBP) and 60 keV (40% ASiR) spectral CT images determined by two radiologists were all >3, indicating clinically acceptable image quality. Conclusions: Single-phase, dual-energy spectral CT used for children with solid abdominal tumors can reduce contrast dose and radiation dose and can also maintain clinically acceptable image quality. PMID:28345547

Contrast Dose and Radiation Dose Reduction in Abdominal Enhanced Computerized Tomography Scans with Single-phase Dual-energy Spectral Computerized Tomography Mode for Children with Solid Tumors.

PubMed

Yu, Tong; Gao, Jun; Liu, Zhi-Min; Zhang, Qi-Feng; Liu, Yong; Jiang, Ling; Peng, Yun

2017-04-05

Contrast dose and radiation dose reduction in computerized tomography (CT) scan for adult has been explored successfully, but there have been few studies on the application of low-concentration contrast in pediatric abdominal CT examinations. This was a feasibility study on the use of dual-energy spectral imaging and adaptive statistical iterative reconstruction (ASiR) for the reduction of radiation dose and iodine contrast dose in pediatric abdominal CT patients with solid tumors. Forty-five patients with solid tumors who had initial CT (Group B) and follow-up CT (Group A) after chemotherapy were enrolled. The initial diagnostic CT scan (Group B) was performed using the standard two-phase enhanced CT with 320 mgI/ml concentration contrast, and the follow-up scan (Group A) was performed using a single-phase enhanced CT at 45 s after the beginning of the 270 mgI/ml contrast injection using spectral mode. Forty percent ASiR was used for the images in Group B and monochromatic images with energy levels ≥60 keV in Group A. In addition, filtered back-projection (FBP) reconstruction was used for monochromatic images <60 keV in Group A. The total radiation dose, total iodine load, contrast injection speed, and maximum injection pressure were compared between the two groups. The 40 keV and 60 keV spectral CT images of Group A were compared with the images of Group B to evaluate overall image quality. The total radiation dose, total iodine load, injection speed, and maximum injection pressure for Group A were decreased by 19%, 15%, 34.4%, and 18.3%, respectively. The optimal energy level in spectral CT for displaying the abdominal vessels was 40 keV. At this level, the CT values in the abdominal aorta and its three branches, the portal vein and its two branches, and the inferior vena cava were all greater than 340 hounsfield unit (HU). The abdominal organs of Groups A and B had similar degrees of absolute and relative enhancement (t = 0.36 and -1.716 for liver, -0.153 and -1.546 for pancreas, and 2.427 and 0.866 for renal cortex, all P> 0.05). Signal-to-noise ratio of the abdominal organs was significantly lower in Group A than in Group B (t = -8.11 for liver, -7.83 for pancreas, and -5.38 for renal cortex, all P< 0.05). However, the subjective scores for the 40 keV (FBP) and 60 keV (40% ASiR) spectral CT images determined by two radiologists were all> 3, indicating clinically acceptable image quality. Single-phase, dual-energy spectral CT used for children with solid abdominal tumors can reduce contrast dose and radiation dose and can also maintain clinically acceptable image quality.

Design and Synthesis of Self-Assembled Polymeric Nanoparticles for Cancer Drug Delivery

NASA Astrophysics Data System (ADS)

Logie, Jennifer

Current chemotherapeutics are plagued by poor solubility and selectivity, requiring toxic excipients in formulations and causing a number of dose limiting side effects. Nanoparticle delivery has emerged as a strategy to more effectively deliver chemotherapeutics to the tumour site. Specifically, polymeric micelles enable the solubilization of hydrophobic small molecule drugs within the core and mitigate the necessity of excipients. Notwithstanding the significant progress made in polymeric micelle delivery, translation is limited by poor stability and low drug loading. In this work, a rational design approach is used to chemically modify poly(D,L-lactide-co-2-methyl-2-carboxytrimethylene carbonate)-graft-poly(ethylene glycol) (P(LA-co-TMCC)-g-PEG) in order to overcome these limitations and effectively deliver drug to tumours. The PEG density of the polymer system was optimized to enhance the stability of our polymeric micelles. Higher PEG densities permitted the lyophilization of micelles and enhanced the serum stability of the system. To increase the drug loading of our system, we facilitated specific intermolecular interactions within the micelle core. For drugs that form colloidal aggregates, such as pentyl-PABC doxazolidine, polymers were used to stabilize the colloidal core against aggregation and protein adsorption. For more challenging molecules, where self-assembly cannot be controlled, such as docetaxel, we modified the polymeric backbone with a peptide from the binding site of the drug to achieve loadings five times higher than those achieved in conventional micelle systems. This novel docetaxel nanoparticle was assessed in vivo in an orthotopic mouse model of breast cancer, where it showed a wider therapeutic index than the conventional ethanolic polysorbate 80 formulation. The improved tolerability of this formulation enabled higher dosing regimens and led to heightened efficacy and survival in this mouse model. Combined, these studies validated P(LA-co-TMCC)-g-PEG nanoparticles as an effective delivery vehicle for two chemotherapeutics, and presents approaches amenable to the delivery of many other clinically relevant hydrophobic drugs or drug combinations.

SU-D-BRB-06: Treating Glioblastoma Multiforme (GBM) as a Chronic Disease: Implication of Temporal-Spatial Dose Fractionation Optimization Including Cancer Stem Cell Dynamics

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

Bayesian dose selection design for a binary outcome using restricted response adaptive randomization.

PubMed

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.

Inverse Planning Approach for 3-D MRI-Based Pulse-Dose Rate Intracavitary Brachytherapy in Cervix Cancer

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

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

A two‐point scheme for optimal breast IMRT treatment planning

PubMed Central

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.

Optimizing Cognitive Load for Learning from Computer-Based Science Simulations

ERIC Educational Resources Information Center

Lee, Hyunjeong; Plass, Jan L.; Homer, Bruce D.

2006-01-01

How can cognitive load in visual displays of computer simulations be optimized? Middle-school chemistry students (N = 257) learned with a simulation of the ideal gas law. Visual complexity was manipulated by separating the display of the simulations in two screens (low complexity) or presenting all information on one screen (high complexity). The…

Influence of the optimization methods on neural state estimation quality of the drive system with elasticity.

PubMed

Orlowska-Kowalska, Teresa; Kaminski, Marcin

2014-01-01

The paper deals with the implementation of optimized neural networks (NNs) for state variable estimation of the drive system with an elastic joint. The signals estimated by NNs are used in the control structure with a state-space controller and additional feedbacks from the shaft torque and the load speed. High estimation quality is very important for the correct operation of a closed-loop system. The precision of state variables estimation depends on the generalization properties of NNs. A short review of optimization methods of the NN is presented. Two techniques typical for regularization and pruning methods are described and tested in detail: the Bayesian regularization and the Optimal Brain Damage methods. Simulation results show good precision of both optimized neural estimators for a wide range of changes of the load speed and the load torque, not only for nominal but also changed parameters of the drive system. The simulation results are verified in a laboratory setup.

Beam-energy-spread minimization using cell-timing optimization

NASA Astrophysics Data System (ADS)

Rose, C. R.; Ekdahl, C.; Schulze, M.

2012-04-01

Beam energy spread, and related beam motion, increase the difficulty in tuning for multipulse radiographic experiments at the dual-axis radiographic hydrodynamic test facility’s axis-II linear induction accelerator (LIA). In this article, we describe an optimization method to reduce the energy spread by adjusting the timing of the cell voltages (both unloaded and loaded), either advancing or retarding, such that the injector voltage and summed cell voltages in the LIA result in a flatter energy profile. We developed a nonlinear optimization routine which accepts as inputs the 74 cell-voltage, injector voltage, and beam current waveforms. It optimizes cell timing per user-selected groups of cells and outputs timing adjustments, one for each of the selected groups. To verify the theory, we acquired and present data for both unloaded and loaded cell-timing optimizations. For the unloaded cells, the preoptimization baseline energy spread was reduced by 34% and 31% for two shots as compared to baseline. For the loaded-cell case, the measured energy spread was reduced by 49% compared to baseline.

Aerostructural Level Set Topology Optimization for a Common Research Model Wing

NASA Technical Reports Server (NTRS)

Dunning, Peter D.; Stanford, Bret K.; Kim, H. Alicia

2014-01-01

The purpose of this work is to use level set topology optimization to improve the design of a representative wing box structure for the NASA common research model. The objective is to minimize the total compliance of the structure under aerodynamic and body force loading, where the aerodynamic loading is coupled to the structural deformation. A taxi bump case was also considered, where only body force loads were applied. The trim condition that aerodynamic lift must balance the total weight of the aircraft is enforced by allowing the root angle of attack to change. The level set optimization method is implemented on an unstructured three-dimensional grid, so that the method can optimize a wing box with arbitrary geometry. Fast matching and upwind schemes are developed for an unstructured grid, which make the level set method robust and efficient. The adjoint method is used to obtain the coupled shape sensitivities required to perform aerostructural optimization of the wing box structure.

Plug-in hybrid electric vehicles in smart grid

NASA Astrophysics Data System (ADS)

Yao, Yin

In this thesis, in order to investigate the impact of charging load from plug-in hybrid electric vehicles (PHEVs), a stochastic model is developed in Matlab. In this model, two main types of PHEVs are defined: public transportation vehicles and private vehicles. Different charging time schedule, charging speed and battery capacity are considered for each type of vehicles. The simulation results reveal that there will be two load peaks (at noon and in evening) when the penetration level of PHEVs increases continuously to 30% in 2030. Therefore, optimization tool is utilized to shift load peaks. This optimization process is based on real time pricing and wind power output data. With the help of smart grid, power allocated to each vehicle could be controlled. As a result, this optimization could fulfill the goal of shifting load peaks to valley areas where real time price is low or wind output is high.

Determination of the wind power systems load to achieve operation in the maximum energy area

NASA Astrophysics Data System (ADS)

Chioncel, C. P.; Tirian, G. O.; Spunei, E.; Gillich, N.

2018-01-01

This paper analyses the operation of the wind turbine, WT, in the maximum power point, MPP, by linking the load of the Permanent Magnet Synchronous Generator, PMSG, with the wind speed value. The load control methods at wind power systems aiming an optimum performance in terms of energy are based on the fact that the energy captured by the wind turbine significantly depends on the mechanical angular speed of the wind turbine. The presented control method consists in determining the optimal mechanical angular speed, ωOPTIM, using an auxiliary low power wind turbine, WTAUX, operating without load, at maximum angular velocity, ωMAX. The method relies on the fact that the ratio ωOPTIM/ωMAX has a constant value for a given wind turbine and does not depend on the time variation of the wind speed values.

Optimum Parameters of a Tuned Liquid Column Damper in a Wind Turbine Subject to Stochastic Load

NASA Astrophysics Data System (ADS)

Alkmim, M. H.; de Morais, M. V. G.; Fabro, A. T.

2017-12-01

Parameter optimization for tuned liquid column dampers (TLCD), a class of passive structural control, have been previously proposed in the literature for reducing vibration in wind turbines, and several other applications. However, most of the available work consider the wind excitation as either a deterministic harmonic load or random load with white noise spectra. In this paper, a global direct search optimization algorithm to reduce vibration of a tuned liquid column damper (TLCD), a class of passive structural control device, is presented. The objective is to find optimized parameters for the TLCD under stochastic load from different wind power spectral density. A verification is made considering the analytical solution of undamped primary system under white noise excitation by comparing with result from the literature. Finally, it is shown that different wind profiles can significantly affect the optimum TLCD parameters.

Adaptive torque estimation of robot joint with harmonic drive transmission

NASA Astrophysics Data System (ADS)

Shi, Zhiguo; Li, Yuankai; Liu, Guangjun

2017-11-01

Robot joint torque estimation using input and output position measurements is a promising technique, but the result may be affected by the load variation of the joint. In this paper, a torque estimation method with adaptive robustness and optimality adjustment according to load variation is proposed for robot joint with harmonic drive transmission. Based on a harmonic drive model and a redundant adaptive robust Kalman filter (RARKF), the proposed approach can adapt torque estimation filtering optimality and robustness to the load variation by self-tuning the filtering gain and self-switching the filtering mode between optimal and robust. The redundant factor of RARKF is designed as a function of the motor current for tolerating the modeling error and load-dependent filtering mode switching. The proposed joint torque estimation method has been experimentally studied in comparison with a commercial torque sensor and two representative filtering methods. The results have demonstrated the effectiveness of the proposed torque estimation technique.

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

Optimizing dosing of oncology drugs.

PubMed

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.

LINKING DERMAL MODELING AND LOADING DATA TO PREDICT LONG-TERM DOSES FROM INTERMITTENT DERMAL CONTACT

EPA Science Inventory

In this paper we assess dermal exposure and dose resulting from intermittent contact with residue-contaminated surfaces. These estimates require an understanding of (1) the quantitative relationship between exposure and absorbed dose; (2) the impact of intermittent exposure on ...

Efficiency Enhancement for an Inductive Wireless Power Transfer System by Optimizing the Impedance Matching Networks.

PubMed

Miao, Zhidong; Liu, Dake; Gong, Chen

2017-10-01

Inductive wireless power transfer (IWPT) is a promising power technology for implantable biomedical devices, where the power consumption is low and the efficiency is the most important consideration. In this paper, we propose an optimization method of impedance matching networks (IMN) to maximize the IWPT efficiency. The IMN at the load side is designed to achieve the optimal load, and the IMN at the source side is designed to deliver the required amount of power (no-more-no-less) from the power source to the load. The theoretical analyses and design procedure are given. An IWPT system for an implantable glaucoma therapeutic prototype is designed as an example. Compared with the efficiency of the resonant IWPT system, the efficiency of our optimized system increases with a factor of 1.73. Besides, the efficiency of our optimized IWPT system is 1.97 times higher than that of the IWPT system optimized by the traditional maximum power transfer method. All the discussions indicate that the optimization method proposed in this paper could achieve a high efficiency and long working time when the system is powered by a battery.

Optimal shutdown management

NASA Astrophysics Data System (ADS)

Bottasso, C. L.; Croce, A.; Riboldi, C. E. D.

2014-06-01

The paper presents a novel approach for the synthesis of the open-loop pitch profile during emergency shutdowns. The problem is of interest in the design of wind turbines, as such maneuvers often generate design driving loads on some of the machine components. The pitch profile synthesis is formulated as a constrained optimal control problem, solved numerically using a direct single shooting approach. A cost function expressing a compromise between load reduction and rotor overspeed is minimized with respect to the unknown blade pitch profile. Constraints may include a load reduction not-to-exceed the next dominating loads, a not-to-be-exceeded maximum rotor speed, and a maximum achievable blade pitch rate. Cost function and constraints are computed over a possibly large number of operating conditions, defined so as to cover as well as possible the operating situations encountered in the lifetime of the machine. All such conditions are simulated by using a high-fidelity aeroservoelastic model of the wind turbine, ensuring the accuracy of the evaluation of all relevant parameters. The paper demonstrates the capabilities of the novel proposed formulation, by optimizing the pitch profile of a multi-MW wind turbine. Results show that the procedure can reliably identify optimal pitch profiles that reduce design-driving loads, in a fully automated way.

Optimal Coordination of Building Loads and Energy Storage for Power Grid and End User Services

DOE PAGES

Hao, He; Wu, Di; Lian, Jianming; ...

2017-01-18

Demand response and energy storage play a profound role in the smart grid. The focus of this study is to evaluate benefits of coordinating flexible loads and energy storage to provide power grid and end user services. We present a Generalized Battery Model (GBM) to describe the flexibility of building loads and energy storage. An optimization-based approach is proposed to characterize the parameters (power and energy limits) of the GBM for flexible building loads. We then develop optimal coordination algorithms to provide power grid and end user services such as energy arbitrage, frequency regulation, spinning reserve, as well as energymore » cost and demand charge reduction. Several case studies have been performed to demonstrate the efficacy of the GBM and coordination algorithms, and evaluate the benefits of using their flexibility for power grid and end user services. We show that optimal coordination yields significant cost savings and revenue. Moreover, the best option for power grid services is to provide energy arbitrage and frequency regulation. Finally and furthermore, when coordinating flexible loads with energy storage to provide end user services, it is recommended to consider demand charge in addition to time-of-use price in order to flatten the aggregate power profile.« less

The effect of code expanding optimizations on instruction cache design

NASA Technical Reports Server (NTRS)

Chen, William Y.; Chang, Pohua P.; Conte, Thomas M.; Hwu, Wen-Mei W.

1991-01-01

It is shown that code expanding optimizations have strong and non-intuitive implications on instruction cache design. Three types of code expanding optimizations are studied: instruction placement, function inline expansion, and superscalar optimizations. Overall, instruction placement reduces the miss ratio of small caches. Function inline expansion improves the performance for small cache sizes, but degrades the performance of medium caches. Superscalar optimizations increases the cache size required for a given miss ratio. On the other hand, they also increase the sequentiality of instruction access so that a simple load-forward scheme effectively cancels the negative effects. Overall, it is shown that with load forwarding, the three types of code expanding optimizations jointly improve the performance of small caches and have little effect on large caches.

Improving stability and strength characteristics of framed structures with nonlinear behavior

NASA Technical Reports Server (NTRS)

Pezeshk, Shahram

1990-01-01

In this paper an optimal design procedure is introduced to improve the overall performance of nonlinear framed structures. The design methodology presented here is a multiple-objective optimization procedure whose objective functions involve the buckling eigenvalues and eigenvectors of the structure. A constant volume with bounds on the design variables is used in conjunction with an optimality criterion approach. The method provides a general tool for solving complex design problems and generally leads to structures with better limit strength and stability. Many algorithms have been developed to improve the limit strength of structures. In most applications geometrically linear analysis is employed with the consequence that overall strength of the design is overestimated. Directly optimizing the limit load of the structure would require a full nonlinear analysis at each iteration which would be prohibitively expensive. The objective of this paper is to develop an algorithm that can improve the limit-load of geometrically nonlinear framed structures while avoiding the nonlinear analysis. One of the novelties of the new design methodology is its ability to efficiently model and design structures under multiple loading conditions. These loading conditions can be different factored loads or any kind of loads that can be applied to the structure simultaneously or independently. Attention is focused on optimal design of space framed structures. Three-dimensional design problems are more complicated to carry out, but they yield insight into real behavior of the structure and can help avoiding some of the problems that might appear in planar design procedure such as the need for out-of-plane buckling constraint. Although researchers in the field of structural engineering generally agree that optimum design of three-dimension building frames especially in the seismic regions would be beneficial, methods have been slow to emerge. Most of the research in this area has dealt with the optimization of truss and plane frame structures.

Research on power source structure optimization for East China Power Grid

NASA Astrophysics Data System (ADS)

Xu, Lingjun; Sang, Da; Zhang, Jianping; Tang, Chunyi; Xu, Da

2017-05-01

The structure of east china power grid is not reasonable for the coal power takes a much higher proportion than hydropower, at present the coal power takes charge of most peak load regulation, and the pressure of peak load regulation cannot be ignored. The nuclear power, wind power, photovoltaic, other clean energy and hydropower, coal power and wind power from outside will be actively developed in future, which increases the pressure of peak load regulation. According to development of economic and social, Load status and load prediction, status quo and planning of power source and the characteristics of power source, the peak load regulation balance is carried out and put forward a reasonable plan of power source allocation. The ultimate aim is to optimize the power source structure and to provide reference for power source allocation in east china.

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.

Speed and convergence properties of gradient algorithms for optimization of IMRT.

PubMed

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.

Treatment regimens of classical and newer taxanes.

PubMed

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.

Vaginal dose de-escalation in image guided adaptive brachytherapy for locally advanced cervical cancer.

PubMed

Mohamed, Sandy; Lindegaard, Jacob Christian; de Leeuw, Astrid A C; Jürgenliemk-Schulz, Ina; Kirchheiner, Kathrin; Kirisits, Christian; Pötter, Richard; Tanderup, Kari

2016-09-01

Vaginal stenosis is a major problem following radiotherapy in cervical cancer. We investigated a new dose planning strategy for vaginal dose de-escalation (VDD). Fifty consecutive locally advanced cervical cancer patients without lower or middle vaginal involvement at diagnosis from 3 institutions were analysed. External beam radiotherapy was combined with MRI-guided brachytherapy. VDD was obtained by decreasing dwell times in ovoid/ring and increasing dwell times in tandem/needles. The aim was to maintain the target dose (D90 of HR-CTV⩾85Gy EQD2) while reducing the dose to the surface of the vagina to <140% of the physical fractional brachytherapy dose corresponding to a total EQD2 of 85Gy. The mean vaginal loading (ovoid/ring) was reduced from 51% to 33% of the total loading with VDD, which significantly reduced the dose to the vaginal dose points (p<0.001) without compromising the target dose. The dose to the ICRU recto-vaginal point was reduced by a mean of 4±4Gy EQD2 (p<0.001), while doses to bladder and rectum (D 2cm 3 ) were reduced by 2±2Gy and 3±2Gy, respectively (p<0.001). VDD significantly reduces dose to the upper vagina which is expected to result in reduction of vaginal stenosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

Porous biodegradable lumbar interbody fusion cage design and fabrication using integrated global-local topology optimization with laser sintering.

PubMed

Kang, Heesuk; Hollister, Scott J; La Marca, Frank; Park, Paul; Lin, Chia-Ying

2013-10-01

Biodegradable cages have received increasing attention for their use in spinal procedures involving interbody fusion to resolve complications associated with the use of nondegradable cages, such as stress shielding and long-term foreign body reaction. However, the relatively weak initial material strength compared to permanent materials and subsequent reduction due to degradation may be problematic. To design a porous biodegradable interbody fusion cage for a preclinical large animal study that can withstand physiological loads while possessing sufficient interconnected porosity for bony bridging and fusion, we developed a multiscale topology optimization technique. Topology optimization at the macroscopic scale provides optimal structural layout that ensures mechanical strength, while optimally designed microstructures, which replace the macroscopic material layout, ensure maximum permeability. Optimally designed cages were fabricated using solid, freeform fabrication of poly(ε-caprolactone) mixed with hydroxyapatite. Compression tests revealed that the yield strength of optimized fusion cages was two times that of typical human lumbar spine loads. Computational analysis further confirmed the mechanical integrity within the human lumbar spine, although the pore structure locally underwent higher stress than yield stress. This optimization technique may be utilized to balance the complex requirements of load-bearing, stress shielding, and interconnected porosity when using biodegradable materials for fusion cages.

Optimization of Treatment Geometry to Reduce Normal Brain Dose in Radiosurgery of Multiple Brain Metastases with Single-Isocenter Volumetric Modulated Arc Therapy.

PubMed

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.

PubMed

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.

Optimal dose selection accounting for patient subpopulations in a randomized Phase II trial to maximize the success probability of a subsequent Phase III trial.

PubMed

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.

Conceptual optimization using genetic algorithms for tube in tube structures

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

Pârv, Bianca Roxana; Hulea, Radu; Mojolic, Cristian

2015-03-10

The purpose of this article is to optimize the tube in tube structural systems for tall buildings under the horizontal wind loads. It is well-known that the horizontal wind loads is the main criteria when choosing the structural system, the types and the dimensions of structural elements in the majority of tall buildings. Thus, the structural response of tall buildings under the horizontal wind loads will be analyzed for 40 story buildings and a total height of 120 meters; the horizontal dimensions will be 30m × 30m for the first two optimization problems and 15m × 15m for the third.more » The optimization problems will have the following as objective function the cross section area, as restrictions the displacement of the building< the admissible displacement (H/500), and as variables the cross section dimensions of the structural elements.« less

Optimization Research on Ampacity of Underground High Voltage Cable Based on Interior Point Method

NASA Astrophysics Data System (ADS)

Huang, Feng; Li, Jing

2017-12-01

The conservative operation method which takes unified current-carrying capacity as maximum load current can’t make full use of the overall power transmission capacity of the cable. It’s not the optimal operation state for the cable cluster. In order to improve the transmission capacity of underground cables in cluster, this paper regards the maximum overall load current as the objective function and the temperature of any cables lower than maximum permissible temperature as constraint condition. The interior point method which is very effective for nonlinear problem is put forward to solve the extreme value of the problem and determine the optimal operating current of each loop. The results show that the optimal solutions obtained with the purposed method is able to increase the total load current about 5%. It greatly improves the economic performance of the cable cluster.

Optimization of Stability Constrained Geometrically Nonlinear Shallow Trusses Using an Arc Length Sparse Method with a Strain Energy Density Approach

NASA Technical Reports Server (NTRS)

Hrinda, Glenn A.; Nguyen, Duc T.

2008-01-01

A technique for the optimization of stability constrained geometrically nonlinear shallow trusses with snap through behavior is demonstrated using the arc length method and a strain energy density approach within a discrete finite element formulation. The optimization method uses an iterative scheme that evaluates the design variables' performance and then updates them according to a recursive formula controlled by the arc length method. A minimum weight design is achieved when a uniform nonlinear strain energy density is found in all members. This minimal condition places the design load just below the critical limit load causing snap through of the structure. The optimization scheme is programmed into a nonlinear finite element algorithm to find the large strain energy at critical limit loads. Examples of highly nonlinear trusses found in literature are presented to verify the method.

Transdermal glimepiride delivery system based on optimized ethosomal nano-vesicles: Preparation, characterization, in vitro, ex vivo and clinical evaluation.

PubMed

Ahmed, Tarek A; El-Say, Khalid M; Aljaeid, Bader M; Fahmy, Usama A; Abd-Allah, Fathy I

2016-03-16

This work aimed to develop an optimized ethosomal formulation of glimepiride then loading into transdermal films to offer lower drug side effect, extended release behavior and avoid first pass effect. Four formulation factors were optimized for their effects on vesicle size (Y1), entrapment efficiency (Y2) and vesicle flexibility (Y3). Optimum desirability was identified and, an optimized formulation was prepared, characterized and loaded into transdermal films. Ex-vivo permeation study for the prepared films was conducted and, the permeation parameters and drug permeation mechanism were identified. Penetration through rat skin was studied using confocal laser microscope. In-vivo study was performed following transdermal application on human volunteers. The percent of alcohol was significantly affecting all the studied responses while the other factors and their interaction effects were varied on their effects on each response. The optimized ethosomal formulation showed observed values for Y1, Y2 and Y3 of 61 nm, 97.12% and 54.03, respectively. Ex-vivo permeation of films loaded with optimized ethosomal formulation was superior to that of the corresponding pure drug transdermal films and this finding was also confirmed after confocal laser microscope study. Permeation of glimepiride from the prepared films was in favor of Higushi-diffusion model and exhibited non-Fickian or anomalous release mechanism. In-vivo study revealed extended drug release behavior and lower maximum drug plasma level from transdermal films loaded with drug ethosomal formulation. So, the ethosomal formulation could be considered a suitable drug delivery system especially when loaded into transdermal vehicle with possible reduction in side effects and controlling the drug release. Copyright © 2016 Elsevier B.V. All rights reserved.

Geometry Design Optimization of Functionally Graded Scaffolds for Bone Tissue Engineering: A Mechanobiological Approach.

PubMed

Boccaccio, Antonio; Uva, Antonio Emmanuele; Fiorentino, Michele; Mori, Giorgio; Monno, Giuseppe

2016-01-01

Functionally Graded Scaffolds (FGSs) are porous biomaterials where porosity changes in space with a specific gradient. In spite of their wide use in bone tissue engineering, possible models that relate the scaffold gradient to the mechanical and biological requirements for the regeneration of the bony tissue are currently missing. In this study we attempt to bridge the gap by developing a mechanobiology-based optimization algorithm aimed to determine the optimal graded porosity distribution in FGSs. The algorithm combines the parametric finite element model of a FGS, a computational mechano-regulation model and a numerical optimization routine. For assigned boundary and loading conditions, the algorithm builds iteratively different scaffold geometry configurations with different porosity distributions until the best microstructure geometry is reached, i.e. the geometry that allows the amount of bone formation to be maximized. We tested different porosity distribution laws, loading conditions and scaffold Young's modulus values. For each combination of these variables, the explicit equation of the porosity distribution law-i.e the law that describes the pore dimensions in function of the spatial coordinates-was determined that allows the highest amounts of bone to be generated. The results show that the loading conditions affect significantly the optimal porosity distribution. For a pure compression loading, it was found that the pore dimensions are almost constant throughout the entire scaffold and using a FGS allows the formation of amounts of bone slightly larger than those obtainable with a homogeneous porosity scaffold. For a pure shear loading, instead, FGSs allow to significantly increase the bone formation compared to a homogeneous porosity scaffolds. Although experimental data is still necessary to properly relate the mechanical/biological environment to the scaffold microstructure, this model represents an important step towards optimizing geometry of functionally graded scaffolds based on mechanobiological criteria.

SU-F-T-193: Evaluation of a GPU-Based Fast Monte Carlo Code for Proton Therapy Biological Optimization

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

An optimization-based approach for facility energy management with uncertainties, and, Power portfolio optimization in deregulated electricity markets with risk management

NASA Astrophysics Data System (ADS)

Xu, Jun

Topic 1. An Optimization-Based Approach for Facility Energy Management with Uncertainties. Effective energy management for facilities is becoming increasingly important in view of the rising energy costs, the government mandate on the reduction of energy consumption, and the human comfort requirements. This part of dissertation presents a daily energy management formulation and the corresponding solution methodology for HVAC systems. The problem is to minimize the energy and demand costs through the control of HVAC units while satisfying human comfort, system dynamics, load limit constraints, and other requirements. The problem is difficult in view of the fact that the system is nonlinear, time-varying, building-dependent, and uncertain; and that the direct control of a large number of HVAC components is difficult. In this work, HVAC setpoints are the control variables developed on top of a Direct Digital Control (DDC) system. A method that combines Lagrangian relaxation, neural networks, stochastic dynamic programming, and heuristics is developed to predict the system dynamics and uncontrollable load, and to optimize the setpoints. Numerical testing and prototype implementation results show that our method can effectively reduce total costs, manage uncertainties, and shed the load, is computationally efficient. Furthermore, it is significantly better than existing methods. Topic 2. Power Portfolio Optimization in Deregulated Electricity Markets with Risk Management. In a deregulated electric power system, multiple markets of different time scales exist with various power supply instruments. A load serving entity (LSE) has multiple choices from these instruments to meet its load obligations. In view of the large amount of power involved, the complex market structure, risks in such volatile markets, stringent constraints to be satisfied, and the long time horizon, a power portfolio optimization problem is of critical importance but difficulty for an LSE to serve the load, maximize its profit, and manage risks. In this topic, a mid-term power portfolio optimization problem with risk management is presented. Key instruments are considered, risk terms based on semi-variances of spot market transactions are introduced, and penalties on load obligation violations are added to the objective function to improve algorithm convergence and constraint satisfaction. To overcome the inseparability of the resulting problem, a surrogate optimization framework is developed enabling a decomposition and coordination approach. Numerical testing results show that our method effectively provides decisions for various instruments to maximize profit, manage risks, and is computationally efficient.

Role of step size and max dwell time in anatomy based inverse optimization for prostate implants

PubMed Central

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

Aeroelastic Wingbox Stiffener Topology Optimization

NASA Technical Reports Server (NTRS)

Stanford, Bret K.

2017-01-01

This work considers an aeroelastic wingbox model seeded with run-out blade stiffeners along the skins. Topology optimization is conducted within the shell webs of the stiffeners, in order to add cutouts and holes for mass reduction. This optimization is done with a global-local approach in order to moderate the computational cost: aeroelastic loads are computed at the wing-level, but the topology and sizing optimization is conducted at the panel-level. Each panel is optimized separately under stress, buckling, and adjacency constraints, and periodically reassembled to update the trimmed aeroelastic loads. The resulting topology is baselined against a design with standard full-depth solid stiffener blades, and found to weigh 7.43% less.

Skeletal adaptation to external loads optimizes mechanical properties: fact or fiction

NASA Technical Reports Server (NTRS)

Turner, R. T.

2001-01-01

The skeleton adapts to a changing mechanical environment but the widely held concept that bone cells are programmed to respond to local mechanical loads to produce an optimal mechanical structure is not consistent with the high frequency of bone fractures. Instead, the author suggests that other important functions of bone compete with mechanical adaptation to determine structure. As a consequence of competing demands, bone architecture never achieves an optimal mechanical structure. c2001 Lippincott Williams & Wilkins, Inc.

Optimization of thermoelectric cooling regimes for heat-loaded elements taking into account the thermal resistance of the heat-spreading system

NASA Astrophysics Data System (ADS)

Vasil'ev, E. N.

2017-09-01

A mathematical model has been proposed for analyzing and optimizing thermoelectric cooling regimes for heat-loaded elements of engineering and electronic devices. The model based on analytic relations employs the working characteristics of thermoelectric modules as the initial data and makes it possible to determine the temperature regime and the optimal values of the feed current for the modules taking into account the thermal resistance of the heat-spreading system.

Design of a modulated orthovoltage stereotactic radiosurgery system.

PubMed

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.

An optimized network for phosphorus load monitoring for Lake Okeechobee, Florida

USGS Publications Warehouse

Gain, W.S.

1997-01-01

Phosphorus load data were evaluated for Lake Okeechobee, Florida, for water years 1982 through 1991. Standard errors for load estimates were computed from available phosphorus concentration and daily discharge data. Components of error were associated with uncertainty in concentration and discharge data and were calculated for existing conditions and for 6 alternative load-monitoring scenarios for each of 48 distinct inflows. Benefit-cost ratios were computed for each alternative monitoring scenario at each site by dividing estimated reductions in load uncertainty by the 5-year average costs of each scenario in 1992 dollars. Absolute and marginal benefit-cost ratios were compared in an iterative optimization scheme to determine the most cost-effective combination of discharge and concentration monitoring scenarios for the lake. If the current (1992) discharge-monitoring network around the lake is maintained, the water-quality sampling at each inflow site twice each year is continued, and the nature of loading remains the same, the standard error of computed mean-annual load is estimated at about 98 metric tons per year compared to an absolute loading rate (inflows and outflows) of 530 metric tons per year. This produces a relative uncertainty of nearly 20 percent. The standard error in load can be reduced to about 20 metric tons per year (4 percent) by adopting an optimized set of monitoring alternatives at a cost of an additional $200,000 per year. The final optimized network prescribes changes to improve both concentration and discharge monitoring. These changes include the addition of intensive sampling with automatic samplers at 11 sites, the initiation of event-based sampling by observers at another 5 sites, the continuation of periodic sampling 12 times per year at 1 site, the installation of acoustic velocity meters to improve discharge gaging at 9 sites, and the improvement of a discharge rating at 1 site.

Patient Dose Management: Focus on Practical Actions

PubMed Central

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

SU-F-19A-03: Dosimetric Advantages in Critical Structure Dose Sparing by Using a Multichannel Cylinder in High Dose Rate Brachytherapy to Treat Vaginal Cuff Cancer

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

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

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

Yarmand, H; Winey, B; Craft, D

2014-06-15

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

A novel adaptive needle insertion sequencing for robotic, single needle MR-guided high-dose-rate prostate brachytherapy

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

Thermal decomposition behavior of nano/micro bimodal feedstock with different solids loading

NASA Astrophysics Data System (ADS)

Oh, Joo Won; Lee, Won Sik; Park, Seong Jin

2018-01-01

Debinding is one of the most critical processes for powder injection molding. The parts in debinding process are vulnerable to defect formation, and long processing time of debinding decreases production rate of whole process. In order to determine the optimal condition for debinding process, decomposition behavior of feedstock should be understood. Since nano powder affects the decomposition behavior of feedstock, nano powder effect needs to be investigated for nano/micro bimodal feedstock. In this research, nano powder effect on decomposition behavior of nano/micro bimodal feedstock has been studied. Bimodal powders were fabricated with different ratios of nano powder, and the critical solids loading of each powder was measured by torque rheometer. Three different feedstocks were fabricated for each powder depending on solids loading condition. Thermogravimetric analysis (TGA) experiment was carried out to analyze the thermal decomposition behavior of the feedstocks, and decomposition activation energy was calculated. The result indicated nano powder showed limited effect on feedstocks in lower solids loading condition than optimal range. Whereas, it highly influenced the decomposition behavior in optimal solids loading condition by causing polymer chain scission with high viscosity.

Design, Optimization, and Evaluation of Integrally-Stiffened Al-2139 Panel with Curved Stiffeners

NASA Technical Reports Server (NTRS)

Havens, David; Shiyekar, Sandeep; Norris, Ashley; Bird, R. Keith; Kapania, Rakesh K.; Olliffe, Robert

2011-01-01

A curvilinear stiffened panel was designed, manufactured, and tested in the Combined Load Test Fixture at NASA Langley Research Center. The panel is representative of a large wing engine pylon rib and was optimized for minimum mass subjected to three combined load cases. The optimization included constraints on web buckling, material yielding, crippling or local stiffener failure, and damage tolerance using a new analysis tool named EBF3PanelOpt. Testing was performed for the critical combined compression-shear loading configuration. The panel was loaded beyond initial buckling, and strains and out-of-plane displacements were extracted from a total of 20 strain gages and 6 linear variable displacement transducers. The VIC-3D system was utilized to obtain full field displacements/strains in the stiffened side of the panel. The experimental data were compared with the strains and out-of-plane deflections from a high fidelity nonlinear finite element analysis. The experimental data were also compared with linear elastic finite element results of the panel/test-fixture assembly. Overall, the panel buckled very near to the predicted load in the web regions.

Finite element analysis of 6 large PMMA skull reconstructions: A multi-criteria evaluation approach

PubMed Central

Ridwan-Pramana, Angela; Marcián, Petr; Borák, Libor; Narra, Nathaniel; Forouzanfar, Tymour; Wolff, Jan

2017-01-01

In this study 6 pre-operative designs for PMMA based reconstructions of cranial defects were evaluated for their mechanical robustness using finite element modeling. Clinical experience and engineering principles were employed to create multiple plan options, which were subsequently computationally analyzed for mechanically relevant parameters under 50N loads: stress, strain and deformation in various components of the assembly. The factors assessed were: defect size, location and shape. The major variable in the cranioplasty assembly design was the arrangement of the fixation plates. An additional study variable introduced was the location of the 50N load within the implant area. It was found that in smaller defects, it was simpler to design a symmetric distribution of plates and under limited variability in load location it was possible to design an optimal for expected loads. However, for very large defects with complex shapes, the variability in the load locations introduces complications to the intuitive design of the optimal assembly. The study shows that it can be beneficial to incorporate multi design computational analyses to decide upon the most optimal plan for a clinical case. PMID:28609471

Finite element analysis of 6 large PMMA skull reconstructions: A multi-criteria evaluation approach.

PubMed

Ridwan-Pramana, Angela; Marcián, Petr; Borák, Libor; Narra, Nathaniel; Forouzanfar, Tymour; Wolff, Jan

2017-01-01

In this study 6 pre-operative designs for PMMA based reconstructions of cranial defects were evaluated for their mechanical robustness using finite element modeling. Clinical experience and engineering principles were employed to create multiple plan options, which were subsequently computationally analyzed for mechanically relevant parameters under 50N loads: stress, strain and deformation in various components of the assembly. The factors assessed were: defect size, location and shape. The major variable in the cranioplasty assembly design was the arrangement of the fixation plates. An additional study variable introduced was the location of the 50N load within the implant area. It was found that in smaller defects, it was simpler to design a symmetric distribution of plates and under limited variability in load location it was possible to design an optimal for expected loads. However, for very large defects with complex shapes, the variability in the load locations introduces complications to the intuitive design of the optimal assembly. The study shows that it can be beneficial to incorporate multi design computational analyses to decide upon the most optimal plan for a clinical case.

Novel Approaches for Visualizing and Analyzing Dose-Timing Data from Electronic Drug Monitors, or "How the 'Broken Window' Theory Pertains to ART Adherence".

PubMed

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.

Optimization of doxorubicin loading for superabsorbent polymer microspheres: in vitro analysis.

PubMed

Liu, David M; Kos, Sebastian; Buczkowski, Andrzej; Kee, Stephen; Munk, Peter L; Klass, Darren; Wasan, Ellen

2012-04-01

This study was designed to establish the ability of super-absorbent polymer microspheres (SAP) to actively uptake doxorubicin and to establish the proof of principle of SAP's ability to phase transfer doxorubicin onto the polymer matrix and to elute into buffer with a loading method that optimizes physical handling and elution characteristics. Phase I: 50-100 μm SAP subject to various prehydration methods (normal saline 10 cc, hypertonic saline 4 cc, iodinated contrast 10 cc) or left in their dry state, and combined with 50 mg of clinical grade lyophilized doxorubicin reconstituted with various methods (normal saline 10 cc and 25 cc, sterile water 4 cc, iodinated contrast 5 cc) were placed in buffer and assessed based on loading, handling, and elution utilizing high-performance liquid chromatography (HPLC). Phase II: top two performing methods were subject to loading of doxorubicin (50, 75, 100 mg) in a single bolus (group A) or as a serial loading method (group B) followed by measurement of loading vs. time and elution vs. time. Phase I revealed the most effective loading mechanisms and easiest handling to be dry (group A) vs. normal saline prehydrated (group B) SAP with normal saline reconstituted doxorubicin (10 mg/mL) with loading efficiencies of 83.1% and 88.4%. Phase II results revealed unstable behavior of SAP with 100 mg of doxorubicin and similar loading/elution profiles of dry and prehydrated SAP, with superior handling characteristics of group B SAP at 50 and 75 mg. SAP demonstrates the ability to load and bulk phase transfer doxorubicin at 50 and 75 mg with ease of handling and optimal efficiency through dry loading of SAP.

Optimization of Doxorubicin Loading for Superabsorbent Polymer Microspheres: in vitro Analysis

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

Liu, David M., E-mail: dave.liu@vch.ca; Kos, Sebastian; Buczkowski, Andrzej

2012-04-15

Purpose: This study was designed to establish the ability of super-absorbent polymer microspheres (SAP) to actively uptake doxorubicin and to establish the proof of principle of SAP's ability to phase transfer doxorubicin onto the polymer matrix and to elute into buffer with a loading method that optimizes physical handling and elution characteristics. Methods: Phase I: 50-100 {mu}m SAP subject to various prehydration methods (normal saline 10 cc, hypertonic saline 4 cc, iodinated contrast 10 cc) or left in their dry state, and combined with 50 mg of clinical grade lyophilized doxorubicin reconstituted with various methods (normal saline 10 cc andmore » 25 cc, sterile water 4 cc, iodinated contrast 5 cc) were placed in buffer and assessed based on loading, handling, and elution utilizing high-performance liquid chromatography (HPLC). Phase II: top two performing methods were subject to loading of doxorubicin (50, 75, 100 mg) in a single bolus (group A) or as a serial loading method (group B) followed by measurement of loading vs. time and elution vs. time. Results: Phase I revealed the most effective loading mechanisms and easiest handling to be dry (group A) vs. normal saline prehydrated (group B) SAP with normal saline reconstituted doxorubicin (10 mg/mL) with loading efficiencies of 83.1% and 88.4%. Phase II results revealed unstable behavior of SAP with 100 mg of doxorubicin and similar loading/elution profiles of dry and prehydrated SAP, with superior handling characteristics of group B SAP at 50 and 75 mg. Conclusions: SAP demonstrates the ability to load and bulk phase transfer doxorubicin at 50 and 75 mg with ease of handling and optimal efficiency through dry loading of SAP.« less

Gamma Radiation Aging Study of a Dow Corning SE 1700 Porous Structure Made by Direct Ink Writing

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

Small, Ward; Alviso, Cindy T.; Metz, Tom R.

Dow Corning SE 1700 (reinforced polydimethylsiloxane) porous structures were made by direct ink writing (DIW). The specimens (~50% porosity) were subjected to a compressive strain of ~25% while exposed to a gamma radiation dose of 1, 5, or 10 Mrad under vacuum. Compression set and load retention of the aged specimens were measured after a ~24 h relaxation period. Compression set (relative to deflection) increased with radiation dose: 11, 35, and 51% after 1, 5, and 10 Mrad, respectively. Load retention was 96-97% for the doses tested. The SE 1700 compared favorably to M9763 cellular silicone tested under the samemore » conditions.« less

"Curcumin-loaded Poly (d, l-lactide-co-glycolide) nanovesicles induce antinociceptive effects and reduce pronociceptive cytokine and BDNF release in spinal cord after acute administration in mice".

PubMed

Pieretti, Stefano; Ranjan, Amalendu P; Di Giannuario, Amalia; Mukerjee, Anindita; Marzoli, Francesca; Di Giovannandrea, Rita; Vishwanatha, Jamboor K

2017-10-01

Given the poor bioavailability of curcumin, its antinociceptive effects are produced after chronic intravenous administration of high doses, while poly (d,l-lactide-co-glycolide)-loaded vesicles (PLGA) can improve drug delivery. This paper investigates the antinociceptive effects of curcumin-loaded PLGA nanovesicles (PLGA-CUR) administered via intravenous (i.v.) or intrathecal (i.t.) routes at low and high doses. The following models of pain were used: formalin test, zymosan-induced hyperalgesia and sciatic nerve ligation inducing neuropathic allodynia and hyperalgesia. PLGA-CUR administered intravenously was able to reduce the response to nociceptive stimuli in the formalin test and hyperalgesia induced by zymosan. Curcumin, instead, was inactive. Low-dose i.t. administration of PLGA-CUR significantly reduced allodynia produced by sciatic nerve ligation, whereas low doses of curcumin did not change the response to nociceptive stimuli. Long-lasting antinociceptive effects were observed when high doses of PLGA-CUR were administered intrathecally. At high doses, i.t. administration of curcumin only exerted rapid and transient antinociceptive effects. Measurement of cytokine and BDNF in the spinal cord of neuropathic mice demonstrate that the antinociceptive effects of PLGA-CUR depend on the reduction in cytokine release and BDNF in the spinal cord. The results demonstrate the effectiveness of PLGA-CUR and suggest that PLGA-CUR nanoformulation might be a new potential drug in the treatment of pain. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of escalating doses of tirofiban on platelet aggregation and major receptor expression in diabetic patients: hitting the TARGET in the TENACITY trial?

PubMed

Serebruany, Victor; Malinin, Alex; Pokov, Alex; Arora, Umesh; Atar, Dan; Angiolillo, Dominick

2007-01-01

Ongoing search for the optimal dosing regimens, and valid concerns that some GPIIb/IIIa inhibitors may cause rebound platelet activation are limiting the use of these agents in patients with acute vascular events. We assessed the in vitro effects of preincubation with escalating (12.5-200 ng/mL) concentrations of tirofiban on platelet biomarkers in 20 diabetic patients. Platelet activity was assessed by ADP-, and collagen-induced conventional plasma aggregometry, and by whole blood flow cytometry measuring expression of PECAM-1, GPIb, GP IIb/IIIa antigen and activity, vitronectin, P-selectin, LAMP-1, GP 37, LAMP-3, activated and intact PAR-1 thrombin receptors, GPIV, and platelet-monocyte formation. All patients were treated with aspirin (at least 81 mg daily for 1 month); other antiplatelet agents were not allowed. Significant decrease of ADP-induced platelet aggregation was observed starting at the low 12.5 ng/mL concentration (p=0.0001), with total inhibition occurring at 50 ng/mL of tirofiban dose. Inhibition of collagen-induced platelet aggregability requires 25 ng/ml of tirofiban (p=0.002), and was complete at 100 ng/mL. Dose-dependent blockade of GP IIb/IIIa activity was observed with tirofiban concentrations over 50 ng/mL (p=0.003). Other receptors were unaffected even with the high doses of tirofiban (100-200 ng/mL). Tirofiban completely inhibits ADP- and, with the higher dose, collagen-induced platelet aggregation. Higher loading dose of tirofiban used in the ongoing TENACITY trial (100 ng/mL) may be superior with regard to clinical outcomes to the regimens used in PRISM-PLUS (25 ng/mL), or TARGET (50 ng/mL). Selective inhibition of GPIIb/IIIa activity, and lack of alternative platelet activation beyond the GP IIb/IIIa blockade may represent the therapeutic advantage of tirofiban over other agents.

TH-CD-202-08: Feasibility Study of Planning Phase Optimization Using Patient Geometry-Driven Information for Better Dose Sparing of Organ at Risks

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.

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.

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.

Impact of imaging approach on radiation dose and associated cancer risk in children undergoing cardiac catheterization

PubMed Central

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

Application of model predictive control for optimal operation of wind turbines

NASA Astrophysics Data System (ADS)

Yuan, Yuan; Cao, Pei; Tang, J.

2017-04-01

For large-scale wind turbines, reducing maintenance cost is a major challenge. Model predictive control (MPC) is a promising approach to deal with multiple conflicting objectives using the weighed sum approach. In this research, model predictive control method is applied to wind turbine to find an optimal balance between multiple objectives, such as the energy capture, loads on turbine components, and the pitch actuator usage. The actuator constraints are integrated into the objective function at the control design stage. The analysis is carried out in both the partial load region and full load region, and the performances are compared with those of a baseline gain scheduling PID controller. The application of this strategy achieves enhanced balance of component loads, the average power and actuator usages in partial load region.

Simplified Design Method for Tension Fasteners

NASA Astrophysics Data System (ADS)

Olmstead, Jim; Barker, Paul; Vandersluis, Jonathan

2012-07-01

Tension fastened joints design has traditionally been an iterative tradeoff between separation and strength requirements. This paper presents equations for the maximum external load that a fastened joint can support and the optimal preload to achieve this load. The equations, based on linear joint theory, account for separation and strength safety factors and variations in joint geometry, materials, preload, load-plane factor and thermal loading. The strength-normalized versions of the equations are applicable to any fastener and can be plotted to create a "Fastener Design Space", FDS. Any combination of preload and tension that falls within the FDS represents a safe joint design. The equation for the FDS apex represents the optimal preload and load capacity of a set of joints. The method can be used for preliminary design or to evaluate multiple pre-existing joints.

Swing-leg trajectory of running guinea fowl suggests task-level priority of force regulation rather than disturbance rejection.

PubMed

Blum, Yvonne; Vejdani, Hamid R; Birn-Jeffery, Aleksandra V; Hubicki, Christian M; Hurst, Jonathan W; Daley, Monica A

2014-01-01

To achieve robust and stable legged locomotion in uneven terrain, animals must effectively coordinate limb swing and stance phases, which involve distinct yet coupled dynamics. Recent theoretical studies have highlighted the critical influence of swing-leg trajectory on stability, disturbance rejection, leg loading and economy of walking and running. Yet, simulations suggest that not all these factors can be simultaneously optimized. A potential trade-off arises between the optimal swing-leg trajectory for disturbance rejection (to maintain steady gait) versus regulation of leg loading (for injury avoidance and economy). Here we investigate how running guinea fowl manage this potential trade-off by comparing experimental data to predictions of hypothesis-based simulations of running over a terrain drop perturbation. We use a simple model to predict swing-leg trajectory and running dynamics. In simulations, we generate optimized swing-leg trajectories based upon specific hypotheses for task-level control priorities. We optimized swing trajectories to achieve i) constant peak force, ii) constant axial impulse, or iii) perfect disturbance rejection (steady gait) in the stance following a terrain drop. We compare simulation predictions to experimental data on guinea fowl running over a visible step down. Swing and stance dynamics of running guinea fowl closely match simulations optimized to regulate leg loading (priorities i and ii), and do not match the simulations optimized for disturbance rejection (priority iii). The simulations reinforce previous findings that swing-leg trajectory targeting disturbance rejection demands large increases in stance leg force following a terrain drop. Guinea fowl negotiate a downward step using unsteady dynamics with forward acceleration, and recover to steady gait in subsequent steps. Our results suggest that guinea fowl use swing-leg trajectory consistent with priority for load regulation, and not for steadiness of gait. Swing-leg trajectory optimized for load regulation may facilitate economy and injury avoidance in uneven terrain.

Swing-Leg Trajectory of Running Guinea Fowl Suggests Task-Level Priority of Force Regulation Rather than Disturbance Rejection

PubMed Central

Blum, Yvonne; Vejdani, Hamid R.; Birn-Jeffery, Aleksandra V.; Hubicki, Christian M.; Hurst, Jonathan W.; Daley, Monica A.

2014-01-01

To achieve robust and stable legged locomotion in uneven terrain, animals must effectively coordinate limb swing and stance phases, which involve distinct yet coupled dynamics. Recent theoretical studies have highlighted the critical influence of swing-leg trajectory on stability, disturbance rejection, leg loading and economy of walking and running. Yet, simulations suggest that not all these factors can be simultaneously optimized. A potential trade-off arises between the optimal swing-leg trajectory for disturbance rejection (to maintain steady gait) versus regulation of leg loading (for injury avoidance and economy). Here we investigate how running guinea fowl manage this potential trade-off by comparing experimental data to predictions of hypothesis-based simulations of running over a terrain drop perturbation. We use a simple model to predict swing-leg trajectory and running dynamics. In simulations, we generate optimized swing-leg trajectories based upon specific hypotheses for task-level control priorities. We optimized swing trajectories to achieve i) constant peak force, ii) constant axial impulse, or iii) perfect disturbance rejection (steady gait) in the stance following a terrain drop. We compare simulation predictions to experimental data on guinea fowl running over a visible step down. Swing and stance dynamics of running guinea fowl closely match simulations optimized to regulate leg loading (priorities i and ii), and do not match the simulations optimized for disturbance rejection (priority iii). The simulations reinforce previous findings that swing-leg trajectory targeting disturbance rejection demands large increases in stance leg force following a terrain drop. Guinea fowl negotiate a downward step using unsteady dynamics with forward acceleration, and recover to steady gait in subsequent steps. Our results suggest that guinea fowl use swing-leg trajectory consistent with priority for load regulation, and not for steadiness of gait. Swing-leg trajectory optimized for load regulation may facilitate economy and injury avoidance in uneven terrain. PMID:24979750

Concurrent Monte Carlo transport and fluence optimization with fluence adjusting scalable transport Monte Carlo

PubMed Central

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

Digoxin: placental transfer, effects on the fetus, and therapeutic use in the newborn.

PubMed

Soyka, L F

1975-03-01

Digoxin rapidly crosses the placenta and reaches equilibrium, with maternal and fetal sera having equal concentrations. Virtually nothing is known about the effects of transplacentally administered digoxin on the fetus. Toxicity has been reported in the fetus of a woman ingesting a huge overdose of digitoxin; the same result would be anticipated with digoxin poisoning. Serum levels in pregnant women receiving the standard dose of 0.25 mg tend to be subnormal and certain patients may require a small increase in dose during the last trimester. While the full-term neonate appears to tolerate relatively high doses and the resultant high serum levels, there is no compelling evidence that such doses are necessary or even useful. Since toxicity can and does occur in neonates, especially during administration of loading (digitalizing) doses, it is recommended that maintenance doses of 0.01 mg per kg per day be used routinely. If the full inotropic effect is needed immediately, a loading dose of 0.03 mg per kg may be employed. Maintenance therapy is then begun on the following day. Without a loading dose cumulation occurs for about 3 days; after 5 or so days, serum levels will equal those found after use of a loading dose followed by maintenance therapy. Results of a single study suggest that the daily dose should be divided and given every 12 hours. After about 1 week of therapy, the serum level should be determined and the dose modified to maintain a serum level of 1 to 2 ng per ml. If the therapeutic effect is less than desired, a cautions increase in dose to as high as 0.02 mg per kg per day or to that dose which produces serum levels up to 3 ng per ml can be tried. Certain infants appear to tolerate serum levels of 3.5 to 4 ng per ml but such infants must be closely monitored. There are no data which indicate that a greater inotropic response will occur at these high serum levels, though this point has not been definitively investigated, and is the highest priority question for research. The intramuscular route should be researved for the unusual situation. Vomiting should be considered an early sign of toxicity and may act as a "safety valve." When adminstered in solution (as in the elixir or solution for intravenous use), oral digoxin is rapidly absorbed an an inotropic response is found within minutes, reaching a peak within hours, so that little is gained by parenteral administration. If an inotropic effect is urgently needed, intravenous administration of ouabain will give an immediate response.

Optimal Control Allocation with Load Sensor Feedback for Active Load Suppression

NASA Technical Reports Server (NTRS)

Miller, Christopher

2017-01-01

These slide sets describe the OCLA formulation and associated algorithms as a set of new technologies in the first practical application of load limiting flight control utilizing load feedback as a primary control measurement. Slide set one describes Experiment Development and slide set two describes Flight-Test Performance.

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

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

Laoui, S; Dietrich, S; Sehgal, V

2016-06-15

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

Enhanced Delivery and Effects of Acid Sphingomyelinase by ICAM-1-Targeted Nanocarriers in Type B Niemann-Pick Disease Mice.

PubMed

Garnacho, Carmen; Dhami, Rajwinder; Solomon, Melani; Schuchman, Edward H; Muro, Silvia

2017-07-05

Acid sphingomyelinase deficiency in type B Niemann-Pick disease leads to lysosomal sphingomyelin storage, principally affecting lungs, liver, and spleen. Infused recombinant enzyme is beneficial, yet its delivery to the lungs is limited and requires higher dosing than liver and spleen, leading to potentially adverse reactions. Previous studies showed increased enzyme pulmonary uptake by nanocarriers targeted to ICAM-1, a protein overexpressed during inflammation. Here, using polystyrene and poly(lactic-co-glycolic acid) nanocarriers, we optimized lung delivery by varying enzyme dose and nanocarrier concentration, verified endocytosis and lysosomal trafficking in vivo, and evaluated delivered activity and effects. Raising the enzyme load of nanocarriers progressively increased absolute enzyme delivery to all lung, liver, and spleen, over the naked enzyme. Varying nanocarrier concentration inversely impacted lung versus liver and spleen uptake. Mouse intravital and postmortem examination verified endocytosis, transcytosis, and lysosomal trafficking using nanocarriers. Compared to naked enzyme, nanocarriers increased enzyme activity in organs and reduced lung sphingomyelin storage and macrophage infiltration. Although old mice with advanced disease showed reactivity (pulmonary leukocyte infiltration) to injections, including buffer without carriers, antibody, or enzyme, younger mice with mild disease did not. We conclude that anti-ICAM nanocarriers may result in effective lung enzyme therapy using low enzyme doses. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Rational design and evaluation of HBsAg polymeric nanoparticles as antigen delivery carriers.

PubMed

Dewangan, Hitesh Kumar; Pandey, Tarun; Maurya, Lakshmi; Singh, Sanjay

2018-05-01

The present work is focused on the development and evaluation of single dose sustained-release Hepatitis B surface antigen (HBsAg) loaded nanovaccine for Hepatitis B. The conventional treatment suffers from repeated administration and hence requires a booster dose. Therefore, polymeric nanovaccine of HBsAg was developed by double emulsion solvent evaporation technique, utilizing central composite design for formulation optimization. The effects of independent variables (like polymer amount, stabilizer concentration, aqueous/organic phase ratio and homogenizer speed) were also studied on critical quality attributes like particle size and entrapment efficiency. Nanovaccine was characterized in terms of physicochemical parameters, release, internalization and in vivo immunological evaluation in BALB/c mice after administration by different routes such as oral, sub-cutaneous, nasal and intramuscular. The designed nanovaccine demonstrated nanometric size with smooth surface, negative zeta potential, maximum entrapment, sustained release and better internalization in macrophage and MRC-5 cell line. The immune-stimulating activity of nanovaccine administered by different routes was evaluated by measuring anti-HBsAg titre like specific immunoglobulin IgG and IgA response and cytokine level (interleukin-2, interferon-Y) measurement. The results indicated that the nanovaccine administered by intramuscular route produced better humoral as well as cellular responses and potential carriers for antigen delivery at single dose administration via intramuscular route. Copyright © 2018 Elsevier B.V. All rights reserved.

Preparation and nanoencapsulation of l-asparaginase II in chitosan-tripolyphosphate nanoparticles and in vitro release study

NASA Astrophysics Data System (ADS)

Bahreini, Elham; Aghaiypour, Khosrow; Abbasalipourkabir, Roghayeh; Mokarram, Ali Rezaei; Goodarzi, Mohammad Taghi; Saidijam, Massoud

2014-07-01

This paper describes the production, purification, and immobilization of l-asparaginase II (ASNase II) in chitosan nanoparticles (CSNPs). ASNase II is an effective antineoplastic agent, used in the acute lymphoblastic leukemia chemotherapy. Cloned ASNase II gene ( ansB) in pAED4 plasmid was transformed into Escherichia coli BL21pLysS (DE3) competent cells and expressed under optimal conditions. The lyophilized enzyme was loaded into CSNPs by ionotropic gelation method. In order to get optimal entrapment efficiency, CSNP preparation, chitosan/tripolyphosphate (CS/TPP) ratio, and protein loading were investigated. ASNase II loading into CSNPs was confirmed by Fourier transform infrared (FTIR) spectroscopy, and morphological observation was carried out by transmission electron microscopy. Three absolute CS/TPP ratios were studied. Entrapment efficiency and loading capacity increased with increasing CS and TPP concentration. The best ratio was applied for obtaining optimal ASNase II-loaded CSNPs with the highest entrapment efficiency. Size, zeta potential, entrapment efficiency, and loading capacity of the optimal ASNase II-CSNPs were 340 ± 12 nm, 21.2 ± 3 mV, 76.2% and 47.6%, respectively. The immobilized enzyme showed an increased in vitro half-life in comparison with the free enzyme. The pH and thermostability of the immobilized enzyme was comparable with the free enzyme. This study leads to a better understanding of how to prepare CSNPs, how to achieve high encapsulation efficiency for a high molecular weight protein, and how to prolong the release of protein from CSNPs. A conceptual understanding of biological responses to ASNase II-loaded CSNPs is needed for the development of novel methods of drug delivery.

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

PubMed

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

2017-06-01

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

Optimal design of structures for earthquake loads by a hybrid RBF-BPSO method

NASA Astrophysics Data System (ADS)

Salajegheh, Eysa; Gholizadeh, Saeed; Khatibinia, Mohsen

2008-03-01

The optimal seismic design of structures requires that time history analyses (THA) be carried out repeatedly. This makes the optimal design process inefficient, in particular, if an evolutionary algorithm is used. To reduce the overall time required for structural optimization, two artificial intelligence strategies are employed. In the first strategy, radial basis function (RBF) neural networks are used to predict the time history responses of structures in the optimization flow. In the second strategy, a binary particle swarm optimization (BPSO) is used to find the optimum design. Combining the RBF and BPSO, a hybrid RBF-BPSO optimization method is proposed in this paper, which achieves fast optimization with high computational performance. Two examples are presented and compared to determine the optimal weight of structures under earthquake loadings using both exact and approximate analyses. The numerical results demonstrate the computational advantages and effectiveness of the proposed hybrid RBF-BPSO optimization method for the seismic design of structures.

Evaluation of the antitumor effect of dexamethasone palmitate and doxorubicin co-loaded liposomes modified with a sialic acid-octadecylamine conjugate.

PubMed

Sun, Jing; Song, Yanzhi; Lu, Mei; Lin, Xiangyun; Liu, Yang; Zhou, Songlei; Su, Yuqing; Deng, Yihui

2016-10-10

Dexamethasone palmitate has the potential to inhibit the activity of tumor-associated macrophages, which promote cancer proliferation, invasion, and metastasis; however, only very high and frequent doses are capable of inducing antitumor effects. With the aim to reduce the anticancer dose and decrease the nonspecific toxicity, we designed a liposomal system to co-deliver dexamethasone palmitate and doxorubicin. Furthermore, a ligand conjugate sialic acid-octadecylamine, with enhanced affinity towards the membrane receptors over-expressed in tumors, was anchored on the surface of the liposomes to increase drug distribution to the tumor tissue. Co-loaded liposomes were developed using lipid film hydration method to load dexamethasone palmitate and remote loading technology to load doxorubicin. The co-loaded liposomes modified with sialic acid-octadecylamine represented comparable physicochemical properties and blood plasma profiles with conventional co-loaded liposomes, but the biodistribution proved that sialic acid-octadecylamine modified liposomes accumulated more in tumor. The co-loaded liposomes showed higher tumor growth suppression than the single-drug loaded liposomes, while showing no additional drug toxicity in S180-bearing Kunming mice. The co-loaded liposomes modified with sialic acid-octadecylamine achieved a significantly better antitumor effect, and induced "shedding" of cancerous tissue in the mice. These finding suggested that co-loaded liposomes modified with sialic acid-octadecylamine provided a safe therapeutic strategy with outstanding anticancer activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Safety and efficacy of dolutegravir in treatment-experienced subjects with raltegravir-resistant HIV type 1 infection: 24-week results of the VIKING Study.

PubMed

Eron, Joseph J; Clotet, Bonaventura; Durant, Jacques; Katlama, Christine; Kumar, Princy; Lazzarin, Adriano; Poizot-Martin, Isabelle; Richmond, Gary; Soriano, Vincent; Ait-Khaled, Mounir; Fujiwara, Tamio; Huang, Jenny; Min, Sherene; Vavro, Cindy; Yeo, Jane

2013-03-01

Dolutegravir (DTG; S/GSK1349572), a human immunodeficiency virus type 1 (HIV-1) integrase inhibitor, has limited cross-resistance to raltegravir (RAL) and elvitegravir in vitro. This phase IIb study assessed the activity of DTG in HIV-1-infected subjects with genotypic evidence of RAL resistance. Subjects received DTG 50 mg once daily (cohort I) or 50 mg twice daily (cohort II) while continuing a failing regimen (without RAL) through day 10, after which the background regimen was optimized, when feasible, for cohort I, and at least 1 fully active drug was mandated for cohort II. The primary efficacy end point was the proportion of subjects on day 11 in whom the plasma HIV-1 RNA load decreased by ≥0.7 log(10) copies/mL from baseline or was <400 copies/mL. A rapid antiviral response was observed. More subjects achieved the primary end point in cohort II (23 of 24 [96%]), compared with cohort I (21 of 27 [78%]) at day 11. At week 24, 41% and 75% of subjects had an HIV-1 RNA load of <50 copies/mL in cohorts I and II, respectively. Further integrase genotypic evolution was uncommon. Dolutegravir had a good, similar safety profile with each dosing regimen. Dolutegravir 50 mg twice daily with an optimized background provided greater and more durable benefit than the once-daily regimen. These data are the first clinical demonstration of the activity of any integrase inhibitor in subjects with HIV-1 resistant to RAL.

Injectable SN-38-loaded Polymeric Depots for Cancer Chemotherapy of Glioblastoma Multiforme.

PubMed

Manaspon, Chawan; Nasongkla, Norased; Chaimongkolnukul, Khuanjit; Nittayacharn, Pinunta; Vejjasilpa, Ketpat; Kengkoom, Kanchana; Boongird, Atthaporn; Hongeng, Suradej

2016-12-01

SN-38, a potent chemotherapeutic drug, has not been used clinically because of its severe side effects and poor solubility. In this work, we aimed to evaluate the effect of dose and multiple injections of SN-38-loaded polymeric depots on antitumor efficacy and toxicity in vivo. Preparation and characterization of SN-38-loaded depots were performed and evaluated in vitro using human glioblastoma cell line, U-87MG. Antitumor efficacy with different depot administrations including dose, position of depot injection and number of injections were evaluated in tumor model in nude mice. Depots encapsulated SN-38 with high encapsulation efficiency (~98.3%). High amount of SN-38 (3.0 ± 0.1 mg) was prolonged and controlled release over time and showed anticancer activity against U-87MG cell line in vitro. For one course administration, depots exhibited better antitumor efficacy and reduced toxicity compared to free SN-38. Elevated doses and multiple injections of SN-38-loaded depots and free SN-38 provided greater tumor growth inhibition and animal survival. All animals received SN-38-loaded depots were well tolerated and survived while most of those received free SN-38 died at day 30. Free SN-38 showed severe toxic effect compared to minimal toxicity from SN-38-loaded depots which was due to lower SN-38 level in systemic circulation. Fluorescence imaging and histopathology confirmed that SN-38 released from depots was detected throughout tumors 35 days post administration. SN-38-loaded depots were proved as a promising new treatment for highly invasive glioblastoma multiforme with low acute toxicity due to controlled release of SN-38.

Investigation of effective decision criteria for multiobjective optimization in IMRT.

PubMed

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.

Poster — Thur Eve — 35: The impact of intensity- and energy-modulated photon radiotherapy (XMRT) optimization on a variety of organ geometries

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

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.

Oil-Free Rotor Support Technologies for an Optimized Helicopter Propulsion System

NASA Technical Reports Server (NTRS)

DellaCorte, Christopher; Bruckner, Robert J.

2007-01-01

An optimized rotorcraft propulsion system incorporating a foil air bearing supported Oil-Free engine coupled to a high power density gearbox using high viscosity gear oil is explored. Foil air bearings have adequate load capacity and temperature capability for the highspeed gas generator shaft of a rotorcraft engine. Managing the axial loads of the power turbine shaft (low speed spool) will likely require thrust load support from the gearbox through a suitable coupling or other design. Employing specially formulated, high viscosity gear oil for the transmission can yield significant improvements (approx. 2X) in allowable gear loading. Though a completely new propulsion system design is needed to implement such a system, improved performance is possible.

Optimized undulator to generate low energy photons from medium to high energy accelerators

NASA Astrophysics Data System (ADS)

Chung, Ting-Yi; Chiu, Mau-Sen; Luo, Hao-Wen; Yang, Chin-Kang; Huang, Jui-Che; Jan, Jyh-Chyuan; Hwang, Ching-Shiang

2017-07-01

While emitting low energy photons from a medium or high energy storage ring, the on-axis heat load on the beam line optics can become a critical issue. In addition, the heat load in the bending magnet chamber, especially in the vertical and circular polarization mode of operation may cause some concern. In this work, we compare the heat loads for the APPLE-II and the Knot-APPLE, both optimized to emit 10 eV photons from the 3 GeV TPS. Under this constraint the heat load analysis, synchrotron radiation performance and features in various polarization modes are presented. Additional consideration is given to beam dynamics effect.

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.

PubMed

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.

Predictive Scheduling for Electric Vehicles Considering Uncertainty of Load and User Behaviors

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

Wang, Bin; Huang, Rui; Wang, Yubo

2016-05-02

Un-coordinated Electric Vehicle (EV) charging can create unexpected load in local distribution grid, which may degrade the power quality and system reliability. The uncertainty of EV load, user behaviors and other baseload in distribution grid, is one of challenges that impedes optimal control for EV charging problem. Previous researches did not fully solve this problem due to lack of real-world EV charging data and proper stochastic model to describe these behaviors. In this paper, we propose a new predictive EV scheduling algorithm (PESA) inspired by Model Predictive Control (MPC), which includes a dynamic load estimation module and a predictive optimizationmore » module. The user-related EV load and base load are dynamically estimated based on the historical data. At each time interval, the predictive optimization program will be computed for optimal schedules given the estimated parameters. Only the first element from the algorithm outputs will be implemented according to MPC paradigm. Current-multiplexing function in each Electric Vehicle Supply Equipment (EVSE) is considered and accordingly a virtual load is modeled to handle the uncertainties of future EV energy demands. This system is validated by the real-world EV charging data collected on UCLA campus and the experimental results indicate that our proposed model not only reduces load variation up to 40% but also maintains a high level of robustness. Finally, IEC 61850 standard is utilized to standardize the data models involved, which brings significance to more reliable and large-scale implementation.« less

A Paradigm for the Development and Evaluation of Novel Implant Topologies for Bone Fixation: In Vivo Evaluation

PubMed Central

Long, Jason P.; Hollister, Scott J.; Goldstein, Steven A.

2012-01-01

While contemporary prosthetic devices restore some function to individuals who have lost a limb, there are efforts to develop bio-integrated prostheses to improve functionality. A critical step in advancing this technology will be to securely attach the device to remnant bone. To investigate mechanisms for establishing robust implant fixation in bone while undergoing loading, we previously used a topology optimization scheme to develop optimized orthopaedic implants and then fabricated selected designs from titanium (Ti)-alloy with selective laser sintering (SLS) technology. In the present study, we examined how implant architecture and mechanical stimulation influence osseointegration within an in vivo environment. To do this, we evaluated three implant designs (two optimized and one non-optimized) using a unique in vivo model that applied cyclic, tension/ compression loads to the implants. Eighteen (six per implant design) adult male canines had implants surgically placed in their proximal, tibial metaphyses. Experimental duration was 12 weeks; daily loading (peak load of ±22N for 1000 cycles) was applied to one of each animal’s bilateral implants for the latter six weeks. Following harvest, osseointegration was assessed by non-destructive mechanical testing, micro-computed tomography (microCT) and back-scatter scanning electron microscopy (SEM). Data revealed that implant loading enhanced osseointegration by significantly increasing construct stiffness, peri-implant trabecular morphology, and percentages of interface connectivity and bone ingrowth. While this experiment did not demonstrate a clear advantage associated with the optimized implant designs, osseointegration was found to be significantly influenced by aspects of implant architecture. PMID:22951278

A paradigm for the development and evaluation of novel implant topologies for bone fixation: in vivo evaluation.

PubMed

Long, Jason P; Hollister, Scott J; Goldstein, Steven A

2012-10-11

While contemporary prosthetic devices restore some function to individuals who have lost a limb, there are efforts to develop bio-integrated prostheses to improve functionality. A critical step in advancing this technology will be to securely attach the device to remnant bone. To investigate mechanisms for establishing robust implant fixation in bone while undergoing loading, we previously used a topology optimization scheme to develop optimized orthopedic implants and then fabricated selected designs from titanium (Ti)-alloy with selective laser sintering (SLS) technology. In the present study, we examined how implant architecture and mechanical stimulation influence osseointegration within an in vivo environment. To do this, we evaluated three implant designs (two optimized and one non-optimized) using a unique in vivo model that applied cyclic, tension/compression loads to the implants. Eighteen (six per implant design) adult male canines had implants surgically placed in their proximal, tibial metaphyses. Experimental duration was 12 weeks; daily loading (peak load of ±22 N for 1000 cycles) was applied to one of each animal's bilateral implants for the latter six weeks. Following harvest, osseointegration was assessed by non-destructive mechanical testing, micro-computed tomography (microCT) and back-scatter scanning electron microscopy (SEM). Data revealed that implant loading enhanced osseointegration by significantly increasing construct stiffness, peri-implant trabecular morphology, and percentages of interface connectivity and bone ingrowth. While this experiment did not demonstrate a clear advantage associated with the optimized implant designs, osseointegration was found to be significantly influenced by aspects of implant architecture. Copyright © 2012 Elsevier Ltd. All rights reserved.

Analysis of gamma ray dose for dried up pond storing low enriched UO2 fuel

NASA Astrophysics Data System (ADS)

Nauchi, Yasushi; Suzuki, Motomu

2017-09-01

Gamma ray dose is calculated for loss of coolant accident in spent fuel pond (SFP) storing irradiated fuels used in light water reactors. Influence of modelling of fuel assemblies, source distributions, and loading fraction of fuel assemblies in the fuel rack on the dose are investigated.

[Is Herceptin(®) (trastuzumab) by subcutaneous a mini revolution? Pharmaco-economic study].

PubMed

Lieutenant, Vincent; Toulza, Émilie; Pommier, Martine; Lortal-Canguilhem, Barbara

2015-03-01

Herceptin(®) injected by intravenous (IV) is one of the key treatment of breast cancer HER2+. The improvement of galenic form allowed a new way of administration, the sub-cutaneous way (SC), authorized by EMEA in 2013. This new way enables a 5-minute infusion, a fixed dose and a fixed volume of preparation. On 2012, saving-time and financial impacts were calculated by extrapolation of the IV way in a cancer treatment center. The study showed a preparing time-saving of 7.5min/loading dose and of 6.5min/maintenance dose, and a nurse time-saving of 4.5min/loading dose and 4.25min/maintenance dose. Moreover, it can be added a saving of consumable of 13,31€ per injection in case of monotherapy. The SC leads to a new adaptation and reorganization in the preparation of monoclonal antibodies and day hospitals. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Optimization of cooling strategy and seeding by FBRM analysis of batch crystallization

NASA Astrophysics Data System (ADS)

Zhang, Dejiang; Liu, Lande; Xu, Shijie; Du, Shichao; Dong, Weibing; Gong, Junbo

2018-03-01

A method is presented for optimizing the cooling strategy and seed loading simultaneously. Focused beam reflectance measurement (FBRM) was used to determine the approximating optimal cooling profile. Using these results in conjunction with constant growth rate assumption, modified Mullin-Nyvlt trajectory could be calculated. This trajectory could suppress secondary nucleation and has the potential to control product's polymorph distribution. Comparing with linear and two step cooling, modified Mullin-Nyvlt trajectory have a larger size distribution and a better morphology. Based on the calculating results, the optimized seed loading policy was also developed. This policy could be useful for guiding the batch crystallization process.

Optimal Decentralized Protocol for Electric Vehicle Charging

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

Gan, LW; Topcu, U; Low, SH

We propose a decentralized algorithm to optimally schedule electric vehicle (EV) charging. The algorithm exploits the elasticity of electric vehicle loads to fill the valleys in electric load profiles. We first formulate the EV charging scheduling problem as an optimal control problem, whose objective is to impose a generalized notion of valley-filling, and study properties of optimal charging profiles. We then give a decentralized algorithm to iteratively solve the optimal control problem. In each iteration, EVs update their charging profiles according to the control signal broadcast by the utility company, and the utility company alters the control signal to guidemore » their updates. The algorithm converges to optimal charging profiles (that are as "flat" as they can possibly be) irrespective of the specifications (e.g., maximum charging rate and deadline) of EVs, even if EVs do not necessarily update their charging profiles in every iteration, and use potentially outdated control signal when they update. Moreover, the algorithm only requires each EV solving its local problem, hence its implementation requires low computation capability. We also extend the algorithm to track a given load profile and to real-time implementation.« less

Concurrent topology optimization for minimization of total mass considering load-carrying capabilities and thermal insulation simultaneously

NASA Astrophysics Data System (ADS)

Long, Kai; Wang, Xuan; Gu, Xianguang

2017-09-01

The present work introduces a novel concurrent optimization formulation to meet the requirements of lightweight design and various constraints simultaneously. Nodal displacement of macrostructure and effective thermal conductivity of microstructure are regarded as the constraint functions, which means taking into account both the load-carrying capabilities and the thermal insulation properties. The effective properties of porous material derived from numerical homogenization are used for macrostructural analysis. Meanwhile, displacement vectors of macrostructures from original and adjoint load cases are used for sensitivity analysis of the microstructure. Design variables in the form of reciprocal functions of relative densities are introduced and used for linearization of the constraint function. The objective function of total mass is approximately expressed by the second order Taylor series expansion. Then, the proposed concurrent optimization problem is solved using a sequential quadratic programming algorithm, by splitting into a series of sub-problems in the form of the quadratic program. Finally, several numerical examples are presented to validate the effectiveness of the proposed optimization method. The various effects including initial designs, prescribed limits of nodal displacement, and effective thermal conductivity on optimized designs are also investigated. An amount of optimized macrostructures and their corresponding microstructures are achieved.

Optimization and modeling of the remote loading of luciferin into liposomes.

PubMed

Hansen, Anders Højgaard; Lomholt, Michael A; Hansen, Per Lyngs; Mouritsen, Ole G; Arouri, Ahmad

2016-07-11

We carried out a mechanistic study to characterize and optimize the remote loading of luciferin into preformed liposomes of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPC/DPPG) 7:3 mixtures. The influence of the loading agent (acetate, propionate, butyrate), the metal counterion (Na(+), K(+), Ca(+2), Mg(+2)), and the initial extra-liposomal amount of luciferin (nL(add)) on the luciferin Loading Efficiency (LE%) and luciferin-to-lipid weight ratio, i.e., Loading Capacity (LC), in the final formulation was determined. In addition, the effect of the loading process on the colloidal stability and phase behavior of the liposomes was monitored. Based on our experimental results, a theoretical model was developed to describe the course of luciferin remote loading. It was found that the highest luciferin loading was obtained with magnesium acetate. The use of longer aliphatic carboxylates or inorganic proton donors pronouncedly reduced luciferin loading, whereas the effect of the counterion was modest. The remote-loading process barely affected the colloidal stability and drug retention of the liposomes, albeit with moderate luciferin-induced membrane perturbations. The correlation between luciferin loading, expressed as LE% and LC, and nL(add) was established, and under our conditions the maximum LC was attained using an nL(add) of around 2.6μmol. Higher amounts of luciferin tend to pronouncedly perturb the liposome stability and luciferin retention. Our theoretical model furnishes a fair quantitative description of the correlation between nL(add) and luciferin loading, and a membrane permeability coefficient for uncharged luciferin of 1×10(-8)cm/s could be determined. We believe that our study will prove very useful to optimize the remote-loading strategies of moderately polar carboxylic acid drugs in general. Copyright © 2016 Elsevier B.V. All rights reserved.

WE-EF-BRA-07: High Performance Preclinical Irradiation Through Optimized Dual Focal Spot Dose Painting and Online Virtual Isocenter Radiation Field Targeting

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

Deterministic methods for multi-control fuel loading optimization

NASA Astrophysics Data System (ADS)

Rahman, Fariz B. Abdul

We have developed a multi-control fuel loading optimization code for pressurized water reactors based on deterministic methods. The objective is to flatten the fuel burnup profile, which maximizes overall energy production. The optimal control problem is formulated using the method of Lagrange multipliers and the direct adjoining approach for treatment of the inequality power peaking constraint. The optimality conditions are derived for a multi-dimensional multi-group optimal control problem via calculus of variations. Due to the Hamiltonian having a linear control, our optimal control problem is solved using the gradient method to minimize the Hamiltonian and a Newton step formulation to obtain the optimal control. We are able to satisfy the power peaking constraint during depletion with the control at beginning of cycle (BOC) by building the proper burnup path forward in time and utilizing the adjoint burnup to propagate the information back to the BOC. Our test results show that we are able to achieve our objective and satisfy the power peaking constraint during depletion using either the fissile enrichment or burnable poison as the control. Our fuel loading designs show an increase of 7.8 equivalent full power days (EFPDs) in cycle length compared with 517.4 EFPDs for the AP600 first cycle.

Renal Response to Acid Load after Phenformin

PubMed Central

Rooth, Gösta; Bandman, Ulf

1973-01-01

Normally the kidneys respond to an acid load by increased ammonia production. In six patients with adult-type diabetes this response was reduced by a mean 50% after a therapeutic dose of phenformin. The reduced ability to compensate for acid loads may be one factor leading to metabolic acidosis and lactoacidosis sometimes associated with phenformin therapy. PMID:4753235

Optimizing Industrial Consumer Demand Response Through Disaggregation, Hour-Ahead Pricing, and Momentary Autonomous Control

NASA Astrophysics Data System (ADS)

Abdulaal, Ahmed

The work in this study addresses the current limitations of the price-driven demand response (DR) approach. Mainly, the dependability on consumers to respond in an energy aware conduct, the response timeliness, the difficulty of applying DR in a busy industrial environment, and the problem of load synchronization are of utmost concern. In order to conduct a simulation study, realistic price simulation model and consumers' building load models are created using real data. DR action is optimized using an autonomous control method, which eliminates the dependency on frequent consumer engagement. Since load scheduling and long-term planning approaches are infeasible in the industrial environment, the proposed method utilizes instantaneous DR in response to hour-ahead price signals (RTP-HA). Preliminary simulation results concluded savings at the consumer-side at the cost of increased supplier-side burden due to the aggregate effect of the universal DR policies. Therefore, a consumer disaggregation strategy is briefly discussed. Finally, a refined discrete-continuous control system is presented, which utilizes multi-objective Pareto optimization, evolutionary programming, utility functions, and bidirectional loads. Demonstrated through a virtual testbed fit with real data, the new system achieves momentary optimized DR in real-time while maximizing the consumer's wellbeing.

SU-E-T-562: Motion Tracking Optimization for Conformal Arc Radiotherapy Plans: A QUASAR Phantom Based Study

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

SU-F-J-105: Towards a Novel Treatment Planning Pipeline Delivering Pareto- Optimal Plans While Enabling Inter- and Intrafraction Plan Adaptation

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.

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

Optimality study of a gust alleviation system for light wing-loading STOL aircraft

NASA Technical Reports Server (NTRS)

Komoda, M.

1976-01-01

An analytical study was made of an optimal gust alleviation system that employs a vertical gust sensor mounted forward of an aircraft's center of gravity. Frequency domain optimization techniques were employed to synthesize the optimal filters that process the corrective signals to the flaps and elevator actuators. Special attention was given to evaluating the effectiveness of lead time, that is, the time by which relative wind sensor information should lead the actual encounter of the gust. The resulting filter is expressed as an implicit function of the prescribed control cost. A numerical example for a light wing loading STOL aircraft is included in which the optimal trade-off between performance and control cost is systematically studied.

Limiting the risk of cardiac toxicity with esophageal-sparing intensity modulated radiotherapy for locally advanced lung cancers.

PubMed

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.

PubMed

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.

A quantitative study of IMRT delivery effects in commercial planning systems for the case of oesophagus and prostate tumours.

PubMed

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.

Gear optimization

NASA Technical Reports Server (NTRS)

Vanderplaats, G. N.; Chen, Xiang; Zhang, Ning-Tian

1988-01-01

The use of formal numerical optimization methods for the design of gears is investigated. To achieve this, computer codes were developed for the analysis of spur gears and spiral bevel gears. These codes calculate the life, dynamic load, bending strength, surface durability, gear weight and size, and various geometric parameters. It is necessary to calculate all such important responses because they all represent competing requirements in the design process. The codes developed here were written in subroutine form and coupled to the COPES/ADS general purpose optimization program. This code allows the user to define the optimization problem at the time of program execution. Typical design variables include face width, number of teeth and diametral pitch. The user is free to choose any calculated response as the design objective to minimize or maximize and may impose lower and upper bounds on any calculated responses. Typical examples include life maximization with limits on dynamic load, stress, weight, etc. or minimization of weight subject to limits on life, dynamic load, etc. The research codes were written in modular form for easy expansion and so that they could be combined to create a multiple reduction optimization capability in future.

A robust two-stage design identifying the optimal biological dose for phase I/II clinical trials.

PubMed

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.

Optimizing Prednisolone Loading into Distiller's Dried Grain Kafirin Microparticles, and In vitro Release for Oral Delivery.

PubMed

Lau, Esther T L; Johnson, Stuart K; Williams, Barbara A; Mikkelsen, Deirdre; McCourt, Elizabeth; Stanley, Roger A; Mereddy, Ram; Halley, Peter J; Steadman, Kathryn J

2017-05-19

Kafirin microparticles have potential as colon-targeted delivery systems because of their ability to protect encapsulated material from digestive processes of the upper gastrointestinal tract (GIT). The aim was to optimize prednisolone loading into kafirin microparticles, and investigate their potential as an oral delivery system. Response surface methodology (RSM) was used to predict the optimal formulation of prednisolone loaded microparticles. Prednisolone release from the microparticles was measured in simulated conditions of the GIT. The RSM models were inadequate for predicting the relationship between starting quantities of kafirin and prednisolone, and prednisolone loading into microparticles. Compared to prednisolone released in the simulated gastric and small intestinal conditions, no additional drug release was observed in simulated colonic conditions. Hence, more insight into factors affecting drug loading into kafirin microparticles is required to improve the robustness of the RSM model. This present method of formulating prednisolone-loaded kafirin microparticles is unlikely to offer clinical benefits over commercially available dosage forms. Nevertheless, the overall amount of prednisolone released from the kafirin microparticles in conditions simulating the human GIT demonstrates their ability to prevent the release of entrapped core material. Further work developing the formulation methods may result in a delivery system that targets the lower GIT.

Predicting the Effects of Powder Feeding Rates on Particle Impact Conditions and Cold Spray Deposited Coatings

NASA Astrophysics Data System (ADS)

Ozdemir, Ozan C.; Widener, Christian A.; Carter, Michael J.; Johnson, Kyle W.

2017-10-01

As the industrial application of the cold spray technology grows, the need to optimize both the cost and the quality of the process grows with it. Parameter selection techniques available today require the use of a coupled system of equations to be solved to involve the losses due to particle loading in the gas stream. Such analyses cause a significant increase in the computational time in comparison with calculations with isentropic flow assumptions. In cold spray operations, engineers and operators may, therefore, neglect the effects of particle loading to simplify the multiparameter optimization process. In this study, two-way coupled (particle-fluid) quasi-one-dimensional fluid dynamics simulations are used to test the particle loading effects under many potential cold spray scenarios. Output of the simulations is statistically analyzed to build regression models that estimate the changes in particle impact velocity and temperature due to particle loading. This approach eases particle loading optimization for more complete analysis on deposition cost and time. The model was validated both numerically and experimentally. Further numerical analyses were completed to test the particle loading capacity and limitations of a nozzle with a commonly used throat size. Additional experimentation helped document the physical limitations to high-rate deposition.

Continuum topology optimization considering uncertainties in load locations based on the cloud model

NASA Astrophysics Data System (ADS)

Liu, Jie; Wen, Guilin

2018-06-01

Few researchers have paid attention to designing structures in consideration of uncertainties in the loading locations, which may significantly influence the structural performance. In this work, cloud models are employed to depict the uncertainties in the loading locations. A robust algorithm is developed in the context of minimizing the expectation of the structural compliance, while conforming to a material volume constraint. To guarantee optimal solutions, sufficient cloud drops are used, which in turn leads to low efficiency. An innovative strategy is then implemented to enormously improve the computational efficiency. A modified soft-kill bi-directional evolutionary structural optimization method using derived sensitivity numbers is used to output the robust novel configurations. Several numerical examples are presented to demonstrate the effectiveness and efficiency of the proposed algorithm.

Mechanical and hydraulic properties of sludge deposit on sludge drying reed beds (SDRBs): influence of sludge characteristics and loading rates.

PubMed

Vincent, Julie; Forquet, Nicolas; Molle, Pascal; Wisniewski, Christelle

2012-07-01

This work was designed to study the hydraulic properties of sludge deposit, focusing on the impact of operating conditions (i.e. loads and feeding frequencies) on air entrance (aerobic mineralization optimization) into the sludge deposit. The studied sludge deposits came from six 2m(2) pilot-scale SDRBs that had been in operation for 50 months with three different loads of 30, 50, and 70 kg of SSm(-2) y(-1). Two influents were assessed (i.e. activated sludge and septage) presenting different characteristics (i.e. pollutant contents, physical properties...). Two experimental approaches were employed based on establishing the water retention curve (capillary pressure versus volumetric water content) and the hydrotextural diagram to determine the hydraulic properties of sludge deposit. The study obtained valuable information for optimizing operating conditions, specifically for efficient management of loading frequency to optimize aerobic conditions within the sludge deposit. Copyright © 2012 Elsevier Ltd. All rights reserved.

Optimal Operation Method of Smart House by Controllable Loads based on Smart Grid Topology

NASA Astrophysics Data System (ADS)

Yoza, Akihiro; Uchida, Kosuke; Yona, Atsushi; Senju, Tomonobu

2013-08-01

From the perspective of global warming suppression and depletion of energy resources, renewable energy such as wind generation (WG) and photovoltaic generation (PV) are getting attention in distribution systems. Additionally, all electrification apartment house or residence such as DC smart house have increased in recent years. However, due to fluctuating power from renewable energy sources and loads, supply-demand balancing fluctuations of power system become problematic. Therefore, "smart grid" has become very popular in the worldwide. This article presents a methodology for optimal operation of a smart grid to minimize the interconnection point power flow fluctuations. To achieve the proposed optimal operation, we use distributed controllable loads such as battery and heat pump. By minimizing the interconnection point power flow fluctuations, it is possible to reduce the maximum electric power consumption and the electric cost. This system consists of photovoltaics generator, heat pump, battery, solar collector, and load. In order to verify the effectiveness of the proposed system, MATLAB is used in simulations.

Optimizing treatment of hypothyroidism.

PubMed

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.

A pragmatic approach to determine the optimal kVp in cone beam CT: balancing contrast-to-noise ratio and radiation dose

PubMed Central

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

SU-E-I-57: Evaluation and Optimization of Effective-Dose Using Different Beam-Hardening Filters in Clinical Pediatric Shunt CT Protocol

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

Coupled Multi-Disciplinary Optimization for Structural Reliability and Affordability

NASA Technical Reports Server (NTRS)

Abumeri, Galib H.; Chamis, Christos C.

2003-01-01

A computational simulation method is presented for Non-Deterministic Multidisciplinary Optimization of engine composite materials and structures. A hypothetical engine duct made with ceramic matrix composites (CMC) is evaluated probabilistically in the presence of combined thermo-mechanical loading. The structure is tailored by quantifying the uncertainties in all relevant design variables such as fabrication, material, and loading parameters. The probabilistic sensitivities are used to select critical design variables for optimization. In this paper, two approaches for non-deterministic optimization are presented. The non-deterministic minimization of combined failure stress criterion is carried out by: (1) performing probabilistic evaluation first and then optimization and (2) performing optimization first and then probabilistic evaluation. The first approach shows that the optimization feasible region can be bounded by a set of prescribed probability limits and that the optimization follows the cumulative distribution function between those limits. The second approach shows that the optimization feasible region is bounded by 0.50 and 0.999 probabilities.

Algorithm and Software for Calculating Optimal Regimes of the Process Water Supply System at the Kalininskaya NPP{sup 1}

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

Murav’ev, V. P., E-mail: murval@mail.ru; Kochetkov, A. V.; Glazova, E. G.

An algorithm and software for calculating the optimal operating regimes of the process water supply system at the Kalininskaya NPP are described. The parameters of the optimal regimes are determined for time varying meteorological conditions and condensation loads of the NPP. The optimal flow of the cooling water in the turbines is determined computationally; a regime map with the data on the optimal water consumption distribution between the coolers and displaying the regimes with an admissible heat load on the natural cooling lakes is composed. Optimizing the cooling system for a 4000-MW NPP will make it possible to conserve atmore » least 155,000 MW · h of electricity per year. The procedure developed can be used to optimize the process water supply systems of nuclear and thermal power plants.« less

Evaluation of load flow and grid expansion in a unit-commitment and expansion optimization model SciGRID International Conference on Power Grid Modelling

NASA Astrophysics Data System (ADS)

Senkpiel, Charlotte; Biener, Wolfgang; Shammugam, Shivenes; Längle, Sven

2018-02-01

Energy system models serve as a basis for long term system planning. Joint optimization of electricity generating technologies, storage systems and the electricity grid leads to lower total system cost compared to an approach in which the grid expansion follows a given technology portfolio and their distribution. Modelers often face the problem of finding a good tradeoff between computational time and the level of detail that can be modeled. This paper analyses the differences between a transport model and a DC load flow model to evaluate the validity of using a simple but faster transport model within the system optimization model in terms of system reliability. The main findings in this paper are that a higher regional resolution of a system leads to better results compared to an approach in which regions are clustered as more overloads can be detected. An aggregation of lines between two model regions compared to a line sharp representation has little influence on grid expansion within a system optimizer. In a DC load flow model overloads can be detected in a line sharp case, which is therefore preferred. Overall the regions that need to reinforce the grid are identified within the system optimizer. Finally the paper recommends the usage of a load-flow model to test the validity of the model results.

Design of piezoelectric transformer for DC/DC converter with stochastic optimization method

NASA Astrophysics Data System (ADS)

Vasic, Dejan; Vido, Lionel

2016-04-01

Piezoelectric transformers were adopted in recent year due to their many inherent advantages such as safety, no EMI problem, low housing profile, and high power density, etc. The characteristics of the piezoelectric transformers are well known when the load impedance is a pure resistor. However, when piezoelectric transformers are used in AC/DC or DC/DC converters, there are non-linear electronic circuits connected before and after the transformer. Consequently, the output load is variable and due to the output capacitance of the transformer the optimal working point change. This paper starts from modeling a piezoelectric transformer connected to a full wave rectifier in order to discuss the design constraints and configuration of the transformer. The optimization method adopted here use the MOPSO algorithm (Multiple Objective Particle Swarm Optimization). We start with the formulation of the objective function and constraints; then the results give different sizes of the transformer and the characteristics. In other word, this method is looking for a best size of the transformer for optimal efficiency condition that is suitable for variable load. Furthermore, the size and the efficiency are found to be a trade-off. This paper proposes the completed design procedure to find the minimum size of PT in need. The completed design procedure is discussed by a given specification. The PT derived from the proposed design procedure can guarantee both good efficiency and enough range for load variation.

Using an artificial neural network to predict the optimal conditions for enzymatic hydrolysis of apple pomace.

PubMed

Gama, Repson; Van Dyk, J Susan; Burton, Mike H; Pletschke, Brett I

2017-06-01

The enzymatic degradation of lignocellulosic biomass such as apple pomace is a complex process influenced by a number of hydrolysis conditions. Predicting optimal conditions, including enzyme and substrate concentration, temperature and pH can improve conversion efficiency. In this study, the production of sugar monomers from apple pomace using commercial enzyme preparations, Celluclast 1.5L, Viscozyme L and Novozyme 188 was investigated. A limited number of experiments were carried out and then analysed using an artificial neural network (ANN) to model the enzymatic hydrolysis process. The ANN was used to simulate the enzymatic hydrolysis process for a range of input variables and the optimal conditions were successfully selected as was indicated by the R 2 value of 0.99 and a small MSE value. The inputs for the ANN were substrate loading, enzyme loading, temperature, initial pH and a combination of these parameters, while release profiles of glucose and reducing sugars were the outputs. Enzyme loadings of 0.5 and 0.2 mg/g substrate and a substrate loading of 30% were optimal for glucose and reducing sugar release from apple pomace, respectively, resulting in concentrations of 6.5 g/L glucose and 28.9 g/L reducing sugars. Apple pomace hydrolysis can be successfully carried out based on the predicted optimal conditions from the ANN.