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

Direct aperture optimization using an inverse form of back-projection.

PubMed

Zhu, Xiaofeng; Cullip, Timothy; Tracton, Gregg; Tang, Xiaoli; Lian, Jun; Dooley, John; Chang, Sha X

2014-03-06

Direct aperture optimization (DAO) has been used to produce high dosimetric quality intensity-modulated radiotherapy (IMRT) treatment plans with fast treatment delivery by directly modeling the multileaf collimator segment shapes and weights. To improve plan quality and reduce treatment time for our in-house treatment planning system, we implemented a new DAO approach without using a global objective function (GFO). An index concept is introduced as an inverse form of back-projection used in the CT multiplicative algebraic reconstruction technique (MART). The index, introduced for IMRT optimization in this work, is analogous to the multiplicand in MART. The index is defined as the ratio of the optima over the current. It is assigned to each voxel and beamlet to optimize the fluence map. The indices for beamlets and segments are used to optimize multileaf collimator (MLC) segment shapes and segment weights, respectively. Preliminary data show that without sacrificing dosimetric quality, the implementation of the DAO reduced average IMRT treatment time from 13 min to 8 min for the prostate, and from 15 min to 9 min for the head and neck using our in-house treatment planning system PlanUNC. The DAO approach has also shown promise in optimizing rotational IMRT with burst mode in a head and neck test case.

Eliciting interval beliefs: An experimental study

PubMed Central

Peeters, Ronald; Wolk, Leonard

2017-01-01

In this paper we study the interval scoring rule as a mechanism to elicit subjective beliefs under varying degrees of uncertainty. In our experiment, subjects forecast the termination time of a time series to be generated from a given but unknown stochastic process. Subjects gradually learn more about the underlying process over time and hence the true distribution over termination times. We conduct two treatments, one with a high and one with a low volatility process. We find that elicited intervals are better when subjects are facing a low volatility process. In this treatment, participants learn to position their intervals almost optimally over the course of the experiment. This is in contrast with the high volatility treatment, where subjects, over the course of the experiment, learn to optimize the location of their intervals but fail to provide the optimal length. PMID:28380020

A modular approach to intensity-modulated arc therapy optimization with noncoplanar trajectories

NASA Astrophysics Data System (ADS)

Papp, Dávid; Bortfeld, Thomas; Unkelbach, Jan

2015-07-01

Utilizing noncoplanar beam angles in volumetric modulated arc therapy (VMAT) has the potential to combine the benefits of arc therapy, such as short treatment times, with the benefits of noncoplanar intensity modulated radiotherapy (IMRT) plans, such as improved organ sparing. Recently, vendors introduced treatment machines that allow for simultaneous couch and gantry motion during beam delivery to make noncoplanar VMAT treatments possible. Our aim is to provide a reliable optimization method for noncoplanar isocentric arc therapy plan optimization. The proposed solution is modular in the sense that it can incorporate different existing beam angle selection and coplanar arc therapy optimization methods. Treatment planning is performed in three steps. First, a number of promising noncoplanar beam directions are selected using an iterative beam selection heuristic; these beams serve as anchor points of the arc therapy trajectory. In the second step, continuous gantry/couch angle trajectories are optimized using a simple combinatorial optimization model to define a beam trajectory that efficiently visits each of the anchor points. Treatment time is controlled by limiting the time the beam needs to trace the prescribed trajectory. In the third and final step, an optimal arc therapy plan is found along the prescribed beam trajectory. In principle any existing arc therapy optimization method could be incorporated into this step; for this work we use a sliding window VMAT algorithm. The approach is demonstrated using two particularly challenging cases. The first one is a lung SBRT patient whose planning goals could not be satisfied with fewer than nine noncoplanar IMRT fields when the patient was treated in the clinic. The second one is a brain tumor patient, where the target volume overlaps with the optic nerves and the chiasm and it is directly adjacent to the brainstem. Both cases illustrate that the large number of angles utilized by isocentric noncoplanar VMAT plans can help improve dose conformity, homogeneity, and organ sparing simultaneously using the same beam trajectory length and delivery time as a coplanar VMAT plan.

Numerical study and ex vivo assessment of HIFU treatment time reduction through optimization of focal point trajectory

NASA Astrophysics Data System (ADS)

Grisey, A.; Yon, S.; Pechoux, T.; Letort, V.; Lafitte, P.

2017-03-01

Treatment time reduction is a key issue to expand the use of high intensity focused ultrasound (HIFU) surgery, especially for benign pathologies. This study aims at quantitatively assessing the potential reduction of the treatment time arising from moving the focal point during long pulses. In this context, the optimization of the focal point trajectory is crucial to achieve a uniform thermal dose repartition and avoid boiling. At first, a numerical optimization algorithm was used to generate efficient trajectories. Thermal conduction was simulated in 3D with a finite difference code and damages to the tissue were modeled using the thermal dose formula. Given an initial trajectory, the thermal dose field was first computed, then, making use of Pontryagin's maximum principle, the trajectory was iteratively refined. Several initial trajectories were tested. Then, an ex vivo study was conducted in order to validate the efficicency of the resulting optimized strategies. Single pulses were performed at 3MHz on fresh veal liver samples with an Echopulse and the size of each unitary lesion was assessed by cutting each sample along three orthogonal planes and measuring the dimension of the whitened area based on photographs. We propose a promising approach to significantly shorten HIFU treatment time: the numerical optimization algorithm was shown to provide a reliable insight on trajectories that can improve treatment strategies. The model must now be improved in order to take in vivo conditions into account and extensively validated.

Full Monte Carlo-Based Biologic Treatment Plan Optimization System for Intensity Modulated Carbon Ion Therapy on Graphics Processing Unit.

PubMed

Qin, Nan; Shen, Chenyang; Tsai, Min-Yu; Pinto, Marco; Tian, Zhen; Dedes, Georgios; Pompos, Arnold; Jiang, Steve B; Parodi, Katia; Jia, Xun

2018-01-01

One of the major benefits of carbon ion therapy is enhanced biological effectiveness at the Bragg peak region. For intensity modulated carbon ion therapy (IMCT), it is desirable to use Monte Carlo (MC) methods to compute the properties of each pencil beam spot for treatment planning, because of their accuracy in modeling physics processes and estimating biological effects. We previously developed goCMC, a graphics processing unit (GPU)-oriented MC engine for carbon ion therapy. The purpose of the present study was to build a biological treatment plan optimization system using goCMC. The repair-misrepair-fixation model was implemented to compute the spatial distribution of linear-quadratic model parameters for each spot. A treatment plan optimization module was developed to minimize the difference between the prescribed and actual biological effect. We used a gradient-based algorithm to solve the optimization problem. The system was embedded in the Varian Eclipse treatment planning system under a client-server architecture to achieve a user-friendly planning environment. We tested the system with a 1-dimensional homogeneous water case and 3 3-dimensional patient cases. Our system generated treatment plans with biological spread-out Bragg peaks covering the targeted regions and sparing critical structures. Using 4 NVidia GTX 1080 GPUs, the total computation time, including spot simulation, optimization, and final dose calculation, was 0.6 hour for the prostate case (8282 spots), 0.2 hour for the pancreas case (3795 spots), and 0.3 hour for the brain case (6724 spots). The computation time was dominated by MC spot simulation. We built a biological treatment plan optimization system for IMCT that performs simulations using a fast MC engine, goCMC. To the best of our knowledge, this is the first time that full MC-based IMCT inverse planning has been achieved in a clinically viable time frame. Copyright © 2017 Elsevier Inc. All rights reserved.

Optimization and performance evaluation for nutrient removal from palm oil mill effluent wastewater using microalgae

NASA Astrophysics Data System (ADS)

Ibrahim, Raheek I.; Wong, Z. H.; Mohammad, A. W.

2015-04-01

Palm oil mill effluent (POME) wastewater was produced in huge amounts in Malaysia, and if it discharged into the environment, it causes a serious problem regarding its high content of nutrients. This study was devoted to POME wastewater treatment with microalgae. The main objective was to find the optimum conditions (retention time, and pH) in the microalgae treatment of POME wastewater considering retention time as a most important parameter in algae treatment, since after the optimum conditions there is a diverse effect of time and pH and so, the process becomes costly. According to our knowledge, there is no existing study optimized the retention time and pH with % removal of nutrients (ammonia nitrogen NH3-N, and orthophosphorous PO43-) for microalgae treatment of POME wastewater. In order to achieve with optimization, a central composite rotatable design with a second order polynomial model was used, regression coefficients and goodness of fit results in removal percentages of nutrients (NH3-N, and PO43-) were estimated.WinQSB technique was used to optimize the surface response objective functionfor the developed model. Also experiments were done to validate the model results.The optimum conditions were found to be 18 day retention time for ammonia nitrogen, and pH of 9.22, while for orthophosphorous, 15 days were indicated as the optimum retention time with a pH value of 9.2.

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.

A fast optimization approach for treatment planning of volumetric modulated arc therapy.

PubMed

Yan, Hui; Dai, Jian-Rong; Li, Ye-Xiong

2018-05-30

Volumetric modulated arc therapy (VMAT) is widely used in clinical practice. It not only significantly reduces treatment time, but also produces high-quality treatment plans. Current optimization approaches heavily rely on stochastic algorithms which are time-consuming and less repeatable. In this study, a novel approach is proposed to provide a high-efficient optimization algorithm for VMAT treatment planning. A progressive sampling strategy is employed for beam arrangement of VMAT planning. The initial beams with equal-space are added to the plan in a coarse sampling resolution. Fluence-map optimization and leaf-sequencing are performed for these beams. Then, the coefficients of fluence-maps optimization algorithm are adjusted according to the known fluence maps of these beams. In the next round the sampling resolution is doubled and more beams are added. This process continues until the total number of beams arrived. The performance of VMAT optimization algorithm was evaluated using three clinical cases and compared to those of a commercial planning system. The dosimetric quality of VMAT plans is equal to or better than the corresponding IMRT plans for three clinical cases. The maximum dose to critical organs is reduced considerably for VMAT plans comparing to those of IMRT plans, especially in the head and neck case. The total number of segments and monitor units are reduced for VMAT plans. For three clinical cases, VMAT optimization takes < 5 min accomplished using proposed approach and is 3-4 times less than that of the commercial system. The proposed VMAT optimization algorithm is able to produce high-quality VMAT plans efficiently and consistently. It presents a new way to accelerate current optimization process of VMAT planning.

The Analysis of Fixed Final State Optimal Control in Bilinear System Applied to Bone Marrow by Cell-Cycle Specific (CCS) Chemotherapy

NASA Astrophysics Data System (ADS)

Rainarli, E.; E Dewi, K.

2017-04-01

The research conducted by Fister & Panetta shown an optimal control model of bone marrow cells against Cell Cycle Specific chemotherapy drugs. The model used was a bilinear system model. Fister & Panetta research has proved existence, uniqueness, and characteristics of optimal control (the chemotherapy effect). However, by using this model, the amount of bone marrow at the final time could achieve less than 50 percent from the amount of bone marrow before given treatment. This could harm patients because the lack of bone marrow cells made the number of leukocytes declining and patients will experience leukemia. This research would examine the optimal control of a bilinear system that applied to fixed final state. It will be used to determine the length of optimal time in administering chemotherapy and kept bone marrow cells on the allowed level at the same time. Before simulation conducted, this paper shows that the system could be controlled by using a theory of Lie Algebra. Afterward, it shows the characteristics of optimal control. Based on the simulation, it indicates that strong chemotherapy drug given in a short time frame is the most optimal condition to keep bone marrow cells spine on the allowed level but still could put playing an effective treatment. It gives preference of the weight of treatment for keeping bone marrow cells. The result of chemotherapy’s effect (u) is not able to reach the maximum value. On the other words, it needs to make adjustments of medicine’s dosage to satisfy the final treatment condition e.g. the number of bone marrow cells should be at the allowed level.

Childhood amblyopia: current management and new trends

PubMed Central

Tailor, Vijay; Bossi, Manuela; Greenwood, John A.; Dahlmann-Noor, Annegret

2016-01-01

Abstract Introduction or background With a prevalence of 2–5%, amblyopia is the most common vision deficit in children in the UK and the second most common cause of functional low vision in children in low-income countries. Sources of data Pubmed, Cochrane library and clinical trial registries (clinicaltrials.gov, ISRCTN, UKCRN portfolio database). Areas of agreement Screening and treatment at the age of 4–5 years are cost efficient and clinically effective. Optical treatment (glasses) alone can improve visual acuity, with residual amblyopia treated by part-time occlusion or pharmacological blurring of the better-seeing eye. Treatment after the end of the conventional ‘critical period’ can improve vision, but in strabismic amblyopia carries a low risk of double vision. Areas of controversy It is not clear whether earlier vision screening would be cost efficient and associated with better outcomes. Optimization of treatment by individualized patching regimes or early start of occlusion, and novel binocular treatment approaches may enhance adherence to treatment, provide better outcomes and shorten treatment duration. Growing points Binocular treatments for amblyopia. Areas timely for developing research Impact of amblyopia on education and quality of life; optimal screening timing and tests; optimal administration of conventional treatments; development of child-friendly, effective and safe binocular treatments. PMID:27543498

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.

MO-FG-CAMPUS-TeP2-05: Optimizing Stereotactic Radiosurgery Treatment of Multiple Brain Metastasis Lesions with Individualized Rotational Arc Trajectories

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

Dong, P; Xing, L; Ma, L

Purpose: Radiosurgery of multiple (n>4) brain metastasis lesions requires 3–4 noncoplanar VMAT arcs with excessively high monitor units and long delivery time. We investigated whether an improved optimization technique would decrease the needed arc numbers and increase the delivery efficiency, while improving or maintaining the plan quality. Methods: The proposed 4pi arc space optimization algorithm consists of two steps: automatic couch angle selection followed by aperture generation for each arc with optimized control points distribution. We use a greedy algorithm to select the couch angles. Starting from a single coplanar arc plan we search through the candidate noncoplanar arcs tomore » pick a single noncoplanar arc that will bring the best plan quality when added into the existing treatment plan. Each time, only one additional noncoplanar arc is considered making the calculation time tractable. This process repeats itself until desired number of arc is reached. The technique is first evaluated in coplanar arc delivery scheme with testing cases and then applied to noncoplanar treatments of a case with 12 brain metastasis lesions. Results: Clinically acceptable plans are created within minutes. For the coplanar testing cases the algorithm yields singlearc plans with better dose distributions than that of two-arc VMAT, simultaneously with a 12–17% reduction in the delivery time and a 14–21% reduction in MUs. For the treatment of 12 brain mets while Paddick conformity indexes of the two plans were comparable the SCG-optimization with 2 arcs (1 noncoplanar and 1 coplanar) significantly improved the conventional VMAT with 3 arcs (2 noncoplanar and 1 coplanar). Specifically V16 V10 and V5 of the brain were reduced by 11%, 11% and 12% respectively. The beam delivery time was shortened by approximately 30%. Conclusion: The proposed 4pi arc space optimization technique promises to significantly reduce the brain toxicity while greatly improving the treatment efficiency.« less

Refusal of treatment, leading to death: towards optimization of informed consent.

PubMed

Trevor-Deutsch, B; Nelson, R F

1996-12-01

Few medical decisions create more anguish than ones involving cessation of treatment, resulting in the death of a patient. In this article, the ethical and legal aspects of the withdrawal of treatment are examined with respect to a case of a 67-year-old man who fell and sustained a fracture of his second cervical vertebra, rendering him paralysed and respirator-dependent. He immediately requested the withdrawal of treatment, but his family baulked. Ethics consultation recommended delaying the decision, to give the patient enough time to foster optimal comprehension and synthesis of information related to his condition and the consequences; we refer to this process as "optimization of informed consent." When the patient was informed of the delay and the reasons for it, he was assured (and subsequently repeatedly reassured) of his ultimate right to refuse treatment at a future date. On balance, optimization of informed consent promotes patients' autonomy, even though it involves suspending this autonomy for a time. It is also consistent with physicians' responsibility to promote life and avoid premature death.

Bayesian Phase II optimization for time-to-event data based on historical information.

PubMed

Bertsche, Anja; Fleischer, Frank; Beyersmann, Jan; Nehmiz, Gerhard

2017-01-01

After exploratory drug development, companies face the decision whether to initiate confirmatory trials based on limited efficacy information. This proof-of-concept decision is typically performed after a Phase II trial studying a novel treatment versus either placebo or an active comparator. The article aims to optimize the design of such a proof-of-concept trial with respect to decision making. We incorporate historical information and develop pre-specified decision criteria accounting for the uncertainty of the observed treatment effect. We optimize these criteria based on sensitivity and specificity, given the historical information. Specifically, time-to-event data are considered in a randomized 2-arm trial with additional prior information on the control treatment. The proof-of-concept criterion uses treatment effect size, rather than significance. Criteria are defined on the posterior distribution of the hazard ratio given the Phase II data and the historical control information. Event times are exponentially modeled within groups, allowing for group-specific conjugate prior-to-posterior calculation. While a non-informative prior is placed on the investigational treatment, the control prior is constructed via the meta-analytic-predictive approach. The design parameters including sample size and allocation ratio are then optimized, maximizing the probability of taking the right decision. The approach is illustrated with an example in lung cancer.

Study on Power Ultrasound Optimization and Its Comparison with Conventional Thermal Processing for Treatment of Raw Honey

PubMed Central

2017-01-01

Summary The present study was done to optimize the power ultrasound processing for maximizing diastase activity of and minimizing hydroxymethylfurfural (HMF) content in honey using response surface methodology. Experimental design with treatment time (1-15 min), amplitude (20-100%) and volume (40-80 mL) as independent variables under controlled temperature conditions was studied and it was concluded that treatment time of 8 min, amplitude of 60% and volume of 60 mL give optimal diastase activity and HMF content, i.e. 32.07 Schade units and 30.14 mg/kg, respectively. Further thermal profile analyses were done with initial heating temperatures of 65, 75, 85 and 95 ºC until temperature of honey reached up to 65 ºC followed by holding time of 25 min at 65 ºC, and the results were compared with thermal profile of honey treated with optimized power ultrasound. The quality characteristics like moisture, pH, diastase activity, HMF content, colour parameters and total colour difference were least affected by optimized power ultrasound treatment. Microbiological analysis also showed lower counts of aerobic mesophilic bacteria and in ultrasonically treated honey than in thermally processed honey samples complete destruction of coliforms, yeasts and moulds. Thus, it was concluded that power ultrasound under suggested operating conditions is an alternative nonthermal processing technique for honey. PMID:29540991

Timing of Operative Debridement in Open Fractures.

PubMed

Rozell, Joshua C; Connolly, Keith P; Mehta, Samir

2017-01-01

The optimal treatment of open fractures continues to be an area of debate in the orthopedic literature. Recent research has challenged the dictum that open fractures should be debrided within 6 hours of injury. However, the expedient administration of intravenous antibiotics remains of paramount importance in infection prevention. Multiple factors, including fracture severity, thoroughness of debridement, time to initial treatment, and antibiotic administration, among other variables, contribute to the incidence of infection and complicate identifying an optimal time to debridement. Copyright © 2016 Elsevier Inc. All rights reserved.

SU-E-T-222: Computational Optimization of Monte Carlo Simulation On 4D Treatment Planning Using the Cloud Computing Technology

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

Chow, J

Purpose: This study evaluated the efficiency of 4D lung radiation treatment planning using Monte Carlo simulation on the cloud. The EGSnrc Monte Carlo code was used in dose calculation on the 4D-CT image set. Methods: 4D lung radiation treatment plan was created by the DOSCTP linked to the cloud, based on the Amazon elastic compute cloud platform. Dose calculation was carried out by Monte Carlo simulation on the 4D-CT image set on the cloud, and results were sent to the FFD4D image deformation program for dose reconstruction. The dependence of computing time for treatment plan on the number of computemore » node was optimized with variations of the number of CT image set in the breathing cycle and dose reconstruction time of the FFD4D. Results: It is found that the dependence of computing time on the number of compute node was affected by the diminishing return of the number of node used in Monte Carlo simulation. Moreover, the performance of the 4D treatment planning could be optimized by using smaller than 10 compute nodes on the cloud. The effects of the number of image set and dose reconstruction time on the dependence of computing time on the number of node were not significant, as more than 15 compute nodes were used in Monte Carlo simulations. Conclusion: The issue of long computing time in 4D treatment plan, requiring Monte Carlo dose calculations in all CT image sets in the breathing cycle, can be solved using the cloud computing technology. It is concluded that the optimized number of compute node selected in simulation should be between 5 and 15, as the dependence of computing time on the number of node is significant.« less

Ramsey waits: allocating public health service resources when there is rationing by waiting.

PubMed

Gravelle, Hugh; Siciliani, Luigi

2008-09-01

The optimal allocation of a public health care budget across treatments must take account of the way in which care is rationed within treatments since this will affect their marginal value. We investigate the optimal allocation rules for public health care systems where user charges are fixed and care is rationed by waiting. The optimal waiting time is higher for treatments with demands more elastic to waiting time, higher costs, lower charges, smaller marginal welfare loss from waiting by treated patients, and smaller marginal welfare losses from under-consumption of care. The results hold for a wide range of welfarist and non-welfarist objective functions and for systems in which there is also a private health care sector. They imply that allocation rules based purely on cost effectiveness ratios are suboptimal because they assume that there is no rationing within treatments.

Online stochastic optimization of radiotherapy patient scheduling.

PubMed

Legrain, Antoine; Fortin, Marie-Andrée; Lahrichi, Nadia; Rousseau, Louis-Martin

2015-06-01

The effective management of a cancer treatment facility for radiation therapy depends mainly on optimizing the use of the linear accelerators. In this project, we schedule patients on these machines taking into account their priority for treatment, the maximum waiting time before the first treatment, and the treatment duration. We collaborate with the Centre Intégré de Cancérologie de Laval to determine the best scheduling policy. Furthermore, we integrate the uncertainty related to the arrival of patients at the center. We develop a hybrid method combining stochastic optimization and online optimization to better meet the needs of central planning. We use information on the future arrivals of patients to provide an accurate picture of the expected utilization of resources. Results based on real data show that our method outperforms the policies typically used in treatment centers.

Interactive multiobjective optimization for anatomy-based three-dimensional HDR brachytherapy

NASA Astrophysics Data System (ADS)

Ruotsalainen, Henri; Miettinen, Kaisa; Palmgren, Jan-Erik; Lahtinen, Tapani

2010-08-01

In this paper, we present an anatomy-based three-dimensional dose optimization approach for HDR brachytherapy using interactive multiobjective optimization (IMOO). In brachytherapy, the goals are to irradiate a tumor without causing damage to healthy tissue. These goals are often conflicting, i.e. when one target is optimized the other will suffer, and the solution is a compromise between them. IMOO is capable of handling multiple and strongly conflicting objectives in a convenient way. With the IMOO approach, a treatment planner's knowledge is used to direct the optimization process. Thus, the weaknesses of widely used optimization techniques (e.g. defining weights, computational burden and trial-and-error planning) can be avoided, planning times can be shortened and the number of solutions to be calculated is small. Further, plan quality can be improved by finding advantageous trade-offs between the solutions. In addition, our approach offers an easy way to navigate among the obtained Pareto optimal solutions (i.e. different treatment plans). When considering a simulation model of clinical 3D HDR brachytherapy, the number of variables is significantly smaller compared to IMRT, for example. Thus, when solving the model, the CPU time is relatively short. This makes it possible to exploit IMOO to solve a 3D HDR brachytherapy optimization problem. To demonstrate the advantages of IMOO, two clinical examples of optimizing a gynecologic cervix cancer treatment plan are presented.

Why the dim light melatonin onset (DLMO) should be measured before treatment of patients with circadian rhythm sleep disorders.

PubMed

Keijzer, Henry; Smits, Marcel G; Duffy, Jeanne F; Curfs, Leopold M G

2014-08-01

Treatment of circadian rhythm sleep disorders (CRSD) may include light therapy, chronotherapy and melatonin. Exogenous melatonin is increasingly being used in patients with insomnia or CRSD. Although pharmacopoeias and the European food safety authority (EFSA) recommend administering melatonin 1-2 h before desired bedtime, several studies have shown that melatonin is not always effective if administered according to that recommendation. Crucial for optimal treatment of CRSD, melatonin and other treatments should be administered at a time related to individual circadian timing (typically assessed using the dim light melatonin onset (DLMO)). If not administered according to the individual patient's circadian timing, melatonin and other treatments may not only be ineffective, they may even result in contrary effects. Endogenous melatonin levels can be measured reliably in saliva collected at the patient's home. A clinically reliably DLMO can be calculated using a fixed threshold. Diary and polysomnographic sleep-onset time do not reliably predict DLMO or circadian timing in patients with CRSD. Knowing the patient's individual circadian timing by assessing DLMO can improve diagnosis and treatment of CRSD with melatonin as well as other therapies such as light or chronotherapy, and optimizing treatment timing will shorten the time required to achieve results. Copyright © 2013 Elsevier Ltd. All rights reserved.

Optimization of a thermal hydrolysis process for sludge pre-treatment.

PubMed

Sapkaite, I; Barrado, E; Fdz-Polanco, F; Pérez-Elvira, S I

2017-05-01

At industrial scale, thermal hydrolysis is the most used process to enhance biodegradability of the sludge produced in wastewater treatment plants. Through statistically guided Box-Behnken experimental design, the present study analyses the effect of TH as pre-treatment applied to activated sludge. The selected process variables were temperature (130-180 °C), time (5-50 min) and decompression mode (slow or steam-explosion effect), and the parameters evaluated were sludge solubilisation and methane production by anaerobic digestion. A quadratic polynomial model was generated to compare the process performance for the 15 different combinations of operation conditions by modifying the process variables evaluated. The statistical analysis performed exhibited that methane production and solubility were significantly affected by pre-treatment time and temperature. During high intensity pre-treatment (high temperature and long times), the solubility increased sharply while the methane production exhibited the opposite behaviour, indicating the formation of some soluble but non-biodegradable materials. Therefore, solubilisation is not a reliable parameter to quantify the efficiency of a thermal hydrolysis pre-treatment, since it is not directly related to methane production. Based on the operational parameters optimization, the estimated optimal thermal hydrolysis conditions to enhance of sewage sludge digestion were: 140-170 °C heating temperature, 5-35min residence time, and one sudden decompression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Simultaneous delivery time and aperture shape optimization for the volumetric-modulated arc therapy (VMAT) treatment planning problem

NASA Astrophysics Data System (ADS)

Mahnam, Mehdi; Gendreau, Michel; Lahrichi, Nadia; Rousseau, Louis-Martin

2017-07-01

In this paper, we propose a novel heuristic algorithm for the volumetric-modulated arc therapy treatment planning problem, optimizing the trade-off between delivery time and treatment quality. We present a new mixed integer programming model in which the multi-leaf collimator leaf positions, gantry speed, and dose rate are determined simultaneously. Our heuristic is based on column generation; the aperture configuration is modeled in the columns and the dose distribution and time restriction in the rows. To reduce the number of voxels and increase the efficiency of the master model, we aggregate similar voxels using a clustering technique. The efficiency of the algorithm and the treatment quality are evaluated on a benchmark clinical prostate cancer case. The computational results show that a high-quality treatment is achievable using a four-thread CPU. Finally, we analyze the effects of the various parameters and two leaf-motion strategies.

Optimization of the prescription isodose line for Gamma Knife radiosurgery using the shot within shot technique.

PubMed

Johnson, Perry B; Monterroso, Maria I; Yang, Fei; Mellon, Eric

2017-11-25

This work explores how the choice of prescription isodose line (IDL) affects the dose gradient, target coverage, and treatment time for Gamma Knife radiosurgery when a smaller shot is encompassed within a larger shot at the same stereotactic coordinates (shot within shot technique). Beam profiles for the 4, 8, and 16 mm collimator settings were extracted from the treatment planning system and characterized using Gaussian fits. The characterized data were used to create over 10,000 shot within shot configurations by systematically changing collimator weighting and choice of prescription IDL. Each configuration was quantified in terms of the dose gradient, target coverage, and beam-on time. By analyzing these configurations, it was found that there are regions of overlap in target size where a higher prescription IDL provides equivalent dose fall-off to a plan prescribed at the 50% IDL. Furthermore, the data indicate that treatment times within these regions can be reduced by up to 40%. An optimization strategy was devised to realize these gains. The strategy was tested for seven patients treated for 1-4 brain metastases (20 lesions total). For a single collimator setting, the gradient in the axial plane was steepest when prescribed to the 56-63% (4 mm), 62-70% (8 mm), and 77-84% (16 mm) IDL, respectively. Through utilization of the optimization technique, beam-on time was reduced by more than 15% in 16/20 lesions. The volume of normal brain receiving 12 Gy or above also decreased in many cases, and in only one instance increased by more than 0.5 cm 3 . This work demonstrates that IDL optimization using the shot within shot technique can reduce treatment times without degrading treatment plan quality.

Optimal insecticide-treated bed-net coverage and malaria treatment in a malaria-HIV co-infection model.

PubMed

Mohammed-Awel, Jemal; Numfor, Eric

2017-03-01

We propose and study a mathematical model for malaria-HIV co-infection transmission and control, in which malaria treatment and insecticide-treated nets are incorporated. The existence of a backward bifurcation is established analytically, and the occurrence of such backward bifurcation is influenced by disease-induced mortality, insecticide-treated bed-net coverage and malaria treatment parameters. To further assess the impact of malaria treatment and insecticide-treated bed-net coverage, we formulate an optimal control problem with malaria treatment and insecticide-treated nets as control functions. Using reasonable parameter values, numerical simulations of the optimal control suggest the possibility of eliminating malaria and reducing HIV prevalence significantly, within a short time horizon.

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

Challenges in the Treatment of Major Depressive Disorder With Psychotic Features

PubMed Central

Rothschild, Anthony J.

2013-01-01

Psychotic depression is associated with significant morbidity and mortality but is underdiagnosed and undertreated. In recent years, there have been several studies that have increased our knowledge regarding the optimal treatment of patients with psychotic depression. The combination of an antidepressant and antipsychotic is significantly more effective than either antidepressant monotherapy or antipsychotic monotherapy for the acute treatment of psychotic depression. Most treatment guidelines recommend either the combination of an antidepressant with an antipsychotic or ECT for the treatment of an acute episode of unipolar psychotic depression. The optimal maintenance treatment after a person responds to either the antidepressant/antipsychotic combination or the ECT is unclear particularly as it pertains to length of time the patient needs to take the antipsychotic medication. Little is known regarding the optimal treatment of a patient with bipolar disorder who has an episode of psychotic depression or the clinical characteristics of responders to medication treatments vs ECT treatments. PMID:23599251

Challenges in the treatment of major depressive disorder with psychotic features.

PubMed

Rothschild, Anthony J

2013-07-01

Psychotic depression is associated with significant morbidity and mortality but is underdiagnosed and undertreated. In recent years, there have been several studies that have increased our knowledge regarding the optimal treatment of patients with psychotic depression. The combination of an antidepressant and antipsychotic is significantly more effective than either antidepressant monotherapy or antipsychotic monotherapy for the acute treatment of psychotic depression. Most treatment guidelines recommend either the combination of an antidepressant with an antipsychotic or ECT for the treatment of an acute episode of unipolar psychotic depression. The optimal maintenance treatment after a person responds to either the antidepressant/antipsychotic combination or the ECT is unclear particularly as it pertains to length of time the patient needs to take the antipsychotic medication. Little is known regarding the optimal treatment of a patient with bipolar disorder who has an episode of psychotic depression or the clinical characteristics of responders to medication treatments vs ECT treatments.

Algorithms for optimizing the treatment of depression: making the right decision at the right time.

PubMed

Adli, M; Rush, A J; Möller, H-J; Bauer, M

2003-11-01

Medication algorithms for the treatment of depression are designed to optimize both treatment implementation and the appropriateness of treatment strategies. Thus, they are essential tools for treating and avoiding refractory depression. Treatment algorithms are explicit treatment protocols that provide specific therapeutic pathways and decision-making tools at critical decision points throughout the treatment process. The present article provides an overview of major projects of algorithm research in the field of antidepressant therapy. The Berlin Algorithm Project and the Texas Medication Algorithm Project (TMAP) compare algorithm-guided treatments with treatment as usual. The Sequenced Treatment Alternatives to Relieve Depression Project (STAR*D) compares different treatment strategies in treatment-resistant patients.

Use of personalized Dynamic Treatment Regimes (DTRs) and Sequential Multiple Assignment Randomized Trials (SMARTs) in mental health studies

PubMed Central

Liu, Ying; ZENG, Donglin; WANG, Yuanjia

2014-01-01

Summary Dynamic treatment regimens (DTRs) are sequential decision rules tailored at each point where a clinical decision is made based on each patient’s time-varying characteristics and intermediate outcomes observed at earlier points in time. The complexity, patient heterogeneity, and chronicity of mental disorders call for learning optimal DTRs to dynamically adapt treatment to an individual’s response over time. The Sequential Multiple Assignment Randomized Trial (SMARTs) design allows for estimating causal effects of DTRs. Modern statistical tools have been developed to optimize DTRs based on personalized variables and intermediate outcomes using rich data collected from SMARTs; these statistical methods can also be used to recommend tailoring variables for designing future SMART studies. This paper introduces DTRs and SMARTs using two examples in mental health studies, discusses two machine learning methods for estimating optimal DTR from SMARTs data, and demonstrates the performance of the statistical methods using simulated data. PMID:25642116

Childhood amblyopia: current management and new trends.

PubMed

Tailor, Vijay; Bossi, Manuela; Greenwood, John A; Dahlmann-Noor, Annegret

2016-09-01

With a prevalence of 2-5%, amblyopia is the most common vision deficit in children in the UK and the second most common cause of functional low vision in children in low-income countries. Pubmed, Cochrane library and clinical trial registries (clinicaltrials.gov, ISRCTN, UKCRN portfolio database). Screening and treatment at the age of 4-5 years are cost efficient and clinically effective. Optical treatment (glasses) alone can improve visual acuity, with residual amblyopia treated by part-time occlusion or pharmacological blurring of the better-seeing eye. Treatment after the end of the conventional 'critical period' can improve vision, but in strabismic amblyopia carries a low risk of double vision. It is not clear whether earlier vision screening would be cost efficient and associated with better outcomes. Optimization of treatment by individualized patching regimes or early start of occlusion, and novel binocular treatment approaches may enhance adherence to treatment, provide better outcomes and shorten treatment duration. Binocular treatments for amblyopia. Impact of amblyopia on education and quality of life; optimal screening timing and tests; optimal administration of conventional treatments; development of child-friendly, effective and safe binocular treatments. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Mathematical Analysis for the Optimization of Wastewater Treatment Systems in Facultative Pond Indicator Organic Matter

NASA Astrophysics Data System (ADS)

Sunarsih; Widowati; Kartono; Sutrisno

2018-02-01

Stabilization ponds are easy to operate and their maintenance is simple. Treatment is carried out naturally and they are recommended in developing countries. The main disadvantage of these systems is large land area they occupy. The aim of this study was to perform an optimization of the wastewater treatment systems in a facultative pond, considering a mathematical analysis of the methodology to determine the model constrains organic matter. Matlab optimization toolbox was used for non linear programming. A facultative pond with the method was designed and then the optimization system was applied. The analyse meet the treated water quality requirements for the discharge to the water bodies. The results show a reduction of hydraulic retention time by 4.83 days, and the efficiency of of wastewater treatment of 84.16 percent.

A new Gamma Knife radiosurgery paradigm: Tomosurgery

NASA Astrophysics Data System (ADS)

Hu, Xiaoliang

The Leksell (Elekta, Stockholm, Sweden) Gamma Knife(TM) (LGK) is the worldwide standard-of-care for the radiosurgical treatment of a wide variety of intracranial lesions. The current LGK utilizes a step-and-shoot dose delivery mechanism where the centroid of each conformal radiation dose (i.e., the shot isocenter) requires repositioning the patient outside of the irradiation field. Perhaps the greatest challenge the LGK treatment team faces is planning the treatment of large and/or complexly shaped lesions that may be in close proximity to critical neural or vascular structures. The standard manual treatment planning approach is a time consuming procedure where additional time spent does not guarantee the identification of an increasingly optimal treatment plan. I propose a new radiosurgery paradigm which I refer to as "Tomosurgery". The Tomosurgery paradigm begins with the division of the target volume into a series of adjacent treatment slices, each with a carefully determined optimal thickness. The use of a continuously moving disk-shaped radiation shot that moves through the lesion in a raster-scanning pattern is expected to improve overall radiation dose conformality and homogeneity. The Tomosurgery treatment planning algorithm recruits a two-stage optimization strategy, which first plans each treatment slice as a simplified 2D problem and secondly optimally assembles the 2D treatment plans into the final 3D treatment plan. Tested on 11 clinical LGK cases, the automated inversely-generated Tomosurgery treatment plans performed as well or better than the neurosurgeon's manually created treatment plans across all criteria: (a) dose volume histograms, (b) dose homogeneity, (c) dose conformality, and (d) critical structure damage, where applicable. LGK Tomosurgery inverse treatment planning required much less time than standard of care, manual (i.e., forward) LGK treatment planning procedures. These results suggest that Tomosurgery might provide an improvement over the current LGK radiosurgery treatment planning software. As regards treatment delivery, a Tomosurgery Investigational Platform (TIP) is proposed to perform the physical validation of radiation dose delivery. The TIP should facilitate translation of the Tomosurgery paradigm to several other radiosurgery and/or radiotherapy devices without the need for expensive modification of commercial devices until the feasibility of delivering Tomosurgical treatment plans has been well established.

Automated construction of an intraoperative high-dose-rate treatment plan library for the Varian brachytherapy treatment planning system.

PubMed

Deufel, Christopher L; Furutani, Keith M; Dahl, Robert A; Haddock, Michael G

2016-01-01

The ability to create treatment plans for intraoperative high-dose-rate (IOHDR) brachytherapy is limited by lack of imaging and time constraints. An automated method for creation of a library of high-dose-rate brachytherapy plans that can be used with standard planar applicators in the intraoperative setting is highly desirable. Nonnegative least squares algebraic methods were used to identify dwell time values for flat, rectangular planar applicators. The planar applicators ranged in length and width from 2 cm to 25 cm. Plans were optimized to deliver an absorbed dose of 10 Gy to three different depths from the patient surface: 0 cm, 0.5 cm, and 1.0 cm. Software was written to calculate the optimized dwell times and insert dwell times and positions into a .XML plan template that can be imported into the Varian brachytherapy treatment planning system. The user may import the .XML template into the treatment planning system in the intraoperative setting to match the patient applicator size and prescribed treatment depth. A total of 1587 library plans were created for IOHDR brachytherapy. Median plan generation time was approximately 1 minute per plan. Plan dose was typically 100% ± 1% (mean, standard deviation) of the prescribed dose over the entire length and width of the applicator. Plan uniformity was best for prescription depths of 0 cm and 0.5 cm from the patient surface. An IOHDR plan library may be created using automated methods. Thousands of plan templates may be optimized and prepared in a few hours to accommodate different applicator sizes and treatment depths and reduce treatment planning time. The automated method also enforces dwell time symmetry for symmetrical applicator geometries, which simplifies quality assurance. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

[Mobile stroke unit for prehospital stroke treatment].

PubMed

Walter, S; Grunwald, I Q; Fassbender, K

2016-01-01

The management of acute stroke patients suffers from several major problems in the daily clinical routine. In order to achieve optimal treatment a complex diagnostic work-up and rapid initiation of therapy are necessary; however, most patients arrive at hospital too late for any type of acute stroke treatment, although all forms of treatment are highly time-dependent according to the generally accepted "time is brain" concept. Recently, two randomized clinical trials demonstrated the feasibility of prehospital stroke diagnostic work-up and treatment. This was accomplished by use of a specialized ambulance, equipped with computed tomography for multimodal imaging and a point-of-care laboratory system. In both trials the results demonstrated a clear superiority of the prehospital treatment group with a significant reduction of treatment times, significantly increased number of patients treated within the first 60 min after symptom onset and an optimized triage to the correct target hospital. Currently, mobile stroke units are in operation in various countries and should lead to an improvement in stroke treatment; nevertheless, intensive research is still needed to analyze the best framework settings for prehospital stroke management.

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

Nguyen, Kham, E-mail: khamdiep@gmail.com; UT MD Anderson Cancer Center, School of Health Professions—Unit 2, Houston, TX; Cummings, David

The purpose of this study was to evaluate the differences between volumetric modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) in the treatment of nasal cavity carcinomas. The treatment of 10 patients, who had completed IMRT treatment for resected tumors of the nasal cavity, was replanned with the Philips Pinnacle{sup 3} Version 9 treatment-planning system. The IMRT plans used a 9-beam technique whereas the VMAT (known as SmartArc) plans used a 3-arc technique. Both types of plans were optimized using Philips Pinnacle{sup 3} Direct Machine Parameter Optimization algorithm. IMRT and VMAT plans' quality was compared by evaluating the maximum,more » minimum, and mean doses to the target volumes and organs at risk, monitor units (MUs), and the treatment delivery time. Our results indicate that VMAT is capable of greatly reducing treatment delivery time and MUs compared with IMRT. The reduction of treatment delivery time and MUs can decrease the effects of intrafractional uncertainties that can occur because of patient movement during treatment delivery. VMAT's plans further reduce doses to critical structures that are in close proximity to the target volume.« less

Optimization and real-time control for laser treatment of heterogeneous soft tissues.

PubMed

Feng, Yusheng; Fuentes, David; Hawkins, Andrea; Bass, Jon M; Rylander, Marissa Nichole

2009-01-01

Predicting the outcome of thermotherapies in cancer treatment requires an accurate characterization of the bioheat transfer processes in soft tissues. Due to the biological and structural complexity of tumor (soft tissue) composition and vasculature, it is often very difficult to obtain reliable tissue properties that is one of the key factors for the accurate treatment outcome prediction. Efficient algorithms employing in vivo thermal measurements to determine heterogeneous thermal tissues properties in conjunction with a detailed sensitivity analysis can produce essential information for model development and optimal control. The goals of this paper are to present a general formulation of the bioheat transfer equation for heterogeneous soft tissues, review models and algorithms developed for cell damage, heat shock proteins, and soft tissues with nanoparticle inclusion, and demonstrate an overall computational strategy for developing a laser treatment framework with the ability to perform real-time robust calibrations and optimal control. This computational strategy can be applied to other thermotherapies using the heat source such as radio frequency or high intensity focused ultrasound.

Model-based optimization of G-CSF treatment during cytotoxic chemotherapy.

PubMed

Schirm, Sibylle; Engel, Christoph; Loibl, Sibylle; Loeffler, Markus; Scholz, Markus

2018-02-01

Although G-CSF is widely used to prevent or ameliorate leukopenia during cytotoxic chemotherapies, its optimal use is still under debate and depends on many therapy parameters such as dosing and timing of cytotoxic drugs and G-CSF, G-CSF pharmaceuticals used and individual risk factors of patients. We integrate available biological knowledge and clinical data regarding cell kinetics of bone marrow granulopoiesis, the cytotoxic effects of chemotherapy and pharmacokinetics and pharmacodynamics of G-CSF applications (filgrastim or pegfilgrastim) into a comprehensive model. The model explains leukocyte time courses of more than 70 therapy scenarios comprising 10 different cytotoxic drugs. It is applied to develop optimized G-CSF schedules for a variety of clinical scenarios. Clinical trial results showed validity of model predictions regarding alternative G-CSF schedules. We propose modifications of G-CSF treatment for the chemotherapies 'BEACOPP escalated' (Hodgkin's disease), 'ETC' (breast cancer), and risk-adapted schedules for 'CHOP-14' (aggressive non-Hodgkin's lymphoma in elderly patients). We conclude that we established a model of human granulopoiesis under chemotherapy which allows predictions of yet untested G-CSF schedules, comparisons between them, and optimization of filgrastim and pegfilgrastim treatment. As a general rule of thumb, G-CSF treatment should not be started too early and patients could profit from filgrastim treatment continued until the end of the chemotherapy cycle.

Treatment selection in a randomized clinical trial via covariate-specific treatment effect curves.

PubMed

Ma, Yunbei; Zhou, Xiao-Hua

2017-02-01

For time-to-event data in a randomized clinical trial, we proposed two new methods for selecting an optimal treatment for a patient based on the covariate-specific treatment effect curve, which is used to represent the clinical utility of a predictive biomarker. To select an optimal treatment for a patient with a specific biomarker value, we proposed pointwise confidence intervals for each covariate-specific treatment effect curve and the difference between covariate-specific treatment effect curves of two treatments. Furthermore, to select an optimal treatment for a future biomarker-defined subpopulation of patients, we proposed confidence bands for each covariate-specific treatment effect curve and the difference between each pair of covariate-specific treatment effect curve over a fixed interval of biomarker values. We constructed the confidence bands based on a resampling technique. We also conducted simulation studies to evaluate finite-sample properties of the proposed estimation methods. Finally, we illustrated the application of the proposed method in a real-world data set.

On-line Adaptive Radiation Treatment of Prostate Cancer

DTIC Science & Technology

2009-01-01

12]. For intensity modulated radiation therapy (IMRT) plans , the beamlet weight can be re-optimized on a daily basis to mini- mize the dose to the OAR...Thongphiew D, Wang Z, Mathayomchan B, Chankong V, Yoo S, et al. On-line re-optimization of prostate IMRT plans for adaptive radiation therapy . Phys Med Biol...time. The treatment planning method for VMAT however is not mature. We are developing a robust VMAT treatment planning method which incorporates

Preparation and Optimization of Vanadium Titanomagnetite Carbon Composite Hot Briquette: A New Type of Blast Furnace Burden

NASA Astrophysics Data System (ADS)

Zhao, W.; Wang, H. T.; Liu, Z. G.; Chu, M. S.; Ying, Z. W.; Tang, J.

2017-10-01

A new type of blast furnace burden, named VTM-CCB (vanadium titanomagnetite carbon composite hot briquette), is proposed and optimized in this paper. The preparation process of VTM-CCB includes two components, hot briquetting and heat treatment. The hot-briquetting and heat-treatment parameters are systematically optimized based on the Taguchi method and single-factor experiment. The optimized preparation parameters of VTM-CCB include a hot-briquetting temperature of 300°C, a coal particle size of <0.075 mm, a vanadium titanomagnetite particle size of <0.075 mm, a coal-added ratio of 28.52%, a heat-treatment temperature of 500°C and a heat-treatment time of 3 h. The compressive strength of VTM-CCB, based on the optimized parameters, reaches 2450 N, which meets the requirement of blast furnace ironmaking. These integrated parameters provide a theoretical basis for the production and application of a blast furnace smelting VTM-CCB.

A method to incorporate leakage and head scatter corrections into a tomotherapy inverse treatment planning algorithm

NASA Astrophysics Data System (ADS)

Holmes, Timothy W.

2001-01-01

A detailed tomotherapy inverse treatment planning method is described which incorporates leakage and head scatter corrections during each iteration of the optimization process, allowing these effects to be directly accounted for in the optimized dose distribution. It is shown that the conventional inverse planning method for optimizing incident intensity can be extended to include a `concurrent' leaf sequencing operation from which the leakage and head scatter corrections are determined. The method is demonstrated using the steepest-descent optimization technique with constant step size and a least-squared error objective. The method was implemented using the MATLAB scientific programming environment and its feasibility demonstrated for 2D test cases simulating treatment delivery using a single coplanar rotation. The results indicate that this modification does not significantly affect convergence of the intensity optimization method when exposure times of individual leaves are stratified to a large number of levels (>100) during leaf sequencing. In general, the addition of aperture dependent corrections, especially `head scatter', reduces incident fluence in local regions of the modulated fan beam, resulting in increased exposure times for individual collimator leaves. These local variations can result in 5% or greater local variation in the optimized dose distribution compared to the uncorrected case. The overall efficiency of the modified intensity optimization algorithm is comparable to that of the original unmodified case.

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.

Development and clinical introduction of automated radiotherapy treatment planning for prostate cancer

NASA Astrophysics Data System (ADS)

Winkel, D.; Bol, G. H.; van Asselen, B.; Hes, J.; Scholten, V.; Kerkmeijer, L. G. W.; Raaymakers, B. W.

2016-12-01

To develop an automated radiotherapy treatment planning and optimization workflow to efficiently create patient specifically optimized clinical grade treatment plans for prostate cancer and to implement it in clinical practice. A two-phased planning and optimization workflow was developed to automatically generate 77Gy 5-field simultaneously integrated boost intensity modulated radiation therapy (SIB-IMRT) plans for prostate cancer treatment. A retrospective planning study (n  =  100) was performed in which automatically and manually generated treatment plans were compared. A clinical pilot (n  =  21) was performed to investigate the usability of our method. Operator time for the planning process was reduced to  <5 min. The retrospective planning study showed that 98 plans met all clinical constraints. Significant improvements were made in the volume receiving 72Gy (V72Gy) for the bladder and rectum and the mean dose of the bladder and the body. A reduced plan variance was observed. During the clinical pilot 20 automatically generated plans met all constraints and 17 plans were selected for treatment. The automated radiotherapy treatment planning and optimization workflow is capable of efficiently generating patient specifically optimized and improved clinical grade plans. It has now been adopted as the current standard workflow in our clinic to generate treatment plans for prostate cancer.

Adsorption performance of mixed dyes on alkalization loofah fibers

NASA Astrophysics Data System (ADS)

Wang, Yongli; Liu, Jinyan; Li, Xingxing

2018-02-01

When the polyporous structures of loofah fiber is adequately exposed after alkali treatment,lignin, hemicellulose and pectin are removed. Specific surface area is increased to maximum, which means the efficiency of absorptivity is highest. In this paper, by using alkalization loofah (AL) as adsorbent, the effect of loofah fiber on waste water treatment is studied under the efficiency of loofah fiber which contain acridine yellow, methylene blue, mixed solution of the two dyes. The optimum treatment conditions of loofah fiber were studied from five aspects which include dosage, temperature, mixing time, pH and concentration. The results showed that the optimal conditions are 30°C, pH 8.0, 20mg dosage of loofah fiber in 40ml solution and mixing time 25min. The optimal treatment conditions of mixed dyes were studied from the aspects of mixing time, the dosage of AL and the molar ratio of the two components in the mixed dyes.

A new optimization method using a compressed sensing inspired solver for real-time LDR-brachytherapy treatment planning

NASA Astrophysics Data System (ADS)

Guthier, C.; Aschenbrenner, K. P.; Buergy, D.; Ehmann, M.; Wenz, F.; Hesser, J. W.

2015-03-01

This work discusses a novel strategy for inverse planning in low dose rate brachytherapy. It applies the idea of compressed sensing to the problem of inverse treatment planning and a new solver for this formulation is developed. An inverse planning algorithm was developed incorporating brachytherapy dose calculation methods as recommended by AAPM TG-43. For optimization of the functional a new variant of a matching pursuit type solver is presented. The results are compared with current state-of-the-art inverse treatment planning algorithms by means of real prostate cancer patient data. The novel strategy outperforms the best state-of-the-art methods in speed, while achieving comparable quality. It is able to find solutions with comparable values for the objective function and it achieves these results within a few microseconds, being up to 542 times faster than competing state-of-the-art strategies, allowing real-time treatment planning. The sparse solution of inverse brachytherapy planning achieved with methods from compressed sensing is a new paradigm for optimization in medical physics. Through the sparsity of required needles and seeds identified by this method, the cost of intervention may be reduced.

A new optimization method using a compressed sensing inspired solver for real-time LDR-brachytherapy treatment planning.

PubMed

Guthier, C; Aschenbrenner, K P; Buergy, D; Ehmann, M; Wenz, F; Hesser, J W

2015-03-21

This work discusses a novel strategy for inverse planning in low dose rate brachytherapy. It applies the idea of compressed sensing to the problem of inverse treatment planning and a new solver for this formulation is developed. An inverse planning algorithm was developed incorporating brachytherapy dose calculation methods as recommended by AAPM TG-43. For optimization of the functional a new variant of a matching pursuit type solver is presented. The results are compared with current state-of-the-art inverse treatment planning algorithms by means of real prostate cancer patient data. The novel strategy outperforms the best state-of-the-art methods in speed, while achieving comparable quality. It is able to find solutions with comparable values for the objective function and it achieves these results within a few microseconds, being up to 542 times faster than competing state-of-the-art strategies, allowing real-time treatment planning. The sparse solution of inverse brachytherapy planning achieved with methods from compressed sensing is a new paradigm for optimization in medical physics. Through the sparsity of required needles and seeds identified by this method, the cost of intervention may be reduced.

[Comparative evaluation of the effectiveness of various treatment modalities for accommodation disorders and acquired progressive myopia].

PubMed

Tarutta, E P; Tarasova, N A

2015-01-01

To evaluate the effectiveness of non-surgical treatment of accommodation disorders and progressive myopia in children. A total of 190 patients (380 eyes) with myopia aged from 6 to 18 years (10.79±0.18 years on average) were enrolled and divided into 9 groups depending on the treatment prescribed. Comparative evaluation of different hardware-based treatment modalities for progressive myopia allowed to work out their optimal combination: "Visotronic", "MACDEL 09", and magnetophoresis of Taufon 4%. Such courses, provided twice a year, were associated with optimization of accommodative response and 1.9-2.8 times reduction of the rate of myopia progression. On the contrary, pleoptic therapy showed a negative effect on accommodative tonus and the rate of progression of acquired myopia. Comparative evaluation of different hardware-based treatment modalities for progressive myopia and accommodation disorders allowed to work out their optimal combination: "Visotronic", "MACDEL 09" and magnetophoresis of Taufon 4%. This treatment, provided twice a year, allows to increase accommodative reserves and volume, improve objective accommodative response, and reduce accommodative hypertonus as well as the rate of myopia progression (1.9-2.8 times over a 1.5-year period). Under pleoptic therapy (specialized software, near field speckles, color pulse therapy, Ambliokor device), both accommodative tonus and the rate of myopia progression increased (1.3-1.5 and 1.6 times correspondingly).

An automated optimization tool for high-dose-rate (HDR) prostate brachytherapy with divergent needle pattern

NASA Astrophysics Data System (ADS)

Borot de Battisti, M.; Maenhout, M.; de Senneville, B. Denis; Hautvast, G.; Binnekamp, D.; Lagendijk, J. J. W.; van Vulpen, M.; Moerland, M. A.

2015-10-01

Focal high-dose-rate (HDR) for prostate cancer has gained increasing interest as an alternative to whole gland therapy as it may contribute to the reduction of treatment related toxicity. For focal treatment, optimal needle guidance and placement is warranted. This can be achieved under MR guidance. However, MR-guided needle placement is currently not possible due to space restrictions in the closed MR bore. To overcome this problem, a MR-compatible, single-divergent needle-implant robotic device is under development at the University Medical Centre, Utrecht: placed between the legs of the patient inside the MR bore, this robot will tap the needle in a divergent pattern from a single rotation point into the tissue. This rotation point is just beneath the perineal skin to have access to the focal prostate tumor lesion. Currently, there is no treatment planning system commercially available which allows optimization of the dose distribution with such needle arrangement. The aim of this work is to develop an automatic inverse dose planning optimization tool for focal HDR prostate brachytherapy with needle insertions in a divergent configuration. A complete optimizer workflow is proposed which includes the determination of (1) the position of the center of rotation, (2) the needle angulations and (3) the dwell times. Unlike most currently used optimizers, no prior selection or adjustment of input parameters such as minimum or maximum dose or weight coefficients for treatment region and organs at risk is required. To test this optimizer, a planning study was performed on ten patients (treatment volumes ranged from 8.5 cm3to 23.3 cm3) by using 2-14 needle insertions. The total computation time of the optimizer workflow was below 20 min and a clinically acceptable plan was reached on average using only four needle insertions.

An optimized treatment for algorithmic differentiation of an important glaciological fixed-point problem

DOE PAGES

Goldberg, Daniel N.; Narayanan, Sri Hari Krishna; Hascoet, Laurent; ...

2016-05-20

We apply an optimized method to the adjoint generation of a time-evolving land ice model through algorithmic differentiation (AD). The optimization involves a special treatment of the fixed-point iteration required to solve the nonlinear stress balance, which differs from a straightforward application of AD software, and leads to smaller memory requirements and in some cases shorter computation times of the adjoint. The optimization is done via implementation of the algorithm of Christianson (1994) for reverse accumulation of fixed-point problems, with the AD tool OpenAD. For test problems, the optimized adjoint is shown to have far lower memory requirements, potentially enablingmore » larger problem sizes on memory-limited machines. In the case of the land ice model, implementation of the algorithm allows further optimization by having the adjoint model solve a sequence of linear systems with identical (as opposed to varying) matrices, greatly improving performance. Finally, the methods introduced here will be of value to other efforts applying AD tools to ice models, particularly ones which solve a hybrid shallow ice/shallow shelf approximation to the Stokes equations.« less

Web-based tool for visualization of electric field distribution in deep-seated body structures and planning of electroporation-based treatments.

PubMed

Marčan, Marija; Pavliha, Denis; Kos, Bor; Forjanič, Tadeja; Miklavčič, Damijan

2015-01-01

Treatments based on electroporation are a new and promising approach to treating tumors, especially non-resectable ones. The success of the treatment is, however, heavily dependent on coverage of the entire tumor volume with a sufficiently high electric field. Ensuring complete coverage in the case of deep-seated tumors is not trivial and can in best way be ensured by patient-specific treatment planning. The basis of the treatment planning process consists of two complex tasks: medical image segmentation, and numerical modeling and optimization. In addition to previously developed segmentation algorithms for several tissues (human liver, hepatic vessels, bone tissue and canine brain) and the algorithms for numerical modeling and optimization of treatment parameters, we developed a web-based tool to facilitate the translation of the algorithms and their application in the clinic. The developed web-based tool automatically builds a 3D model of the target tissue from the medical images uploaded by the user and then uses this 3D model to optimize treatment parameters. The tool enables the user to validate the results of the automatic segmentation and make corrections if necessary before delivering the final treatment plan. Evaluation of the tool was performed by five independent experts from four different institutions. During the evaluation, we gathered data concerning user experience and measured performance times for different components of the tool. Both user reports and performance times show significant reduction in treatment-planning complexity and time-consumption from 1-2 days to a few hours. The presented web-based tool is intended to facilitate the treatment planning process and reduce the time needed for it. It is crucial for facilitating expansion of electroporation-based treatments in the clinic and ensuring reliable treatment for the patients. The additional value of the tool is the possibility of easy upgrade and integration of modules with new functionalities as they are developed.

Web-based tool for visualization of electric field distribution in deep-seated body structures and planning of electroporation-based treatments

PubMed Central

2015-01-01

Background Treatments based on electroporation are a new and promising approach to treating tumors, especially non-resectable ones. The success of the treatment is, however, heavily dependent on coverage of the entire tumor volume with a sufficiently high electric field. Ensuring complete coverage in the case of deep-seated tumors is not trivial and can in best way be ensured by patient-specific treatment planning. The basis of the treatment planning process consists of two complex tasks: medical image segmentation, and numerical modeling and optimization. Methods In addition to previously developed segmentation algorithms for several tissues (human liver, hepatic vessels, bone tissue and canine brain) and the algorithms for numerical modeling and optimization of treatment parameters, we developed a web-based tool to facilitate the translation of the algorithms and their application in the clinic. The developed web-based tool automatically builds a 3D model of the target tissue from the medical images uploaded by the user and then uses this 3D model to optimize treatment parameters. The tool enables the user to validate the results of the automatic segmentation and make corrections if necessary before delivering the final treatment plan. Results Evaluation of the tool was performed by five independent experts from four different institutions. During the evaluation, we gathered data concerning user experience and measured performance times for different components of the tool. Both user reports and performance times show significant reduction in treatment-planning complexity and time-consumption from 1-2 days to a few hours. Conclusions The presented web-based tool is intended to facilitate the treatment planning process and reduce the time needed for it. It is crucial for facilitating expansion of electroporation-based treatments in the clinic and ensuring reliable treatment for the patients. The additional value of the tool is the possibility of easy upgrade and integration of modules with new functionalities as they are developed. PMID:26356007

CyberArc: a non-coplanar-arc optimization algorithm for CyberKnife

NASA Astrophysics Data System (ADS)

Kearney, Vasant; Cheung, Joey P.; McGuinness, Christopher; Solberg, Timothy D.

2017-07-01

The goal of this study is to demonstrate the feasibility of a novel non-coplanar-arc optimization algorithm (CyberArc). This method aims to reduce the delivery time of conventional CyberKnife treatments by allowing for continuous beam delivery. CyberArc uses a 4 step optimization strategy, in which nodes, beams, and collimator sizes are determined, source trajectories are calculated, intermediate radiation models are generated, and final monitor units are calculated, for the continuous radiation source model. The dosimetric results as well as the time reduction factors for CyberArc are presented for 7 prostate and 2 brain cases. The dosimetric quality of the CyberArc plans are evaluated using conformity index, heterogeneity index, local confined normalized-mutual-information, and various clinically relevant dosimetric parameters. The results indicate that the CyberArc algorithm dramatically reduces the treatment time of CyberKnife plans while simultaneously preserving the dosimetric quality of the original plans.

CyberArc: a non-coplanar-arc optimization algorithm for CyberKnife.

PubMed

Kearney, Vasant; Cheung, Joey P; McGuinness, Christopher; Solberg, Timothy D

2017-06-26

The goal of this study is to demonstrate the feasibility of a novel non-coplanar-arc optimization algorithm (CyberArc). This method aims to reduce the delivery time of conventional CyberKnife treatments by allowing for continuous beam delivery. CyberArc uses a 4 step optimization strategy, in which nodes, beams, and collimator sizes are determined, source trajectories are calculated, intermediate radiation models are generated, and final monitor units are calculated, for the continuous radiation source model. The dosimetric results as well as the time reduction factors for CyberArc are presented for 7 prostate and 2 brain cases. The dosimetric quality of the CyberArc plans are evaluated using conformity index, heterogeneity index, local confined normalized-mutual-information, and various clinically relevant dosimetric parameters. The results indicate that the CyberArc algorithm dramatically reduces the treatment time of CyberKnife plans while simultaneously preserving the dosimetric quality of the original plans.

Efficiency of analytical and sampling-based uncertainty propagation in intensity-modulated proton therapy

NASA Astrophysics Data System (ADS)

Wahl, N.; Hennig, P.; Wieser, H. P.; Bangert, M.

2017-07-01

The sensitivity of intensity-modulated proton therapy (IMPT) treatment plans to uncertainties can be quantified and mitigated with robust/min-max and stochastic/probabilistic treatment analysis and optimization techniques. Those methods usually rely on sparse random, importance, or worst-case sampling. Inevitably, this imposes a trade-off between computational speed and accuracy of the uncertainty propagation. Here, we investigate analytical probabilistic modeling (APM) as an alternative for uncertainty propagation and minimization in IMPT that does not rely on scenario sampling. APM propagates probability distributions over range and setup uncertainties via a Gaussian pencil-beam approximation into moments of the probability distributions over the resulting dose in closed form. It supports arbitrary correlation models and allows for efficient incorporation of fractionation effects regarding random and systematic errors. We evaluate the trade-off between run-time and accuracy of APM uncertainty computations on three patient datasets. Results are compared against reference computations facilitating importance and random sampling. Two approximation techniques to accelerate uncertainty propagation and minimization based on probabilistic treatment plan optimization are presented. Runtimes are measured on CPU and GPU platforms, dosimetric accuracy is quantified in comparison to a sampling-based benchmark (5000 random samples). APM accurately propagates range and setup uncertainties into dose uncertainties at competitive run-times (GPU ≤slant {5} min). The resulting standard deviation (expectation value) of dose show average global γ{3% / {3}~mm} pass rates between 94.2% and 99.9% (98.4% and 100.0%). All investigated importance sampling strategies provided less accuracy at higher run-times considering only a single fraction. Considering fractionation, APM uncertainty propagation and treatment plan optimization was proven to be possible at constant time complexity, while run-times of sampling-based computations are linear in the number of fractions. Using sum sampling within APM, uncertainty propagation can only be accelerated at the cost of reduced accuracy in variance calculations. For probabilistic plan optimization, we were able to approximate the necessary pre-computations within seconds, yielding treatment plans of similar quality as gained from exact uncertainty propagation. APM is suited to enhance the trade-off between speed and accuracy in uncertainty propagation and probabilistic treatment plan optimization, especially in the context of fractionation. This brings fully-fledged APM computations within reach of clinical application.

Efficiency of analytical and sampling-based uncertainty propagation in intensity-modulated proton therapy.

PubMed

Wahl, N; Hennig, P; Wieser, H P; Bangert, M

2017-06-26

The sensitivity of intensity-modulated proton therapy (IMPT) treatment plans to uncertainties can be quantified and mitigated with robust/min-max and stochastic/probabilistic treatment analysis and optimization techniques. Those methods usually rely on sparse random, importance, or worst-case sampling. Inevitably, this imposes a trade-off between computational speed and accuracy of the uncertainty propagation. Here, we investigate analytical probabilistic modeling (APM) as an alternative for uncertainty propagation and minimization in IMPT that does not rely on scenario sampling. APM propagates probability distributions over range and setup uncertainties via a Gaussian pencil-beam approximation into moments of the probability distributions over the resulting dose in closed form. It supports arbitrary correlation models and allows for efficient incorporation of fractionation effects regarding random and systematic errors. We evaluate the trade-off between run-time and accuracy of APM uncertainty computations on three patient datasets. Results are compared against reference computations facilitating importance and random sampling. Two approximation techniques to accelerate uncertainty propagation and minimization based on probabilistic treatment plan optimization are presented. Runtimes are measured on CPU and GPU platforms, dosimetric accuracy is quantified in comparison to a sampling-based benchmark (5000 random samples). APM accurately propagates range and setup uncertainties into dose uncertainties at competitive run-times (GPU [Formula: see text] min). The resulting standard deviation (expectation value) of dose show average global [Formula: see text] pass rates between 94.2% and 99.9% (98.4% and 100.0%). All investigated importance sampling strategies provided less accuracy at higher run-times considering only a single fraction. Considering fractionation, APM uncertainty propagation and treatment plan optimization was proven to be possible at constant time complexity, while run-times of sampling-based computations are linear in the number of fractions. Using sum sampling within APM, uncertainty propagation can only be accelerated at the cost of reduced accuracy in variance calculations. For probabilistic plan optimization, we were able to approximate the necessary pre-computations within seconds, yielding treatment plans of similar quality as gained from exact uncertainty propagation. APM is suited to enhance the trade-off between speed and accuracy in uncertainty propagation and probabilistic treatment plan optimization, especially in the context of fractionation. This brings fully-fledged APM computations within reach of clinical application.

Enhanced charge transport and photovoltaic performance of PBDTTT-C-T/PC70BM solar cells via UV-ozone treatment.

PubMed

Adhikary, Prajwal; Venkatesan, Swaminathan; Adhikari, Nirmal; Maharjan, Purna P; Adebanjo, Olusegun; Chen, Jihua; Qiao, Qiquan

2013-10-21

In this work, the electron transport layer of PBDTTT-C-T/PC70BM polymer solar cells were subjected to UV-ozone treatment, leading to improved cell performances from 6.46% to 8.34%. The solar cell efficiency reached a maximum of 8.34% after an optimal 5 minute UV-ozone treatment, and then decreased if treated for a longer time. To the best of our knowledge, the mechanism behind the effects of UV-ozone treatment on the improvement of charge transport and cell performance is not fully understood. We have developed a fundamental understanding of the UV-ozone treatment mechanism, which explains both the enhancements in charge transport and photovoltaic performance at an optimal treatment time, and also the phenomenon whereby further treatment time leads to a drop in cell efficiency. Transient photocurrent measurements indicated that the cell charge transport times were 1370 ns, 770 ns, 832 ns, 867 ns, and 1150 ns for the 0 min, 5 min, 10 min, 15 min, and 20 min UV-ozone treatment times, respectively. Therefore the 5 min UV-ozone treatment time led to the shortest transport time and the most efficient charge transport in the cells. The 5 min UV-ozone treated sample exhibited the highest peak intensity (E2) in the Raman spectra of the treated films, at about 437 cm(-1), indicating that it possessed the best wurtzite phase crystallinity of the ZnO films. Further increasing the UV-ozone treatment time from 5 to 20 min induced the formation of p-type defects (e.g. interstitial oxygen atoms), pushing the ZnO Fermi-level further away from the vacuum level, and decreasing the wurtzite crystallinity.

Optimization Study of Pulsed DC Nitrogen-Hydrogen Plasma in the Presence of an Active Screen Cage

NASA Astrophysics Data System (ADS)

Saeed, A.; W. Khan, A.; F., Jan; U. Shah, H.; Abrar, M.; Zaka-Ul-Islam, M.; Khalid, M.; Zakaullah, M.

2014-05-01

A glow discharge plasma nitriding reactor in the presence of an active screen cage is optimized in terms of current density, filling pressure and hydrogen concentrations using optical emission spectroscopy (OES). The samples of AISI 304 are nitrided for different treatment times under optimum conditions. The treated samples were analyzed by X-ray diffraction (XRD) to explore the changes induced in the crystallographic structure. The XRD pattern confirmed the formation of iron and chromium nitrides arising from incorporation of nitrogen as an interstitial solid solution in the iron lattice. A Vickers microhardness tester was used to evaluate the surface hardness as a function of treatment time (h). The results showed clear evidence of improved surface hardness and a substantial amount of decrease in the treatment time compared with the previous work.

Complaint-adaptive power density optimization as a tool for HTP-guided steering in deep hyperthermia treatment of pelvic tumors

NASA Astrophysics Data System (ADS)

Canters, R. A. M.; Franckena, M.; van der Zee, J.; Van Rhoon, G. C.

2008-12-01

For an efficient clinical use of HTP (hyperthermia treatment planning), optimization methods are needed. In this study, a complaint-adaptive PD (power density) optimization as a tool for HTP-guided steering in deep hyperthermia of pelvic tumors is developed and tested. PD distribution in patients is predicted using FE-models. Two goal functions, Opt1 and Opt2, are applied to optimize PD distributions. Optimization consists of three steps: initial optimization, adaptive optimization after a first complaint and increasing the weight of a region after recurring complaints. Opt1 initially considers only target PD whereas Opt2 also takes into account hot spots. After patient complaints though, both limit PD in a region. Opt1 and Opt2 are evaluated in a phantom test, using patient models and during hyperthermia treatment. The phantom test and a sensitivity study in ten patient models, show that HTP-guided steering is most effective in peripheral complaint regions. Clinical evaluation in two groups of five patients shows that time between complaints is longer using Opt2 (p = 0.007). However, this does not lead to significantly different temperatures (T50s of 40.3 (Opt1) versus 40.1 °C (Opt2) (p = 0.898)). HTP-guided steering is feasible in terms of PD reduction in complaint regions and in time consumption. Opt2 is preferable in future use, because of better complaint reduction and control.

Efficacy and Safety of Amphetamine Extended-Release Oral Suspension in Children with Attention-Deficit/Hyperactivity Disorder.

PubMed

Childress, Ann C; Wigal, Sharon B; Brams, Matthew N; Turnbow, John M; Pincus, Yulia; Belden, Heidi W; Berry, Sally A

2018-06-01

To determine the efficacy and safety of amphetamine extended-release oral suspension (AMPH EROS) in the treatment of attention-deficit/hyperactivity disorder (ADHD) in a dose-optimized, randomized, double-blind, parallel-group study. Boys and girls aged 6 to 12 years diagnosed with ADHD were enrolled. During a 5-week, open-label, dose-optimization phase, patients began treatment with 2.5 or 5 mg/day of AMPH EROS; doses were titrated until an optimal dose (maximum 20 mg/day) was reached. During the double-blind phase, patients were randomized to receive treatment with either their optimized dose (10-20 mg/day) of AMPH EROS or placebo for 1 week. Efficacy was assessed in a laboratory classroom setting on the final day of double-blind treatment using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product Measure of Performance (PERMP) test. Safety was assessed measuring adverse events (AEs) and vital signs. The study was completed by 99 patients. The primary efficacy endpoint (change from predose SKAMP-Combined score at 4 hours postdose) and secondary endpoints (change from predose SKAMP-Combined scores at 1, 2, 6, 8, 10, 12, and 13 hours postdose) were statistically significantly improved with AMPH EROS treatment versus placebo at all time points. Onset of treatment effect was present by 1 hour postdosing, the first time point measured, and duration of efficacy lasted 13 hours postdosing. PERMP data mirrored the SKAMP-Combined score data. AEs (>5%) reported during dose optimization were decreased appetite, insomnia, affect lability, upper abdominal pain, mood swings, and headache. AMPH EROS was effective in reducing symptoms of ADHD and had a rapid onset and extended duration of effect. Reported AEs were consistent with those of other extended-release amphetamine products.

Linear quadratic tracking problems in Hilbert space - Application to optimal active noise suppression

NASA Technical Reports Server (NTRS)

Banks, H. T.; Silcox, R. J.; Keeling, S. L.; Wang, C.

1989-01-01

A unified treatment of the linear quadratic tracking (LQT) problem, in which a control system's dynamics are modeled by a linear evolution equation with a nonhomogeneous component that is linearly dependent on the control function u, is presented; the treatment proceeds from the theoretical formulation to a numerical approximation framework. Attention is given to two categories of LQT problems in an infinite time interval: the finite energy and the finite average energy. The behavior of the optimal solution for finite time-interval problems as the length of the interval tends to infinity is discussed. Also presented are the formulations and properties of LQT problems in a finite time interval.

Integration of tobacco cessation services into multidisciplinary lung cancer care: rationale, state of the art, and future directions

PubMed Central

Warren, Graham W.

2015-01-01

Tobacco use is the largest risk factor for lung cancer and many lung cancer patients still smoke at the time of diagnosis. Although clinical practice guidelines recommend that all patients receive evidence-based tobacco treatment, implementation of these services in oncology practices is inconsistent and inadequate. Multidisciplinary lung cancer treatment programs offer an ideal environment to optimally deliver effective smoking cessation services. This article reviews best practice recommendations and current status of tobacco treatment for oncology patients, and provides recommendations to optimize delivery of tobacco treatment in multidisciplinary practice. PMID:26380175

Comparative evaluation of two dose optimization methods for image-guided, highly-conformal, tandem and ovoids cervix brachytherapy planning

NASA Astrophysics Data System (ADS)

Ren, Jiyun; Menon, Geetha; Sloboda, Ron

2013-04-01

Although the Manchester system is still extensively used to prescribe dose in brachytherapy (BT) for locally advanced cervix cancer, many radiation oncology centers are transitioning to 3D image-guided BT, owing to the excellent anatomy definition offered by modern imaging modalities. As automatic dose optimization is highly desirable for 3D image-based BT, this study comparatively evaluates the performance of two optimization methods used in BT treatment planning—Nelder-Mead simplex (NMS) and simulated annealing (SA)—for a cervix BT computer simulation model incorporating a Manchester-style applicator. Eight model cases were constructed based on anatomical structure data (for high risk-clinical target volume (HR-CTV), bladder, rectum and sigmoid) obtained from measurements on fused MR-CT images for BT patients. D90 and V100 for HR-CTV, D2cc for organs at risk (OARs), dose to point A, conformation index and the sum of dwell times within the tandem and ovoids were calculated for optimized treatment plans designed to treat the HR-CTV in a highly conformal manner. Compared to the NMS algorithm, SA was found to be superior as it could perform optimization starting from a range of initial dwell times, while the performance of NMS was strongly dependent on their initial choice. SA-optimized plans also exhibited lower D2cc to OARs, especially the bladder and sigmoid, and reduced tandem dwell times. For cases with smaller HR-CTV having good separation from adjoining OARs, multiple SA-optimized solutions were found which differed markedly from each other and were associated with different choices for initial dwell times. Finally and importantly, the SA method yielded plans with lower dwell time variability compared with the NMS method.

Decision making with regard to antiviral intervention during an influenza pandemic.

PubMed

Shim, Eunha; Chapman, Gretchen B; Galvani, Alison P

2010-01-01

Antiviral coverage is defined by the proportion of the population that takes antiviral prophylaxis or treatment. High coverage of an antiviral drug has epidemiological and evolutionary repercussions. Antivirals select for drug resistance within the population, and individuals may experience adverse effects. To determine optimal antiviral coverage in the context of an influenza outbreak, we compared 2 perspectives: 1) the individual level (the Nash perspective), and 2) the population level (utilitarian perspective). We developed an epidemiological game-theoretic model of an influenza pandemic. The data sources were published literature and a national survey. The target population was the US population. The time horizon was 6 months. The perspective was individuals and the population overall. The interventions were antiviral prophylaxis and treatment. The outcome measures were the optimal coverage of antivirals in an influenza pandemic. At current antiviral pricing, the optimal Nash strategy is 0% coverage for prophylaxis and 30% coverage for treatment, whereas the optimal utilitarian strategy is 19% coverage for prophylaxis and 100% coverage for treatment. Subsidizing prophylaxis by $440 and treatment by $85 would bring the Nash and utilitarian strategies into alignment. For both prophylaxis and treatment, the optimal antiviral coverage decreases as pricing of antivirals increases. Our study does not incorporate the possibility of an effective vaccine and lacks probabilistic sensitivity analysis. Our survey also does not completely represent the US population. Because our model assumes a homogeneous population and homogeneous antiviral pricing, it does not incorporate heterogeneity of preference. The optimal antiviral coverage from the population perspective and individual perspectives differs widely for both prophylaxis and treatment strategies. Optimal population and individual strategies for prophylaxis and treatment might be aligned through subsidization.

Decision Making with Regard to Antiviral Intervention during an Influenza Pandemic

PubMed Central

Shim, Eunha; Chapman, Gretchen B.; Galvani, Alison P.

2012-01-01

Background Antiviral coverage is defined by the proportion of the population that takes antiviral prophylaxis or treatment. High coverage of an antiviral drug has epidemiological and evolutionary repercussions. Antivirals select for drug resistance within the population, and individuals may experience adverse effects. To determine optimal antiviral coverage in the context of an influenza outbreak, we compared 2 perspectives: 1) the individual level (the Nash perspective), and 2) the population level (utilitarian perspective). Methods We developed an epidemiological game-theoretic model of an influenza pandemic. The data sources were published literature and a national survey. The target population was the US population. The time horizon was 6 months. The perspective was individuals and the population overall. The interventions were antiviral prophylaxis and treatment. The outcome measures were the optimal coverage of antivirals in an influenza pandemic. Results At current antiviral pricing, the optimal Nash strategy is 0% coverage for prophylaxis and 30% coverage for treatment, whereas the optimal utilitarian strategy is 19% coverage for prophylaxis and 100% coverage for treatment. Subsidizing prophylaxis by $440 and treatment by $85 would bring the Nash and utilitarian strategies into alignment. For both prophylaxis and treatment, the optimal antiviral coverage decreases as pricing of antivirals increases. Our study does not incorporate the possibility of an effective vaccine and lacks probabilistic sensitivity analysis. Our survey also does not completely represent the US population. Because our model assumes a homogeneous population and homogeneous antiviral pricing, it does not incorporate heterogeneity of preference. Conclusions The optimal antiviral coverage from the population perspective and individual perspectives differs widely for both prophylaxis and treatment strategies. Optimal population and individual strategies for prophylaxis and treatment might be aligned through subsidization. PMID:20634545

Optimization of combination therapy of arsenic trioxide and fractionated radiotherapy for malignant glioma

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

Ning Shoucheng; Knox, Susan J.

2006-06-01

Purpose: The primary objective was to optimize the combined treatment regimen using arsenic trioxide (ATO) and fractionated radiotherapy for the treatment of malignant glioma. Methods and Materials: Nude mice with human glioma xenograft tumors were treated with fractionated local tumor radiation of 250 cGy/fraction/day and 5 mg/kg ATO for 5-10 days. Results: Time course experiments demonstrated that maximal tumor growth delay occurred when ATO was administered between 0 and 4 h after radiation. The combination treatment of ATO and radiation synergistically inhibited tumor growth and produced a tumor growth delay time of 13.2 days, compared with 1.4 days and 6.5more » days for ATO and radiation alone (p < 0.01), respectively. The use of concurrent therapy of radiation and ATO initially, followed by ATO as maintenance therapy, was superior to the use of preloading with ATO before combined therapy and produced a tumor growth delay time of 22.7 days as compared with 11.7 days for the ATO preloading regimen (p < 0.01). The maintenance dose of ATO after concurrent therapy was effective and important for continued inhibition of tumor growth. Conclusions: The combined use of fractionated radiation and ATO is effective for the treatment of glioma xenograft tumors. ATO was most effective when administered 0-4 h after radiation without pretreatment with ATO. These results have important implications for the optimization of treatment regimen using ATO and fractionated radiotherapy for the treatment of brain tumors.« less

[Optimization of acupoint application scheme in the treatment of bronchial asthma based on the orthogonal design method].

PubMed

Shi, Kuan; Wu, Wenzhong; Liu, Lanying; Wang, Hesheng; Chen, Dong; Liu, Chengyong; Zhang, Cong

2017-06-12

To study the primary and secondary factors of the allergic history, the frequency of acupoint application and the time of acupoint application in the treatment of bronchial asthma and optimize its scheme. Eighty patients of bronchial asthma were selected as the subjects in the orthogonal trial. The herbal medicines were the empirical formula of acupoint application (prepared at the ratio as 2:2:1:1:1:1:1:1:1 of semen brassicae , rhizome corydalis , unprocessed radix kansui , asarum sieboldii , ephedra , semen lepidii , syzygium aromaticum , cortex cinnamomi and fructus gleditsiae ) and used on bilateral Feishu (BL 13), Xinshu (BL 15), Geshu (BL 17) and Shenshu (BL 23). Firstly, two groups were divided according to allergic history (40 cases with allergic history and 40 cases without allergic history), and then four subgroups were divided on the basis of the two main groups, 10 cases in each one. Through studying three factors and two levels, i.e. allergic history (Factor A:A Ⅰ :with allergic history; A Ⅱ :without allergic history), the frequency of acupoint application (Factor B:B Ⅰ :4 times; B Ⅱ :10 times, in which, in the group of 4-time applications, the application was given once every 10 days; in the group of 10-time applications, the application was given once every 4 days); and the time of application (Factor C:C Ⅰ :4 h; C Ⅱ :8 h), the optimal scheme was screened on the basis of the attack frequency before and after treatment and the score of the asthma quality life questionnaire (AQLQ) before treatment and 6 months after treatment in the patients of each group. ① The orthogonal trial indicated that the best optimal scheme was A Ⅰ B Ⅱ C Ⅰ , meaning the patients with allergic history were treated with acupoint application for 10 times, remained for 4 h. ②Factor B (frequency of acupoint application) and C (time of acpoint application) were the significant influential factors of AQLQ scores (both P <0.05). ③The comparison of the attack frequency and AQLQ score before and after treatment in all of the patients showed that the different combinations of factor levels induced the different impacts on the asthma attack frequency and AQLQ scores. Except in the group No.1 and the group No.5, the improvements were all significant in the rest groups, indicating the significant differences ( P <0.05, P <0.01). Acupoint application reduces apparently the attack frequency of asthma in the patients and improves the living quality. The primary and secondary relationship among the allergic history, the frequency of acupoint application and the time of acupoint application for the impacts on the therapeutic effects are:the frequency of acupoint application > the time of acupoint application > the allergic history. The best optimal scheme is A Ⅰ B Ⅱ C Ⅰ , meaning the patients with allergic history are treated with acupoint application for 10 times, remained for 4h.

SU-E-T-213: Comparison of Treatment Efficiency of Gamma Knife SRS Plans for Brain Metastases with Different Planning Methods

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

Feng, Y; Huang, Z; Lo, S

2015-06-15

Purpose: To improve Gamma Knife SRS treatment efficiency for brain metastases and compare the differences of treatment time and radiobiological effects between two different planning methods of automatic filling and manual placement of shots with inverse planning. Methods: T1-weighted MRI images with gadolinium contrast from five patients with a single brain metastatic-lesion were used in this retrospective study. Among them, two were from primary breast cancer, two from primary melanoma cancer and one from primary prostate cancer. For each patient, two plans were generated in Leksell GammaPlan10.1.1 for radiosurgical treatment with a Leksell GammaKnife Perfexion machine: one with automatic filling,more » automatic sector configuration and inverse optimization (Method1); and the other with manual placement of shots, manual setup of collimator sizes, manual setup of sector blocking and inverse optimization (Method2). Dosimetric quality of the plans was evaluated with parameters of Coverage, Selectivity, Gradient-Index and DVH. Beam-on Time, Number-of-Shots and Tumor Control Probability(TCP) were compared for the two plans while keeping their dosimetric quality very similar. Relative reduction of Beam-on Time and Number-of-Shots were calculated as the ratios among the two plans and used for quantitative analysis. Results: With very similar dosimetric and radiobiological plan quality, plans created with Method 2 had significantly reduced treatment time. Relative reduction of Beam-on Time ranged from 20% to 51 % (median:29%,p=0.001), and reduction of Number-of-Shots ranged from 5% to 67% (median:40%,p=0.0002), respectively. Time of plan creation for Method1 and Method2 was similar, approximately 20 minutes, excluding the time for tumor delineation. TCP calculated for the tumors from differential DVHs did not show significant difference between the two plans (p=0.35). Conclusion: The method of manual setup combined with inverse optimization in LGP for treatment of brain metastatic lesions with the Perfexion can achieve significantly higher time efficiency without degrading treatment quality.« less

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.

A continuous arc delivery optimization algorithm for CyberKnife m6.

PubMed

Kearney, Vasant; Descovich, Martina; Sudhyadhom, Atchar; Cheung, Joey P; McGuinness, Christopher; Solberg, Timothy D

2018-06-01

This study aims to reduce the delivery time of CyberKnife m6 treatments by allowing for noncoplanar continuous arc delivery. To achieve this, a novel noncoplanar continuous arc delivery optimization algorithm was developed for the CyberKnife m6 treatment system (CyberArc-m6). CyberArc-m6 uses a five-step overarching strategy, in which an initial set of beam geometries is determined, the robotic delivery path is calculated, direct aperture optimization is conducted, intermediate MLC configurations are extracted, and the final beam weights are computed for the continuous arc radiation source model. This algorithm was implemented on five prostate and three brain patients, previously planned using a conventional step-and-shoot CyberKnife m6 delivery technique. The dosimetric quality of the CyberArc-m6 plans was assessed using locally confined mutual information (LCMI), conformity index (CI), heterogeneity index (HI), and a variety of common clinical dosimetric objectives. Using conservative optimization tuning parameters, CyberArc-m6 plans were able to achieve an average CI difference of 0.036 ± 0.025, an average HI difference of 0.046 ± 0.038, and an average LCMI of 0.920 ± 0.030 compared with the original CyberKnife m6 plans. Including a 5 s per minute image alignment time and a 5-min setup time, conservative CyberArc-m6 plans achieved an average treatment delivery speed up of 1.545x ± 0.305x compared with step-and-shoot plans. The CyberArc-m6 algorithm was able to achieve dosimetrically similar plans compared to their step-and-shoot CyberKnife m6 counterparts, while simultaneously reducing treatment delivery times. © 2018 American Association of Physicists in Medicine.

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

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

A fast inverse treatment planning strategy facilitating optimized catheter selection in image-guided high-dose-rate interstitial gynecologic brachytherapy.

PubMed

Guthier, Christian V; Damato, Antonio L; Hesser, Juergen W; Viswanathan, Akila N; Cormack, Robert A

2017-12-01

Interstitial high-dose rate (HDR) brachytherapy is an important therapeutic strategy for the treatment of locally advanced gynecologic (GYN) cancers. The outcome of this therapy is determined by the quality of dose distribution achieved. This paper focuses on a novel yet simple heuristic for catheter selection for GYN HDR brachytherapy and their comparison against state of the art optimization strategies. The proposed technique is intended to act as a decision-supporting tool to select a favorable needle configuration. The presented heuristic for catheter optimization is based on a shrinkage-type algorithm (SACO). It is compared against state of the art planning in a retrospective study of 20 patients who previously received image-guided interstitial HDR brachytherapy using a Syed Neblett template. From those plans, template orientation and position are estimated via a rigid registration of the template with the actual catheter trajectories. All potential straight trajectories intersecting the contoured clinical target volume (CTV) are considered for catheter optimization. Retrospectively generated plans and clinical plans are compared with respect to dosimetric performance and optimization time. All plans were generated with one single run of the optimizer lasting 0.6-97.4 s. Compared to manual optimization, SACO yields a statistically significant (P ≤ 0.05) improved target coverage while at the same time fulfilling all dosimetric constraints for organs at risk (OARs). Comparing inverse planning strategies, dosimetric evaluation for SACO and "hybrid inverse planning and optimization" (HIPO), as gold standard, shows no statistically significant difference (P > 0.05). However, SACO provides the potential to reduce the number of used catheters without compromising plan quality. The proposed heuristic for needle selection provides fast catheter selection with optimization times suited for intraoperative treatment planning. Compared to manual optimization, the proposed methodology results in fewer catheters without a clinically significant loss in plan quality. The proposed approach can be used as a decision support tool that guides the user to find the ideal number and configuration of catheters. © 2017 American Association of Physicists in Medicine.

Optimal two-stage dynamic treatment regimes from a classification perspective with censored survival data.

PubMed

Hager, Rebecca; Tsiatis, Anastasios A; Davidian, Marie

2018-05-18

Clinicians often make multiple treatment decisions at key points over the course of a patient's disease. A dynamic treatment regime is a sequence of decision rules, each mapping a patient's observed history to the set of available, feasible treatment options at each decision point, and thus formalizes this process. An optimal regime is one leading to the most beneficial outcome on average if used to select treatment for the patient population. We propose a method for estimation of an optimal regime involving two decision points when the outcome of interest is a censored survival time, which is based on maximizing a locally efficient, doubly robust, augmented inverse probability weighted estimator for average outcome over a class of regimes. By casting this optimization as a classification problem, we exploit well-studied classification techniques such as support vector machines to characterize the class of regimes and facilitate implementation via a backward iterative algorithm. Simulation studies of performance and application of the method to data from a sequential, multiple assignment randomized clinical trial in acute leukemia are presented. © 2018, The International Biometric Society.

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.

Quality of mango nectar processed by high-pressure homogenization with optimized heat treatment.

PubMed

Tribst, Alline Artigiani Lima; Franchi, Mark Alexandrow; de Massaguer, Pilar Rodriguez; Cristianini, Marcelo

2011-03-01

This work aimed to evaluate the effect of high-pressure homogenization (HPH) with heat shock on Aspergillus niger, vitamin C, and color of mango nectar. The nectar was processed at 200 MPa followed by heat shock, which was optimized by response surface methodology by using mango nectar ratio (45 to 70), heat time (10 to 20), and temperature (60 to 85 °C) as variables. The color of mango nectar and vitamin C retention were evaluated at the optimized treatments, that is, 200 MPa + 61.5 °C/20 min or 73.5 °C/10 min. The mathematical model indicates that heat shock time and temperature showed a positive effect in the mould inactivation, whereas increasing ratio resulted in a protective effect on A. niger. The optimized treatments did not increase the retention of vitamin C, but had positive effect for the nectar color, in particular for samples treated at 200 MPa + 61.5 °C/20 min. The results obtained in this study show that the conidia can be inactivated by applying HPH with heat shock, particularly to apply HPH as an option to pasteurize fruit nectar for industries.

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.

Investigation of parameters affecting treatment time in MRI-guided transurethral ultrasound therapy

NASA Astrophysics Data System (ADS)

N'Djin, W. A.; Burtnyk, M.; Chopra, R.; Bronskill, M. J.

2010-03-01

MRI-guided transurethral ultrasound therapy shows promise for minimally invasive treatment of localized prostate cancer. Real-time MR temperature feedback enables the 3D control of thermal therapy to define an accurate region within the prostate. Previous in-vivo canine studies showed the feasibility of this method using transurethral planar transducers. The aim of this simulation study was to reduce the procedure time, while maintaining treatment accuracy by investigating new combinations of treatment parameters. A numerical model was used to simulate a multi-element heating applicator rotating inside the urethra in 10 human prostates. Acoustic power and rotation rate were varied based on the feedback of the temperature in the prostate. Several parameters were investigated for improving the treatment time. Maximum acoustic power and rotation rate were optimized interdependently as a function of prostate radius and transducer operating frequency, while avoiding temperatures >90° C in the prostate. Other trials were performed on each parameter separately, with the other parameter fixed. The concept of using dual-frequency transducers was studied, using the fundamental frequency or the 3rd harmonic component depending on the prostate radius. The maximum acoustic power which could be used decreased as a function of the prostate radius and the frequency. Decreasing the frequency (9.7-3.0 MHz) or increasing the power (10-20 W.cm-2) led to treatment times shorter by up to 50% under appropriate conditions. Dual-frequency configurations, while helpful, tended to have less impact on treatment times. Treatment accuracy was maintained and critical adjacent tissues like the rectal wall remained protected. The interdependence between power and frequency may require integrating multi-parametric functions inside the controller for future optimizations. As a first approach, however, even slight modifications of key parameters can be sufficient to reduce treatment time.

Accuracy and optimal timing of activity measurements in estimating the absorbed dose of radioiodine in the treatment of Graves' disease

NASA Astrophysics Data System (ADS)

Merrill, S.; Horowitz, J.; Traino, A. C.; Chipkin, S. R.; Hollot, C. V.; Chait, Y.

2011-02-01

Calculation of the therapeutic activity of radioiodine 131I for individualized dosimetry in the treatment of Graves' disease requires an accurate estimate of the thyroid absorbed radiation dose based on a tracer activity administration of 131I. Common approaches (Marinelli-Quimby formula, MIRD algorithm) use, respectively, the effective half-life of radioiodine in the thyroid and the time-integrated activity. Many physicians perform one, two, or at most three tracer dose activity measurements at various times and calculate the required therapeutic activity by ad hoc methods. In this paper, we study the accuracy of estimates of four 'target variables': time-integrated activity coefficient, time of maximum activity, maximum activity, and effective half-life in the gland. Clinical data from 41 patients who underwent 131I therapy for Graves' disease at the University Hospital in Pisa, Italy, are used for analysis. The radioiodine kinetics are described using a nonlinear mixed-effects model. The distributions of the target variables in the patient population are characterized. Using minimum root mean squared error as the criterion, optimal 1-, 2-, and 3-point sampling schedules are determined for estimation of the target variables, and probabilistic bounds are given for the errors under the optimal times. An algorithm is developed for computing the optimal 1-, 2-, and 3-point sampling schedules for the target variables. This algorithm is implemented in a freely available software tool. Taking into consideration 131I effective half-life in the thyroid and measurement noise, the optimal 1-point time for time-integrated activity coefficient is a measurement 1 week following the tracer dose. Additional measurements give only a slight improvement in accuracy.

Process-time Optimization of Vacuum Degassing Using a Genetic Alloy Design Approach

PubMed Central

Dilner, David; Lu, Qi; Mao, Huahai; Xu, Wei; van der Zwaag, Sybrand; Selleby, Malin

2014-01-01

This paper demonstrates the use of a new model consisting of a genetic algorithm in combination with thermodynamic calculations and analytical process models to minimize the processing time during a vacuum degassing treatment of liquid steel. The model sets multiple simultaneous targets for final S, N, O, Si and Al levels and uses the total slag mass, the slag composition, the steel composition and the start temperature as optimization variables. The predicted optimal conditions agree well with industrial practice. For those conditions leading to the shortest process time the target compositions for S, N and O are reached almost simultaneously. PMID:28788286

MO-FG-CAMPUS-TeP2-01: A Graph Form ADMM Algorithm for Constrained Quadratic Radiation Treatment Planning

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

Liu, X; Belcher, AH; Wiersma, R

Purpose: In radiation therapy optimization the constraints can be either hard constraints which must be satisfied or soft constraints which are included but do not need to be satisfied exactly. Currently the voxel dose constraints are viewed as soft constraints and included as a part of the objective function and approximated as an unconstrained problem. However in some treatment planning cases the constraints should be specified as hard constraints and solved by constrained optimization. The goal of this work is to present a computation efficiency graph form alternating direction method of multipliers (ADMM) algorithm for constrained quadratic treatment planning optimizationmore » and compare it with several commonly used algorithms/toolbox. Method: ADMM can be viewed as an attempt to blend the benefits of dual decomposition and augmented Lagrangian methods for constrained optimization. Various proximal operators were first constructed as applicable to quadratic IMRT constrained optimization and the problem was formulated in a graph form of ADMM. A pre-iteration operation for the projection of a point to a graph was also proposed to further accelerate the computation. Result: The graph form ADMM algorithm was tested by the Common Optimization for Radiation Therapy (CORT) dataset including TG119, prostate, liver, and head & neck cases. Both unconstrained and constrained optimization problems were formulated for comparison purposes. All optimizations were solved by LBFGS, IPOPT, Matlab built-in toolbox, CVX (implementing SeDuMi) and Mosek solvers. For unconstrained optimization, it was found that LBFGS performs the best, and it was 3–5 times faster than graph form ADMM. However, for constrained optimization, graph form ADMM was 8 – 100 times faster than the other solvers. Conclusion: A graph form ADMM can be applied to constrained quadratic IMRT optimization. It is more computationally efficient than several other commercial and noncommercial optimizers and it also used significantly less computer memory.« less

Simulation and optimization of an experimental membrane wastewater treatment plant using computational intelligence methods.

PubMed

Ludwig, T; Kern, P; Bongards, M; Wolf, C

2011-01-01

The optimization of relaxation and filtration times of submerged microfiltration flat modules in membrane bioreactors used for municipal wastewater treatment is essential for efficient plant operation. However, the optimization and control of such plants and their filtration processes is a challenging problem due to the underlying highly nonlinear and complex processes. This paper presents the use of genetic algorithms for this optimization problem in conjunction with a fully calibrated simulation model, as computational intelligence methods are perfectly suited to the nonconvex multi-objective nature of the optimization problems posed by these complex systems. The simulation model is developed and calibrated using membrane modules from the wastewater simulation software GPS-X based on the Activated Sludge Model No.1 (ASM1). Simulation results have been validated at a technical reference plant. They clearly show that filtration process costs for cleaning and energy can be reduced significantly by intelligent process optimization.

Study on Treatment of Landfill Leachate by Electrochemical, Flocculation and Photocatalysis

NASA Astrophysics Data System (ADS)

Yang, Yue; Jin, Xiuping; Pan, Yunbo; Zuo, Xiaoran

2018-01-01

In this study, the landfill leachate of different seasons in Liaoyang City is as the research object, and COD removal rate is as the main indicator. The electrochemical section’s results show that the optimal treatment conditions for the water of 2016 summer are as follows: voltage is 7.0V, current density is 40.21 A/m2, pH is equal to the raw water, electrolysis time is 1h, and the COD removal rate is 80.41%. The optimal treatment conditions for the 2017 fall’s water are: electrolysis voltage is 7.0 V, current density is 45.06 A/m2, electrolysis time is 4 hours, and COD removal rate is 28.03%. The flow rate of continuous electrolysis is 6.4 L/h using the water of 2016 fall, and the COD removal rate is 10.28%. The results of the flocculation process show that the optimal treatment conditions are as follows: pH is equal to the raw water; the optimal flocculant species is Fe-Al composite flocculant, wherein the optimal ratio of Fe-Al is n (Fe):n (Al)=0.5:1; the best dosage of flocculant is 2.0 g/L and COD removal rate is of 21.11%. The results of photocatalytic show that the optimal conditions are: pH is 4.5, Al2(SO4)3 is 1.0 g/L, FeSO4.7H2O is 700mg/L, H2O2(30%) is 4 mL/L, stirring and standing UV lamp light irradiation 3 hours, and adjusting pH to 6.0 or so, COD removal rate is 36.15%. +

Event-driven time-optimal control for a class of discontinuous bioreactors.

PubMed

Moreno, Jaime A; Betancur, Manuel J; Buitrón, Germán; Moreno-Andrade, Iván

2006-07-05

Discontinuous bioreactors may be further optimized for processing inhibitory substrates using a convenient fed-batch mode. To do so the filling rate must be controlled in such a way as to push the reaction rate to its maximum value, by increasing the substrate concentration just up to the point where inhibition begins. However, an exact optimal controller requires measuring several variables (e.g., substrate concentrations in the feed and in the tank) and also good model knowledge (e.g., yield and kinetic parameters), requirements rarely satisfied in real applications. An environmentally important case, that exemplifies all these handicaps, is toxicant wastewater treatment. There the lack of online practical pollutant sensors may allow unforeseen high shock loads to be fed to the bioreactor, causing biomass inhibition that slows down the treatment process and, in extreme cases, even renders the biological process useless. In this work an event-driven time-optimal control (ED-TOC) is proposed to circumvent these limitations. We show how to detect a "there is inhibition" event by using some computable function of the available measurements. This event drives the ED-TOC to stop the filling. Later, by detecting the symmetric event, "there is no inhibition," the ED-TOC may restart the filling. A fill-react cycling then maintains the process safely hovering near its maximum reaction rate, allowing a robust and practically time-optimal operation of the bioreactor. An experimental study case of a wastewater treatment process application is presented. There the dissolved oxygen concentration was used to detect the events needed to drive the controller. (c) 2006 Wiley Periodicals, Inc.

Determination of proline in honey: comparison between official methods, optimization and validation of the analytical methodology.

PubMed

Truzzi, Cristina; Annibaldi, Anna; Illuminati, Silvia; Finale, Carolina; Scarponi, Giuseppe

2014-05-01

The study compares official spectrophotometric methods for the determination of proline content in honey - those of the International Honey Commission (IHC) and the Association of Official Analytical Chemists (AOAC) - with the original Ough method. Results show that the extra time-consuming treatment stages added by the IHC method with respect to the Ough method are pointless. We demonstrate that the AOACs method proves to be the best in terms of accuracy and time saving. The optimized waiting time for the absorbance recording is set at 35min from the removal of reaction tubes from the boiling bath used in the sample treatment. The optimized method was validated in the matrix: linearity up to 1800mgL(-1), limit of detection 20mgL(-1), limit of quantification 61mgL(-1). The method was applied to 43 unifloral honey samples from the Marche region, Italy. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

Duan, J

Purpose: The aim of this work is to study the dosimetric impact of leaf interdigitation in prostate cancer dynamic IMRT treatment planning. Methods: Fifteen previously treated prostate cancer patients were replanned for dynamic IMRT (dMLC) with and without leaf interdigitation using Monaco 3.3 TPS on the Elekta Synergy linear accelerator. The prescription dose of PTV was 70Gy/35 fractions. Various dosimetric variables, such as PTV coverage, OAR sparing, delivery efficiency and optimization time, were evaluated for each plan. Results: Interdigitation did not improve the coverage, HI and CI for PTV. Regarding OARs, sparing was equivalent with and without interdigitation. Interdigitation shownmore » an increase in MUs and segments. It was worth noting that leaf interdigitation saved the optimization time. Conclusion: This study shows that leaf interdigitation does not improve plan quality when performing dMLC treatment plan for prostate cancer. However, it influences delivery efficiency and optimization time. Interdigitation may gain efficiency for dosimetrist when designing the prostate cancer dMLC plans.« less

Optimization of radiotherapy. Some notes on the principles and practice of optimization in cancer treatment and implications for clinical research.

PubMed

Andrews, J R

1981-01-01

Two methods dominate cancer treatment--one, the traditional best practice, individualized treatment method and two, the a priori determined decision method of the interinstitutional, cooperative, clinical trial. In the first, choices are infinite and can be made at the time of treatment; in the second, choices are finite and are made in advance of treatment on a random basis. Neither method systematically selects, identifies, or formalizes the optimum level of effect in the treatment chosen. Of the two, it can be argued that the first, other things being equal, is more likely to select the optimum treatment. The determination of level of effect for the optimization of cancer treatment requires the generation of dose-response relationships for both benefit and risk and the introduction of benefit and risk considerations and judgements. The clinical trial, as presently constituted, doses not yield this kind of information, it being, generally, of the binary yes or no, better or worse type. The best practice, individualized treatment method can yield, when adequately documented, both a range of dose-response relationships and a variety of benefit and risk considerations. The presentation will be limited to a consideration of a single modality of cancer treatment, radiation therapy, but an analogy with other modalities of cancer treatment will be inferred. Criteria for optimization will be developed and graphic means for its identification and formalization will be demonstrated with examples taken from the radiotherapy literature. The general problem of optimization theory and practice will be discussed; the necessity for its exploration in relation to the increasing complexity of cancer treatment will be developed; and recommendations for clinical research will be made including a proposal for the support of clinics as an alternative to the support of programs.

Electrochemical treatment of domestic wastewater using boron-doped diamond and nanostructured amorphous carbon electrodes.

PubMed

Daghrir, Rimeh; Drogui, Patrick; Tshibangu, Joel; Delegan, Nazar; El Khakani, My Ali

2014-05-01

The performance of the electrochemical oxidation process for efficient treatment of domestic wastewater loaded with organic matter was studied. The process was firstly evaluated in terms of its capability of producing an oxidant agent (H2O2) using amorphous carbon (or carbon felt) as cathode, whereas Ti/BDD electrode was used as anode. Relatively high concentrations of H2O2 (0.064 mM) was produced after 90 min of electrolysis time, at 4.0 A of current intensity and using amorphous carbon at the cathode. Factorial design and central composite design methodologies were successively used to define the optimal operating conditions to reach maximum removal of chemical oxygen demand (COD) and color. Current intensity and electrolysis time were found to influence the removal of COD and color. The contribution of current intensity on the removal of COD and color was around 59.1 and 58.8%, respectively, whereas the contribution of treatment time on the removal of COD and color was around 23.2 and 22.9%, respectively. The electrochemical treatment applied under 3.0 A of current intensity, during 120 min of electrolysis time and using Ti/BDD as anode, was found to be the optimal operating condition in terms of cost/effectiveness. Under these optimal conditions, the average removal rates of COD and color were 78.9 ± 2 and 85.5 ± 2 %, whereas 70% of total organic carbon removal was achieved.

Three dimensional intensity modulated brachytherapy (IMBT): dosimetry algorithm and inverse treatment planning.

PubMed

Shi, Chengyu; Guo, Bingqi; Cheng, Chih-Yao; Esquivel, Carlos; Eng, Tony; Papanikolaou, Niko

2010-07-01

The feasibility of intensity modulated brachytherapy (IMBT) to improve dose conformity for irregularly shaped targets has been previously investigated by researchers by means of using partially shielded sources. However, partial shielding does not fully explore the potential of IMBT. The goal of this study is to introduce the concept of three dimensional (3D) intensity modulated brachytherapy and solve two fundamental issues regarding the application of 3D IMBT treatment planning: The dose calculation algorithm and the inverse treatment planning method. A 3D IMBT treatment planning system prototype was developed using the MATLAB platform. This system consists of three major components: (1) A comprehensive IMBT source calibration method with dosimetric inputs from Monte Carlo (EGSnrc) simulations; (2) a "modified TG-43" (mTG-43) dose calculation formalism for IMBT dosimetry; and (3) a physical constraint based inverse IMBT treatment planning platform utilizing a simulated annealing optimization algorithm. The model S700 Axxent electronic brachytherapy source developed by Xoft, Inc. (Fremont, CA), was simulated in this application. Ten intracavitary accelerated partial breast irradiation (APBI) cases were studied. For each case, an "isotropic plan" with only optimized source dwell time and a fully optimized IMBT plan were generated and compared to the original plan in various dosimetric aspects, such as the plan quality, planning, and delivery time. The issue of the mechanical complexity of the IMBT applicator is not addressed in this study. IMBT approaches showed superior plan quality compared to the original plans and tht isotropic plans to different extents in all studied cases. An extremely difficult case with a small breast and a small distance to the ribs and skin, the IMBT plan minimized the high dose volume V200 by 16.1% and 4.8%, respectively, compared to the original and the isotropic plans. The conformity index for the target was increased by 0.13 and 0.04, respectively. The maximum dose to the skin was reduced by 56 and 28 cGy, respectively, per fraction. Also, the maximum dose to the ribs was reduced by 104 and 96 cGy, respectively, per fraction. The mean dose to the ipsilateral and contralateral breasts and lungs were also slightly reduced by the IMBT plan. The limitations of IMBT are the longer planning and delivery time. The IMBT plan took around 2 h to optimize, while the isotropic plan optimization could reach the global minimum within 5 min. The delivery time for the IMBT plan is typically four to six times longer than the corresponding isotropic plan. In this study, a dosimetry method for IMBT sources was proposed and an inverse treatment planning system prototype for IMBT was developed. The improvement of plan quality by 3D IMBT was demonstrated using ten APBI case studies. Faster computers and higher output of the source can further reduce plan optimization and delivery time, respectively.

Optically Based Rapid Screening Method for Proven Optimal Treatment Strategies Before Treatment Begins

DTIC Science & Technology

to rapidly test /screen breast cancer therapeutics as a strategy to streamline drug development and provide individualized treatment. The results...system can therefore be used to streamline pre-clinical drug development, by reducing the number of animals , cost, and time required to screen new drugs

SU-E-T-593: Clinical Evaluation of Direct Aperture Optimization in Head/Neck and Prostate IMRT Treatment

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

Hosini, M; GALAL, M; Emam, I

2014-06-01

Purpose: To investigate the planning and dosimetric advantages of direct aperture optimization (DAO) over beam-let optimization in IMRT treatment of head and neck (H/N) and prostate cancers. Methods: Five Head and Neck as well as five prostate patients were planned using the beamlet optimizer in Elekta-Xio ver 4.6 IMRT treatment planning system. Based on our experience in beamlet IMRT optimization, PTVs in H/N plans were prescribed to 70 Gy delivered by 7 fields. While prostate PTVs were prescribed to 76 Gy with 9 fields. In all plans, fields were set to be equally spaced. All cases were re-planed using Directmore » Aperture optimizer in Prowess Panther ver 5.01 IMRT planning system at same configurations and dose constraints. Plans were evaluated according to ICRU criteria, number of segments, number of monitor units and planning time. Results: For H/N plans, the near maximum dose (D2) and the dose that covers 95% D95 of PTV has improved by 4% in DAO. For organs at risk (OAR), DAO reduced the volume covered by 30% (V30) in spinal cord, right parotid, and left parotid by 60%, 54%, and 53% respectively. This considerable dosimetric quality improvement achieved using 25% less planning time and lower number of segments and monitor units by 46% and 51% respectively. In DAO prostate plans, Both D2 and D95 for the PTV were improved by only 2%. The V30 of the right femur, left femur and bladder were improved by 35%, 15% and 3% respectively. On the contrary, the rectum V30 got even worse by 9%. However, number of monitor units, and number of segments decreased by 20% and 25% respectively. Moreover the planning time reduced significantly too. Conclusion: DAO introduces considerable advantages over the beamlet optimization in regards to organs at risk sparing. However, no significant improvement occurred in most studied PTVs.« less

Biodegradability and toxicity assessment of a real textile wastewater effluent treated by an optimized electrocoagulation process.

PubMed

Manenti, Diego R; Módenes, Aparecido N; Soares, Petrick A; Boaventura, Rui A R; Palácio, Soraya M; Borba, Fernando H; Espinoza-Quiñones, Fernando R; Bergamasco, Rosângela; Vilar, Vítor J P

2015-01-01

In this work, the application of an iron electrode-based electrocoagulation (EC) process on the treatment of a real textile wastewater (RTW) was investigated. In order to perform an efficient integration of the EC process with a biological oxidation one, an enhancement in the biodegradability and low toxicity of final compounds was sought. Optimal values of EC reactor operation parameters (pH, current density and electrolysis time) were achieved by applying a full factorial 3(3) experimental design. Biodegradability and toxicity assays were performed on treated RTW samples obtained at the optimal values of: pH of the solution (7.0), current density (142.9 A m(-2)) and different electrolysis times. As response variables for the biodegradability and toxicity assessment, the Zahn-Wellens test (Dt), the ratio values of dissolved organic carbon (DOC) relative to low-molecular-weight carboxylates anions (LMCA) and lethal concentration 50 (LC50) were used. According to the Dt, the DOC/LMCA ratio and LC50, an electrolysis time of 15 min along with the optimal values of pH and current density were suggested as suitable for a next stage of treatment based on a biological oxidation process.

Numerical analysis of heat treatment of TiCN coated AA7075 aluminium alloy

NASA Astrophysics Data System (ADS)

Srinath, M. K.; Prasad, M. S. Ganesha

2018-04-01

The Numerical analysis of heat treatments of TiCN coated AA7075 aluminium alloys is presented in this paper. The Convection-Diffusion-Reaction (CDR) equation with solutions in the Streamlined-Upward Petrov-Galerkin (SUPG) method for different parameters is provided for the understanding of the process. An experimental process to improve the surface properties of AA-7075 aluminium alloy was attempted through the coatings of TiCN and subsequent heat treatments. From the experimental process, optimized temperature and time was obtained which gave the maximum surface hardness and corrosion resistance. The paper gives an understanding and use of the CDR equation for application of the process. Expression to determine convection, diffusion and reaction parameters are provided which is used to obtain the overall expression of the heat treatment process. With the substitution of the optimized temperature and time, the governing equation may be obtained. Additionally, the total energy consumed during the heat treatment process is also developed to give a mathematical formulation of the energy consumed.

Intensity modulated neutron radiotherapy optimization by photon proxy

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

Snyder, Michael; Hammoud, Ahmad; Bossenberger, Todd

2012-08-15

Purpose: Introducing intensity modulation into neutron radiotherapy (IMNRT) planning has the potential to mitigate some normal tissue complications seen in past neutron trials. While the hardware to deliver IMNRT plans has been in use for several years, until recently the IMNRT planning process has been cumbersome and of lower fidelity than conventional photon plans. Our in-house planning system used to calculate neutron therapy plans allows beam weight optimization of forward planned segments, but does not provide inverse optimization capabilities. Commercial treatment planning systems provide inverse optimization capabilities, but currently cannot model our neutron beam. Methods: We have developed a methodologymore » and software suite to make use of the robust optimization in our commercial planning system while still using our in-house planning system to calculate final neutron dose distributions. Optimized multileaf collimator (MLC) leaf positions for segments designed in the commercial system using a 4 MV photon proxy beam are translated into static neutron ports that can be represented within our in-house treatment planning system. The true neutron dose distribution is calculated in the in-house system and then exported back through the MATLAB software into the commercial treatment planning system for evaluation. Results: The planning process produces optimized IMNRT plans that reduce dose to normal tissue structures as compared to 3D conformal plans using static MLC apertures. The process involves standard planning techniques using a commercially available treatment planning system, and is not significantly more complex than conventional IMRT planning. Using a photon proxy in a commercial optimization algorithm produces IMNRT plans that are more conformal than those previously designed at our center and take much less time to create. Conclusions: The planning process presented here allows for the optimization of IMNRT plans by a commercial treatment planning optimization algorithm, potentially allowing IMNRT to achieve similar conformality in treatment as photon IMRT. The only remaining requirements for the delivery of very highly modulated neutron treatments are incremental improvements upon already implemented hardware systems that should be readily achievable.« less

SERDP ER-1376 Enhancement of In Situ Bioremediation of Energetic Compounds by Coupled Abiotic/Biotic Processes:Final Report for 2004 - 2006

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

Szecsody, James E.; Comfort, Steve; Fredrickson, Herbert L.

2007-08-07

This project was initiated by SERDP to quantify processes and determine the effectiveness of abiotic/biotic mineralization of energetics (RDX, HMX, TNT) in aquifer sediments by combinations of biostimulation (carbon, trace nutrient additions) and chemical reduction of sediment to create a reducing environment. Initially it was hypothesized that a balance of chemical reduction of sediment and biostimulation would increase the RDX, HMX, and TNT mineralization rate significantly (by a combination of abiotic and biotic processes) so that this abiotic/biotic treatment may be a more efficient for remediation than biotic treatment alone in some cases. Because both abiotic and biotic processes aremore » involved in energetic mineralization in sediments, it was further hypothesized that consideration for both abiotic reduction and microbial growth was need to optimize the sediment system for the most rapid mineralization rate. Results show that there are separate optimal abiotic/biostimulation aquifer sediment treatments for RDX/HMX and for TNT. Optimal sediment treatment for RDX and HMX (which have chemical similarities and similar degradation pathways) is mainly chemical reduction of sediment, which increased the RDX/HMX mineralization rate 100 to150 times (relative to untreated sediment), with additional carbon or trace nutrient addition, which increased the RDX/HMX mineralization rate an additional 3 to 4 times. In contrast, the optimal aquifer sediment treatment for TNT involves mainly biostimulation (glucose addition), which stimulates a TNT/glucose cometabolic degradation pathway (6.8 times more rapid than untreated sediment), degrading TNT to amino-intermediates that irreversibly sorb (i.e., end product is not CO2). The TNT mass migration risk is minimized by these transformation reactions, as the triaminotoluene and 2,4- and 2,6-diaminonitrotoluene products that irreversibly sorb are no longer mobile in the subsurface environment. These transformation rates are increased 13 times further by chemical reduction of sediment. Dithionite reduction alone is not an effective treatment for TNT (intermediates that irreversibly sorb are not produced), even though the TNT degradation rate (to 2- or 4-aminodinitrotoluene) increases.« less

Acquiring the optimal time for hyperbaric therapy in the rat model of CFA induced arthritis.

PubMed

Koo, Sung Tae; Lee, Chang-Hyung; Shin, Yong Il; Ko, Hyun Yoon; Lee, Da Gyo; Jeong, Han-Sol

2014-01-01

We previously published an article about the pressure effect using a rheumatoid animal model. Hyperbaric therapy appears to be beneficial in treating rheumatoid arthritis (RA) by reducing the inflammatory process in an animal model. In this sense, acquiring the optimal pressure-treatment time parameter for RA is important and no optimal hyperbaric therapy time has been suggested up to now. The purpose of our study was to acquire the optimal time for hyperbaric therapy in the RA rat model. Controlled animal study. Following injection of complete Freund's adjuvant (CFA) into one side of the knee joint, 32 rats were randomly assigned to 3 different time groups (1, 3, 5 hours a day) under 1.5 atmospheres absolute (ATA) hyperbaric chamber for 12 days. The pain levels were assessed daily for 2 weeks by weight bearing force (WBF) of the affected limb. In addition, the levels of gelatinase, MMP-2, and MMP-9 expression in the synovial fluids of the knees were analyzed. The reduction of WBF was high at 2 days after injection and then it was spontaneously increased up to 14 days in all 3 groups. There were significant differences of WBF between 5 hours and control during the third through twelfth days, between 3 hours and control during the third through fifth and tenth through twelfth days, and between 3 hours and 5 hours during the third through seventh days (P < 0.05). The MMP-9/MMP-2 ratio increased at 14 days after the CFA injection in all groups compared to the initial findings, however, the 3 hour group showed a smaller MMP-9/MMP-2 ratio than the control group. Although enough samples were used for the study to support our hypothesis, more samples will be needed to raise the validity and reliability. The effect of hyperbaric treatment appears to be dependent upon the elevated therapy time under 1.5 ATA pressure for a short period of time; however, the long-term effects were similar in all pressure groups. Further study will be needed to acquire the optimal pressure-treatment parameter relationship in various conditions for clinical application.

Dosimetric quality, accuracy, and deliverability of modulated radiotherapy treatments for spinal metastases

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

Kairn, Tanya, E-mail: t.kairn@gmail.com; School of Chemistry, Physics, and Mechanical Engineering, Queensland University of Technology, Brisbane; Papworth, Daniel

2016-10-01

Cancer often metastasizes to the vertebra, and such metastases can be treated successfully using simple, static posterior or opposed-pair radiation fields. However, in some cases, including when re-irradiation is required, spinal cord avoidance becomes necessary and more complex treatment plans must be used. This study evaluated 16 sample intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) treatment plans designed to treat 6 typical vertebral and paraspinal volumes using a standard prescription, with the aim of investigating the advantages and limitations of these treatment techniques and providing recommendations for their optimal use in vertebral treatments. Treatment plan quality and beammore » complexity metrics were evaluated using the Treatment And Dose Assessor (TADA) code. A portal-imaging–based quality assurance (QA) system was used to evaluate treatment delivery accuracy, and radiochromic film measurements were used to provide high-resolution verification of treatment plan dose accuracy, especially in the steep dose gradient regions between each vertebral target and spinal cord. All treatment modalities delivered approximately the same doses and the same levels of dose heterogeneity to each planning target volume (PTV), although the minimum PTV doses in the vertebral plans were substantially lower than the prescription, because of the requirement that the plans meet a strict constraint on the dose to the spinal cord and cord planning risk volume (PRV). All plans met required dose constraints on all organs at risk, and all measured PTV-cord dose gradients were steeper than planned. Beam complexity analysis suggested that the IMRT treatment plans were more deliverable (less complex, leading to greater QA success) than the VMAT treatment plans, although the IMRT plans also took more time to deliver. The accuracy and deliverability of VMAT treatment plans were found to be substantially increased by limiting the number of monitor units (MU) per beam at the optimization stage, and thereby limiting beam modulation complexity. The VMAT arcs that were optimized with MU limitation had higher QA pass rates as well as higher modulation complexity scores (less complexity), lower modulation indices (less modulation), lower MU per beam, larger beam segments, and fewer small apertures than the VMAT arcs that were optimized without MU limitation. It is recommended that VMAT treatments for vertebral volumes, where the PTV abuts or surrounds the spinal cord, should be optimized with MU limitation. IMRT treatments may be preferable to the VMAT treatments, for dosimetry and deliverability reasons, but may be inappropriate for some patients because of their increased treatment delivery time.« less

Optimizing biological therapy in Crohn's disease.

PubMed

Gecse, Krisztina Barbara; Végh, Zsuzsanna; Lakatos, Péter László

2016-01-01

Anti-TNF therapy has revolutionized the treatment of inflammatory bowel diseases, including both Crohn's disease and ulcerative colitis. However, a significant proportion of patients does not respond to anti-TNF agents or lose response over time. Recently, therapeutic drug monitoring has gained a major role in identifying the mechanism and management of loss of response. The aim of this review article is to summarize the predictors of efficacy and outcomes, the different mechanisms of anti-TNF/biological failure in Crohn's disease and identify strategies to optimize biological treatment.

Optimizing mini-ridge filter thickness to reduce proton treatment times in a spot-scanning synchrotron system.

PubMed

Courneyea, Lorraine; Beltran, Chris; Tseung, Hok Seum Wan Chan; Yu, Juan; Herman, Michael G

2014-06-01

Study the contributors to treatment time as a function of Mini-Ridge Filter (MRF) thickness to determine the optimal choice for breath-hold treatment of lung tumors in a synchrotron-based spot-scanning proton machine. Five different spot-scanning nozzles were simulated in TOPAS: four with MRFs of varying maximal thicknesses (6.15-24.6 mm) and one with no MRF. The MRFs were designed with ridges aligned along orthogonal directions transverse to the beam, with the number of ridges (4-16) increasing with MRF thickness. The material thickness given by these ridges approximately followed a Gaussian distribution. Using these simulations, Monte Carlo data were generated for treatment planning commissioning. For each nozzle, standard and stereotactic (SR) lung phantom treatment plans were created and assessed for delivery time and plan quality. Use of a MRF resulted in a reduction of the number of energy layers needed in treatment plans, decreasing the number of synchrotron spills needed and hence the treatment time. For standard plans, the treatment time per field without a MRF was 67.0 ± 0.1 s, whereas three of the four MRF plans had treatment times of less than 20 s per field; considered sufficiently low for a single breath-hold. For SR plans, the shortest treatment time achieved was 57.7 ± 1.9 s per field, compared to 95.5 ± 0.5 s without a MRF. There were diminishing gains in time reduction as the MRF thickness increased. Dose uniformity of the PTV was comparable across all plans; however, when the plans were normalized to have the same coverage, dose conformality decreased with MRF thickness, as measured by the lung V20%. Single breath-hold treatment times for plans with standard fractionation can be achieved through the use of a MRF, making this a viable option for motion mitigation in lung tumors. For stereotactic plans, while a MRF can reduce treatment times, multiple breath-holds would still be necessary due to the limit imposed by the proton extraction time. To balance treatment time and normal tissue dose, the ideal MRF choice was shown to be the thinnest option that is able to achieve the desired breath-hold timing.

Measurement of the main and critical parameters for optimal laser treatment of heart disease

NASA Astrophysics Data System (ADS)

Kabeya, FB; Abrahamse, H.; Karsten, AE

2017-10-01

Laser light is frequently used in the diagnosis and treatment of patients. As in traditional treatments such as medication, bypass surgery, and minimally invasive ways, laser treatment can also fail and present serious side effects. The true reason for laser treatment failure or the side effects thereof, remains unknown. From the literature review conducted, and experimental results generated we conclude that an optimal laser treatment for coronary artery disease (named heart disease) can be obtained if certain critical parameters are correctly measured and understood. These parameters include the laser power, the laser beam profile, the fluence rate, the treatment time, as well as the absorption and scattering coefficients of the target treatment tissue. Therefore, this paper proposes different, accurate methods for the measurement of these critical parameters to determine the optimal laser treatment of heart disease with a minimal risk of side effects. The results from the measurement of absorption and scattering properties can be used in a computer simulation package to predict the fluence rate. The computing technique is a program based on the random number (Monte Carlo) process and probability statistics to track the propagation of photons through a biological tissue.

Optimal medical treatment versus carotid endarterectomy: the rationale and design of the Aggressive Medical Treatment Evaluation for Asymptomatic Carotid Artery Stenosis (AMTEC) study.

PubMed

Kolos, Igor; Loukianov, Mikhail; Dupik, Nikolay; Boytsov, Sergey; Deev, Alexandr

2015-02-01

Carotid endarterectomy and medical therapy (aspirin) were shown superior to medical therapy alone for asymptomatic (≥ 60%) carotid stenosis. The role of modern medical therapy (statins, antihypertensive treatment, and aspirin) in the treatment of such patients is undefined. Establishing the safety, efficacy, and durability of optimal medical therapy and lifestyle modification requires rigorous comparison with carotid endarterectomy in asymptomatic patients. The objective is to compare the efficacy of carotid endarterectomy + optimal medical therapy versus optimal medical therapy alone in patients with asymptomatic (70-79%) extracranial carotid stenosis. The Aggressive Medical Treatment Evaluation for Asymptomatic Carotid Artery Stenosis study is a prospective, randomized, parallel, two-arm, multicenter trial. Primary end-points will be analyzed using standard time-to-event statistical modeling with adjustment for major baseline covariates. The primary analysis is on an intent-to-treat basis. The primary outcome is nonfatal stroke, nonfatal myocardial infarction, and death during follow-up of up to five-years, and the secondary outcome includes death from any cause and stroke. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Optimization of rotational speed and hydraulic retention time of a rotational sponge reactor for sewage treatment.

PubMed

Hewawasam, Choolaka; Matsuura, Norihisa; Takimoto, Yuya; Hatamoto, Masashi; Yamaguchi, Takashi

2018-05-26

A rotational sponge (RS) reactor was proposed as an alternative sewage treatment process. Prior to the application of an RS reactor for sewage treatment, this study evaluated reactor performance with regard to organic removal, nitrification, and nitrogen removal and sought to optimize the rotational speed and hydraulic retention time (HRT) of the system. RS reactor obtained highest COD removal, nitrification, and nitrogen removal efficiencies of 91%, 97%, and 65%, respectively. For the optimization, response surface methodology (RSM) was employed and optimum conditions of rotational speed and HRT were 18 rounds per hour and 4.8 h, respectively. COD removal, nitrification, and nitrogen removal efficiencies at the optimum conditions were 85%, 85%, and 65%, respectively. Corresponding removal rates at optimum conditions were 1.6 kg-COD m -3 d -1 , 0.3 kg-NH 4 + -N m -3 d -1 , and 0.12 kg-N m -3 d -1 . Microbial community analysis revealed an abundance of nitrifying and denitrifying bacteria in the reactor, which contributed to nitrification and nitrogen removal. Copyright © 2018 Elsevier Ltd. All rights reserved.

Achieving high convection volumes in postdilution online hemodiafiltration: a prospective multicenter study

PubMed Central

Chapdelaine, Isabelle; Nubé, Menso J; Blankestijn, Peter J; Bots, Michiel L; Konings, Constantijn J A M; Kremer Hovinga, Ton K; Molenaar, Femke M; van der Weerd, Neelke C; Grooteman, Muriel P C

2017-01-01

Abstract Background. Available evidence suggests a reduced mortality risk for patients treated with high-volume postdilution hemodiafiltration (HDF) when compared with hemodialysis (HD) patients. As the magnitude of the convection volume depends on treatment-related factors rather than patient-related characteristics, we prospectively investigated whether a high convection volume (defined as ≥22 L/session) is feasible in the majority of patients (>75%). Methods. A multicenter study was performed in adult prevalent dialysis patients. Nonparticipating eligible patients formed the control group. Using a stepwise protocol, treatment time (up to 4 hours), blood flow rate (up to 400 mL/min) and filtration fraction (up to 33%) were optimized as much as possible. The convection volume was determined at the end of this optimization phase and at 4 and 8 weeks thereafter. Results. Baseline characteristics were comparable in participants (n = 86) and controls (n = 58). At the end of the optimization and 8 weeks thereafter, 71/86 (83%) and 66/83 (80%) of the patients achieved high-volume HDF (mean 25.5 ± 3.6 and 26.0 ± 3.4 L/session, respectively). While treatment time remained unaltered, mean blood flow rate increased by 27% and filtration fraction increased by 23%. Patients with <22 L/session had a higher percentage of central venous catheters (CVCs), a shorter treatment time and lower blood flow rate when compared with patients with ≥22 L/session. Conclusions. High-volume HDF is feasible in a clear majority of dialysis patients. Since none of the patients agreed to increase treatment time, these findings indicate that high-volume HDF is feasible just by increasing blood flow rate and filtration fraction. PMID:29225810

Optimization of the fiber laser parameters for local high-temperature impact on metal

NASA Astrophysics Data System (ADS)

Yatsko, Dmitrii S.; Polonik, Marina V.; Dudko, Olga V.

2016-11-01

This paper presents the local laser heating process of surface layer of the metal sample. The aim is to create the molten pool with the required depth by laser thermal treatment. During the heating the metal temperature at any point of the molten zone should not reach the boiling point of the main material. The laser power, exposure time and the spot size of a laser beam are selected as the variable parameters. The mathematical model for heat transfer in a semi-infinite body, applicable to finite slab, is used for preliminary theoretical estimation of acceptable parameters values of the laser thermal treatment. The optimization problem is solved by using an algorithm based on the scanning method of the search space (the zero-order method of conditional optimization). The calculated values of the parameters (the optimal set of "laser radiation power - exposure time - spot radius") are used to conduct a series of natural experiments to obtain a molten pool with the required depth. A two-stage experiment consists of: a local laser treatment of metal plate (steel) and then the examination of the microsection of the laser irradiated region. According to the experimental results, we can judge the adequacy of the ongoing calculations within the selected models.

Cancer treatment as a game: integrating evolutionary game theory into the optimal control of chemotherapy

NASA Astrophysics Data System (ADS)

Orlando, Paul A.; Gatenby, Robert A.; Brown, Joel S.

2012-12-01

Chemotherapy for metastatic cancer commonly fails due to evolution of drug resistance in tumor cells. Here, we view cancer treatment as a game in which the oncologists choose a therapy and tumors ‘choose’ an adaptive strategy. We propose the oncologist can gain an upper hand in the game by choosing treatment strategies that anticipate the adaptations of the tumor. In particular, we examine the potential benefit of exploiting evolutionary tradeoffs in tumor adaptations to therapy. We analyze a math model where cancer cells face tradeoffs in allocation of resistance to two drugs. The tumor ‘chooses’ its strategy by natural selection and the oncologist chooses her strategy by solving a control problem. We find that when tumor cells perform best by investing resources to maximize response to one drug the optimal therapy is a time-invariant delivery of both drugs simultaneously. However, if cancer cells perform better using a generalist strategy allowing resistance to both drugs simultaneously, then the optimal protocol is a time varying solution in which the two drug concentrations negatively covary. However, drug interactions can significantly alter these results. We conclude that knowledge of both evolutionary tradeoffs and drug interactions is crucial in planning optimal chemotherapy schedules for individual patients.

Radiobiological evaluation of the influence of dwell time modulation restriction in HIPO optimized HDR prostate brachytherapy implants.

PubMed

Mavroidis, Panayiotis; Katsilieri, Zaira; Kefala, Vasiliki; Milickovic, Natasa; Papanikolaou, Nikos; Karabis, Andreas; Zamboglou, Nikolaos; Baltas, Dimos

2010-09-01

One of the issues that a planner is often facing in HDR brachytherapy is the selective existence of high dose volumes around some few dominating dwell positions. If there is no information available about its necessity (e.g. location of a GTV), then it is reasonable to investigate whether this can be avoided. This effect can be eliminated by limiting the free modulation of the dwell times. HIPO, an inverse treatment plan optimization algorithm, offers this option. In treatment plan optimization there are various methods that try to regularize the variation of dose non-uniformity using purely dosimetric measures. However, although these methods can help in finding a good dose distribution they do not provide any information regarding the expected treatment outcome as described by radiobiology based indices. The quality of 12 clinical HDR brachytherapy implants for prostate utilizing HIPO and modulation restriction (MR) has been compared to alternative plans with HIPO and free modulation (without MR). All common dose-volume indices for the prostate and the organs at risk have been considered together with radiobiological measures. The clinical effectiveness of the different dose distributions was investigated by calculating the response probabilities of the tumors and organs-at-risk (OARs) involved in these prostate cancer cases. The radiobiological models used are the Poisson and the relative seriality models. Furthermore, the complication-free tumor control probability, P + and the biologically effective uniform dose ([Formula: see text]) were used for treatment plan evaluation and comparison. Our results demonstrate that HIPO with a modulation restriction value of 0.1-0.2 delivers high quality plans which are practically equivalent to those achieved with free modulation regarding the clinically used dosimetric indices. In the comparison, many of the dosimetric and radiobiological indices showed significantly different results. The modulation restricted clinical plans demonstrated a lower total dwell time by a mean of 1.4% that was proved to be statistically significant ( p = 0.002). The HIPO with MR treatment plans produced a higher P + by 0.5%, which stemmed from a better sparing of the OARs by 1.0%. Both the dosimetric and radiobiological comparison shows that the modulation restricted optimization gives on average similar results with the optimization without modulation restriction in the examined clinical cases. Concluding, based on our results, it appears that the applied dwell time regularization technique is expected to introduce a minor improvement in the effectiveness of the optimized HDR dose distributions.

Radiobiological evaluation of the influence of dwell time modulation restriction in HIPO optimized HDR prostate brachytherapy implants

PubMed Central

Katsilieri, Zaira; Kefala, Vasiliki; Milickovic, Natasa; Papanikolaou, Nikos; Karabis, Andreas; Zamboglou, Nikolaos; Baltas, Dimos

2010-01-01

Purpose One of the issues that a planner is often facing in HDR brachytherapy is the selective existence of high dose volumes around some few dominating dwell positions. If there is no information available about its necessity (e.g. location of a GTV), then it is reasonable to investigate whether this can be avoided. This effect can be eliminated by limiting the free modulation of the dwell times. HIPO, an inverse treatment plan optimization algorithm, offers this option. In treatment plan optimization there are various methods that try to regularize the variation of dose non-uniformity using purely dosimetric measures. However, although these methods can help in finding a good dose distribution they do not provide any information regarding the expected treatment outcome as described by radiobiology based indices. Material and methods The quality of 12 clinical HDR brachytherapy implants for prostate utilizing HIPO and modulation restriction (MR) has been compared to alternative plans with HIPO and free modulation (without MR). All common dose-volume indices for the prostate and the organs at risk have been considered together with radiobiological measures. The clinical effectiveness of the different dose distributions was investigated by calculating the response probabilities of the tumors and organs-at-risk (OARs) involved in these prostate cancer cases. The radiobiological models used are the Poisson and the relative seriality models. Furthermore, the complication-free tumor control probability, P+ and the biologically effective uniform dose (D¯¯) were used for treatment plan evaluation and comparison. Results Our results demonstrate that HIPO with a modulation restriction value of 0.1-0.2 delivers high quality plans which are practically equivalent to those achieved with free modulation regarding the clinically used dosimetric indices. In the comparison, many of the dosimetric and radiobiological indices showed significantly different results. The modulation restricted clinical plans demonstrated a lower total dwell time by a mean of 1.4% that was proved to be statistically significant (p = 0.002). The HIPO with MR treatment plans produced a higher P+ by 0.5%, which stemmed from a better sparing of the OARs by 1.0%. Conclusions Both the dosimetric and radiobiological comparison shows that the modulation restricted optimization gives on average similar results with the optimization without modulation restriction in the examined clinical cases. Concluding, based on our results, it appears that the applied dwell time regularization technique is expected to introduce a minor improvement in the effectiveness of the optimized HDR dose distributions. PMID:27853473

The timing and probability of treatment switch under cost uncertainty: an application to patients with gastrointestinal stromal tumor.

PubMed

de Mello-Sampayo, Felipa

2014-03-01

Cost fluctuations render the outcome of any treatment switch uncertain, so that decision makers might have to wait for more information before optimally switching treatments, especially when the incremental cost per quality-adjusted life year (QALY) gained cannot be fully recovered later on. To analyze the timing of treatment switch under cost uncertainty. A dynamic stochastic model for the optimal timing of a treatment switch is developed and applied to a problem in medical decision taking, i.e. to patients with unresectable gastrointestinal stromal tumour (GIST). The theoretical model suggests that cost uncertainty reduces expected net benefit. In addition, cost volatility discourages switching treatments. The stochastic model also illustrates that as technologies become less cost competitive, the cost uncertainty becomes more dominant. With limited substitutability, higher quality of technologies will increase the demand for those technologies disregarding the cost uncertainty. The results of the empirical application suggest that the first-line treatment may be the better choice when considering lifetime welfare. Under uncertainty and irreversibility, low-risk patients must begin the second-line treatment as soon as possible, which is precisely when the second-line treatment is least valuable. As the costs of reversing current treatment impacts fall, it becomes more feasible to provide the option-preserving treatment to these low-risk individuals later on. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Online total organic carbon (TOC) monitoring for water and wastewater treatment plants processes and operations optimization

NASA Astrophysics Data System (ADS)

Assmann, Céline; Scott, Amanda; Biller, Dondra

2017-08-01

Organic measurements, such as biological oxygen demand (BOD) and chemical oxygen demand (COD) were developed decades ago in order to measure organics in water. Today, these time-consuming measurements are still used as parameters to check the water treatment quality; however, the time required to generate a result, ranging from hours to days, does not allow COD or BOD to be useful process control parameters - see (1) Standard Method 5210 B; 5-day BOD Test, 1997, and (2) ASTM D1252; COD Test, 2012. Online organic carbon monitoring allows for effective process control because results are generated every few minutes. Though it does not replace BOD or COD measurements still required for compliance reporting, it allows for smart, data-driven and rapid decision-making to improve process control and optimization or meet compliances. Thanks to the smart interpretation of generated data and the capability to now take real-time actions, municipal drinking water and wastewater treatment facility operators can positively impact their OPEX (operational expenditure) efficiencies and their capabilities to meet regulatory requirements. This paper describes how three municipal wastewater and drinking water plants gained process insights, and determined optimization opportunities thanks to the implementation of online total organic carbon (TOC) monitoring.

Enhancement of volatile fatty acid production and biogas yield from food waste following sonication pretreatment.

PubMed

Liu, Nuo; Jiang, Jianguo; Yan, Feng; Gao, Yuchen; Meng, Yuan; Aihemaiti, Aikelaimu; Ju, Tongyao

2018-07-01

The positive effect of sonication on volatile fatty acid (VFA) and hydrogen production was investigated by batch experiments. Several sonication densities (2, 1.6, and 1.2 W/mL) and times (5, 10, and 15 min) were tested. The optimal sonication condition was ultrasonic density 2 W/mL and ultrasonic time 15 min (2-U15). The FW particle size larger than 50 μm (d > 50 μm) were more susceptible to the sonication treatment than the smaller particle size (d ≤ 50 μm). The SCOD increased and VS reduction accelerated under sonication treatment. The maximum VFA production and the highest proportion of hydrogen in the biogas increased 65.3% and 59.1%, respectively, under the optimal sonication conditions compared to the unsonicated batch. Moreover, a reduction of over 50% in the time required to reach its maximum production was also observed. Butyric acid fermentation type was obtained whether following sonication treatment or not. The composition of key microbial community differed under the various sonication conditions. The genera Clostridium and Parabacteroides are predominantly responsible for VFA generation and both were found to be abundant under the optimal condition. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

A novel method for vaginal cylinder treatment planning: a seamless transition to 3D brachytherapy

PubMed Central

Wu, Vincent; Wang, Zhou; Patil, Sachin

2012-01-01

Purpose Standard treatment plan libraries are often used to ensure a quick turn-around time for vaginal cylinder treatments. Recently there is increasing interest in transitioning from conventional 2D radiograph based brachytherapy to 3D image based brachytherapy, which has resulted in a substantial increase in treatment planning time and decrease in patient through-put. We describe a novel technique that significantly reduces the treatment planning time for CT-based vaginal cylinder brachytherapy. Material and methods Oncentra MasterPlan TPS allows multiple sets of data points to be classified as applicator points which has been harnessed in this method. The method relies on two hard anchor points: the first dwell position in a catheter and an applicator configuration specific dwell position as the plan origin and a soft anchor point beyond the last active dwell position to define the axis of the catheter. The spatial location of various data points on the applicator's surface and at 5 mm depth are stored in an Excel file that can easily be transferred into a patient CT data set using window operations and then used for treatment planning. The remainder of the treatment planning process remains unaffected. Results The treatment plans generated on the Oncentra MasterPlan TPS using this novel method yielded results comparable to those generated on the Plato TPS using a standard treatment plan library in terms of treatment times, dwell weights and dwell times for a given optimization method and normalization points. Less than 2% difference was noticed between the treatment times generated between both systems. Using the above method, the entire planning process, including CT importing, catheter reconstruction, multiple data point definition, optimization and dose prescription, can be completed in ~5–10 minutes. Conclusion The proposed method allows a smooth and efficient transition to 3D CT based vaginal cylinder brachytherapy planning. PMID:23349650

Formulation, development and characterization of mucoadhesive film for treatment of vaginal candidiasis.

PubMed

Mishra, Renuka; Joshi, Priyanka; Mehta, Tejal

2016-01-01

The objective of the present investigation was formulation, optimization and characterization of mucoadhesive film of clotrimazole (CT) which is patient-convenient and provides an effective alternative for the treatment of vaginal candidiasis. CT is an antimycotic drug applied locally for the treatment of vaginal candidiasis. Mucoadhesive vaginal films were prepared by solvent casting technique using hydroxyl propylcellulose and sodium alginate as polymers. Propylene glycol and polyethylene glycol-400 were evaluated as plasticizers. The mucoadhesive vaginal films were evaluated for percentage elongation, tensile strength, folding endurance, drug content, in vitro disintegration time, in vitro dissolution study, swelling index, bioadhesive strength, and diffusion study. Among various permeation enhancers used, isopropyl myristate was found to be suitable. To evaluate the role of the concentration of permeation enhancer and concentration of polymers in the optimization of mucoadhesive vaginal film, 3(2) full factorial design was employed. Optimized batch showed in vitro disintegration time, 18 min; drug content, 99.83%; and tensile strength, 502.1 g/mm(2). In vitro diffusion study showed that 77% drug diffusion occurred in 6 h. This batch was further evaluated by scanning electron microscopy indicating uniformity of the film. In vitro Lactobacillus inhibition and in vitro antifungal activity of optimized batch showed an inhibitory effect against Candida albicans and no effect on Lactobacillus, which is a normal component of vaginal flora. Mucoadhesive vaginal film of CT is an effective dosage form for the treatment of vaginal candidiasis.

Process optimization of ultrasound-assisted alcoholic-alkaline treatment for granular cold water swelling starches.

PubMed

Zhu, Bo; Liu, Jianli; Gao, Weidong

2017-09-01

This paper reports on the process optimization of ultrasonic assisted alcoholic-alkaline treatment to prepare granular cold water swelling (GCWS) starches. In this work, three statistical approaches such as Plackett-Burman, steepest ascent path analysis and Box-Behnken design were successfully combined to investigate the effects of major treatment process variables including starch concentration, ethanol volume fraction, sodium hydroxide dosage, ultrasonic power and treatment time, and drying operation, that is, vacuum degree and drying time on cold-water solubility. Results revealed that ethanol volume fraction, sodium hydroxide dosage, applied power and ultrasonic treatment time were significant factors that affected the cold-water solubility of GCWS starches. The maximum cold-water solubility was obtained when treated at 400W of applied power for 27.38min. Optimum volume fraction of ethanol and sodium hydroxide dosage were 66.85% and 53.76mL, respectively. The theoretical values (93.87%) and the observed values (93.87%) were in reasonably good agreement and the deviation was less than 1%. Verification and repeated trial results indicated that the ultrasound-assisted alcoholic-alkaline treatment could be successfully used for the preparation of granular cold water swelling starches at room temperatures and had excellent improvement on the cold-water solubility of GCWS starches. Copyright © 2016. Published by Elsevier B.V.

Study on Coagulant Dosing Control System of Micro Vortex Water Treatment

NASA Astrophysics Data System (ADS)

Fengping, Hu; Qi, Fan; Wenjie, Hu; Xizhen, He; Hongling, Dai

2018-03-01

In view of the characteristics of nonlinearity, large time delay and multi disturbance in the process of coagulant dosing in water treatment, it is difficult to control the dosage of coagulant. According to the four indexes of raw water quality parameters (raw water flow, turbidity, pH value) and turbidity of sedimentation tank, the micro vortex coagulation dosing control model is constructed based on BP neural network and GA. The forecast results of BP neural network model are ideal, and after the optimization of GA, the prediction accuracy of the model is partly improved. The prediction error of the optimized network is ±0.5 mg/L, and has a better performance than non-optimized network.

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

[Management of spine injuries in polytraumatized patients].

PubMed

Heyde, C E; Ertel, W; Kayser, R

2005-09-01

The management of spine injuries in polytraumatized patients remains a great challenge for the diagnostic procedures and institution of appropriate treatment by integrating spinal trauma treatment into the whole treatment concept as well as following the treatment steps for the injured spine itself. The established concept of "damage control" and criteria regarding the optimal time and manner for operative treatment of the injured spine in the polytrauma setting is presented and discussed.

Relationship between radiation treatment time and overall survival after induction chemotherapy for locally advanced head-and-neck carcinoma: a subset analysis of TAX 324.

PubMed

Sher, David J; Posner, Marshall R; Tishler, Roy B; Sarlis, Nicholas J; Haddad, Robert I; Holupka, Edward J; Devlin, Phillip M

2011-12-01

To analyze the relationship between overall survival (OS) and radiation treatment time (RTT) and overall treatment time (OTT) in a well-described sequential therapy paradigm for locally advanced head-and-neck carcinoma (LAHNC). TAX 324 is a Phase III study comparing TPF (docetaxel, cisplatin, and fluorouracil) with PF (cisplatin and fluorouracil) induction chemotherapy (IC) in LAHNC patients; both arms were followed by carboplatin-based chemoradiotherapy (CRT). Prospective radiotherapy quality assurance was performed. This analysis includes all patients who received three cycles of IC and a radiation dose of ≥70 Gy. Radiotherapy treatment time was analyzed as binary (≤8 weeks vs. longer) and continuous (number of days beyond 8 weeks) functions. The primary analysis assessed the relationship between RTT, OTT, and OS, and the secondary analysis explored the association between treatment times and locoregional recurrence (LRR). A total of 333 (of 501) TAX 324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in baseline or treatment characteristics. On multivariable analysis, PF IC, World Health Organization performance status of 1, non-oropharynx site, T3/4 stage, N3 status, and prolonged RTT (hazard ratio 1.63, p=0.006) were associated with significantly inferior survival. Performance status, T3/4 disease, and prolonged RTT (odds ratio 1.68, p=0.047) were independently and negatively related to LRR on multivariable analysis, whereas PF was not. Overall treatment time was not independently associated with either OS or LRR. In this secondary analysis of the TAX 324 trial, TPF IC remains superior to PF IC after controlling for radiotherapy delivery time. Even with optimal IC and concurrent chemotherapy, a non-prolonged RTT is a crucial determinant of treatment success. Appropriate delivery of radiotherapy after IC remains essential for optimizing OS in LAHNC. Copyright © 2011 Elsevier Inc. All rights reserved.

Relationship Between Radiation Treatment Time and Overall Survival After Induction Chemotherapy for Locally Advanced Head-and-Neck Carcinoma: A Subset Analysis of TAX 324

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

Sher, David J., E-mail: dsher@partners.org; Posner, Marshall R.; Tishler, Roy B.

2011-12-01

Purpose: To analyze the relationship between overall survival (OS) and radiation treatment time (RTT) and overall treatment time (OTT) in a well-described sequential therapy paradigm for locally advanced head-and-neck carcinoma (LAHNC). Methods and Materials: TAX 324 is a Phase III study comparing TPF (docetaxel, cisplatin, and fluorouracil) with PF (cisplatin and fluorouracil) induction chemotherapy (IC) in LAHNC patients; both arms were followed by carboplatin-based chemoradiotherapy (CRT). Prospective radiotherapy quality assurance was performed. This analysis includes all patients who received three cycles of IC and a radiation dose of {>=} 70 Gy. Radiotherapy treatment time was analyzed as binary ({<=} 8more » weeks vs. longer) and continuous (number of days beyond 8 weeks) functions. The primary analysis assessed the relationship between RTT, OTT, and OS, and the secondary analysis explored the association between treatment times and locoregional recurrence (LRR). Results: A total of 333 (of 501) TAX 324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in baseline or treatment characteristics. On multivariable analysis, PF IC, World Health Organization performance status of 1, non-oropharynx site, T3/4 stage, N3 status, and prolonged RTT (hazard ratio 1.63, p = 0.006) were associated with significantly inferior survival. Performance status, T3/4 disease, and prolonged RTT (odds ratio 1.68, p = 0.047) were independently and negatively related to LRR on multivariable analysis, whereas PF was not. Overall treatment time was not independently associated with either OS or LRR. Conclusions: In this secondary analysis of the TAX 324 trial, TPF IC remains superior to PF IC after controlling for radiotherapy delivery time. Even with optimal IC and concurrent chemotherapy, a non-prolonged RTT is a crucial determinant of treatment success. Appropriate delivery of radiotherapy after IC remains essential for optimizing OS in LAHNC.« less

SU-E-T-610: Comparison of Treatment Times Between the MLCi and Agility Multileaf Collimators

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

Ramsey, C; Bowling, J

2014-06-01

Purpose: The Agility is a new 160-leaf MLC developed by Elekta for use in their Infinity and Versa HD linacs. As compared to the MLCi, the Agility increased the maximum leaf speed from 2 cm/s to 3.5 cm/s, and the maximum primary collimator speed from 1.5 cm/s to 9.0 cm/s. The purpose of this study was to determine if the Agility MLC resulted in improved plan quality and/or shorter treatment times. Methods: An Elekta Infinity that was originally equipped with a 80 leaf MLCi was upgraded to an 160 leaf Agility. Treatment plan quality was evaluated using the Pinnacle planningmore » system with SmartArc. Optimization was performed once for the MLCi and once for the Agility beam models using the same optimization parameters and the same number of iterations. Patient treatment times were measured for all IMRT, VMAT, and SBRT patients treated on the Infinity with the MLCi and Agility MLCs. Treatment times were extracted from the EMR and measured from when the patient first walked into the treatment room until exiting the treatment room. Results: 11,380 delivery times were measured for patients treated with the MLCi, and 1,827 measurements have been made for the Agility MLC. The average treatment times were 19.1 minutes for the MLCi and 20.8 minutes for the Agility. Using a t-test analysis, there was no difference between the two groups (t = 0.22). The dose differences between patients planned with the MLCi and the Agility MLC were minimal. For example, the dose difference for the PTV, GTV, and cord for a head and neck patient planned using Pinnacle were effectively equivalent. However, the dose to the parotid glands was slightly worse with the Agility MLC. Conclusion: There was no statistical difference in treatment time, or any significant dosimetric difference between the Agility MLC and the MLCi.« less

SU-E-J-53: Dosimetric Evaluation at Volumetric Modulated Arc Therapy for Treatment of Prostate Cancer Using Single Or Double Arcs

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

Silva, D; Salmon, H; Pavan, G

2014-06-01

Purpose: Evaluate and compare retrospective prostate treatment plan using Volumetric Modulated Arc Therapy (RapidArc™ - Varian) technique with single or double arcs at COI Group. Methods: Ten patients with present prostate and seminal vesicle neoplasia were replanned as a target treatment volume and a prescribed dose of 78 Gy. A baseline planning, using single arc, was developed for each case reaching for the best result on PTV, in order to minimize the dose on organs at risk (OAR). Maintaining the same optimization objectives used on baseline plan, two copies for optimizing single and double arcs, have been developed. The plansmore » were performed with 10 MV photon beam energy on Eclipse software, version 11.0, making use of Trilogy linear accelerator with Millenium HD120 multileaf collimator. Comparisons on PTV have been performed, such as: maximum, minimum and mean dose, gradient dose, as well as the quantity of monitor units, treatment time and homogeneity and conformity index. OARs constrains dose have been evaluated, comparing both optimizations. Results: Regarding PTV coverage, the difference of the minimum, maximum and mean dose were 1.28%, 0.7% and 0.2% respectively higher for single arc. When analyzed the index of homogeneity found a difference of 0.99% higher when compared with double arcs. However homogeneity index was 0.97% lower on average by using single arc. The doses on the OARs, in both cases, were in compliance to the recommended limits RTOG 0415. With the use of single arc, the quantity of monitor units was 10,1% lower, as well as the Beam-On time, 41,78%, when comparing double arcs, respectively. Conclusion: Concerning the optimization of patients with present prostate and seminal vesicle neoplasia, the use of single arc reaches similar objectives, when compared to double arcs, in order to decrease the treatment time and the quantity of monitor units.« less

Automatically Finding the Control Variables for Complex System Behavior

NASA Technical Reports Server (NTRS)

Gay, Gregory; Menzies, Tim; Davies, Misty; Gundy-Burlet, Karen

2010-01-01

Testing large-scale systems is expensive in terms of both time and money. Running simulations early in the process is a proven method of finding the design faults likely to lead to critical system failures, but determining the exact cause of those errors is still time-consuming and requires access to a limited number of domain experts. It is desirable to find an automated method that explores the large number of combinations and is able to isolate likely fault points. Treatment learning is a subset of minimal contrast-set learning that, rather than classifying data into distinct categories, focuses on finding the unique factors that lead to a particular classification. That is, they find the smallest change to the data that causes the largest change in the class distribution. These treatments, when imposed, are able to identify the factors most likely to cause a mission-critical failure. The goal of this research is to comparatively assess treatment learning against state-of-the-art numerical optimization techniques. To achieve this, this paper benchmarks the TAR3 and TAR4.1 treatment learners against optimization techniques across three complex systems, including two projects from the Robust Software Engineering (RSE) group within the National Aeronautics and Space Administration (NASA) Ames Research Center. The results clearly show that treatment learning is both faster and more accurate than traditional optimization methods.

SU-E-T-230: Creating a Large Number of Focused Beams with Variable Patient Head Tilt to Improve Dose Fall-Off for Brain Radiosurgery

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

Chiu, J; Ma, L

2015-06-15

Purpose: To develop a treatment delivery and planning strategy by increasing the number of beams to minimize dose to brain tissue surrounding a target, while maximizing dose coverage to the target. Methods: We analyzed 14 different treatment plans via Leksell PFX and 4C. For standardization, single tumor cases were chosen. Original treatment plans were compared with two optimized plans. The number of beams was increased in treatment plans by varying tilt angles of the patient head, while maintaining original isocenter and the beam positions in the x-, y- and z-axes, collimator size, and beam blocking. PFX optimized plans increased beammore » numbers with three pre-set tilt angles, 70, 90, 110, and 4C optimized plans increased beam numbers with tilt angles increasing arbitrarily from range of 30 to 150 degrees. Optimized treatment plans were compared dosimetrically with original treatment plans. Results: Comparing total normal tissue isodose volumes between original and optimized plans, the low-level percentage isodose volumes decreased in all plans. Despite the addition of multiple beams up to a factor of 25, beam-on times for 1 tilt angle versus 3 or more tilt angles were comparable (<1 min.). In 64% (9/14) of the studied cases, the volume percentage decrease by >5%, with the highest value reaching 19%. The addition of more tilt angles correlates to a greater decrease in normal brain irradiated volume. Selectivity and coverage for original and optimized plans remained comparable. Conclusion: Adding large number of additional focused beams with variable patient head tilt shows improvement for dose fall-off for brain radiosurgery. The study demonstrates technical feasibility of adding beams to decrease target volume.« less

Patient-centered clinical trials.

PubMed

Chaudhuri, Shomesh E; Ho, Martin P; Irony, Telba; Sheldon, Murray; Lo, Andrew W

2018-02-01

We apply Bayesian decision analysis (BDA) to incorporate patient preferences in the regulatory approval process for new therapies. By assigning weights to type I and type II errors based on patient preferences, the significance level (α) and power (1-β) of a randomized clinical trial (RCT) for a new therapy can be optimized to maximize the value to current and future patients and, consequently, to public health. We find that for weight-loss devices, potentially effective low-risk treatments have optimal αs larger than the traditional one-sided significance level of 5%, whereas potentially less effective and riskier treatments have optimal αs below 5%. Moreover, the optimal RCT design, including trial size, varies with the risk aversion and time-to-access preferences and the medical need of the target population. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Radiofrequency in cosmetic dermatology.

PubMed

Beasley, Karen L; Weiss, Robert A

2014-01-01

The demand for noninvasive methods of facial and body rejuvenation has experienced exponential growth over the last decade. There is a particular interest in safe and effective ways to decrease skin laxity and smooth irregular body contours and texture without downtime. These noninvasive treatments are being sought after because less time for recovery means less time lost from work and social endeavors. Radiofrequency (RF) treatments are traditionally titrated to be nonablative and are optimal for those wishing to avoid recovery time. Not only is there minimal recovery but also a high level of safety with aesthetic RF treatments. Copyright © 2014 Elsevier Inc. All rights reserved.

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

Impaired movement timing in neurological disorders: rehabilitation and treatment strategies.

PubMed

Hove, Michael J; Keller, Peter E

2015-03-01

Timing abnormalities have been reported in many neurological disorders, including Parkinson's disease (PD). In PD, motor-timing impairments are especially debilitating in gait. Despite impaired audiomotor synchronization, PD patients' gait improves when they walk with an auditory metronome or with music. Building on that research, we make recommendations for optimizing sensory cues to improve the efficacy of rhythmic cuing in gait rehabilitation. Adaptive rhythmic metronomes (that synchronize with the patient's walking) might be especially effective. In a recent study we showed that adaptive metronomes synchronized consistently with PD patients' footsteps without requiring attention; this improved stability and reinstated healthy gait dynamics. Other strategies could help optimize sensory cues for gait rehabilitation. Groove music strongly engages the motor system and induces movement; bass-frequency tones are associated with movement and provide strong timing cues. Thus, groove and bass-frequency pulses could deliver potent rhythmic cues. These strategies capitalize on the close neural connections between auditory and motor networks; and auditory cues are typically preferred. However, moving visual cues greatly improve visuomotor synchronization and could warrant examination in gait rehabilitation. Together, a treatment approach that employs groove, auditory, bass-frequency, and adaptive (GABA) cues could help optimize rhythmic sensory cues for treating motor and timing deficits. © 2014 New York Academy of Sciences.

Antifouling strategies and corrosion control in cooling circuits.

PubMed

Cristiani, P; Perboni, G

2014-06-01

Biofouling and corrosion phenomena dramatically reduce the functionality of industrial cooling circuits, especially in marine environments. This study underlines the effectiveness of a low level chlorination treatment of seawater to prevent biological fouling and biocorrosion. Reported examples emphasize the reaction of chlorine with bromide, ammonia and organic compounds in seawater and the effectiveness of a treatment performed in such a way to guarantee a residual concentration lower than 3μM at the outlet of the condensers. In a brief review of antifouling strategies, alternatives to chlorination and the monitoring approach able to optimize the treatments are also reported. An integrated, on-line system based on electrochemical probes (Biox system and a linear polarization resistance probe) demonstrated to be sufficient to monitor in real time: corrosion, biofilm growth and chemical treatments based on chlorine or alternative oxidant products (chlorine dioxide, etc.). A careful electrochemical monitoring and the optimized treatments help the plant operators of industrial cooling circuits prevent the decay of the equipment performance, allowing at the same time the control of the halogenated by-products formation. Copyright © 2014 Elsevier B.V. All rights reserved.

Optimization of pulsed electric field pre-treatments to enhance health-promoting glucosinolates in broccoli flowers and stalk.

PubMed

Aguiló-Aguayo, Ingrid; Suarez, Manuel; Plaza, Lucia; Hossain, Mohammad B; Brunton, Nigel; Lyng, James G; Rai, Dilip K

2015-07-01

The effect of pulsed electric field (PEF) treatment variables (electric field strength and treatment time) on the glucosinolate content of broccoli flowers and stalks was evaluated. Samples were subjected to electric field strengths from 1 to 4 kV cm(-1) and treatment times from 50 to 1000 µs at 5 Hz. Data fitted significantly (P < 0.0014) the proposed second-order response functions. The results showed that PEF combined treatment conditions of 4 kV cm(-1) for 525 and 1000 µs were optimal to maximize glucosinolate levels in broccoli flowers (ranging from 187.1 to 212.5%) and stalks (ranging from 110.6 to 203.0%) respectively. The predicted values from the developed quadratic polynomial equation were in close agreement with the actual experimental values, with low average mean deviations (E%) ranging from 0.59 to 8.80%. The use of PEF processing at moderate conditions could be a suitable method to stimulate production of broccoli with high health-promoting glucosinolate content. © 2014 Society of Chemical Industry.

The roles of xylan and lignin in oxalic acid pretreated corncob during separate enzymatic hydrolysis and ethanol fermentation

Treesearch

Jae-Won Lee; Rita C.L.B. Rodrigues; Hyun Joo Kim; In-Gyu Choi; Thomas W. Jeffries

2010-01-01

High yields of hemicellulosic and cellulosic sugars are critical in obtaining economical conversion of agricultural residues to ethanol. To optimize pretreatment conditions, we evaluated oxalic acid loading rates, treatment temperatures and times in a 23 full factorial design. Response-surface analysis revealed an optimal oxalic acid pretreatment...

Treatment of an actual slaughterhouse wastewater by integration of biological and advanced oxidation processes: Modeling, optimization, and cost-effectiveness analysis.

PubMed

Bustillo-Lecompte, Ciro Fernando; Mehrvar, Mehrab

2016-11-01

Biological and advanced oxidation processes are combined to treat an actual slaughterhouse wastewater (SWW) by a sequence of an anaerobic baffled reactor, an aerobic activated sludge reactor, and a UV/H2O2 photoreactor with recycle in continuous mode at laboratory scale. In the first part of this study, quadratic modeling along with response surface methodology are used for the statistical analysis and optimization of the combined process. The effects of the influent total organic carbon (TOC) concentration, the flow rate, the pH, the inlet H2O2 concentration, and their interaction on the overall treatment efficiency, CH4 yield, and H2O2 residual in the effluent of the photoreactor are investigated. The models are validated at different operating conditions using experimental data. Maximum TOC and total nitrogen (TN) removals of 91.29 and 86.05%, respectively, maximum CH4 yield of 55.72%, and minimum H2O2 residual of 1.45% in the photoreactor effluent were found at optimal operating conditions. In the second part of this study, continuous distribution kinetics is applied to establish a mathematical model for the degradation of SWW as a function of time. The agreement between model predictions and experimental values indicates that the proposed model could describe the performance of the combined anaerobic-aerobic-UV/H2O2 processes for the treatment of SWW. In the final part of the study, the optimized combined anaerobic-aerobic-UV/H2O2 processes with recycle were evaluated using a cost-effectiveness analysis to minimize the retention time, the electrical energy consumption, and the overall incurred treatment costs required for the efficient treatment of slaughterhouse wastewater effluents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Assessing the impact of heart failure specialist services on patient populations.

PubMed

Lyratzopoulos, Georgios; Cook, Gary A; McElduff, Patrick; Havely, Daniel; Edwards, Richard; Heller, Richard F

2004-05-24

The assessment of the impact of healthcare interventions may help commissioners of healthcare services to make optimal decisions. This can be particularly the case if the impact assessment relates to specific patient populations and uses timely local data. We examined the potential impact on readmissions and mortality of specialist heart failure services capable of delivering treatments such as b-blockers and Nurse-Led Educational Intervention (N-LEI). Statistical modelling of prevented or postponed events among previously hospitalised patients, using estimates of: treatment uptake and contraindications (based on local audit data); treatment effectiveness and intolerance (based on literature); and annual number of hospitalization per patient and annual risk of death (based on routine data). Optimal treatment uptake among eligible but untreated patients would over one year prevent or postpone 11% of all expected readmissions and 18% of all expected deaths for spironolactone, 13% of all expected readmisisons and 22% of all expected deaths for b-blockers (carvedilol) and 20% of all expected readmissions and an uncertain number of deaths for N-LEI. Optimal combined treatment uptake for all three interventions during one year among all eligible but untreated patients would prevent or postpone 37% of all expected readmissions and a minimum of 36% of all expected deaths. In a population of previously hospitalised patients with low previous uptake of b-blockers and no uptake of N-LEI, optimal combined uptake of interventions through specialist heart failure services can potentially help prevent or postpone approximately four times as many readmissions and a minimum of twice as many deaths compared with simply optimising uptake of spironolactone (not necessarily requiring specialist services). Examination of the impact of different heart failure interventions can inform rational planning of relevant healthcare services.

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.

Robustness of IPSA optimized high-dose-rate prostate brachytherapy treatment plans to catheter displacements

PubMed Central

Whitaker, May

2016-01-01

Purpose Inverse planning simulated annealing (IPSA) optimized brachytherapy treatment plans are characterized with large isolated dwell times at the first or last dwell position of each catheter. The potential of catheter shifts relative to the target and organs at risk in these plans may lead to a more significant change in delivered dose to the volumes of interest relative to plans with more uniform dwell times. Material and methods This study aims to determine if the Nucletron Oncentra dwell time deviation constraint (DTDC) parameter can be optimized to improve the robustness of high-dose-rate (HDR) prostate brachytherapy plans to catheter displacements. A set of 10 clinically acceptable prostate plans were re-optimized with a DTDC parameter of 0 and 0.4. For each plan, catheter displacements of 3, 7, and 14 mm were retrospectively applied and the change in dose volume histogram (DVH) indices and conformity indices analyzed. Results The robustness of clinically acceptable prostate plans to catheter displacements in the caudal direction was found to be dependent on the DTDC parameter. A DTDC value of 0 improves the robustness of planning target volume (PTV) coverage to catheter displacements, whereas a DTDC value of 0.4 improves the robustness of the plans to changes in hotspots. Conclusions The results indicate that if used in conjunction with a pre-treatment catheter displacement correction protocol and a tolerance of 3 mm, a DTDC value of 0.4 may produce clinically superior plans. However, the effect of the DTDC parameter in plan robustness was not observed to be as strong as initially suspected. PMID:27504129

Robustness of IPSA optimized high-dose-rate prostate brachytherapy treatment plans to catheter displacements.

PubMed

Poder, Joel; Whitaker, May

2016-06-01

Inverse planning simulated annealing (IPSA) optimized brachytherapy treatment plans are characterized with large isolated dwell times at the first or last dwell position of each catheter. The potential of catheter shifts relative to the target and organs at risk in these plans may lead to a more significant change in delivered dose to the volumes of interest relative to plans with more uniform dwell times. This study aims to determine if the Nucletron Oncentra dwell time deviation constraint (DTDC) parameter can be optimized to improve the robustness of high-dose-rate (HDR) prostate brachytherapy plans to catheter displacements. A set of 10 clinically acceptable prostate plans were re-optimized with a DTDC parameter of 0 and 0.4. For each plan, catheter displacements of 3, 7, and 14 mm were retrospectively applied and the change in dose volume histogram (DVH) indices and conformity indices analyzed. The robustness of clinically acceptable prostate plans to catheter displacements in the caudal direction was found to be dependent on the DTDC parameter. A DTDC value of 0 improves the robustness of planning target volume (PTV) coverage to catheter displacements, whereas a DTDC value of 0.4 improves the robustness of the plans to changes in hotspots. The results indicate that if used in conjunction with a pre-treatment catheter displacement correction protocol and a tolerance of 3 mm, a DTDC value of 0.4 may produce clinically superior plans. However, the effect of the DTDC parameter in plan robustness was not observed to be as strong as initially suspected.

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

Q-learning residual analysis: application to the effectiveness of sequences of antipsychotic medications for patients with schizophrenia.

PubMed

Ertefaie, Ashkan; Shortreed, Susan; Chakraborty, Bibhas

2016-06-15

Q-learning is a regression-based approach that uses longitudinal data to construct dynamic treatment regimes, which are sequences of decision rules that use patient information to inform future treatment decisions. An optimal dynamic treatment regime is composed of a sequence of decision rules that indicate how to optimally individualize treatment using the patients' baseline and time-varying characteristics to optimize the final outcome. Constructing optimal dynamic regimes using Q-learning depends heavily on the assumption that regression models at each decision point are correctly specified; yet model checking in the context of Q-learning has been largely overlooked in the current literature. In this article, we show that residual plots obtained from standard Q-learning models may fail to adequately check the quality of the model fit. We present a modified Q-learning procedure that accommodates residual analyses using standard tools. We present simulation studies showing the advantage of the proposed modification over standard Q-learning. We illustrate this new Q-learning approach using data collected from a sequential multiple assignment randomized trial of patients with schizophrenia. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Optimal control of vancomycin-resistant enterococci using preventive care and treatment of infections.

PubMed

Lowden, Jonathan; Miller Neilan, Rachael; Yahdi, Mohammed

2014-03-01

The rising prevalence of vancomycin-resistant enterococci (VRE) is a major health problem in intensive care units (ICU) because of its association with increased mortality and high health care costs. We present a mathematical framework for determining cost-effective strategies for prevention and treatment of VRE in the ICU. A system of five ordinary differential equations describes the movement of ICU patients in and out of five VRE-related states. Two control variables representing the prevention and treatment of VRE are incorporated into the system. The basic reproductive number is derived and calculated for different levels of the two controls. An optimal control problem is formulated to minimize VRE-related deaths and costs associated with prevention and treatment controls over a finite time period. Numerical solutions illustrate optimal single and dual allocations of the controls for various cost values. Results show that preventive care has the greatest impact in reducing the basic reproductive number, while treatment of VRE infections has the most impact on reducing VRE-related deaths. Copyright © 2014 Elsevier Inc. All rights reserved.

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

Statistical investigation of Kluyveromyces lactis cells permeabilization with ethanol by response surface methodology.

PubMed

de Faria, Janaína T; Rocha, Pollyana F; Converti, Attilio; Passos, Flávia M L; Minim, Luis A; Sampaio, Fábio C

2013-12-01

The aim of our study was to select the optimal operating conditions to permeabilize Kluyveromyces lactis cells using ethanol as a solvent as an alternative to cell disruption and extraction. Cell permeabilization was carried out by a non-mechanical method consisting of chemical treatment with ethanol, and the results were expressed as β-galactosidase activity. Experiments were conducted under different conditions of ethanol concentration, treatment time and temperature according to a central composite rotatable design (CCRD), and the collected results were then worked out by response surface methodology (RSM). Cell permeabilization was improved by an increase in ethanol concentration and simultaneous decreases in the incubation temperature and treatment time. Such an approach allowed us to identify an optimal range of the independent variables within which the β-galactosidase activity was optimized. A maximum permeabilization of 2,816 mmol L(-1) oNP min(-1) g(-1) was obtained by treating cells with 75.0% v/v of ethanol at 20.0 °C for 15.0 min. The proposed methodology resulted to be effective and suited for K. lactis cells permeabilization at a lab-scale and promises to be of possible interest for future applications mainly in the food industry.

Selective Oxidation of Amorphous Carbon Layers without Damaging Embedded Single Wall Carbon Nanotube Bundles

NASA Astrophysics Data System (ADS)

Choi, Young Chul; Lim, Seong Chu

2013-11-01

Single wall carbon nanotubes (SWCNTs) were synthesized by arc discharge, and then purified by selective oxidation of amorphous carbon layers that were found to encase SWCNT bundles and catalyst metal particles. In order to remove selectively the amorphous carbon layers with SWCNTs being intact, we have systematically investigated the thermal treatment conditions; firstly, setting the temperature by measuring the activation energies of SWCNTs and amorphous carbon layers, and then, secondly, finding the optimal process time. As a consequence, the optimal temperature and time for the thermal treatment was found to be 460 °C and 20 min, respectively. The complete elimination of surrounding amorphous carbon layers makes it possible to efficiently disperse the SWCNT bundles, resulting in high absorbance of SWCNT-ink. The SWCNTs which were thermal-treated at optimized temperature (460 °C) and duration (20 min) showed much better crystallinity, dispersibility, and transparent conducting properties, compared with as-synthesized and the nanotubes thermal-treated at different experimental conditions.

Optimizing the location of fuel treatments over time at landscape scales

Treesearch

Greg Jones; Woodam Chung

2011-01-01

Fuel treatments are a vital part of forest management - but when faced with limited budgets, narrow burning windows, and air quality restrictions, it can be challenging to prioritize where, when, and how fuel treatments should be applied across the landscape to achieve the most benefi t. To help ease this process, land managers can turn to various standalone models,...

Towards optimizing the sequence of bevacizumab and nitrosoureas in recurrent malignant glioma.

PubMed

Wiestler, Benedikt; Radbruch, Alexander; Osswald, Matthias; Combs, Stephanie E; Jungk, Christine; Winkler, Frank; Bendszus, Martin; Unterberg, Andreas; Platten, Michael; Wick, Wolfgang; Wick, Antje

2014-03-01

Studies on the monoclonal VEGF-A antibody bevacizumab gave raise to questions regarding the lack of an overall survival benefit, the optimal timing in the disease course and potential combination and salvage therapies. We retrospectively assessed survival, radiological progression type on bevacizumab and efficacy of salvage therapies in 42 patients with recurrent malignant gliomas who received bevacizumab and nitrosourea sequentially. 15 patients received bevacizumab followed by nitrosourea at progression and 27 patients vice versa. Time to treatment failure, defined as time from initiation of one to failure of the other treatment, was similar in both groups (9.6 vs. 9.2 months, log rank p = 0.19). Progression-free survival on nitrosoureas was comparable in both groups, while progression-free survival on bevacizumab was longer in the group receiving bevacizumab first (5.3 vs. 4.1 months, log rank p = 0.03). Survival times were similar for patients with grade III (n = 9) and grade IV (n = 33) tumors. Progression-free survival on bevacizumab for patients developing contrast-enhancing T1 progression was longer than for patients who displayed a non-enhancing T2 progression. However, post-progression survival times after bevacizumab failure were not different. Earlier treatment with bevacizumab was not associated with better outcome in this series. The fact that earlier as compared to later bevacizumab treatment does not result in a different time to treatment failure highlights the challenge for first-line or recurrence trials with bevacizumab to demonstrate an overall survival benefit if crossover of bevacizumab-naïve patients after progression occurs.

Optimization of physico-chemical properties of gelatin extracted from fish skin of rainbow trout (Onchorhynchus mykiss).

PubMed

Tabarestani, H Shahiri; Maghsoudlou, Y; Motamedzadegan, A; Mahoonak, A R Sadeghi

2010-08-01

Physico-chemical properties of gelatin extracted from rainbow trout (Onchorhynchus mykiss) skin were optimized using response surface methodology (RSM). Central rotatable composite design was applied to study the combined effects of NaOH concentration (0.01-0.21 N), acetic acid concentration (0.01-0.21 N) and pre-treatment time (1-3h) on yield, molecular weight distribution, gel strength, viscosity and melting point of gelatin. Regression models were developed to predict the variables. Predict values of multiple response at optimal condition were that yield=9.36%, alpha(1)/alpha(2) chain ratio=1.76, beta chain percent=32.81, gel strength=459 g, viscosity=3.2 mPa s and melting point=20.4 degrees C. The optimal condition was obtained using 0.19 N NaOH and 0.121 N acetic acid for 3h. The results showed that the concentration of H(+) during pre-treatment had significant effect on molecular weight distribution, melting point and gel strength. The concentration of OH(-) had significant effect on viscosity and for extraction yield, pretreatment time was the critical factor. (c) 2010 Elsevier Ltd. All rights reserved.

Time-dependent density-functional theory with optimized effective potential and self-interaction correction and derivative discontinuity for the treatment of double ionization of He and Be atoms in intense laser fields

NASA Astrophysics Data System (ADS)

Heslar, John; Telnov, Dmitry A.; Chu, Shih-I.

2013-05-01

We present a self-interaction-free time-dependent density-functional theory (TDDFT) for the treatment of double-ionization processes of many-electron systems. The method is based on the extension of the Krieger-Li-Iafrate (KLI) treatment of the optimized effective potential (OEP) theory and the incorporation of an explicit self-interaction correction (SIC) term. In the framework of the time-dependent density functional theory, we have performed three-dimensional (3D) calculations of double ionization of He and Be atoms by intense near-infrared laser fields. We make use of the exchange-correlation potential with the integer discontinuity which improves the description of the double-ionization process. We found that a proper description of the double ionization requires the TDDFT exchange-correlation potential with the discontinuity with respect to the variation of the total particle number (TPN). The results for the intensity-dependent rates of double ionization of He and Be atoms are presented.

[Coupling AFM fluid imaging with micro-flocculation filtration process for the technological optimization].

PubMed

Zheng, Bei; Ge, Xiao-peng; Yu, Zhi-yong; Yuan, Sheng-guang; Zhang, Wen-jing; Sun, Jing-fang

2012-08-01

Atomic force microscope (AFM) fluid imaging was applied to the study of micro-flocculation filtration process and the optimization of micro-flocculation time and the agitation intensity of G values. It can be concluded that AFM fluid imaging proves to be a promising tool in the observation and characterization of floc morphology and the dynamic coagulation processes under aqueous environmental conditions. Through the use of AFM fluid imaging technique, optimized conditions for micro-flocculation time of 2 min and the agitation intensity (G value) of 100 s(-1) were obtained in the treatment of dye-printing industrial tailing wastewater by the micro-flocculation filtration process with a good performance.

Automated medial axis seeding and guided evolutionary simulated annealing for optimization of gamma knife radiosurgery treatment plans

NASA Astrophysics Data System (ADS)

Zhang, Pengpeng

The Leksell Gamma KnifeRTM (LGK) is a tool for providing accurate stereotactic radiosurgical treatment of brain lesions, especially tumors. Currently, the treatment planning team "forward" plans radiation treatment parameters while viewing a series of 2D MR scans. This primarily manual process is cumbersome and time consuming because the difficulty in visualizing the large search space for the radiation parameters (i.e., shot overlap, number, location, size, and weight). I hypothesize that a computer-aided "inverse" planning procedure that utilizes tumor geometry and treatment goals could significantly improve the planning process and therapeutic outcome of LGK radiosurgery. My basic observation is that the treatment team is best at identification of the location of the lesion and prescribing a lethal, yet safe, radiation dose. The treatment planning computer is best at determining both the 3D tumor geometry and optimal LGK shot parameters necessary to deliver a desirable dose pattern to the tumor while sparing adjacent normal tissue. My treatment planning procedure asks the neurosurgeon to identify the tumor and critical structures in MR images and the oncologist to prescribe a tumoricidal radiation dose. Computer-assistance begins with geometric modeling of the 3D tumor's medial axis properties. This begins with a new algorithm, a Gradient-Phase Plot (G-P Plot) decomposition of the tumor object's medial axis. I have found that medial axis seeding, while insufficient in most cases to produce an acceptable treatment plan, greatly reduces the solution space for Guided Evolutionary Simulated Annealing (GESA) treatment plan optimization by specifying an initial estimate for shot number, size, and location, but not weight. They are used to generate multiple initial plans which become initial seed plans for GESA. The shot location and weight parameters evolve and compete in the GESA procedure. The GESA objective function optimizes tumor irradiation (i.e., as close to the prescribed dose as possible) and minimizes normal tissue and critical structure damage. In tests of five patient data sets (4 acoustic neuromas and 1 meningioma), the G-P Plot/GESA-generated treatment plans improved conformality of the lethal dose to the tumor, required no human interaction, improved dose homogeneity, suggested use of fewer shots, and reduced treatment administration time.

Optimizing time management after perforation by colonoscopy results in better outcome for the patients.

PubMed

Rumstadt, Bernhard; Schilling, Dieter

2008-01-01

Perforation during colonoscopy is a rare but severe complication. The aim of this study was to assess the time management and laparoscopic therapy of this complication and to evaluate patient outcomes. A retrospective analysis was done on 15 patients operated for a perforation from colonoscopy between January 2000 and December 2006. Three perforations occurred during diagnostic and 12 perforations during interventional colonoscopy. Two perforations occurred as transmural thermal injury to the colon wall. Peritonitis was found in 4 cases and significantly correlated with the mean time between perforation and operation. Twelve perforations were oversewn laparoscopically and 3 perforations were oversewn by laparotomy. After laparoscopic treatment, hospital stay was significantly shorter than after laparotomy. One patient had a postoperative wound infection, mortality was 0%. Laparoscopic oversewing is a safe and effective method in the treatment of perforation from colonoscopy. Optimizing the time range between perforation and laparoscopic therapy results in a better outcome for the patients.

Interpolation of longitudinal shape and image data via optimal mass transport

NASA Astrophysics Data System (ADS)

Gao, Yi; Zhu, Liang-Jia; Bouix, Sylvain; Tannenbaum, Allen

2014-03-01

Longitudinal analysis of medical imaging data has become central to the study of many disorders. Unfortunately, various constraints (study design, patient availability, technological limitations) restrict the acquisition of data to only a few time points, limiting the study of continuous disease/treatment progression. Having the ability to produce a sensible time interpolation of the data can lead to improved analysis, such as intuitive visualizations of anatomical changes, or the creation of more samples to improve statistical analysis. In this work, we model interpolation of medical image data, in particular shape data, using the theory of optimal mass transport (OMT), which can construct a continuous transition from two time points while preserving "mass" (e.g., image intensity, shape volume) during the transition. The theory even allows a short extrapolation in time and may help predict short-term treatment impact or disease progression on anatomical structure. We apply the proposed method to the hippocampus-amygdala complex in schizophrenia, the heart in atrial fibrillation, and full head MR images in traumatic brain injury.

A feasibility study: Selection of a personalized radiotherapy fractionation schedule using spatiotemporal optimization

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

Kim, Minsun, E-mail: mk688@uw.edu; Stewart, Robert D.; Phillips, Mark H.

2015-11-15

Purpose: To investigate the impact of using spatiotemporal optimization, i.e., intensity-modulated spatial optimization followed by fractionation schedule optimization, to select the patient-specific fractionation schedule that maximizes the tumor biologically equivalent dose (BED) under dose constraints for multiple organs-at-risk (OARs). Methods: Spatiotemporal optimization was applied to a variety of lung tumors in a phantom geometry using a range of tumor sizes and locations. The optimal fractionation schedule for a patient using the linear-quadratic cell survival model depends on the tumor and OAR sensitivity to fraction size (α/β), the effective tumor doubling time (T{sub d}), and the size and location of tumormore » target relative to one or more OARs (dose distribution). The authors used a spatiotemporal optimization method to identify the optimal number of fractions N that maximizes the 3D tumor BED distribution for 16 lung phantom cases. The selection of the optimal fractionation schedule used equivalent (30-fraction) OAR constraints for the heart (D{sub mean} ≤ 45 Gy), lungs (D{sub mean} ≤ 20 Gy), cord (D{sub max} ≤ 45 Gy), esophagus (D{sub max} ≤ 63 Gy), and unspecified tissues (D{sub 05} ≤ 60 Gy). To assess plan quality, the authors compared the minimum, mean, maximum, and D{sub 95} of tumor BED, as well as the equivalent uniform dose (EUD) for optimized plans to conventional intensity-modulated radiation therapy plans prescribing 60 Gy in 30 fractions. A sensitivity analysis was performed to assess the effects of T{sub d} (3–100 days), tumor lag-time (T{sub k} = 0–10 days), and the size of tumors on optimal fractionation schedule. Results: Using an α/β ratio of 10 Gy, the average values of tumor max, min, mean BED, and D{sub 95} were up to 19%, 21%, 20%, and 19% larger than those from conventional prescription, depending on T{sub d} and T{sub k} used. Tumor EUD was up to 17% larger than the conventional prescription. For fast proliferating tumors with T{sub d} less than 10 days, there was no significant increase in tumor BED but the treatment course could be shortened without a loss in tumor BED. The improvement in the tumor mean BED was more pronounced with smaller tumors (p-value = 0.08). Conclusions: Spatiotemporal optimization of patient plans has the potential to significantly improve local tumor control (larger BED/EUD) of patients with a favorable geometry, such as smaller tumors with larger distances between the tumor target and nearby OAR. In patients with a less favorable geometry and for fast growing tumors, plans optimized using spatiotemporal optimization and conventional (spatial-only) optimization are equivalent (negligible differences in tumor BED/EUD). However, spatiotemporal optimization yields shorter treatment courses than conventional spatial-only optimization. Personalized, spatiotemporal optimization of treatment schedules can increase patient convenience and help with the efficient allocation of clinical resources. Spatiotemporal optimization can also help identify a subset of patients that might benefit from nonconventional (large dose per fraction) treatments that are ineligible for the current practice of stereotactic body radiation therapy.« less

SU-F-T-382: Volumetric Modulated Arc Therapy (VMAT) Beam Angle Optimization in Pulsed Partial Brain Irradiation (PPBI) for Newly Diagnosed Glioblastoma

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

Zhou, J; Wang, Y; Ding, X

Purpose: To optimize VMAT beam parameters in PPBI to minimize treatment time. We investigate the coverage and organs at risk (OR) avoidance capability of shorter arcs with shorter treatment times. Methods: We evaluated the treatment plans for eleven previously treated PPBI patients. Each patient received 46Gy (2Gy×23) to the initial target and an additional 14Gy (2Gy×7) as a sequential boost. Each daily 2-Gy fraction was delivered as ten 0.2-Gy pulses separated by 3-minute intervals using VMAT. Each pulse was delivered using the same arc and covered at least 95% of the PTV with at least 95% of the prescription dose.more » To optimize the VMAT beam angle, an initial 360° full-arc VMAT plan was implemented. Beam control points and their corresponding dose rates were exported. A curve of the product of control point and dose rate was plotted against treatment beam angle. The optimum angle range was determined from this relationship. We chose the minimum continuous angle range that covered 85% of the area under the curve. Planning parameters, including treatment time for each pulse (T-pulse), PTV coverage, maximum dose (Dmax), homogeneity index (HI=D5/D95), R50 (50%IDL/PTV), and Dmax to ORs, were compared. Results: Mean PTV volume was 364.1±181.5cc. Mean T-pulse of partial-arc beams was 34.3±10.6s, vs. 63.0±1.7s (p<0.001) for that of full-arc beams. No significant differences were found for PTV V95, Dmax and R50, 99.4%±1.2% vs. 99.7%±0.5% (p=0.066), 108.0%±1.2% vs. 107.5%±1.1% (p=0.107), 2.95±0.38 vs. 2.87±0.35 (p=0.165), for the plans with partial-arc and full-arc beams, respectively. However, plans using full-arc do provide better PTV V100 and HI, 96.0%±3.0% vs. 97.2%±2.0% (p=0.025) and 1.06±0.03 vs. 1.04±0.01 (p=0.009). No significant difference was found on Dmax to ORs. Conclusion: PPBI with optimized partial-arc plans are clinically comparable to full-arc plans, while treatment time be significantly reduced, average saving of 287s for a 10-pulse treatment.« less

Melt-in-Mouth Multi-particulate System for the Treatment of ADHD: A Convenient Platform for Pediatric Use.

PubMed

Patadia, Jalashri; Tripathi, Rahul; Joshi, Amita

2016-08-01

Generally, pellets obtained from extrusion/spheronization, containing microcrystalline cellulose (MCC), do not disintegrate. An attempt has been made to develop melt-in-mouth pellets of taste-masked atomoxetine hydrochloride, using extrusion-spheronization, for pediatric patients. Melt-in-mouth pellets were prepared using extrusion-spheronization method and optimized using 3(3) FFD. MCC (X1, %), mannitol (X2, %) and Indion 414: Pharmaburst 500 ratio (X3, ratio) were the factors (independent variables) studied, whereas responses studied (dependent variables) were friability (Y1, %), yield (Y2, %) shape (Y3, roundness) in vitro disintegration time (Y4, seconds). The optimized formulation obtained from FFD was characterized for friability, shape and morphology, in vitro disintegration time, porosity, moisture uptake, in vitro release study and in vivo taste and disintegration time in healthy human volunteers. Randomized, two-treatment, two-sequence, two-period, single dose, crossover sensory evaluation study of taste-masked melt-in-mouth pellet was carried out in 10 healthy human subjects. A statistically significant polynomial mathematical relationship was generated between the factors and responses to obtain an optimized formulation. The optimized formulation was characterized (in vitro and in vivo) and exhibited a rapid drug release in vitro attributed to fast disintegration of pellets and high solubility of drug in 0.1 N HCl and buffer (pH 6.8). In vivo, 40% of volunteers ranked taste-masked optimized formulation as slightly bitter while 60% ranked it as no taste. The optimized pellets were conveniently administered in volunteers and exhibited rapid in-vivo disintegration in the oral cavity. Melt-in-mouth pellets can be a used as a platform technology for administering drugs to paediatric patients accurately and conveniently resulting in patient compliance.

Factors influencing uptake of intermittent preventive treatment of malaria in pregnancy using sulphadoxine pyrimethamine in Sunyani Municipality, Ghana.

PubMed

Ibrahim, Hajira; Maya, Ernest Tei; Issah, Kofi; Apanga, Paschal Awingura; Bachan, Emmanuel George; Noora, Charles Lwanga

2017-01-01

Malaria continues to pose a public health challenge in Ghana particularly in pregnant women. Ghana adopted intermittent preventive treatment of malaria in pregnancy policy using sulphadoxine pyrimethamine. Despite its implementation, its coverage still remains low. This study sought to investigate factors that influence the uptake of intermittent preventive treatment of malaria in pregnancy in the Sunyani Municipality. This was a cross sectional study which employed a quantitative method. The study was conducted in five selected facilities in the Sunyani Municipality within the period of January to June 2015. Structured questionnaires were administered to 400 pregnant women randomly sampled from antenatal clinics of selected health facilities. Descriptive, bivariate and multivariate analysis of quantitative data was done using Stata12. A total of 400 pregnant women at 36 weeks or more gestational age were studied. The study revealed that 98.5% of the pregnant women received at least one (1) dose of sulphadoxine pyrimethamine during the current pregnancy with 71% receiving optimal (at least 3 doses) doses of sulphadoxine pyrimethamine for intermittent preventive treatment of malaria in pregnancy at the time of study. The study revealed that women who attended ANC ≥4 times (Adjusted OR = 4.7, 95% CI 1.31-17.2), knowledge of malaria in pregnancy (Adjusted OR = 2.2, 95% CI 1.03-4.62) and knowledge of intermittent preventive treatment for malaria in pregnancy (Adjusted OR = 1.8, 95% CI 1.15-2.96) were found to be positively associated with the uptake of optimal doses of sulphadoxine pyrimethamine. This study has demonstrated that having a good knowledge of malaria in pregnancy and intermittent preventive treatment of malaria in pregnancy can significantly influence the uptake of optimal doses of sulphadoxine pyrimethamine. Encouraging women to attend antenatal care regularly (at least four visits) could also increase the optimal uptake of sulphadoxine pyrimethamine.

SU-E-T-197: Helical Cranial-Spinal Treatments with a Linear Accelerator

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

Anderson, J; Bernard, D; Liao, Y

2014-06-01

Purpose: Craniospinal irradiation (CSI) of systemic disease requires a high level of beam intensity modulation to reduce dose to bone marrow and other critical structures. Current helical delivery machines can take 30 minutes or more of beam-on time to complete these treatments. This pilot study aims to test the feasibility of performing helical treatments with a conventional linear accelerator using longitudinal couch travel during multiple gantry revolutions. Methods: The VMAT optimization package of the Eclipse 10.0 treatment planning system was used to optimize pseudo-helical CSI plans of 5 clinical patient scans. Each gantry revolution was divided into three 120° arcsmore » with each isocenter shifted longitudinally. Treatments requiring more than the maximum 10 arcs used multiple plans with each plan after the first being optimized including the dose of the others (Figure 1). The beam pitch was varied between 0.2 and 0.9 (couch speed 5- 20cm/revolution and field width of 22cm) and dose-volume histograms of critical organs were compared to tomotherapy plans. Results: Viable pseudo-helical plans were achieved using Eclipse. Decreasing the pitch from 0.9 to 0.2 lowered the maximum lens dose by 40%, the mean bone marrow dose by 2.1% and the maximum esophagus dose by 17.5%. (Figure 2). Linac-based helical plans showed dose results comparable to tomotherapy delivery for both target coverage and critical organ sparing, with the D50 of bone marrow and esophagus respectively 12% and 31% lower in the helical linear accelerator plan (Figure 3). Total mean beam-on time for the linear accelerator plan was 8.3 minutes, 54% faster than the tomotherapy average for the same plans. Conclusions: This pilot study has demonstrated the feasibility of planning pseudo-helical treatments for CSI targets using a conventional linac and dynamic couch movement, and supports the ongoing development of true helical optimization and delivery.« less

Numerical study of entrainment of the human circadian system and recovery by light treatment.

PubMed

Kim, Soon Ho; Goh, Segun; Han, Kyungreem; Kim, Jong Won; Choi, MooYoung

2018-05-09

While the effects of light as a zeitgeber are well known, the way the effects are modulated by features of the sleep-wake system still remains to be studied in detail. A mathematical model for disturbance and recovery of the human circadian system is presented. The model combines a circadian oscillator and a sleep-wake switch that includes the effects of orexin. By means of simulations, we characterize the period-locking zone of the model, where a stable 24-hour circadian rhythm exists, and the occurrence of circadian disruption due to both insufficient light and imbalance in orexin. We also investigate how daily bright light treatments of short duration can recover the normal circadian rhythm. It is found that the system exhibits continuous phase advance/delay at lower/higher orexin levels. Bright light treatment simulations disclose two optimal time windows, corresponding to morning and evening light treatments. Among the two, the morning light treatment is found effective in a wider range of parameter values, with shorter recovery time. This approach offers a systematic way to determine the conditions under which circadian disruption occurs, and to evaluate the effects of light treatment. In particular, it could potentially offer a way to optimize light treatments for patients with circadian disruption, e.g., sleep and mood disorders, in clinical settings.

Use of plan quality degradation to evaluate tradeoffs in delivery efficiency and clinical plan metrics arising from IMRT optimizer and sequencer compromises

PubMed Central

Wilkie, Joel R.; Matuszak, Martha M.; Feng, Mary; Moran, Jean M.; Fraass, Benedick A.

2013-01-01

Purpose: Plan degradation resulting from compromises made to enhance delivery efficiency is an important consideration for intensity modulated radiation therapy (IMRT) treatment plans. IMRT optimization and/or multileaf collimator (MLC) sequencing schemes can be modified to generate more efficient treatment delivery, but the effect those modifications have on plan quality is often difficult to quantify. In this work, the authors present a method for quantitative assessment of overall plan quality degradation due to tradeoffs between delivery efficiency and treatment plan quality, illustrated using comparisons between plans developed allowing different numbers of intensity levels in IMRT optimization and/or MLC sequencing for static segmental MLC IMRT plans. Methods: A plan quality degradation method to evaluate delivery efficiency and plan quality tradeoffs was developed and used to assess planning for 14 prostate and 12 head and neck patients treated with static IMRT. Plan quality was evaluated using a physician's predetermined “quality degradation” factors for relevant clinical plan metrics associated with the plan optimization strategy. Delivery efficiency and plan quality were assessed for a range of optimization and sequencing limitations. The “optimal” (baseline) plan for each case was derived using a clinical cost function with an unlimited number of intensity levels. These plans were sequenced with a clinical MLC leaf sequencer which uses >100 segments, assuring delivered intensities to be within 1% of the optimized intensity pattern. Each patient's optimal plan was also sequenced limiting the number of intensity levels (20, 10, and 5), and then separately optimized with these same numbers of intensity levels. Delivery time was measured for all plans, and direct evaluation of the tradeoffs between delivery time and plan degradation was performed. Results: When considering tradeoffs, the optimal number of intensity levels depends on the treatment site and on the stage in the process at which the levels are limited. The cost of improved delivery efficiency, in terms of plan quality degradation, increased as the number of intensity levels in the sequencer or optimizer decreased. The degradation was more substantial for the head and neck cases relative to the prostate cases, particularly when fewer than 20 intensity levels were used. Plan quality degradation was less severe when the number of intensity levels was limited in the optimizer rather than the sequencer. Conclusions: Analysis of plan quality degradation allows for a quantitative assessment of the compromises in clinical plan quality as delivery efficiency is improved, in order to determine the optimal delivery settings. The technique is based on physician-determined quality degradation factors and can be extended to other clinical situations where investigation of various tradeoffs is warranted. PMID:23822412

Implementation of a volumetric modulated arc therapy treatment planning solution for kidney and adrenal stereotactic body radiation therapy

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

Sonier, Marcus, E-mail: Marcus.Sonier@bccancer.bc.ca; Chu, William; Department of Radiation Oncology, University of Toronto, Toronto, ON

To develop a volumetric modulated arc therapy (VMAT) treatment planning solution in the treatment of primary renal cell carcinoma and oligometastatic adrenal lesions with stereotactic body radiation therapy. Single-arc VMAT plans (n = 5) were compared with clinically delivered step-and-shoot intensity-modulated radiotherapy (IMRT) with planning target volume coverage normalized between techniques. Target volume conformity, organ-at-risk (OAR) dose, treatment time, and monitor units were compared. A VMAT planning solution, created from a combination of arc settings and optimization constraints, auto-generated treatment plans in a single optimization. The treatment planning solution was evaluated on 15 consecutive patients receiving kidney and adrenal stereotacticmore » body radiation therapy. Treatment time was reduced from 13.0 ± 2.6 to 4.0 ± 0.9 minutes for IMRT and VMAT, respectively. The VMAT planning solution generated treatment plans with increased target homogeneity, improved 95% conformity index, and a reduced maximum point dose to nearby OARs but with increased intermediate dose to distant OARs. The conformity of the 95% isodose improved from 1.32 ± 0.39 to 1.12 ± 0.05 for IMRT and VMAT treatment plans, respectively. Evaluation of the planning solution showed clinically acceptable dose distributions for 13 of 15 cases with tight conformity of the prescription isodose to the planning target volume of 1.07 ± 0.04, delivering minimal dose to OARs. The introduction of a stereotactic body radiation therapy VMAT treatment planning solution improves the efficiency of planning and delivery time, producing treatment plans of comparable or superior quality to IMRT in the case of primary renal cell carcinoma and oligometastatic adrenal lesions.« less

Effects of dissolved oxygen concentration on photosynthetic bacteria wastewater treatment: Pollutants removal, cell growth and pigments production.

PubMed

Meng, Fan; Yang, Anqi; Zhang, Guangming; Wang, Hangyao

2017-10-01

Dissolved oxygen (DO) is an important parameter in photosynthetic bacteria (PSB) wastewater treatment. This study set different DO levels and detected the pollutants removal, PSB growth and pigments production. Results showed that DO significantly influenced the performances of PSB wastewater treatment process. The highest COD (93%) and NH 3 -N removal (83%) was achieved under DO of 4-8mg/L, but DO of 2-4mg/L was recommended considering the aeration cost. PSB biomass reached 1645mg/L under DO of 4-8mg/L with satisfying co-enzyme Q10 content. The biomass yield was relatively stable at all DO levels. For bacteriochlorophyll and carotenoids, DO>1mg/L could satisfy their production. On the other hand, DO<0.5mg/L led to the highest dehydrogenase activity. According to the different purposes, the optimal treatment time was different. The most pigments production occurred at 24h; biomass reached peak at 48h; and the optimal time for pollutants removal was 72h. Copyright © 2017 Elsevier Ltd. All rights reserved.

Breaking down patient and physician barriers to optimize glycemic control in type 2 diabetes.

PubMed

Ross, Stuart A

2013-09-01

Approximately half of patients with type 2 diabetes (T2D) do not achieve globally recognized blood glucose targets, despite the availability of a wide range of effective glucose-lowering therapies. Failure to maintain good glycemic control increases the risk of diabetes-related complications and long-term health care costs. Patients must be brought under glycemic control to improve treatment outcomes, but existing barriers to optimizing glycemic control must first be overcome, including patient nonadherence to treatment, the failure of physicians to intensify therapy in a timely manner, and inadequacies in the health care system itself. The reasons for such barriers include treatment side effects, complex treatment regimens, needle anxiety, poor patient education, and the absence of an adequate patient care plan; however, newer therapies and devices, combined with comprehensive care plans involving adequate patient education, can help to minimize barriers and improve treatment outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

Modeling of endoluminal and interstitial ultrasound hyperthermia and thermal ablation: applications to device design, feedback control, and treatment planning

PubMed Central

Prakash, Punit; Salgaonkar, Vasant A.; Diederich, Chris J.

2014-01-01

Endoluminal and catheter-based ultrasound applicators are currently under development and are in clinical use for minimally invasive hyperthermia and thermal ablation of various tissue targets. Computational models play a critical role in in device design and optimization, assessment of therapeutic feasibility and safety, devising treatment monitoring and feedback control strategies, and performing patient-specific treatment planning with this technology. The critical aspects of theoretical modeling, applied specifically to endoluminal and interstitial ultrasound thermotherapy, are reviewed. Principles and practical techniques for modeling acoustic energy deposition, bioheat transfer, thermal tissue damage, and dynamic changes in the physical and physiological state of tissue are reviewed. The integration of these models and applications of simulation techniques in identification of device design parameters, development of real time feedback-control platforms, assessing the quality and safety of treatment delivery strategies, and optimization of inverse treatment plans are presented. PMID:23738697

Ultrasound-assisted lipase-catalyzed synthesis of D-isoascorbyl palmitate: process optimization and Kinetic evaluation.

PubMed

Cui, Feng-Jie; Zhao, Hong-Xia; Sun, Wen-Jing; Wei, Zhuan; Yu, Si-Lian; Zhou, Qiang; Dong, Ying

2013-12-09

D-isoascorbic acid is a food antioxidant additive and used in accordance with Good Manufacturing Practice (GMP). High solubility in water (about 150 g/L at 25°C) reduces its effectiveness in stabilizing fats and oils. Our research group had successfully synthesized D-isoascorbyl palmitate using immobilized lipase Novozym 435 as a biocatalyst. Low production efficiency of D-isoascorbyl palmitate is still a problem for industrial production due to the long reaction time of over 24 h. In the present work, ultrasonic treatment was applied for accelerating the reaction process. The operation parameters were optimized to obtain the maximum D-isoascorbyl palmitate conversion rate by using a 5-level-4-factor Central Composite Design (CCD) and Response Surface Methdology (RSM). The reaction apparent kinetic parameters under the ultrasound treatment and mechanical shaking conditions were also determined and compared. Results showed that ultrasound treatment decreased the reaction time by over 50%. D-isoascorbyl palmitate yielded to 94.32 ± 0.17% and the productivity reached to 8.67 g L-1 h-1 under the optimized conditions as: 9% of enzyme load (w/w), 61°C of reaction temperature, 1:5 of D- isoascorbic-to-palmitic acid molar ratio, and 137 W of the ultrasound power. The immobilized lipase Novozym 435 could be reused for 7 times with 65% of the remained D-isoascorbyl palmitate conversion rate. The reaction kinetics showed that the maximum apparent reaction rate (vmax) of the ultrasound-assisted reaction was 2.85 times higher than that of the mechanical shaking, which proved that ultrasound treatment significantly enhanced the reaction efficiency. A systematic study on ultrasound-assisted enzymatic esterification for D-isoascorbyl palmitate production is reported. The results show a promising perspective of the ultrasound technique to reduce the reaction time and improve the production efficiency. The commercial D-isoascorbyl palmitate synthesis will be potentially realized due to this ultrasound-promoted esters synthesis method.

Volatile Fatty Acids Production from Codigestion of Food Waste and Sewage Sludge Based on β-Cyclodextrins and Alkaline Treatments

PubMed Central

Yang, Xue; Liu, Xiang; Chen, Si; Wu, Shuyan

2016-01-01

Volatile fatty acids (VFAs) are preferred valuable resources, which can be produced from anaerobic digestion process. This study presents a novel technology using β-cyclodextrins (β-CD) pretreatment integrated alkaline method to enhance VFAs production from codigestion of food waste and sewage sludge. Experiment results showed that optimized ratio of food waste to sewage sludge was 3 : 2 because it provided adequate organic substance and seed microorganisms. Based on this optimized ratio, the integrated treatment of alkaline pH 10 and β-CD addition (0.2 g/g TS) performed the best enhancement on VFAs production, and the maximum VFAs production was 8631.7 mg/L which was 6.13, 1.38, and 1.57 times higher than that of control, initial pH 10, and 0.2 g β-CD/g TS treatment, respectively. Furthermore, the hydrolysis rate of protein and polysaccharides was greatly improved in integration treatment, which was 1.18–3.45 times higher than that of other tests. Though the VFAs production and hydrolysis of polymeric organics were highly enhanced, the primary bacterial communities with different treatments did not show substantial differences. PMID:28096735

Volatile Fatty Acids Production from Codigestion of Food Waste and Sewage Sludge Based on β-Cyclodextrins and Alkaline Treatments.

PubMed

Yang, Xue; Liu, Xiang; Chen, Si; Liu, Guangmin; Wu, Shuyan; Wan, Chunli

2016-01-01

Volatile fatty acids (VFAs) are preferred valuable resources, which can be produced from anaerobic digestion process. This study presents a novel technology using β -cyclodextrins ( β -CD) pretreatment integrated alkaline method to enhance VFAs production from codigestion of food waste and sewage sludge. Experiment results showed that optimized ratio of food waste to sewage sludge was 3 : 2 because it provided adequate organic substance and seed microorganisms. Based on this optimized ratio, the integrated treatment of alkaline pH 10 and β -CD addition (0.2 g/g TS) performed the best enhancement on VFAs production, and the maximum VFAs production was 8631.7 mg/L which was 6.13, 1.38, and 1.57 times higher than that of control, initial pH 10, and 0.2 g β -CD/g TS treatment, respectively. Furthermore, the hydrolysis rate of protein and polysaccharides was greatly improved in integration treatment, which was 1.18-3.45 times higher than that of other tests. Though the VFAs production and hydrolysis of polymeric organics were highly enhanced, the primary bacterial communities with different treatments did not show substantial differences.

How should immunomodulators be optimized when used as combination therapy with anti-tumor necrosis factor agents in the management of inflammatory bowel disease?

PubMed

Ward, Mark G; Irving, Peter M; Sparrow, Miles P

2015-10-28

In the last 15 years the management of inflammatory bowel disease has evolved greatly, largely through the increased use of immunomodulators and, especially, anti-tumor necrosis factor (anti-TNF) biologic agents. Within this time period, confidence in the use of anti-TNFs has increased, whilst, especially in recent years, the efficacy and safety of thiopurines has been questioned. Yet despite recent concerns regarding the risk: benefit profile of thiopurines, combination therapy with an immunomodulator and an anti-TNF has emerged as the recommended treatment strategy for the majority of patients with moderate-severe disease, especially those who are recently diagnosed. Concurrently, therapeutic drug monitoring has emerged as a means of optimizing the dosage of both immunomodulators and anti-TNFs. However the recommended therapeutic target levels for both drug classes were largely derived from studies of monotherapy with either agent, or studies underpowered to analyze outcomes in combination therapy patients. It has been assumed that these target levels are applicable to patients on combination therapy also, however there are few data to support this. Similarly, the timing and duration of treatment with immunomodulators when used in combination therapy remains unknown. Recent attention, including post hoc analyses of the pivotal registration trials, has focused on the optimization of anti-TNF agents, when used as either monotherapy or combination therapy. This review will instead focus on how best to optimize immunomodulators when used in combination therapy, including an evaluation of recent data addressing unanswered questions regarding the optimal timing, dosage and duration of immunomodulator therapy in combination therapy patients.

Surgical Treatment of Recurrent Endometrial Cancer: Time for a Paradigm Shift.

PubMed

Papadia, Andrea; Bellati, Filippo; Ditto, Antonino; Bogani, Giorgio; Gasparri, Maria Luisa; Di Donato, Violante; Martinelli, Fabio; Lorusso, Domenica; Benedetti-Panici, Pierluigi; Raspagliesi, Francesco

2015-12-01

Although surgery represents the cornerstone treatment of endometrial cancer at initial diagnosis, scarce data are available in recurrent setting. The purpose of this study was to review the outcome of surgery in these patients. Medical records of all patients undergoing surgery for recurrent endometrial cancer at NCI Milano between January 2003 and January 2014 were reviewed. Survival was determined from the time of surgery for recurrence to last follow-up. Survival was estimated using Kaplan-Meier methods. Differences in survival were analyzed using the log-rank test. The Fisher's exact test was used to compare optimal versus suboptimal cytoreduction against possible predictive factors. Sixty-four patients were identified. Median age was 66 years. Recurrences were multiple in 38 % of the cases. Optimal cytoreduction was achieved in 65.6 %. Median OR time was 165 min, median postoperative hemoglobin drop was 2.4 g/dl, and median length hospital stay was 5.5 days. Eleven patients developed postoperative complications, but only four required surgical management. Estimated 5-year progression-free survival (PFS) was 42 and 19 % in optimally and suboptimally cytoreduced patients, respectively. At multivariate analysis, only residual disease was associated with PFS. Estimated 5-year overall survival (OS) was 60 and 30 % in optimally and suboptimally cytoreduced patients, respectively. At multivariate analysis, residual disease and histotype were associated with OS. At multivariate analysis, only performance status was associated with optimal cytoreduction. Secondary cytoreduction in endometrial cancer is associated with long PFS and OS. The only factors associated with improved long-term outcome are the absence of residual disease at the end of surgical resection and histotype.

Evaluating optimal therapy robustness by virtual expansion of a sample population, with a case study in cancer immunotherapy

PubMed Central

Barish, Syndi; Ochs, Michael F.; Sontag, Eduardo D.; Gevertz, Jana L.

2017-01-01

Cancer is a highly heterogeneous disease, exhibiting spatial and temporal variations that pose challenges for designing robust therapies. Here, we propose the VEPART (Virtual Expansion of Populations for Analyzing Robustness of Therapies) technique as a platform that integrates experimental data, mathematical modeling, and statistical analyses for identifying robust optimal treatment protocols. VEPART begins with time course experimental data for a sample population, and a mathematical model fit to aggregate data from that sample population. Using nonparametric statistics, the sample population is amplified and used to create a large number of virtual populations. At the final step of VEPART, robustness is assessed by identifying and analyzing the optimal therapy (perhaps restricted to a set of clinically realizable protocols) across each virtual population. As proof of concept, we have applied the VEPART method to study the robustness of treatment response in a mouse model of melanoma subject to treatment with immunostimulatory oncolytic viruses and dendritic cell vaccines. Our analysis (i) showed that every scheduling variant of the experimentally used treatment protocol is fragile (nonrobust) and (ii) discovered an alternative region of dosing space (lower oncolytic virus dose, higher dendritic cell dose) for which a robust optimal protocol exists. PMID:28716945

Optimal management of substrates in anaerobic co-digestion: An ant colony algorithm approach.

PubMed

Verdaguer, Marta; Molinos-Senante, María; Poch, Manel

2016-04-01

Sewage sludge (SWS) is inevitably produced in urban wastewater treatment plants (WWTPs). The treatment of SWS on site at small WWTPs is not economical; therefore, the SWS is typically transported to an alternative SWS treatment center. There is increased interest in the use of anaerobic digestion (AnD) with co-digestion as an SWS treatment alternative. Although the availability of different co-substrates has been ignored in most of the previous studies, it is an essential issue for the optimization of AnD co-digestion. In a pioneering approach, this paper applies an Ant-Colony-Optimization (ACO) algorithm that maximizes the generation of biogas through AnD co-digestion in order to optimize the discharge of organic waste from different waste sources in real-time. An empirical application is developed based on a virtual case study that involves organic waste from urban WWTPs and agrifood activities. The results illustrate the dominate role of toxicity levels in selecting contributions to the AnD input. The methodology and case study proposed in this paper demonstrate the usefulness of the ACO approach in supporting a decision process that contributes to improving the sustainability of organic waste and SWS management. Copyright © 2016 Elsevier Ltd. All rights reserved.

WE-H-BRA-03: Development of a Model to Include the Evolution of Resistant Tumor Subpopulations Into the Treatment Optimization Process for Schedules Involving Targeted Agents in Chemoradiation Therapy

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

Grassberger, C; Paganetti, H

Purpose: To develop a model that includes the process of resistance development into the treatment optimization process for schedules that include targeted therapies. Further, to validate the approach using clinical data and to apply the model to assess the optimal induction period with targeted agents before curative treatment with chemo-radiation in stage III lung cancer. Methods: Growth of the tumor and its subpopulations is modeled by Gompertzian growth dynamics, resistance induction as a stochastic process. Chemotherapy induced cell kill is modeled by log-cell kill dynamics, targeted agents similarly but restricted to the sensitive population. Radiation induced cell kill is assumedmore » to follow the linear-quadratic model. The validation patient data consist of a cohort of lung cancer patients treated with tyrosine kinase inhibitors that had longitudinal imaging data available. Results: The resistance induction model was successfully validated using clinical trial data from 49 patients treated with targeted agents. The observed recurrence kinetics, with tumors progressing from 1.4–63 months, result in tumor growth equaling a median volume doubling time of 92 days [34–248] and a median fraction of pre-existing resistance of 0.035 [0–0.22], in agreement with previous clinical studies. The model revealed widely varying optimal time points for the use of curative therapy, reaching from ∼1m to >6m depending on the patient’s growth rate and amount of pre-existing resistance. This demonstrates the importance of patient-specific treatment schedules when targeted agents are incorporated into the treatment. Conclusion: We developed a model including evolutionary dynamics of resistant sub-populations with traditional chemotherapy and radiation cell kill models. Fitting to clinical data yielded patient specific growth rates and resistant fraction in agreement with previous studies. Further application of the model demonstrated how proper timing of chemo-radiation could minimize the probability of resistance, increasing tumor control significantly.« less

Optimal approaches for balancing invasive species eradication and endangered species management.

PubMed

Lampert, Adam; Hastings, Alan; Grosholz, Edwin D; Jardine, Sunny L; Sanchirico, James N

2014-05-30

Resolving conflicting ecosystem management goals-such as maintaining fisheries while conserving marine species or harvesting timber while preserving habitat-is a widely recognized challenge. Even more challenging may be conflicts between two conservation goals that are typically considered complementary. Here, we model a case where eradication of an invasive plant, hybrid Spartina, threatens the recovery of an endangered bird that uses Spartina for nesting. Achieving both goals requires restoration of native Spartina. We show that the optimal management entails less intensive treatment over longer time scales to fit with the time scale of natural processes. In contrast, both eradication and restoration, when considered separately, would optimally proceed as fast as possible. Thus, managers should simultaneously consider multiple, potentially conflicting goals, which may require flexibility in the timing of expenditures. Copyright © 2014, American Association for the Advancement of Science.

Recovery time for inflamed middle ear mucosa in chronic otitis media.

PubMed

Pakır, Onur; Dinç, Aykut Erdem; Damar, Murat; Akyıldız, İlker; Eliçora, Sultan Şevik; Erdem, Duygu

2016-01-01

The present study shows that 2-3 weeks after medical treatment the status of middle ear mucosa in draining ears is similar to that of dry ears for at least 3 months. To measure the time required for an inflamed middle ear mucosa to return into optimal state after appropriate medical treatment in chronic suppurative otitis media (CSOM). To assess optimal timing for elective surgical treatment of draining ears in uncomplicated CSOM. In this prospective study, the Eustachian tube (ET) mucociliary clearance time (MCT) was used as the method to demonstrate the status of middle ear mucosa. In group 1 (28 patients) ET-MCT was measured in ears that were free of drainage for at least 3 months. In Group 2 (21 patients), ET-MCT was measured in draining ears, who responded to 10-14 days medical treatment, at presentation, after 10 days and 1 month. The ET-MCT was 8.63 ± 1.32 min in group 1 and 28.96 ± 8.19 min in group 2 at presentation; and the difference was statistically significant (p < 0.001). The ET-MCT was 14.76 ± 5.11 min after 10 days and 9.31 ± 2.33 min after 1 month in group 2. The ET-MCT was indifferent between groups 1 and 2 after 1 month (p = 0.235).

Effects of heat treatment on the antioxidative and anti-inflammatory properties of orange by-products.

PubMed

Li, Chien-Chun; Hsu, Hui-Jin; Wang, Yu-Shiang; Cassidy, Jennifer; Sheen, Shiowshuh; Liu, Shih-Chuan

2017-07-19

This study investigated the changes in the functional components, antioxidative activities, antibacterial activities, anti-inflammatory activities of orange (Citrus sinensis (L.) Osbeck) by-products (OBP) on heat treatment at 50 and 100 °C (hereafter denoted 50D and 100D extracts, respectively). Optimal heating conditions were also investigated. The total phenolic content, flavonoid content and antioxidative activities of OBP extracts significantly increased on heat treatment. The lag time of Cu 2+ -induced oxidation of human LDL was increased by 2.61, 8.61 and 8.76-fold with the addition of 0.6, 0.8 and 1.0 mg ml -1 100D extracts, respectively. The 100D extracts may significantly inhibit the growth of E. coli O157, Salmonella typhimurium and Listeria monocytogenes. 1 μg mL -1 of 100D extract may suppress the TNF-α-induced ICAM-1 protein expression. The optimal heating time for OBP was 26 h at 100 °C, which resulted in the highest antioxidant activities.

Effective Thermal Inactivation of the Spores of Bacillus cereus Biofilms Using Microwave.

PubMed

Park, Hyong Seok; Yang, Jungwoo; Choi, Hee Jung; Kim, Kyoung Heon

2017-07-28

Microwave sterilization was performed to inactivate the spores of biofilms of Bacillus cereus involved in foodborne illness. The sterilization conditions, such as the amount of water and the operating temperature and treatment time, were optimized using statistical analysis based on 15 runs of experimental results designed by the Box-Behnken method. Statistical analysis showed that the optimal conditions for the inactivation of B. cereus biofilms were 14 ml of water, 108°C of temperature, and 15 min of treatment time. Interestingly, response surface plots showed that the amount of water is the most important factor for microwave sterilization under the present conditions. Complete inactivation by microwaves was achieved in 5 min, and the inactivation efficiency by microwave was obviously higher than that by conventional steam autoclave. Finally, confocal laser scanning microscopy images showed that the principal effect of microwave treatment was cell membrane disruption. Thus, this study can contribute to the development of a process to control food-associated pathogens.

[The establishment of environmental endocrine disruptors induced precocious puberty Macaca fascicularis model and the intervention of yin nourishing fire purging Chinese materia medica].

PubMed

Zhu, Lin; Cai, De-pei

2012-12-01

To establish the environmental endocrine disruptors (EEDs) induced precocious puberty macaca fascicularis model, thus verifying the antagonism of yin nourishing fire purging Chinese materia medica (YNFPCMM) against the estrogenic effects. (1) The female prepubescent monkeys at different months old were fed with high dose and low dose EEDs. By observing EEDs' estrogenic effects, the optimal age, the optimal exposure dose, and the optimal exposure time were determined. (2) Fifteen female prepubescent monkeys were randomly divided into the exposure group, the treatment group, and the control group, 5 in each group. Those in the exposure group were fed with EEDs such as nonylphenol (4-NP) and bisphenol A (BPA). Those in the treatment group were fed with EEDs and YNFPCMM. Those in the control group were fed with dissolvent such as corn oil. The therapeutic course was 4 weeks. By the end of the treatment, the serum estrogen level was measured and the maturation index of the vaginal keratinocytes was calculated. The uterus was extracted to measure the wet weight, the endometrial thickness, the ring-shaped myometrium thickness, the endometrial epithelial cells, and the glandular epithelium height. (1) Twenty month was the optimal exposure age. The low dose EEDs was the best exposure dose, and 4 weeks was the optimal exposure time. (2) Compared with the control group, the serum estrogen level obviously increased, the maturation index of the vaginal keratinocytes significantly increased, the wet uterus weight, the endometrial thickness, the ring-shaped myometrium thickness, the endometrial epithelial cells, and the glandular epithelium height significantly increased in the exposure group (P<0.05). Compared with the exposure group, the aforesaid indices significantly decreased in the treatment group (P<0.05). The EEDs induced precocious puberty macaca fascicularis model was successfully established in this study. The EEDs were proved to have estrogenic-like activities. YNFPC-MM was proved to have significant antagonism like estrogenic activities.

Analysis of the tenderisation of jumbo squid (Dosidicus gigas) meat by ultrasonic treatment using response surface methodology.

PubMed

Hu, Yaqin; Yu, Hiaxia; Dong, Kaicheng; Yang, Shuibing; Ye, Xingqian; Chen, Shiguo

2014-10-01

Due to its unique structure, jumbo squid (Dosidicus gigas) meat is sensitive to heat treatment, which makes the traditional squid products taste tough and hard. This study aimed to tenderise jumbo squid meat through ultrasonic treatment. Response surface methodology (RSM) was used to predict the tenderising effect of various treatment conditions. According to the results of RSM, the optimal conditions appeared to be a power of 186.9 W, a frequency of 25.6 kHz, and a time of 30.8 min, and the predicted values of flexibility and firmness under these optimal conditions were 2.40 mm and 435.1 g, respectively. Protein degradation and a broken muscle fibre structure were observed through histological assay and SDS-PAGE, which suggests a satisfactory tenderisation effect. Copyright © 2014. Published by Elsevier Ltd.

An adaptive corridor-wide signal timing optimization methodology for traffic network with multiple highway-rail grade crossings.

DOT National Transportation Integrated Search

2016-06-01

Highway-rail grade crossings (HRGCs) and the intersections in their proximity are areas where potential problems in terms of safety and efficiency often arise if only simple or outdated treatments, such as normal signal timing or passive railroad war...

Annealing optimization in the process of making membrane PSF19%DMFEVA2 for wastewater treatment of palm oil mill effluent

NASA Astrophysics Data System (ADS)

Said, A. A.; Mustafa

2018-02-01

A small proportion of the Palm Oil Mill Effluent (POME) treatment has used its wastewater to converted to methane gas which will then be converted again into electrical energy. However, for Palm Oil Mill whose has a value of Chemical Oxygen Demand in its wastewater is less than 60.000 mg / L this can’t so that the purpose wastewater treatment only to reach the standard that can be safe to dispose into the environment. Wastewater treatment systems that are general applied by Palm Oil Mill especially in North Sumatera are aerobic and anaerobic, this method takes a relatively long time due to very dependent on microbial activity. An alternative method for wastewater treatment offered is membrane technology because the process is much more effective, the time is relatively short, and expected to give more optimal result. The optimum membrane obtained is PSF19%DMFEVA2T75 membrane,while the parameter condition of the permeate analysis produced in the treatment of POME wastewater with membrane PSF19%DMFEVA2T75 obtained at pH = 7.0; TSS = 148 mg / L; BOD = 149 mg / L; And COD = 252 mg / L. The results obtained is accordance with the standard of the quality of POME.

Basic principles of dental office logistics: organizing dental supplies and equipment for optimal accessibility.

PubMed

Mamoun, John

2012-01-01

To maximize office production, dentists should continuously perform treatment-related tasks throughout the workday. To this end, the office should logically organize and store dental instruments, disposables, materials, handpieces, and small equipment to optimize accessibility of these items at the moment when the dentist needs them. The office needs multiple copies of these items to prevent their inaccessibility during the workday due to breakdown, inventory depletion, or lack of a sterilized copy of the item when needed. Staff should know where all items are located in the office at all times to minimize the time needed to search for them. This article describes how to organize dental items in an office for optimal accessibility to the dentist during procedures.

Impact of Matrix-Assisted Laser Desorption and Ionization Time-of-Flight and Antimicrobial Stewardship Intervention on Treatment of Bloodstream Infections in Hospitalized Children.

PubMed

Malcolmson, Caroline; Ng, Karen; Hughes, Shevaun; Kissoon, Niranjan; Schina, Jillian; Tilley, Peter A; Roberts, Ashley

2017-06-01

Early definitive identification of infectious pathogens coupled with antimicrobial stewardship interventions allow for targeted and timely administration of antimicrobials. We investigated the combined impact of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) technology and an antimicrobial stewardship program (ASP) in pediatric patients with blood stream infections (BSIs). This is a single-center study comparing a control group of patients from October 2009 to July 2010 with BSIs to a cohort of patients postimplementation of MALDI-TOF and an ASP, from October 2013 to July 2014. Primary outcome was time to optimal therapy. Secondary outcomes included time to effective therapy, 30-day all-cause mortality, 30-day readmission rate, hospital length of stay, and intensive care admission. One hundred episodes of BSIs were identified in the preintervention period, and 121 episodes were identified in the postintervention period. Time from blood culture collection to organism identification was significantly reduced in the prospective cohort compared with historical controls (18.8 vs 43.7 hours, respectively). A total of 73 ASP interventions were made on the treatment of BSIs in the postintervention period. Combined use of MALDI-TOF and ASP significantly reduced time to optimal therapy (77.0 to 54.2 hours, P < .001). In the subgroup analysis of Gram-negative bacteremia, time to effective and optimal therapy were significantly reduced (2.0 vs 0.7 hours and 146.8 vs 48.0 hours, respectively). There were no significant differences in clinical outcomes. The combined use of MALDI-TOF and ASP allows early optimization of antimicrobial therapy in pediatric inpatients with BSIs. © The Author 2016. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

C-learning: A new classification framework to estimate optimal dynamic treatment regimes.

PubMed

Zhang, Baqun; Zhang, Min

2017-12-11

A dynamic treatment regime is a sequence of decision rules, each corresponding to a decision point, that determine that next treatment based on each individual's own available characteristics and treatment history up to that point. We show that identifying the optimal dynamic treatment regime can be recast as a sequential optimization problem and propose a direct sequential optimization method to estimate the optimal treatment regimes. In particular, at each decision point, the optimization is equivalent to sequentially minimizing a weighted expected misclassification error. Based on this classification perspective, we propose a powerful and flexible C-learning algorithm to learn the optimal dynamic treatment regimes backward sequentially from the last stage until the first stage. C-learning is a direct optimization method that directly targets optimizing decision rules by exploiting powerful optimization/classification techniques and it allows incorporation of patient's characteristics and treatment history to improve performance, hence enjoying advantages of both the traditional outcome regression-based methods (Q- and A-learning) and the more recent direct optimization methods. The superior performance and flexibility of the proposed methods are illustrated through extensive simulation studies. © 2017, The International Biometric Society.

Optimal therapies of a virus replication model with pharmacological delays based on reverse transcriptase inhibitors and protease inhibitors

NASA Astrophysics Data System (ADS)

Pei, Yongzhen; Li, Changguo; Liang, Xiyin

2017-11-01

A short delay in the pharmacological effect on account of the time required for drug absorption, distribution, and penetration into target cells after application of any anti-viral drug, is defined by the pharmacological delay (Herz et al 1996 Proc. Natl Acad. Sci. USA 93 7247-51). In this paper, a virus replication model with Beddington-DeAngelis incidence rate and the pharmacological and intracellular delays is presented to describe the treatment to cure the virus infection. The optimal controls represent the efficiency of reverse transcriptase inhibitors and protease inhibitors in suppressing viral production and prohibiting new infections. Due to the fact that both the control and state variables contain delays, we derive a necessary conditions for our optimal problem. Based on these results, numerical simulations are implemented not only to show the optimal therapeutic schedules for different infection and release rates, but also to compare the effective of three treatment programs. Furthermore, comparison of therapeutic effects under different maximum tolerable dosages is shown. Our research indicates that (1) the proper and specific treatment program should be determined according to the infection rates of different virus particles; (2) the optimal combined drug treatment is the most efficient; (3) the appropriate proportion of medicament must be formulated during the therapy due to the non-monotonic relationship between maximum tolerable dosages and therapeutic effects; (4) the therapeutic effect is advantageous when the pharmacological delay is considered.

Optimal blood glucose level control using dynamic programming based on minimal Bergman model

NASA Astrophysics Data System (ADS)

Rettian Anggita Sari, Maria; Hartono

2018-03-01

The purpose of this article is to simulate the glucose dynamic and the insulin kinetic of diabetic patient. The model used in this research is a non-linear Minimal Bergman model. Optimal control theory is then applied to formulate the problem in order to determine the optimal dose of insulin in the treatment of diabetes mellitus such that the glucose level is in the normal range for some specific time range. The optimization problem is solved using dynamic programming. The result shows that dynamic programming is quite reliable to represent the interaction between glucose and insulin levels in diabetes mellitus patient.

SU-E-T-268: Differences in Treatment Plan Quality and Delivery Between Two Commercial Treatment Planning Systems for Volumetric Arc-Based Radiation Therapy

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

Chen, S; Zhang, H; Zhang, B

2015-06-15

Purpose: To clinically evaluate the differences in volumetric modulated arc therapy (VMAT) treatment plan and delivery between two commercial treatment planning systems. Methods: Two commercial VMAT treatment planning systems with different VMAT optimization algorithms and delivery approaches were evaluated. This study included 16 clinical VMAT plans performed with the first system: 2 spine, 4 head and neck (HN), 2 brain, 4 pancreas, and 4 pelvis plans. These 16 plans were then re-optimized with the same number of arcs using the second treatment planning system. Planning goals were invariant between the two systems. Gantry speed, dose rate modulation, MLC modulation, planmore » quality, number of monitor units (MUs), VMAT quality assurance (QA) results, and treatment delivery time were compared between the 2 systems. VMAT QA results were performed using Mapcheck2 and analyzed with gamma analysis (3mm/3% and 2mm/2%). Results: Similar plan quality was achieved with each VMAT optimization algorithm, and the difference in delivery time was minimal. Algorithm 1 achieved planning goals by highly modulating the MLC (total distance traveled by leaves (TL) = 193 cm average over control points per plan), while maintaining a relatively constant dose rate (dose-rate change <100 MU/min). Algorithm 2 involved less MLC modulation (TL = 143 cm per plan), but greater dose-rate modulation (range = 0-600 MU/min). The average number of MUs was 20% less for algorithm 2 (ratio of MUs for algorithms 2 and 1 ranged from 0.5-1). VMAT QA results were similar for all disease sites except HN plans. For HN plans, the average gamma passing rates were 88.5% (2mm/2%) and 96.9% (3mm/3%) for algorithm 1 and 97.9% (2mm/2%) and 99.6% (3mm/3%) for algorithm 2. Conclusion: Both VMAT optimization algorithms achieved comparable plan quality; however, fewer MUs were needed and QA results were more robust for Algorithm 2, which more highly modulated dose rate.« less

Combined treatment: impact of optimal psychotherapy and medication in bipolar disorder.

PubMed

Parikh, Sagar V; Hawke, Lisa D; Velyvis, Vytas; Zaretsky, Ari; Beaulieu, Serge; Patelis-Siotis, Irene; MacQueen, Glenda; Young, L Trevor; Yatham, Lakshmi N; Cervantes, Pablo

2015-02-01

The current study investigated the longitudinal course of symptoms in bipolar disorder among individuals receiving optimal treatment combining pharmacotherapy and psychotherapy, as well as predictors of the course of illness. A total of 160 participants with bipolar disorder (bipolar I disorder: n = 115; bipolar II disorder: n = 45) received regular pharmacological treatment, complemented by a manualized, evidence-based psychosocial treatment - that is, cognitive behavioral therapy or psychoeducation. Participants were assessed at baseline and prospectively for 72 weeks using the Longitudinal Interval Follow-up Evaluation (LIFE) scale scores for mania/hypomania and depression, as well as comparison measures (clinicaltrials.gov identifier: NCT00188838). Over a 72-week period, patients spent a clear majority (about 65%) of time euthymic. Symptoms were experienced more than 50% of the time by only a quarter of the sample. Depressive symptoms strongly dominated over (hypo)manic symptoms, while subsyndromal symptoms were more common than full diagnosable episodes for both polarities. Mixed symptoms were rare, but present for a minority of participants. Individuals experienced approximately six significant mood changes per year, with a full relapse on average every 7.5 months. Participants who had fewer depressive symptoms at intake, a later age at onset, and no history of psychotic symptoms spent more weeks well over the course of the study. Combined pharmacological and adjunctive psychosocial treatments appeared to provide an improved course of illness compared to the results of previous studies. Efforts to further improve the course of illness beyond that provided by current optimal treatment regimens will require a substantial focus on both subsyndromal and syndromal depressive symptoms. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Robotic path-finding in inverse treatment planning for stereotactic radiosurgery with continuous dose delivery

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

Vandewouw, Marlee M., E-mail: marleev@mie.utoronto

Purpose: Continuous dose delivery in radiation therapy treatments has been shown to decrease total treatment time while improving the dose conformity and distribution homogeneity over the conventional step-and-shoot approach. The authors develop an inverse treatment planning method for Gamma Knife® Perfexion™ that continuously delivers dose along a path in the target. Methods: The authors’ method is comprised of two steps: find a path within the target, then solve a mixed integer optimization model to find the optimal collimator configurations and durations along the selected path. Robotic path-finding techniques, specifically, simultaneous localization and mapping (SLAM) using an extended Kalman filter, aremore » used to obtain a path that travels sufficiently close to selected isocentre locations. SLAM is novelly extended to explore a 3D, discrete environment, which is the target discretized into voxels. Further novel extensions are incorporated into the steering mechanism to account for target geometry. Results: The SLAM method was tested on seven clinical cases and compared to clinical, Hamiltonian path continuous delivery, and inverse step-and-shoot treatment plans. The SLAM approach improved dose metrics compared to the clinical plans and Hamiltonian path continuous delivery plans. Beam-on times improved over clinical plans, and had mixed performance compared to Hamiltonian path continuous plans. The SLAM method is also shown to be robust to path selection inaccuracies, isocentre selection, and dose distribution. Conclusions: The SLAM method for continuous delivery provides decreased total treatment time and increased treatment quality compared to both clinical and inverse step-and-shoot plans, and outperforms existing path methods in treatment quality. It also accounts for uncertainty in treatment planning by accommodating inaccuracies.« less

Analysis of Regional Timelines To Set Up a Global Phase III Clinical Trial in Breast Cancer: The Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Experience

PubMed Central

de Azambuja, Evandro; Bradbury, Ian; Saini, Kamal S.; Bines, José; Simon, Sergio D.; Dooren, Veerle Van; Aktan, Gursel; Pritchard, Kathleen I.; Wolff, Antonio C.; Smith, Ian; Jackisch, Christian; Lang, Istvan; Untch, Michael; Boyle, Frances; Xu, Binghe; Baselga, Jose; Perez, Edith A.; Piccart-Gebhart, Martine

2013-01-01

Purpose. This study measured the time taken for setting up the different facets of Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO), an international phase III study being conducted in 44 participating countries. Methods. Time to regulatory authority (RA) approval, time to ethics committee/institutional review board (EC/IRB) approval, time from study approval by EC/IRB to first randomized patient, and time from first to last randomized patient were prospectively collected in the ALTTO study. Analyses were conducted by grouping countries into either geographic regions or economic classes as per the World Bank's criteria. Results. South America had a significantly longer time to RA approval (median: 236 days, range: 21–257 days) than Europe (median: 52 days, range: 0–151 days), North America (median: 26 days, range: 22–30 days), and Asia-Pacific (median: 62 days, range: 37–75 days). Upper-middle economies had longer times to RA approval (median: 123 days, range: 21–257 days) than high-income (median: 47 days, range: 0–112 days) and lower-middle income economies (median: 57 days, range: 37–62 days). No significant difference was observed for time to EC/IRB approval across the studied regions (median: 59 days, range 0–174 days). Overall, the median time from EC/IRB approval to first recruited patient was 169 days (range: 26–412 days). Conclusion. This study highlights the long time intervals required to activate a global phase III trial. Collaborative research groups, pharmaceutical industry sponsors, and regulatory authorities should analyze the current system and enter into dialogue for optimizing local policies. This would enable faster access of patients to innovative therapies and enhance the efficiency of clinical research. PMID:23359433

Optimization of the Alkaline Pretreatment of Rice Straw for Enhanced Methane Yield

PubMed Central

Song, Zilin; Yang, Gaihe; Han, Xinhui; Feng, Yongzhong; Ren, Guangxin

2013-01-01

The lime pretreatment process for rice straw was optimized to enhance the biodegradation performance and increase biogas yield. The optimization was implemented using response surface methodology (RSM) and Box-Behnken experimental design. The effects of biodegradation, as well as the interactive effects of Ca(OH)2 concentration, pretreatment time, and inoculum amount on biogas improvement, were investigated. Rice straw compounds, such as lignin, cellulose, and hemicellulose, were significantly degraded with increasing Ca(OH)2 concentration. The optimal conditions for the use of pretreated rice straw in anaerobic digestion were 9.81% Ca(OH)2 (w/w TS), 5.89 d treatment time, and 45.12% inoculum content, which resulted in a methane yield of 225.3 mL/g VS. A determination coefficient (R 2) of 96% was obtained, indicating that the model used to predict the anabolic digestion process shows a favorable fit with the experimental parameters. PMID:23509824

Optimization of the pretreatment of wastewater from a slaughterhouse and packing plant through electrocoagulation in a batch reactor.

PubMed

Orssatto, Fábio; Ferreira Tavares, Maria Hermínia; Manente da Silva, Flávia; Eyng, Eduardo; Farias Biassi, Brendown; Fleck, Leandro

2017-10-01

The purpose of this study is to evaluate the removal of chemical oxygen demand (COD), turbidity and color of wastewater from a pig slaughterhouse and packing plant through the electrochemical technique and to optimize the ΔV (electric potential difference) and HRT (hydraulic retention time) variables in an electrocoagulation batch reactor using aluminum electrodes. The experimental design used was rotatable central composite design. For turbidity, the values for removal efficiency obtained varied from 92.85% to 99.28%; for color, they varied from 81.34% to 98.93% and for COD, they varied from 58.61% to 81.01%. The best optimized conditions of treatment were at 25 min for the HRT and 25 V for the ΔV, which correspond to electrical current of 1.08 A and a current density of 21.6 mA cm -2 . The aluminum residue varied from 15.254 to 54.291 mg L -1 and the cost of the treatment was US$4.288 m -3 . The novelty of the work was the simultaneous optimization of three response variables using the desirability function applied to the treatment of wastewater from slaughterhouses.

TH-E-BRF-06: Kinetic Modeling of Tumor Response to Fractionated Radiotherapy

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

Zhong, H; Gordon, J; Chetty, I

2014-06-15

Purpose: Accurate calibration of radiobiological parameters is crucial to predicting radiation treatment response. Modeling differences may have a significant impact on calibrated parameters. In this study, we have integrated two existing models with kinetic differential equations to formulate a new tumor regression model for calibrating radiobiological parameters for individual patients. Methods: A system of differential equations that characterizes the birth-and-death process of tumor cells in radiation treatment was analytically solved. The solution of this system was used to construct an iterative model (Z-model). The model consists of three parameters: tumor doubling time Td, half-life of dying cells Tr and cellmore » survival fraction SFD under dose D. The Jacobian determinant of this model was proposed as a constraint to optimize the three parameters for six head and neck cancer patients. The derived parameters were compared with those generated from the two existing models, Chvetsov model (C-model) and Lim model (L-model). The C-model and L-model were optimized with the parameter Td fixed. Results: With the Jacobian-constrained Z-model, the mean of the optimized cell survival fractions is 0.43±0.08, and the half-life of dying cells averaged over the six patients is 17.5±3.2 days. The parameters Tr and SFD optimized with the Z-model differ by 1.2% and 20.3% from those optimized with the Td-fixed C-model, and by 32.1% and 112.3% from those optimized with the Td-fixed L-model, respectively. Conclusion: The Z-model was analytically constructed from the cellpopulation differential equations to describe changes in the number of different tumor cells during the course of fractionated radiation treatment. The Jacobian constraints were proposed to optimize the three radiobiological parameters. The developed modeling and optimization methods may help develop high-quality treatment regimens for individual patients.« less

WE-DE-201-01: BEST IN PHYSICS (THERAPY): A Fast Multi-Target Inverse Treatment Planning Strategy Optimizing Dosimetric Measures for High-Dose-Rate (HDR) Brachytherapy

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

Guthier, C; University Medical Center Mannheim, Mannheim; Harvard Medical School, Boston, MA

Purpose: Inverse treatment planning (ITP) for interstitial HDR brachytherapy of gynecologic cancers seeks to maximize coverage of the clinical target volumes (tumor and vagina) while respecting dose-volume-histogram related dosimetric measures (DMs) for organs at risk (OARs). Commercially available ITP tools do not support DM-based planning because it is computationally too expensive to solve. In this study we present a novel approach that allows fast ITP for gynecologic cancers based on DMs for the first time. Methods: This novel strategy is an optimization model based on a smooth DM-based objective function. The smooth approximation is achieved by utilizing a logistic functionmore » for the evaluation of DMs. The resulting nonconvex and constrained optimization problem is then optimized with a BFGS algorithm. The model was evaluated using the implant geometry extracted from 20 patient treatment plans under an IRB-approved retrospective study. For each plan, the final DMs were evaluated and compared to the original clinical plans. The CTVs were the contoured tumor volume and the contoured surface of the vagina. Statistical significance was evaluated with a one-sided paired Wilcoxon signed-rank test. Results: As did the clinical plans, all generated plans fulfilled the defined DMs for OARs. The proposed strategy showed a statistically significant improvement (p<0.001) in coverage of the tumor and vagina, with absolute improvements of related DMs of (6.9 +/− 7.9)% and (28.2 +/− 12.0)%, respectively. This was achieved with a statistically significant (p<0.01) decrease of the high-dose-related DM for the tumor. The runtime of the optimization was (2.3 +/− 2.0) seconds. Conclusion: We demonstrated using clinical data that our novel approach allows rapid DM-based optimization with improved coverage of CTVs with fewer hot spots. Being up to three orders of magnitude faster than the current clinical practice, the method dramatically shortens planning time.« less

Designing clinical trials to test disease-modifying agents: application to the treatment trials of Alzheimer's disease.

PubMed

Xiong, Chengjie; van Belle, Gerald; Miller, J Philip; Morris, John C

2011-02-01

Therapeutic trials of disease-modifying agents on Alzheimer's disease (AD) require novel designs and analyses involving switch of treatments for at least a portion of subjects enrolled. Randomized start and randomized withdrawal designs are two examples of such designs. Crucial design parameters such as sample size and the time of treatment switch are important to understand in designing such clinical trials. The purpose of this article is to provide methods to determine sample sizes and time of treatment switch as well as optimum statistical tests of treatment efficacy for clinical trials of disease-modifying agents on AD. A general linear mixed effects model is proposed to test the disease-modifying efficacy of novel therapeutic agents on AD. This model links the longitudinal growth from both the placebo arm and the treatment arm at the time of treatment switch for these in the delayed treatment arm or early withdrawal arm and incorporates the potential correlation on the rate of cognitive change before and after the treatment switch. Sample sizes and the optimum time for treatment switch of such trials as well as optimum test statistic for the treatment efficacy are determined according to the model. Assuming an evenly spaced longitudinal design over a fixed duration, the optimum treatment switching time in a randomized start or a randomized withdrawal trial is half way through the trial. With the optimum test statistic for the treatment efficacy and over a wide spectrum of model parameters, the optimum sample size allocations are fairly close to the simplest design with a sample size ratio of 1:1:1 among the treatment arm, the delayed treatment or early withdrawal arm, and the placebo arm. The application of the proposed methodology to AD provides evidence that much larger sample sizes are required to adequately power disease-modifying trials when compared with those for symptomatic agents, even when the treatment switch time and efficacy test are optimally chosen. The proposed method assumes that the only and immediate effect of treatment switch is on the rate of cognitive change. Crucial design parameters for the clinical trials of disease-modifying agents on AD can be optimally chosen. Government and industry officials as well as academia researchers should consider the optimum use of the clinical trials design for disease-modifying agents on AD in their effort to search for the treatments with the potential to modify the underlying pathophysiology of AD.

Using pilot data to size a two-arm randomized trial to find a nearly optimal personalized treatment strategy.

PubMed

Laber, Eric B; Zhao, Ying-Qi; Regh, Todd; Davidian, Marie; Tsiatis, Anastasios; Stanford, Joseph B; Zeng, Donglin; Song, Rui; Kosorok, Michael R

2016-04-15

A personalized treatment strategy formalizes evidence-based treatment selection by mapping patient information to a recommended treatment. Personalized treatment strategies can produce better patient outcomes while reducing cost and treatment burden. Thus, among clinical and intervention scientists, there is a growing interest in conducting randomized clinical trials when one of the primary aims is estimation of a personalized treatment strategy. However, at present, there are no appropriate sample size formulae to assist in the design of such a trial. Furthermore, because the sampling distribution of the estimated outcome under an estimated optimal treatment strategy can be highly sensitive to small perturbations in the underlying generative model, sample size calculations based on standard (uncorrected) asymptotic approximations or computer simulations may not be reliable. We offer a simple and robust method for powering a single stage, two-armed randomized clinical trial when the primary aim is estimating the optimal single stage personalized treatment strategy. The proposed method is based on inverting a plugin projection confidence interval and is thereby regular and robust to small perturbations of the underlying generative model. The proposed method requires elicitation of two clinically meaningful parameters from clinical scientists and uses data from a small pilot study to estimate nuisance parameters, which are not easily elicited. The method performs well in simulated experiments and is illustrated using data from a pilot study of time to conception and fertility awareness. Copyright © 2015 John Wiley & Sons, Ltd.

Application of characteristic time concepts for hydraulic fracture configuration design, control, and optimization

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

Advani, S.H.; Lee, T.S.; Moon, H.

1992-10-01

The analysis of pertinent energy components or affiliated characteristic times for hydraulic stimulation processes serves as an effective tool for fracture configuration designs optimization, and control. This evaluation, in conjunction with parametric sensitivity studies, provides a rational base for quantifying dominant process mechanisms and the roles of specified reservoir properties relative to controllable hydraulic fracture variables for a wide spectrum of treatment scenarios. Results are detailed for the following multi-task effort: (a) Application of characteristic time concept and parametric sensitivity studies for specialized fracture geometries (rectangular, penny-shaped, elliptical) and three-layered elliptic crack models (in situ stress, elastic moduli, and fracturemore » toughness contrasts). (b) Incorporation of leak-off effects for models investigated in (a). (c) Simulation of generalized hydraulic fracture models and investigation of the role of controllable vaxiables and uncontrollable system properties. (d) Development of guidelines for hydraulic fracture design and optimization.« less

Application of characteristic time concepts for hydraulic fracture configuration design, control, and optimization. Final report

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

Advani, S.H.; Lee, T.S.; Moon, H.

1992-10-01

The analysis of pertinent energy components or affiliated characteristic times for hydraulic stimulation processes serves as an effective tool for fracture configuration designs optimization, and control. This evaluation, in conjunction with parametric sensitivity studies, provides a rational base for quantifying dominant process mechanisms and the roles of specified reservoir properties relative to controllable hydraulic fracture variables for a wide spectrum of treatment scenarios. Results are detailed for the following multi-task effort: (a) Application of characteristic time concept and parametric sensitivity studies for specialized fracture geometries (rectangular, penny-shaped, elliptical) and three-layered elliptic crack models (in situ stress, elastic moduli, and fracturemore » toughness contrasts). (b) Incorporation of leak-off effects for models investigated in (a). (c) Simulation of generalized hydraulic fracture models and investigation of the role of controllable vaxiables and uncontrollable system properties. (d) Development of guidelines for hydraulic fracture design and optimization.« less

Effect of water-cooling treatment times on properties of friction stir welded joints of 7N01-T4 aluminum alloy

NASA Astrophysics Data System (ADS)

Zhang, T. H.; Wang, Y.; Fang, X. F.; Liang, P.; Zhao, Y.; Li, Y. H.; Liu, X. M.

2018-02-01

Due to the deformation caused by residual stress in the welding process, welded components need treatment to reduce welding distortion. In this paper, several different times of flame-heating and water-cooling treatment were subjected to the friction stir welding joints of 15mm thick 7N01P-T4 aluminum alloy sheets to study the microstructure variation of friction stir welding joints of 7N01P-T4 aluminum alloy, and to analyze the effect on micro-hardness, tensile and fracture mechanical properties. This investigation will be helpful to optimize treatment methods and provide instruction on industrial production.

MCTP system model based on linear programming optimization of apertures obtained from sequencing patient image data maps.

PubMed

Ureba, A; Salguero, F J; Barbeiro, A R; Jimenez-Ortega, E; Baeza, J A; Miras, H; Linares, R; Perucha, M; Leal, A

2014-08-01

The authors present a hybrid direct multileaf collimator (MLC) aperture optimization model exclusively based on sequencing of patient imaging data to be implemented on a Monte Carlo treatment planning system (MC-TPS) to allow the explicit radiation transport simulation of advanced radiotherapy treatments with optimal results in efficient times for clinical practice. The planning system (called CARMEN) is a full MC-TPS, controlled through aMATLAB interface, which is based on the sequencing of a novel map, called "biophysical" map, which is generated from enhanced image data of patients to achieve a set of segments actually deliverable. In order to reduce the required computation time, the conventional fluence map has been replaced by the biophysical map which is sequenced to provide direct apertures that will later be weighted by means of an optimization algorithm based on linear programming. A ray-casting algorithm throughout the patient CT assembles information about the found structures, the mass thickness crossed, as well as PET values. Data are recorded to generate a biophysical map for each gantry angle. These maps are the input files for a home-made sequencer developed to take into account the interactions of photons and electrons with the MLC. For each linac (Axesse of Elekta and Primus of Siemens) and energy beam studied (6, 9, 12, 15 MeV and 6 MV), phase space files were simulated with the EGSnrc/BEAMnrc code. The dose calculation in patient was carried out with the BEAMDOSE code. This code is a modified version of EGSnrc/DOSXYZnrc able to calculate the beamlet dose in order to combine them with different weights during the optimization process. Three complex radiotherapy treatments were selected to check the reliability of CARMEN in situations where the MC calculation can offer an added value: A head-and-neck case (Case I) with three targets delineated on PET/CT images and a demanding dose-escalation; a partial breast irradiation case (Case II) solved with photon and electron modulated beams (IMRT + MERT); and a prostatic bed case (Case III) with a pronounced concave-shaped PTV by using volumetric modulated arc therapy. In the three cases, the required target prescription doses and constraints on organs at risk were fulfilled in a short enough time to allow routine clinical implementation. The quality assurance protocol followed to check CARMEN system showed a high agreement with the experimental measurements. A Monte Carlo treatment planning model exclusively based on maps performed from patient imaging data has been presented. The sequencing of these maps allows obtaining deliverable apertures which are weighted for modulation under a linear programming formulation. The model is able to solve complex radiotherapy treatments with high accuracy in an efficient computation time.

[A systemic risk analysis of hospital management processes by medical employees--an effective basis for improving patient safety].

PubMed

Sobottka, Stephan B; Eberlein-Gonska, Maria; Schackert, Gabriele; Töpfer, Armin

2009-01-01

Due to the knowledge gap that exists between patients and health care staff the quality of medical treatment usually cannot be assessed securely by patients. For an optimization of safety in treatment-related processes of medical care, the medical staff needs to be actively involved in preventive and proactive quality management. Using voluntary, confidential and non-punitive systematic employee surveys, vulnerable topics and areas in patient care revealing preventable risks can be identified at an early stage. Preventive measures to continuously optimize treatment quality can be defined by creating a risk portfolio and a priority list of vulnerable topics. Whereas critical incident reporting systems are suitable for continuous risk assessment by detecting safety-relevant single events, employee surveys permit to conduct a systematic risk analysis of all treatment-related processes of patient care at any given point in time.

Optimized evaporation technique for leachate treatment: Small scale implementation.

PubMed

Benyoucef, Fatima; Makan, Abdelhadi; El Ghmari, Abderrahman; Ouatmane, Aziz

2016-04-01

This paper introduces an optimized evaporation technique for leachate treatment. For this purpose and in order to study the feasibility and measure the effectiveness of the forced evaporation, three cuboidal steel tubs were designed and implemented. The first control-tub was installed at the ground level to monitor natural evaporation. Similarly, the second and the third tub, models under investigation, were installed respectively at the ground level (equipped-tub 1) and out of the ground level (equipped-tub 2), and provided with special equipment to accelerate the evaporation process. The obtained results showed that the evaporation rate at the equipped-tubs was much accelerated with respect to the control-tub. It was accelerated five times in the winter period, where the evaporation rate was increased from a value of 0.37 mm/day to reach a value of 1.50 mm/day. In the summer period, the evaporation rate was accelerated more than three times and it increased from a value of 3.06 mm/day to reach a value of 10.25 mm/day. Overall, the optimized evaporation technique can be applied effectively either under electric or solar energy supply, and will accelerate the evaporation rate from three to five times whatever the season temperature. Copyright © 2016. Published by Elsevier Ltd.

Ethnic variation in localized prostate cancer: a pilot study of preferences, optimism, and quality of life among black and white veterans.

PubMed

Knight, Sara J; Siston, Amy K; Chmiel, Joan S; Slimack, Nicholas; Elstein, Arthur S; Chapman, Gretchen B; Nadler, Robert B; Bennett, Charles L

2004-06-01

Ethnic variations that may influence the preferences and outcomes associated with prostate cancer treatment are not well delineated. Our objective was to evaluate prospectively preferences, optimism, involvement in care, and quality of life (QOL) in black and white veterans newly diagnosed with localized prostate cancer. A total of 95 men who identified themselves as black/African-American or white who had newly diagnosed, localized prostate cancer completed a "time trade-off" task to assess utilities for current health and mild, moderate, and severe functional impairment; importance rankings for attributes associated with prostate cancer (eg, urinary function); and baseline and follow-up measures of optimism, involvement in care, and QOL. Interviews were scheduled before treatment, and at 3 and 12 months after treatment. At baseline, both blacks and whites ranked pain, bowel, and bladder function as their most important concerns. Optimism, involvement in care, and QOL were similar. Utilities for mild impairment were lower for blacks than whites, but were similar for moderate and severe problems. Decline in QOL at 3 and 12 months compared to baseline occurred for both groups. However, even with adjustment for marital status, education level, and treatment, blacks had less increase in nausea and vomiting and more increase in difficulty with sexual interest and weight gain compared with whites. Black and white veterans entered localized prostate cancer treatment with similar priorities, optimism, and involvement in care. Quality-of-life declines were common to both groups during the first year after diagnosis, but ethnic variation occurred with respect to nausea and vomiting, sexual interest, and weight gain.

Optimization of magnetic field-assisted ultrasonication for the disintegration of waste activated sludge using Box-Behnken design with response surface methodology.

PubMed

Guan, Su; Deng, Feng; Huang, Si-Qi; Liu, Shu-Yang; Ai, Le-Xian; She, Pu-Ying

2017-09-01

This study investigated for the first time the feasibility of using a magnetic field for sludge disintegration. Approximately 41.01% disintegration degree (DD) was reached after 30min at 180mT magnetic field intensity upon separate magnetic field treatment. Protein and polysaccharide contents significantly increased. This test was optimized using a Box-Behnken design (BBD) with response surface methodology (RSM) to fit the multiple equation of the DD. The maximum DD was 43.75% and the protein and polysaccharide contents increased to 56.71 and 119.44mg/L, respectively, when the magnetic field strength was 119.69mT, reaction time was 30.49min, and pH was 9.82 in the optimization experiment. We then analyzed the effects of ultrasound alone. We are the first to combine magnetic field with ultrasound to disintegrate waste-activated sludge (WAS). The optimum effect was obtained with the application of ultrasound alone at 45kHz frequency, with a DD of about 58.09%. By contrast, 62.62% DD was reached in combined magnetic field and ultrasound treatment. This combined test was also optimized using BBD with RSM to fit the multiple equation of DD. The maximum DD of 64.59% was achieved when the magnetic field intensity was 197.87mT, ultrasonic frequency was 42.28kHz, reaction time was 33.96min, and pH was 8.90. These results were consistent with those of particle size and electron microscopy analyses. This research proved that a magnetic field can effectively disintegrate WAS and can be combined with other physical techniques such as ultrasound for optimal results. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Optimal control in adaptive optics modeling of nonlinear systems

NASA Astrophysics Data System (ADS)

Herrmann, J.

The problem of using an adaptive optics system to correct for nonlinear effects like thermal blooming is addressed using a model containing nonlinear lenses through which Gaussian beams are propagated. The best correction of this nonlinear system can be formulated as a deterministic open loop optimal control problem. This treatment gives a limit for the best possible correction. Aspects of adaptive control and servo systems are not included at this stage. An attempt is made to determine that control in the transmitter plane which minimizes the time averaged area or maximizes the fluence in the target plane. The standard minimization procedure leads to a two-point-boundary-value problem, which is ill-conditioned in the case. The optimal control problem was solved using an iterative gradient technique. An instantaneous correction is introduced and compared with the optimal correction. The results of the calculations show that for short times or weak nonlinearities the instantaneous correction is close to the optimal correction, but that for long times and strong nonlinearities a large difference develops between the two types of correction. For these cases the steady state correction becomes better than the instantaneous correction and approaches the optimum correction.

Computerized optimization of multiple isocentres in stereotactic convergent beam irradiation

NASA Astrophysics Data System (ADS)

Treuer, U.; Treuer, H.; Hoevels, M.; Müller, R. P.; Sturm, V.

1998-01-01

A method for the fully computerized determination and optimization of positions of target points and collimator sizes in convergent beam irradiation is presented. In conventional interactive trial and error methods, which are very time consuming, the treatment parameters are chosen according to the operator's experience and improved successively. This time is reduced significantly by the use of a computerized procedure. After the definition of target volume and organs at risk in the CT or MR scans, an initial configuration is created automatically. In the next step the target point positions and collimator diameters are optimized by the program. The aim of the optimization is to find a configuration for which a prescribed dose at the target surface is approximated as close as possible. At the same time dose peaks inside the target volume are minimized and organs at risk and tissue surrounding the target are spared. To enhance the speed of the optimization a fast method for approximate dose calculation in convergent beam irradiation is used. A possible application of the method for calculating the leaf positions when irradiating with a micromultileaf collimator is briefly discussed. The success of the procedure has been demonstrated for several clinical cases with up to six target points.

Development of an adjoint sensitivity field-based treatment-planning technique for the use of newly designed directional LDR sources in brachytherapy.

PubMed

Chaswal, V; Thomadsen, B R; Henderson, D L

2012-02-21

The development and application of an automated 3D greedy heuristic (GH) optimization algorithm utilizing the adjoint sensitivity fields for treatment planning to assess the advantage of directional interstitial prostate brachytherapy is presented. Directional and isotropic dose kernels generated using Monte Carlo simulations based on Best Industries model 2301 I-125 source are utilized for treatment planning. The newly developed GH algorithm is employed for optimization of the treatment plans for seven interstitial prostate brachytherapy cases using mixed sources (directional brachytherapy) and using only isotropic sources (conventional brachytherapy). All treatment plans resulted in V100 > 98% and D90 > 45 Gy for the target prostate region. For the urethra region, the D10(Ur), D90(Ur) and V150(Ur) and for the rectum region the V100cc, D2cc, D90(Re) and V90(Re) all are reduced significantly when mixed sources brachytherapy is used employing directional sources. The simulations demonstrated that the use of directional sources in the low dose-rate (LDR) brachytherapy of the prostate clearly benefits in sparing the urethra and the rectum sensitive structures from overdose. The time taken for a conventional treatment plan is less than three seconds, while the time taken for a mixed source treatment plan is less than nine seconds, as tested on an Intel Core2 Duo 2.2 GHz processor with 1GB RAM. The new 3D GH algorithm is successful in generating a feasible LDR brachytherapy treatment planning solution with an extra degree of freedom, i.e. directionality in very little time.

Development of an adjoint sensitivity field-based treatment-planning technique for the use of newly designed directional LDR sources in brachytherapy

NASA Astrophysics Data System (ADS)

Chaswal, V.; Thomadsen, B. R.; Henderson, D. L.

2012-02-01

The development and application of an automated 3D greedy heuristic (GH) optimization algorithm utilizing the adjoint sensitivity fields for treatment planning to assess the advantage of directional interstitial prostate brachytherapy is presented. Directional and isotropic dose kernels generated using Monte Carlo simulations based on Best Industries model 2301 I-125 source are utilized for treatment planning. The newly developed GH algorithm is employed for optimization of the treatment plans for seven interstitial prostate brachytherapy cases using mixed sources (directional brachytherapy) and using only isotropic sources (conventional brachytherapy). All treatment plans resulted in V100 > 98% and D90 > 45 Gy for the target prostate region. For the urethra region, the D10Ur, D90Ur and V150Ur and for the rectum region the V100cc, D2cc, D90Re and V90Re all are reduced significantly when mixed sources brachytherapy is used employing directional sources. The simulations demonstrated that the use of directional sources in the low dose-rate (LDR) brachytherapy of the prostate clearly benefits in sparing the urethra and the rectum sensitive structures from overdose. The time taken for a conventional treatment plan is less than three seconds, while the time taken for a mixed source treatment plan is less than nine seconds, as tested on an Intel Core2 Duo 2.2 GHz processor with 1GB RAM. The new 3D GH algorithm is successful in generating a feasible LDR brachytherapy treatment planning solution with an extra degree of freedom, i.e. directionality in very little time.

Automation of radiation treatment planning : Evaluation of head and neck cancer patient plans created by the Pinnacle3 scripting and Auto-Planning functions.

PubMed

Speer, Stefan; Klein, Andreas; Kober, Lukas; Weiss, Alexander; Yohannes, Indra; Bert, Christoph

2017-08-01

Intensity-modulated radiotherapy (IMRT) techniques are now standard practice. IMRT or volumetric-modulated arc therapy (VMAT) allow treatment of the tumor while simultaneously sparing organs at risk. Nevertheless, treatment plan quality still depends on the physicist's individual skills, experiences, and personal preferences. It would therefore be advantageous to automate the planning process. This possibility is offered by the Pinnacle 3 treatment planning system (Philips Healthcare, Hamburg, Germany) via its scripting language or Auto-Planning (AP) module. AP module results were compared to in-house scripts and manually optimized treatment plans for standard head and neck cancer plans. Multiple treatment parameters were scored to judge plan quality (100 points = optimum plan). Patients were initially planned manually by different physicists and re-planned using scripts or AP. Script-based head and neck plans achieved a mean of 67.0 points and were, on average, superior to manually created (59.1 points) and AP plans (62.3 points). Moreover, they are characterized by reproducibility and lower standard deviation of treatment parameters. Even less experienced staff are able to create at least a good starting point for further optimization in a short time. However, for particular plans, experienced planners perform even better than scripts or AP. Experienced-user input is needed when setting up scripts or AP templates for the first time. Moreover, some minor drawbacks exist, such as the increase of monitor units (+35.5% for scripted plans). On average, automatically created plans are superior to manually created treatment plans. For particular plans, experienced physicists were able to perform better than scripts or AP; thus, the benefit is greatest when time is short or staff inexperienced.

An OPTIMIZE study retrospective analysis for management of telaprevir-treated hepatitis C virus (HCV)-infected patients by use of the Abbott RealTime HCV RNA assay.

PubMed

Sarrazin, Christoph; Dierynck, Inge; Cloherty, Gavin; Ghys, Anne; Janssen, Katrien; Luo, Donghan; Witek, James; Buti, Maria; Picchio, Gaston; De Meyer, Sandra

2015-04-01

Protease inhibitor (PI)-based response-guided triple therapies for hepatitis C virus (HCV) infection are still widely used. Noncirrhotic treatment-naive and prior relapser patients receiving telaprevir-based treatment are eligible for shorter, 24-week total therapy if HCV RNA is undetectable at both weeks 4 and 12. In this study, the concordance in HCV RNA assessments between the Roche High Pure System/Cobas TaqMan and Abbott RealTime HCV RNA assays and the impacts of different HCV RNA cutoffs on treatment outcome were evaluated. A total of 2,629 samples from 663 HCV genotype 1 patients receiving telaprevir/pegylated interferon/ribavirin in OPTIMIZE were analyzed using the High Pure System and reanalyzed using Abbott RealTime (limits of detection, 15.1 IU/ml versus 8.3 IU/ml; limits of quantification, 25 IU/ml versus 12 IU/ml, respectively). Overall, good concordance was observed between the assays. Using undetectable HCV RNA at week 4, 34% of the patients would be eligible for shorter treatment duration with Abbott RealTime versus 72% with the High Pure System. However, using <12 IU/ml for Abbott RealTime, a similar proportion (74%) would be eligible. Of the patients receiving 24-week total therapy, 87% achieved a sustained virologic response with undetectable HCV RNA by the High Pure System or <12 IU/ml by Abbott RealTime; however, 92% of the patients with undetectable HCV RNA by Abbott RealTime achieved a sustained virologic response. Using undetectable HCV RNA as the cutoff, the more sensitive Abbott RealTime assay would identify fewer patients eligible for shorter treatment than the High Pure System. Our data confirm the <12-IU/ml cutoff, as previously established in other studies of the Abbott RealTime assay, to determine eligibility for shortened PI-based HCV treatment. (The study was registered with ClinicalTrials.gov under registration no. NCT01241760.). Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Investigation on pretreatment of centrifugal mother liquid produced in the production of polyvinyl chloride by air-Fenton technique.

PubMed

Sun, Yingying; Hua, Xiuyi; Ge, Rui; Guo, Aitong; Guo, Zhiyong; Dong, Deming; Sun, Wentian

2013-08-01

Centrifugal mother liquid (CML) is one of the main sources of wastewater produced during the production of polyvinyl chloride in chlor-alkali industry. CML is a typical poorly biodegradable organic wastewater, containing many kinds of refractory pollutants. Specifically, it contains dissolved refractory polymers, especially polyvinyl alcohol (PVA), which can pass though the biotreatment processes and clog the membranes used for further treatment. In this study, to ensure the CML applicable to biotreatment and membrane treatment, a novel efficient and mild technique, air-Fenton treatment, was employed as a pretreatment technique to improve biodegradability of the CML and to break down the polymers in the CML. Firstly, the technique was optimized for the CML treatment by optimizing the main parameters, including the dosage of ferrous sulfate, initial pH of the wastewater, [H2O2]/[Fe(2+)], aeration rate, reaction time, and temperature, based on removal efficiency of COD and PVA from the CML. Then, the optimized technique was tested and evaluated. The results indicated that under the optimized conditions, the air-Fenton treatment could remove 66, 98, and 55 % of the COD, PVA, and TOC, respectively, from the CML. After the treatment, biodegradability of the wastewater increased significantly (BOD/COD increased from 0.31 to 0.68), and almost all of the PVA polymers were removed or broken down. Meanwhile, concentration of the remaining iron ions, which were added during the treatment, was also quite low (only 2.9 mg/L). Furthermore, most of the suspended materials and ammonia nitrogen, and some of the phosphorus in the wastewater were removed simultaneously.

Pain in children--are we accomplishing the optimal pain treatment?

PubMed

Lundeberg, Stefan

2015-01-01

Morphine, paracetamol and local anesthetics have for a long time been the foremost used analgesics in the pediatric patient by tradition but not always enough effective and associated with side effects. The purpose with this article is to propose alternative approaches in pain management, not always supported up by substantial scientific work but from a combination of science and clinical experience in the field. The scientific literature has been reviewed in parts regarding different aspects of pain assessment and analgesics used for treatment of diverse pain conditions with focus on procedural and acute pain. Clinical experience has been added to form the suggested improvements in accomplishing an improved pain management in pediatric patients. The aim with pain management in children should be a tailored analgesic medication with an individual acceptable pain level and optimal degree of mobilization with as little side effects as possible. Simple techniques of pain control are as effective as and complex techniques in pediatrics but the technique used is not of the highest importance in achieving a good pain management. Increased interest and improved education of the doctors prescribing analgesics is important in accomplishing a better pain management. The optimal treatment with analgesics is depending on the analysis of pain origin and analgesics used should be adjusted thereafter. A multimodal treatment regime is advocated for optimal analgesic effect. © 2014 John Wiley & Sons Ltd.

SU-E-T-266: Development of Evaluation System of Optimal Synchrotron Controlling Parameter for Spot Scanning Proton Therapy with Multiple Gate Irradiations in One Operation Cycle

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

Yamada, T; Fujii, Y; Hitachi Ltd., Hitachi-shi, Ibaraki

2015-06-15

Purpose: We have developed a gated spot scanning proton beam therapy system with real-time tumor-tracking. This system has the ability of multiple-gated irradiation in a single synchrotron operation cycle controlling the wait-time for consecutive gate signals during a flat-top phase so that the decrease in irradiation efficiency induced by irregular variation of gate signal is reduced. Our previous studies have shown that a 200 ms wait-time is appropriate to increase the average irradiation efficiency, but the optimal wait-time can vary patient by patient and day by day. In this research, we have developed an evaluation system of the optimal wait-timemore » in each irradiation based on the log data of the real-time-image gated proton beam therapy (RGPT) system. Methods: The developed system consists of logger for operation of RGPT system and software for evaluation of optimal wait-time. The logger records timing of gate on/off, timing and the dose of delivered beam spots, beam energy and timing of X-ray irradiation. The evaluation software calculates irradiation time in the case of different wait-time by simulating the multiple-gated irradiation operation using several timing information. Actual data preserved in the log data are used for gate on and off time, spot irradiation time, and time moving to the next spot. Design values are used for the acceleration and deceleration times. We applied this system to a patient treated with the RGPT system. Results: The evaluation system found the optimal wait-time of 390 ms that reduced the irradiation time by about 10 %. The irradiation time with actual wait-time used in treatment was reproduced with accuracy of 0.2 ms. Conclusion: For spot scanning proton therapy system with multiple-gated irradiation in one synchrotron operation cycle, an evaluation system of the optimal wait-time in each irradiation based on log data has been developed. Funding Support: Japan Society for the Promotion of Science (JSPS) through the FIRST Program.« less

Multicriteria plan optimization in the hands of physicians: a pilot study in prostate cancer and brain tumors.

PubMed

Müller, Birgit S; Shih, Helen A; Efstathiou, Jason A; Bortfeld, Thomas; Craft, David

2017-11-06

The purpose of this study was to demonstrate the feasibility of physician driven planning in intensity modulated radiotherapy (IMRT) with a multicriteria optimization (MCO) treatment planning system and template based plan optimization. Exploiting the full planning potential of MCO navigation, this alternative planning approach intends to improve planning efficiency and individual plan quality. Planning was retrospectively performed on 12 brain tumor and 10 post-prostatectomy prostate patients previously treated with MCO-IMRT. For each patient, physicians were provided with a template-based generated Pareto surface of optimal plans to navigate, using the beam angles from the original clinical plans. We compared physician generated plans to clinically delivered plans (created by dosimetrists) in terms of dosimetric differences, physician preferences and planning times. Plan qualities were similar, however physician generated and clinical plans differed in the prioritization of clinical goals. Physician derived prostate plans showed significantly better sparing of the high dose rectum and bladder regions (p(D1) < 0.05; D1: dose received by 1% of the corresponding structure). Physicians' brain tumor plans indicated higher doses for targets and brainstem (p(D1) < 0.05). Within blinded plan comparisons physicians preferred the clinical plans more often (brain: 6:3 out of 12, prostate: 2:6 out of 10) (not statistically significant). While times of physician involvement were comparable for prostate planning, the new workflow reduced the average involved time for brain cases by 30%. Planner times were reduced for all cases. Subjective benefits, such as a better understanding of planning situations, were observed by clinicians through the insight into plan optimization and experiencing dosimetric trade-offs. We introduce physician driven planning with MCO for brain and prostate tumors as a feasible planning workflow. The proposed approach standardizes the planning process by utilizing site specific templates and integrates physicians more tightly into treatment planning. Physicians' navigated plan qualities were comparable to the clinical plans. Given the reduction of planning time of the planner and the equal or lower planning time of physicians, this approach has the potential to improve departmental efficiencies.

Research in Prevention and Treatment of Noise-Induced Hearing Loss (NIHL)

DTIC Science & Technology

2016-06-01

The current study identified optimal protective D-methionine (D-met) dose and delayed time response from steady state and impulse noise -induced hearing loss (NIHL) in groups of Chinchillas laniger (n=10/group).

Optimizing electrocoagulation process using experimental design for COD removal from unsanitary landfill leachate.

PubMed

Ogedey, Aysenur; Tanyol, Mehtap

2017-12-01

Leachate is the most difficult wastewater to be treated due to its complex content and high pollution release. For this reason, since it is not possible to be treated with a single process, a pre-treatment is needed. In the present study, a batch electrocoagulation reactor containing aluminum and iron electrodes was used to reduce chemical oxygen demand (COD) from landfill leachate (Tunceli, Turkey). Optimization of COD elimination was carried out with response surface methodology to describe the interaction effect of four main process independent parameters (current density, inter-electrode distance, pH and time of electrolysis). The optimum current density, inter-electrode distance, pH and time of electrolysis for maximum COD removal (43%) were found to be 19.42 mA/m 2 , 0.96 cm, 7.23 and 67.64 min, respectively. The results shown that the electrocoagulation process can be used as a pre-treatment step for leachate.

An effective tool to manage the distribution of medicines and monitor the treatment in hospital pharmacies.

PubMed

Franzoso, Gianpaolo

2014-01-01

Introduction The purpose of the article is to share a modus operandi and a tool that allows the recruitment and management of thousands of patients and their treatment by using a simple software created by the author and made freely available to all colleague-pharmacists. The author, a pharmacist, created this database because there were no tools on the market with all the features needed to manage the treatment of patients and the orders of drugs to ensure continuity of care without waste of public money. Methods The data collection is facilitated by the software and allows the monitoring of treatment of the patients and their re-evaluation. This tool can create a table containing all the information needed to predict the demand for drugs, the timing of therapies and of the treatment plans. It is an effective instrument to calculate the optimal purchase of drugs and the delivery of therapies to patients. Conclusions A simple tool that allows the management of many patients, reduces research time and facilitates the control of therapies. It allows us to optimize inventory and minimize the stock of drugs. It allows the pharmacist to focus attention on the clinical management of the patient by helping him to follow therapy and respond to his needs.

Commissioning of a 3D image‐based treatment planning system for high‐dose‐rate brachytherapy of cervical cancer

PubMed Central

Kim, Yongbok; Modrick, Joseph M.; Pennington, Edward C.

2016-01-01

The objective of this work is to present commissioning procedures to clinically implement a three‐dimensional (3D), image‐based, treatment‐planning system (TPS) for high‐dose‐rate (HDR) brachytherapy (BT) for gynecological (GYN) cancer. The physical dimensions of the GYN applicators and their values in the virtual applicator library were varied by 0.4 mm of their nominal values. Reconstruction uncertainties of the titanium tandem and ovoids (T&O) were less than 0.4 mm on CT phantom studies and on average between 0.8‐1.0 mm on MRI when compared with X‐rays. In‐house software, HDRCalculator, was developed to check HDR plan parameters such as independently verifying active tandem or cylinder probe length and ovoid or cylinder size, source calibration and treatment date, and differences between average Point A dose and prescription dose. Dose‐volume histograms were validated using another independent TPS. Comprehensive procedures to commission volume optimization algorithms and process in 3D image‐based planning were presented. For the difference between line and volume optimizations, the average absolute differences as a percentage were 1.4% for total reference air KERMA (TRAK) and 1.1% for Point A dose. Volume optimization consistency tests between versions resulted in average absolute differences in 0.2% for TRAK and 0.9 s (0.2%) for total treatment time. The data revealed that the optimizer should run for at least 1 min in order to avoid more than 0.6% dwell time changes. For clinical GYN T&O cases, three different volume optimization techniques (graphical optimization, pure inverse planning, and hybrid inverse optimization) were investigated by comparing them against a conventional Point A technique. End‐to‐end testing was performed using a T&O phantom to ensure no errors or inconsistencies occurred from imaging through to planning and delivery. The proposed commissioning procedures provide a clinically safe implementation technique for 3D image‐based TPS for HDR BT for GYN cancer. PACS number(s): 87.55.D‐ PMID:27074463

In vivo multiphoton-microscopy of picosecond-laser-induced optical breakdown in human skin.

PubMed

Balu, Mihaela; Lentsch, Griffin; Korta, Dorota Z; König, Karsten; Kelly, Kristen M; Tromberg, Bruce J; Zachary, Christopher B

2017-08-01

Improvements in skin appearance resulting from treatment with fractionated picosecond-lasers have been noted, but optimizing the treatment efficacy depends on a thorough understanding of the specific skin response. The development of non-invasive laser imaging techniques in conjunction with laser therapy can potentially provide feedback for guidance and optimizing clinical outcome. The purpose of this study was to demonstrate the capability of multiphoton microscopy (MPM), a high-resolution, label-free imaging technique, to characterize in vivo the skin response to a fractionated non-ablative picosecond-laser treatment. Two areas on the arm of a volunteer were treated with a fractionated picosecond laser at the Dermatology Clinic, UC Irvine. The skin response to treatment was imaged in vivo with a clinical MPM-based tomograph at 3 hours and 24 hours after treatment and seven additional time points over a 4-week period. MPM revealed micro-injuries present in the epidermis. Pigmented cells were particularly damaged in the process, suggesting that melanin is likely the main absorber for laser induced optical breakdown. Damaged individual cells were distinguished as early as 3 hours post pico-laser treatment with the 532 nm wavelength, and 24 hours post-treatment with both 532 and 1064 nm wavelengths. At later time points, clusters of cellular necrotic debris were imaged across the treated epidermis. After 24 hours of treatment, inflammatory cells were imaged in the proximity of epidermal micro-injuries. The epidermal injuries were exfoliated over a 4-week period. This observational and descriptive pilot study demonstrates that in vivo MPM imaging can be used non-invasively to provide label-free contrast for describing changes in human skin following a fractionated non-ablative laser treatment. The results presented in this study represent the groundwork for future longitudinal investigations on an expanded number of subjects to understand the response to treatment in different skin types with different laser parameters, critical factors in optimizing treatment outcome. Lasers Surg. Med. 49:555-562, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Real-Time Dosimetry and Optimization of Prostate Photodynamic Therapy

DTIC Science & Technology

2006-09-01

photodynamic therapy in patients with prostate cancer,” IPA 9th World Congress of Photodynamic Medicine, (2003). 2. Zhu TC, Diana S, Dimofte A...photodynamic therapy,” IPA 9th World Congress of Photodynamic Medicine, (2003). 3. Zhu TC, Altschuler M, Xiao Y, Finlay J, Dimofte A, Hahn SM, “Light...Optimization of treatment plan using Cimmino algorithm in prostate photodynamic therapy,” IPA 10th World Congress of Photodynamic Medicine, Munich

Adaptive model-predictive controller for magnetic resonance guided focused ultrasound therapy.

PubMed

de Bever, Joshua; Todd, Nick; Payne, Allison; Christensen, Douglas A; Roemer, Robert B

2014-11-01

Minimising treatment time and protecting healthy tissues are conflicting goals that play major roles in making magnetic resonance image-guided focused ultrasound (MRgFUS) therapies clinically practical. We have developed and tested in vivo an adaptive model-predictive controller (AMPC) that reduces treatment time, ensures safety and efficacy, and provides flexibility in treatment set-up. The controller realises time savings by modelling the heated treatment cell's future temperatures and thermal dose accumulation in order to anticipate the optimal time to switch to the next cell. Selected tissues are safeguarded by a configurable temperature constraint. Simulations quantified the time savings realised by each controller feature as well as the trade-offs between competing safety and treatment time parameters. In vivo experiments in rabbit thighs established the controller's effectiveness and reliability. In all in vivo experiments the target thermal dose of at least 240 CEM43 was delivered everywhere in the treatment volume. The controller's temperature safety limit reliably activated and constrained all protected tissues to <9 CEM43. Simulations demonstrated the path independence of the controller, and that a path which successively proceeds to the hottest untreated neighbouring cell leads to significant time savings, e.g. when compared to a concentric spiral path. Use of the AMPC produced a compounding time-saving effect; reducing the treatment cells' heating times concurrently reduced heating of normal tissues, which eliminated cooling periods. Adaptive model-predictive control can automatically deliver safe, effective MRgFUS treatments while significantly reducing treatment times.

Metabolomic approach to optimizing and evaluating antibiotic treatment in the axenic culture of cyanobacterium Nostoc flagelliforme.

PubMed

Han, Pei-pei; Jia, Shi-ru; Sun, Ying; Tan, Zhi-lei; Zhong, Cheng; Dai, Yu-jie; Tan, Ning; Shen, Shi-gang

2014-09-01

The application of antibiotic treatment with assistance of metabolomic approach in axenic isolation of cyanobacterium Nostoc flagelliforme was investigated. Seven antibiotics were tested at 1-100 mg L(-1), and order of tolerance of N. flagelliforme cells was obtained as kanamycin > ampicillin, tetracycline > chloromycetin, gentamicin > spectinomycin > streptomycin. Four antibiotics were selected based on differences in antibiotic sensitivity of N. flagelliforme and associated bacteria, and their effects on N. flagelliforme cells including the changes of metabolic activity with antibiotics and the metabolic recovery after removal were assessed by a metabolomic approach based on gas chromatography-mass spectrometry combined with multivariate analysis. The results showed that antibiotic treatment had affected cell metabolism as antibiotics treated cells were metabolically distinct from control cells, but the metabolic activity would be recovered via eliminating antibiotics and the sequence of metabolic recovery time needed was spectinomycin, gentamicin > ampicillin > kanamycin. The procedures of antibiotic treatment have been accordingly optimized as a consecutive treatment starting with spectinomycin, then gentamicin, ampicillin and lastly kanamycin, and proved to be highly effective in eliminating the bacteria as examined by agar plating method and light microscope examination. Our work presented a strategy to obtain axenic culture of N. flagelliforme and provided a method for evaluating and optimizing cyanobacteria purification process through diagnosing target species cellular state.

Novel Electrokinetic Microfluidic Detector for Evaluating Effectiveness of Microalgae Disinfection in Ship Ballast Water

PubMed Central

Maw, Myint Myint; Wang, Junsheng; Li, Fabo; Jiang, Jinhu; Song, Younan; Pan, Xinxiang

2015-01-01

Ship ballast water treatment methods face many technical challenges. The effectiveness of every treatment method usually is evaluated by using large scale equipment and a large volume of samples, which involves time-consuming, laborious, and complex operations. This paper reports the development of a novel, simple and fast platform of methodology in evaluating the efficiency and the best parameters for ballast water treatment systems, particularly in chemical disinfection. In this study, a microfluidic chip with six sample wells and a waste well was designed, where sample transportation was controlled by electrokinetic flow. The performance of this microfluidic platform was evaluated by detecting the disinfection of Dunaliella salina (D. salina) algae in ballast water treated by sodium hypochlorite (NaClO) solution. Light-induced chlorophyll fluorescence (LICF) intensity was used to determine the viability of microalgae cells in the system, which can be operated automatically with the dimension of the detector as small as 50 mm × 24 mm × 5 mm. The 40 µL volume of sample solution was used for each treatment condition test and the validity of detection can be accomplished within about five min. The results show that the viability of microalgae cells under different treatment conditions can be determined accurately and further optimal treatment conditions including concentrations of NaClO and treatment time can also be obtained. These results can provide accurate evaluation and optimal parameters for ballast water treatment methods. PMID:26516836

Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants.

PubMed

Hehlmann, R; Lauseker, M; Saußele, S; Pfirrmann, M; Krause, S; Kolb, H J; Neubauer, A; Hossfeld, D K; Nerl, C; Gratwohl, A; Baerlocher, G M; Heim, D; Brümmendorf, T H; Fabarius, A; Haferlach, C; Schlegelberger, B; Müller, M C; Jeromin, S; Proetel, U; Kohlbrenner, K; Voskanyan, A; Rinaldetti, S; Seifarth, W; Spieß, B; Balleisen, L; Goebeler, M C; Hänel, M; Ho, A; Dengler, J; Falge, C; Kanz, L; Kremers, S; Burchert, A; Kneba, M; Stegelmann, F; Köhne, C A; Lindemann, H W; Waller, C F; Pfreundschuh, M; Spiekermann, K; Berdel, W E; Müller, L; Edinger, M; Mayer, J; Beelen, D W; Bentz, M; Link, H; Hertenstein, B; Fuchs, R; Wernli, M; Schlegel, F; Schlag, R; de Wit, M; Trümper, L; Hebart, H; Hahn, M; Thomalla, J; Scheid, C; Schafhausen, P; Verbeek, W; Eckart, M J; Gassmann, W; Pezzutto, A; Schenk, M; Brossart, P; Geer, T; Bildat, S; Schäfer, E; Hochhaus, A; Hasford, J

2017-11-01

Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400 mg/day (n=400) could be optimized by doubling the dose (n=420), adding interferon (IFN) (n=430) or cytarabine (n=158) or using IM after IFN-failure (n=128). From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase were randomized into a 5-arm study. The study was powered to detect a survival difference of 5% at 5 years. After a median observation time of 9.5 years, 10-year overall survival was 82%, 10-year progression-free survival was 80% and 10-year relative survival was 92%. Survival between IM400 mg and any experimental arm was not different. In a multivariate analysis, risk group, major-route chromosomal aberrations, comorbidities, smoking and treatment center (academic vs other) influenced survival significantly, but not any form of treatment optimization. Patients reaching the molecular response milestones at 3, 6 and 12 months had a significant survival advantage. For responders, monotherapy with IM400 mg provides a close to normal life expectancy independent of the time to response. Survival is more determined by patients' and disease factors than by initial treatment selection. Although improvements are also needed for refractory disease, more life-time can currently be gained by carefully addressing non-CML determinants of survival.

Pitfalls of Ovarian Ablative Magnetic Resonance-guided Radiation Therapy for Refractory Endometriosis

PubMed Central

Tetar, Shyama; Bohoudi, Omar; Nieboer, Theodoor; Lagerwaard, Frank

2018-01-01

In this case presentation, we describe the challenges of performing magnetic resonance-guided radiation therapy (MRgRT) with plan adaptation in a patient with advanced endometriosis, in whom several prior therapeutic attempts were unsuccessful and extensive pelvic irradiation was regarded as being too toxic. Treatment was delivered in two sessions, first for the seemingly only active right ovary, and at a later stage for the left ovary. Some logistical problems were encountered during the preparation of the first treatment, which were subsequently optimized for the second treatment by using transvaginal ultrasound to determine the optimum time point for simulation and delivery. Using breath-hold gated delivery and plan adaptation, radiation dose to the bowel could be minimized, resulting in good tolerance of treatment. Because of the need to simulate and deliver in a brief optimal time span for visibility of the follicles in the ovaries, a single fraction dose of 8 Gy was used in our patient. Hormonal outcome after her second treatment is still pending. In conclusion, MRgRT with plan adaptation is feasible for the occasional patient with refractory endometriosis. Simulation and delivery needs to be synchronized with the menstrual cycle, ensuring that the Graafian follicles allow the ovaries to be visible on magnetic resonance imaging (MRI). Because the ovaries are only visible on T2-weighted MRI for a very brief period of time, we suggest that it is preferable to use single fraction radiotherapy with a brief interval between simulation imaging and delivery. PMID:29750135

Application of mathematical models to metronomic chemotherapy: What can be inferred from minimal parameterized models?

PubMed

Ledzewicz, Urszula; Schättler, Heinz

2017-08-10

Metronomic chemotherapy refers to the frequent administration of chemotherapy at relatively low, minimally toxic doses without prolonged treatment interruptions. Different from conventional or maximum-tolerated-dose chemotherapy which aims at an eradication of all malignant cells, in a metronomic dosing the goal often lies in the long-term management of the disease when eradication proves elusive. Mathematical modeling and subsequent analysis (theoretical as well as numerical) have become an increasingly more valuable tool (in silico) both for determining conditions under which specific treatment strategies should be preferred and for numerically optimizing treatment regimens. While elaborate, computationally-driven patient specific schemes that would optimize the timing and drug dose levels are still a part of the future, such procedures may become instrumental in making chemotherapy effective in situations where it currently fails. Ideally, mathematical modeling and analysis will develop into an additional decision making tool in the complicated process that is the determination of efficient chemotherapy regimens. In this article, we review some of the results that have been obtained about metronomic chemotherapy from mathematical models and what they infer about the structure of optimal treatment regimens. Copyright © 2017 Elsevier B.V. All rights reserved.

Implications for managed care and specialty pharmacy in rheumatoid arthritis.

PubMed

Cardarelli, William J

2012-12-01

Treatment of rheumatoid arthritis (RA) can be very costly. Cost-effectiveness studies provide insight into the value of treatment from a number of perspectives (eg, societal, healthcare). In most cases, the indirect costs of RA can offset the direct costs in 2 ways. Prevention of disease progression can limit future costs, such as those related to surgery and hospitalization. When disease progression is minimized, patients feel better and can have improved work productivity. Disease control of RA has improved over time, and this is attributed primarily to the introduction of more effective therapies. Despite the effectiveness of new therapies, there are a number of barriers to optimal treatment. Barriers include lack of education for patients and practitioners about RA, poor patient-provider communication, uncertainty regarding which treatments to choose, cost, and lack of adherence. Specialty pharmacy and disease therapy management programs can assist patients by providing structure, education, and mechanisms to improve treatment adherence and persistence to optimize therapy.

[Possibilities of treatment optimization in children and adolescents with epilepsy and disturbances of emotion and volition (disphoria)].

PubMed

Popov, Yu V; Yakovleva, Yu A; Semenova, S V

To optimize the treatment of dysphoriain children and adolescents in regard to sex and disease severity. Seventy children and adolescents (boys - 45, girls - 25), aged from 6 to 18 years, with different forms of epilepsy and emotion and dysphoric disturbances were studied using CPRS andGCIscales Depending on dysphoria severity, patients were stratified into three groups: mild (n=19 (27.1%), moderate (n=27 (38.6%)) and severe (n=24 (34.3%)). Dysphoric disorders were significantly more prevalent in boys, hostility and aggression were characteristic of boys as well. These facts impactedtreatment options. Neuroleptics were more frequently used in boys (35.5%) compared to girls(16%).Mild dysphoria didn't require additional treatment besides AED in 78,4%. In 75% cases of moderate dysphoria,systemic treatment with neuroleptics for 6 months was necessary. One-time recommendations for neuroleptic treatment were made in all three groups with the prevalence in a groupof children with severe and moderate dysphoria.

Optimal Design for Informative Protocols in Xenograft Tumor Growth Inhibition Experiments in Mice.

PubMed

Lestini, Giulia; Mentré, France; Magni, Paolo

2016-09-01

Tumor growth inhibition (TGI) models are increasingly used during preclinical drug development in oncology for the in vivo evaluation of antitumor effect. Tumor sizes are measured in xenografted mice, often only during and shortly after treatment, thus preventing correct identification of some TGI model parameters. Our aims were (i) to evaluate the importance of including measurements during tumor regrowth and (ii) to investigate the proportions of mice included in each arm. For these purposes, optimal design theory based on the Fisher information matrix implemented in PFIM4.0 was applied. Published xenograft experiments, involving different drugs, schedules, and cell lines, were used to help optimize experimental settings and parameters using the Simeoni TGI model. For each experiment, a two-arm design, i.e., control versus treatment, was optimized with or without the constraint of not sampling during tumor regrowth, i.e., "short" and "long" studies, respectively. In long studies, measurements could be taken up to 6 g of tumor weight, whereas in short studies the experiment was stopped 3 days after the end of treatment. Predicted relative standard errors were smaller in long studies than in corresponding short studies. Some optimal measurement times were located in the regrowth phase, highlighting the importance of continuing the experiment after the end of treatment. In the four-arm designs, the results showed that the proportions of control and treated mice can differ. To conclude, making measurements during tumor regrowth should become a general rule for informative preclinical studies in oncology, especially when a delayed drug effect is suspected.

Optimal design for informative protocols in xenograft tumor growth inhibition experiments in mice

PubMed Central

Lestini, Giulia; Mentré, France; Magni, Paolo

2016-01-01

Tumor growth inhibition (TGI) models are increasingly used during preclinical drug development in oncology for the in vivo evaluation of antitumor effect. Tumor sizes are measured in xenografted mice, often only during and shortly after treatment, thus preventing correct identification of some TGI model parameters. Our aims were i) to evaluate the importance of including measurements during tumor regrowth; ii) to investigate the proportions of mice included in each arm. For these purposes, optimal design theory based on the Fisher information matrix implemented in PFIM4.0 was applied. Published xenograft experiments, involving different drugs, schedules and cell lines, were used to help optimize experimental settings and parameters using the Simeoni TGI model. For each experiment, a two-arm design, i.e. control vs treatment, was optimized with or without the constraint of not sampling during tumor regrowth, i.e. “short” and “long” studies, respectively. In long studies, measurements could be taken up to 6 grams of tumor weight, whereas in short studies the experiment was stopped three days after the end of treatment. Predicted relative standard errors were smaller in long studies than in corresponding short studies. Some optimal measurement times were located in the regrowth phase, highlighting the importance of continuing the experiment after the end of treatment. In the four-arm designs, the results showed that the proportions of control and treated mice can differ. To conclude, making measurements during tumor regrowth should become a general rule for informative preclinical studies in oncology, especially when a delayed drug effect is suspected. PMID:27306546

Minimizing patient waiting time in emergency department of public hospital using simulation optimization approach

NASA Astrophysics Data System (ADS)

Ibrahim, Ireen Munira; Liong, Choong-Yeun; Bakar, Sakhinah Abu; Ahmad, Norazura; Najmuddin, Ahmad Farid

2017-04-01

Emergency department (ED) is the main unit of a hospital that provides emergency treatment. Operating 24 hours a day with limited number of resources invites more problems to the current chaotic situation in some hospitals in Malaysia. Delays in getting treatments that caused patients to wait for a long period of time are among the frequent complaints against government hospitals. Therefore, the ED management needs a model that can be used to examine and understand resource capacity which can assist the hospital managers to reduce patients waiting time. Simulation model was developed based on 24 hours data collection. The model developed using Arena simulation replicates the actual ED's operations of a public hospital in Selangor, Malaysia. The OptQuest optimization in Arena is used to find the possible combinations of a number of resources that can minimize patients waiting time while increasing the number of patients served. The simulation model was modified for improvement based on results from OptQuest. The improvement model significantly improves ED's efficiency with an average of 32% reduction in average patients waiting times and 25% increase in the total number of patients served.

Optimization of Time Controlled 6-mercaptopurine Delivery for Site- Specific Targeting to Colon Diseases.

PubMed

Hude, Rahul U; Jagdale, Swati C

2016-01-01

6-MP has short elimination time (<2 h) and low bioavailability (~ 50%). Present study was aimed to develop time controlled and site targeted delivery of 6-Mercaptopurine (6-MP) for treatment of colon diseases. Compression coating technique was used. 32 full factorial design was designed for optimization of the outer coat for the core tablet. For outer coat amount of Eudragit RS 100 and hydroxypropyl methylcellulose (HPMC K100) were employed as independent variables each at three levels while responses evaluated were swelling index and bursting time. Direct compression method was used for tablets formulation. 80% w/w of microcrystalline cellulose and 20% w/w of croscarmellose sodium were found to be optimum concentration for the core tablet. The outer coat of optimized batch (ED) contains 21.05% w/w Eudragit RS 100 and 78.95% w/w HPMC K100 of total polymer weight. In-vitro dissolution study indicated that combination of polymer retards the drug release in gastric region and releases ≥95% of drug in colonic region after ≥7 h. Whereas in case of in-vivo placebo x-ray imaging study had shown that the tablet reaches colonic part after 5±0.5 h providing the proof of arrival in the colon. Stability study indicated that the optimized formulation were physically and chemically stable. Present research work concluded that compression coating by Eudragit RS 100 and HPMC K100 to 6-MP core provides potential colon targeted system with advantages of reduced gastric exposure and enhanced bioavailability. Formulation can be considered as potential and promising candidate for the treatment of colon diseases.

Properties of Wheat-Straw Boards with Frw Based on Interface Treatment

NASA Astrophysics Data System (ADS)

Zhu, X. D.; Wang, F. H.; Liu, Y.

This paper explored the effect of MDI, UF and FRW content on the mechanical and fire retardant property of straw based panels with surface alkali liquor processing. In order to manufacture the straw based panel with high quality, low toxic and fire retardant, the interface of wheat-straw was treated with alkaline liquid, and the orthogonal test was carried out to optimize the technical parameters. The conductivity and diffusion coefficient K of the straw material after alkaline liquid treatment increased obviously. This indicated that alkaline liquid treatment improved the surface wet ability of straw, which is helpful for the infiltration of resin. The results of orthogonal test showed that the optimized treating condition was alkaline liquid concentration as 0.4-0.8%, alkaline dosage as 1:2.5-1:4.5, alkalinetreated time as 12h-48 h.The physical and mechanical properties of wheat-straw boards after treated increased remarkably and it could satisfy the national standard. The improvement of the straw surface wet ability is helpful to the forming of chemical bond. Whereas the variance analysis of the fire retardant property of straw based panel showed that TTI, pkHRR and peak value appearance time were not affected by the MDI, UF and FRW content significantly. The results of orthogonal test showed that the optimized processing condition was MDI content as 3%, UF resin content as 6% and the FRW content as 10%.

Specific oral tolerance induction in childhood.

PubMed

Peters, Rachel L; Dang, Thanh D; Allen, Katrina J

2016-12-01

Food allergy continues to be a significant public health concern for which there are no approved treatments and management strategies primarily include allergen avoidance and pharmacological measures for accidental exposures. Food allergy is thought to result from either a failure to establish oral tolerance or the breakdown of existing oral tolerance, and therefore, experimental preventative and treatment strategies are now aimed at inducing specific oral tolerance. This may occur in infancy prior to the development of food allergy through the optimal timing of dietary exposure (primary oral tolerance induction) or as a treatment for established food allergy through oral immunotherapy (secondary oral tolerance induction). Trials examining the effectiveness of early dietary allergen exposure to prevent food allergy have yielded promising results for peanut allergy but not so for other allergens, although the results of several trials are yet to be published. Although infant feeding guidelines no longer advise to avoid allergenic foods and exposure to food allergens orally is an important step in inducing food tolerance by the immune system, evidence regarding the optimal timing, dose and form of these foods into the infant's diet is lacking. Likewise, oral immunotherapy trials appear promising for inducing desensitization; however, the long-term efficacy in achieving sustained desensitization and optimal protocols to achieve this is unknown. More research is needed in this emerging field. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Tentorial dural arteriovenous fistula presenting as myelopathy: Case series and review of literature

PubMed Central

Gross, Robert; Ali, Rushna; Kole, Max; Dorbeistein, Curtis; Jayaraman, Mahesh V; Khan, Muhib

2014-01-01

Dural arteriovenous fistula (DAVF) is a rare type of cerebral arteriovenous malformation. Common presenting symptoms are related to hemorrhage. However, rarely these patients may present with myelopathy. We present two cases of DAVF presenting as rapidly progressive myelopathy. Two treatment options are available: microsurgical interruption of the fistula and endovascular embolization. These treatment options of DAVFs have improved significantly in the last decade. The optimal treatment of DAVFs remains controversial, and there is an ongoing debate as to whether primary endovascular or primary microsurgical treatment is the optimal management for these lesions. However, despite treatment a high percentage of patients are still left with severe disability. The potential for functional ambulation in patients with DAVF is related to the time of intervention. This emphasizes the important of early diagnosis and early intervention in DAVF. The eventual outcome may depend on several factors, such as the duration of symptoms, the degree of disability before treatment, and the success of the initial procedure to close the fistula. The usage of magnetic resonance imaging and selective angiography has significantly improved the ability to characterize DAVFs, however, these lesions remain inefficiently diagnosed. If intervention is delayed even prolonged time in rehabilitation does not change the grave prognosis. This review outlines the presentation, classication and management of DAVF as well as discussing patient outcomes. PMID:25516869

The association between substance use and sub-optimal HIV treatment engagement among HIV-infected female sex workers in Lilongwe, Malawi.

PubMed

Lancaster, Kathryn E; Lungu, Thandie; Mmodzi, Pearson; Hosseinipour, Mina C; Chadwick, Katy; Powers, Kimberly A; Pence, Brian W; Go, Vivian F; Hoffman, Irving F; Miller, William C

2017-02-01

Female sex workers (FSW) have a high prevalence of substance use and HIV, but the impact of substance use on HIV treatment engagement is not well established. We evaluated the association between alcohol and marijuana use and sub-optimal HIV treatment engagement outcomes among HIV-infected FSW in Lilongwe, Malawi. We enroled FSW using venue-based recruitment into a cross-sectional evaluation assessing substance use and HIV treatment engagement. Seropositive FSW, identified through HIV rapid testing, received rapid CD4 count and viral load testing. We used Poisson regression with robust variance estimates to ascertain associations of alcohol and marijuana use with sub-optimal HIV treatment outcomes: (1) lack of ART use among previously diagnosed, ART-eligible FSW and (2) viral nonsuppression among FSW on ART. Of previously diagnosed, ART-eligible FSW (n = 96), 29% were not using ART. Patterns of hazardous drinking were identified in 30%, harmful drinking in 10%, and alcohol dependence in 12%. ART-eligible FSW with harmful drinking or alcohol dependency were 1.9 (95% CI: 1.0, 3.8) times as likely to not use ART compared to FSW without harmful or dependent drinking. Among those on ART, 14% were virally nonsuppressed. The prevalence ratio for viral nonsuppression was 2.0 (95% CI: 0.6, 6.5) for harmful drinkers and alcohol-dependent FSW. Over 30% of ART-eligible FSW reported using marijuana. Marijuana-using FSW were 1.9 (95% CI: 0.8, 4.6) times as likely to not use ART compared to FSW who were not using marijuana. Given the high prevalence of alcohol use and its association with lack of ART use, ART uptake and alcohol reduction strategies should be tailored for alcohol-using FSW in Malawi.

The association between substance use and sub-optimal HIV treatment engagement among HIV-infected female sex workers in Lilongwe, Malawi

PubMed Central

Lancaster, Kathryn E.; Lungu, Thandie; Mmodzi, Pearson; Hosseinipour, Mina C.; Chadwick, Katy; Powers, Kimberly A.; Pence, Brian W.; Go, Vivian F.; Hoffman, Irving F.; Miller, William C.

2016-01-01

Female sex workers (FSW) have a high prevalence of substance use and HIV, but the impact of substance use on HIV treatment engagement is not well established. We evaluated the association between alcohol and marijuana use and sub-optimal HIV treatment engagement outcomes among HIV-infected FSW in Lilongwe, Malawi. We enroled FSW using venue-based recruitment into a cross-sectional evaluation assessing substance use and HIV treatment engagement. Seropositive FSW, identified through HIV rapid testing, received rapid CD4 count and viral load testing. We used Poisson regression with robust variance estimates to ascertain associations of alcohol and marijuana use with sub-optimal HIV treatment outcomes: (1) lack of ART use among previously diagnosed, ART-eligible FSW and (2) viral nonsuppression among FSW on ART. Of previously diagnosed, ART-eligible FSW (n = 96), 29% were not using ART. Patterns of hazardous drinking were identified in 30%, harmful drinking in 10%, and alcohol dependence in 12%. ART-eligible FSW with harmful drinking or alcohol dependency were 1.9 (95% CI: 1.0, 3.8) times as likely to not use ART compared to FSW without harmful or dependent drinking. Among those on ART, 14% were virally nonsuppressed. The prevalence ratio for viral nonsuppression was 2.0 (95% CI: 0.6, 6.5) for harmful drinkers and alcohol-dependent FSW. Over 30% of ART-eligible FSW reported using marijuana. Marijuana-using FSW were 1.9 (95% CI: 0.8, 4.6) times as likely to not use ART compared to FSW who were not using marijuana. Given the high prevalence of alcohol use and its association with lack of ART use, ART uptake and alcohol reduction strategies should be tailored for alcohol-using FSW in Malawi. PMID:27442009

Treatment of crystallized-fruit wastewater by UV-A LED photo-Fenton and coagulation-flocculation.

PubMed

Rodríguez-Chueca, Jorge; Amor, Carlos; Fernandes, José R; Tavares, Pedro B; Lucas, Marco S; Peres, José A

2016-02-01

This work reports the treatment of crystallized-fruit effluents, characterized by a very low biodegradability (BOD5/COD <0.19), through the application of a UV-A LED photo-Fenton process. Firstly, a Box-Behnken design of Response Surface Methodology was applied to achieve the optimal conditions for the UV-A LED photo-Fenton process, trying to maximize the efficiency by saving chemicals and time. Under the optimal conditions ([H2O2] = 5459 mg/L; [Fe(3+)] = 286 mg/L; time >180 min), a COD removal of 45, 64 and 74% was achieved after 360 min, using an irradiance of 23, 70 and 85 W/m(2) respectively. Then a combination of UV-A LED photo-Fenton with coagulation-flocculation-decantation attained a higher COD removal (80%), as well as almost total removal of turbidity (99%) and total suspended solids (95%). Subsequent biodegradability of treated effluents increased, allowing the application of a biological treatment step after the photochemical/CFD with 85 W/m(2). Copyright © 2015 Elsevier Ltd. All rights reserved.

Optimizing Timing of Immunotherapy Improves Control of Tumors by Hypofractionated Radiation Therapy

PubMed Central

Baird, Jason R.; Savage, Talicia; Cottam, Benjamin; Friedman, David; Bambina, Shelly; Messenheimer, David J.; Fox, Bernard; Newell, Pippa; Bahjat, Keith S.; Gough, Michael J.; Crittenden, Marka R.

2016-01-01

The anecdotal reports of promising results seen with immunotherapy and radiation in advanced malignancies have prompted several trials combining immunotherapy and radiation. However, the ideal timing of immunotherapy with radiation has not been clarified. Tumor bearing mice were treated with 20Gy radiation delivered only to the tumor combined with either anti-CTLA4 antibody or anti-OX40 agonist antibody. Immunotherapy was delivered at a single timepoint around radiation. Surprisingly, the optimal timing of these therapies varied. Anti-CTLA4 was most effective when given prior to radiation therapy, in part due to regulatory T cell depletion. Administration of anti-OX40 agonist antibody was optimal when delivered one day following radiation during the post-radiation window of increased antigen presentation. Combination treatment of anti-CTLA4, radiation, and anti-OX40 using the ideal timing in a transplanted spontaneous mammary tumor model demonstrated tumor cures. These data demonstrate that the combination of immunotherapy and radiation results in improved therapeutic efficacy, and that the ideal timing of administration with radiation is dependent on the mechanism of action of the immunotherapy utilized. PMID:27281029

Real-time tracking of tumor motions and deformations along the leaf travel direction with the aid of a synchronized dynamic MLC leaf sequencer.

PubMed

Tacke, Martin; Nill, Simeon; Oelfke, Uwe

2007-11-21

Advanced radiotherapeutical techniques like intensity-modulated radiation therapy (IMRT) are based on an accurate knowledge of the location of the radiation target. An accurate dose delivery, therefore, requires a method to account for the inter- and intrafractional target motion and the target deformation occurring during the course of treatment. A method to compensate in real time for changes in the position and shape of the target is the use of a dynamic multileaf collimator (MLC) technique which can be devised to automatically arrange the treatment field according to real-time image information. So far, various approaches proposed for leaf sequencers have had to rely on a priori known target motion data and have aimed to optimize the overall treatment time. Since for a real-time dose delivery the target motion is not known a priori, the velocity range of the leading leaves is restricted by a safety margin to c x v(max) while the following leaves can travel with an additional maximum speed to compensate for the respective target movements. Another aspect to be considered is the tongue and groove effect. A uniform radiation field can only be achieved if the leaf movements are synchronized. The method presented in this note is the first to combine a synchronizing sequencer and real-time tracking with a dynamic MLC. The newly developed algorithm is capable of online optimizing the leaf velocities by minimizing the overall treatment time while at the same time it synchronizes the leaf trajectories in order to avoid the tongue and groove effect. The simultaneous synchronization is performed with the help of an online-calculated mid-time leaf trajectory which is common for all leaf pairs and which takes into account the real-time target motion and deformation information.

Applications of Fluorescence Spectroscopy for dissolved organic matter characterization in wastewater treatment plants

NASA Astrophysics Data System (ADS)

Goffin, Angélique; Guérin, Sabrina; Rocher, Vincent; Varrault, Gilles

2016-04-01

Dissolved organic matter (DOM) influences wastewater treatment plants efficiency (WTTP): variations in its quality and quantity can induce a foaming phenomenon and a fouling event inside biofiltration processes. Moreover, in order to manage denitrification step (control and optimization of the nitrate recirculation), it is important to be able to estimate biodegradable organic matter quantity before biological treatment. But the current methods used to characterize organic matter quality, like biological oxygen demand are laborious, time consuming and sometimes not applicable to directly monitor organic matter in situ. In the context of MOCOPEE research program (www.mocopee.com), this study aims to assess the use of optical techniques, such as UV-Visible absorbance and more specifically fluorescence spectroscopy in order to monitor and to optimize process efficiency in WWTP. Fluorescence excitation-emission matrix (EEM) spectroscopy was employed to prospect the possibility of using this technology online and in real time to characterize dissolved organic matter in different effluents of the WWTP Seine Centre (240,000 m3/day) in Paris, France. 35 sewage water influent samples were collected on 10 days at different hours. Data treatment were performed by two methods: peak picking and parallel factor analysis (PARAFAC). An evolution of DOM quality (position of excitation - emission peaks) and quantity (intensity of fluorescence) was observed between the different treatment steps (influent, primary treatment, biological treatment, effluent). Correlations were found between fluorescence indicators and different water quality key parameters in the sewage influents. We developed different multivariate linear regression models in order to predict a variety of water quality parameters by fluorescence intensity at specific excitation-emission wavelengths. For example dissolved biological oxygen demand (r2=0,900; p<0,0001) and ammonium concentration (r2=0,898; p<0,0001) present good correlation with specific fluorescence peaks and indicators. These indicators derived from 3D spectrofluorescence could be used in order to characterize DOM online and thus to optimize process efficiency in WWTP.

Optimal Xylocoris flavipes (Reuter) (Hemiptera: Anthocoridae) density and time of introduction for suppression of bruchid progeny in stored legumes

Treesearch

Sharlene E. Sing; Richard T. Arbogast

2008-01-01

The influences of both predator density and elapsed time between initial infestation and introduction of predators were determined for suppression of bruchids infesting stored grain legumes by Xylocoris flavipes (Reuter) (Hemiptera: Anthocoridae). Predator density treatments consisted of zero, one, two, three, or five male:female pairs of adult

Improved dose-volume histogram estimates for radiopharmaceutical therapy by optimizing quantitative SPECT reconstruction parameters

NASA Astrophysics Data System (ADS)

Cheng, Lishui; Hobbs, Robert F.; Segars, Paul W.; Sgouros, George; Frey, Eric C.

2013-06-01

In radiopharmaceutical therapy, an understanding of the dose distribution in normal and target tissues is important for optimizing treatment. Three-dimensional (3D) dosimetry takes into account patient anatomy and the nonuniform uptake of radiopharmaceuticals in tissues. Dose-volume histograms (DVHs) provide a useful summary representation of the 3D dose distribution and have been widely used for external beam treatment planning. Reliable 3D dosimetry requires an accurate 3D radioactivity distribution as the input. However, activity distribution estimates from SPECT are corrupted by noise and partial volume effects (PVEs). In this work, we systematically investigated OS-EM based quantitative SPECT (QSPECT) image reconstruction in terms of its effect on DVHs estimates. A modified 3D NURBS-based Cardiac-Torso (NCAT) phantom that incorporated a non-uniform kidney model and clinically realistic organ activities and biokinetics was used. Projections were generated using a Monte Carlo (MC) simulation; noise effects were studied using 50 noise realizations with clinical count levels. Activity images were reconstructed using QSPECT with compensation for attenuation, scatter and collimator-detector response (CDR). Dose rate distributions were estimated by convolution of the activity image with a voxel S kernel. Cumulative DVHs were calculated from the phantom and QSPECT images and compared both qualitatively and quantitatively. We found that noise, PVEs, and ringing artifacts due to CDR compensation all degraded histogram estimates. Low-pass filtering and early termination of the iterative process were needed to reduce the effects of noise and ringing artifacts on DVHs, but resulted in increased degradations due to PVEs. Large objects with few features, such as the liver, had more accurate histogram estimates and required fewer iterations and more smoothing for optimal results. Smaller objects with fine details, such as the kidneys, required more iterations and less smoothing at early time points post-radiopharmaceutical administration but more smoothing and fewer iterations at later time points when the total organ activity was lower. The results of this study demonstrate the importance of using optimal reconstruction and regularization parameters. Optimal results were obtained with different parameters at each time point, but using a single set of parameters for all time points produced near-optimal dose-volume histograms.

A search for the optimal duration of treatment with 6-mercaptopurine for ulcerative colitis.

PubMed

Lobel, Efrat Z; Korelitz, Burton I; Xuereb, Mark A; Panagopoulos, Georgia

2004-03-01

6-mercaptopurine has proven to be effective in the treatment and maintenance of remission of ulcerative colitis (UC). The optimal duration of treatment with 6-MP is unknown. The intention of this study was to determine the best duration of treatment with 6-MP in terms of maintenance efficacy once remission has been achieved. We reviewed the records from the inflammatory bowel disease (IBD) center at Lenox Hill Hospital and one large IBD practice in New York City of 334 patients treated with 6-MP for UC. These patients were followed from 4 months to 28.7 yr. Sixty-one patients were treated with 6-MP for at least 6 months and had at least a 3-month disease-free interval off steroids while on the medication. These patients were divided into two groups: Group 1 continued 6-MP and group 2 discontinued the drug at various times for reasons other than relapse. Time to relapse was calculated for both groups. A Kaplan-Meier survival analysis was employed and differences between the two groups were analyzed using the log-rank test. The median time to relapse in group 2 was 24 wk and in group 1 was 58 wk (p < 0.05). There were no significant differences between the two groups in age, gender, extent of disease, use of concomitant 5-ASA products, dose of 6-MP during remission, duration of UC, and duration of treatment with 6-MP before remission was achieved. Discontinuation of treatment with 6-MP while UC is in remission leads to a higher relapse rate than maintenance on 6-MP. Therefore, we favor the indefinite treatment with 6-MP in most patients.

Robust optimization based upon statistical theory.

PubMed

Sobotta, B; Söhn, M; Alber, M

2010-08-01

Organ movement is still the biggest challenge in cancer treatment despite advances in online imaging. Due to the resulting geometric uncertainties, the delivered dose cannot be predicted precisely at treatment planning time. Consequently, all associated dose metrics (e.g., EUD and maxDose) are random variables with a patient-specific probability distribution. The method that the authors propose makes these distributions the basis of the optimization and evaluation process. The authors start from a model of motion derived from patient-specific imaging. On a multitude of geometry instances sampled from this model, a dose metric is evaluated. The resulting pdf of this dose metric is termed outcome distribution. The approach optimizes the shape of the outcome distribution based on its mean and variance. This is in contrast to the conventional optimization of a nominal value (e.g., PTV EUD) computed on a single geometry instance. The mean and variance allow for an estimate of the expected treatment outcome along with the residual uncertainty. Besides being applicable to the target, the proposed method also seamlessly includes the organs at risk (OARs). The likelihood that a given value of a metric is reached in the treatment is predicted quantitatively. This information reveals potential hazards that may occur during the course of the treatment, thus helping the expert to find the right balance between the risk of insufficient normal tissue sparing and the risk of insufficient tumor control. By feeding this information to the optimizer, outcome distributions can be obtained where the probability of exceeding a given OAR maximum and that of falling short of a given target goal can be minimized simultaneously. The method is applicable to any source of residual motion uncertainty in treatment delivery. Any model that quantifies organ movement and deformation in terms of probability distributions can be used as basis for the algorithm. Thus, it can generate dose distributions that are robust against interfraction and intrafraction motion alike, effectively removing the need for indiscriminate safety margins.

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

Volumetric‐modulated arc therapy planning using multicriteria optimization for localized prostate cancer

PubMed Central

Ghandour, Sarah; Matzinger, Oscar

2015-01-01

The purpose of this work is to evaluate the volumetric‐modulated arc therapy (VMAT) multicriteria optimization (MCO) algorithm clinically available in the RayStation treatment planning system (TPS) and its ability to reduce treatment planning time while providing high dosimetric plan quality. Nine patients with localized prostate cancer who were previously treated with 78 Gy in 39 fractions using VMAT plans and rayArc system based on the direct machine parameter optimization (DMPO) algorithm were selected and replanned using the VMAT‐MCO system. First, the dosimetric quality of the plans was evaluated using multiple conformity metrics that account for target coverage and sparing of healthy tissue, used in our departmental clinical protocols. The conformity and homogeneity index, number of monitor units, and treatment planning time for both modalities were assessed. Next, the effects of the technical plan parameters, such as constraint leaf motion CLM (cm/°) and maximum arc delivery time T (s), on the accuracy of delivered dose were evaluated using quality assurance passing rates (QAs) measured using the Delta4 phantom from ScandiDos. For the dosimetric plan's quality analysis, the results show that the VMAT‐MCO system provides plans comparable to the rayArc system with no statistical difference for V95% (p<0.01), D1% (p<0.01), CI (p<0.01), and HI (p<0.01) of the PTV, bladder (p<0.01), and rectum (p<0.01) constraints, except for the femoral heads and healthy tissues, for which a dose reduction was observed using MCO compared with rayArc (p<0.01). The technical parameter study showed that a combination of CLM equal to 0.5 cm/degree and a maximum delivery time of 72 s allowed the accurate delivery of the VMAT‐MCO plan on the Elekta Versa HD linear accelerator. Planning evaluation and dosimetric measurements showed that VMAT‐MCO can be used clinically with the advantage of enhanced planning process efficiency by reducing the treatment planning time without impairing dosimetric quality. PACS numbers: 87.55.D, 87.55.de, 87.55.Qr PMID:26103500

Endoscopic vs. Surgical Interventions for Painful Chronic Pancreatitis: What is Needed for Future Clinical Trials

PubMed Central

Windsor, John A; Reddy, Nageshwar D

2017-01-01

The treatment of painful chronic pancreatitis remains controversial. The available evidence from two randomized controlled trials favor surgical intervention, whereas an endotherapy-first approach is widely practiced. Chronic pancreatitis is complex disease with different genetic and environmental factors, different pain mechanisms and different treatment modalities including medical, endoscopic, and surgical. The widely practiced step-up approach remains unproven. In designing future clinical trials there are some important pre-requisites including a more comprehensive pain assessment tool, the optimization of conservative medical treatment and interventional techniques. Consideration should be given to the need of a control arm and the optimal timing of intervention. Pending better designed studies, the practical way forward is to identify subgroups of patients who clearly warrant endotherapy or surgery first, and to design the future clinical trials for the remainder. PMID:28079861

A Mathematical Tumor Model with Immune Resistance and Drug Therapy: An Optimal Control Approach

DOE PAGES

De Pillis, L. G.; Radunskaya, A.

2001-01-01

We present a competition model of cancer tumor growth that includes both the immune system response and drug therapy. This is a four-population model that includes tumor cells, host cells, immune cells, and drug interaction. We analyze the stability of the drug-free equilibria with respect to the immune response in order to look for target basins of attraction. One of our goals was to simulate qualitatively the asynchronous tumor-drug interaction known as “Jeffs phenomenon.” The model we develop is successful in generating this asynchronous response behavior. Our other goal was to identify treatment protocols that could improve standard pulsed chemotherapymore » regimens. Using optimal control theory with constraints and numerical simulations, we obtain new therapy protocols that we then compare with traditional pulsed periodic treatment. The optimal control generated therapies produce larger oscillations in the tumor population over time. However, by the end of the treatment period, total tumor size is smaller than that achieved through traditional pulsed therapy, and the normal cell population suffers nearly no oscillations.« less

A Mathematical Tumor Model with Immune Resistance and Drug Therapy: An Optimal Control Approach

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

De Pillis, L. G.; Radunskaya, A.

We present a competition model of cancer tumor growth that includes both the immune system response and drug therapy. This is a four-population model that includes tumor cells, host cells, immune cells, and drug interaction. We analyze the stability of the drug-free equilibria with respect to the immune response in order to look for target basins of attraction. One of our goals was to simulate qualitatively the asynchronous tumor-drug interaction known as “Jeffs phenomenon.” The model we develop is successful in generating this asynchronous response behavior. Our other goal was to identify treatment protocols that could improve standard pulsed chemotherapymore » regimens. Using optimal control theory with constraints and numerical simulations, we obtain new therapy protocols that we then compare with traditional pulsed periodic treatment. The optimal control generated therapies produce larger oscillations in the tumor population over time. However, by the end of the treatment period, total tumor size is smaller than that achieved through traditional pulsed therapy, and the normal cell population suffers nearly no oscillations.« less

Modeling analysis on germination and seedling growth using ultrasound seed pretreatment in switchgrass.

PubMed

Wang, Quanzhen; Chen, Guo; Yersaiyiti, Hayixia; Liu, Yuan; Cui, Jian; Wu, Chunhui; Zhang, Yunwei; He, Xueqing

2012-01-01

Switchgrass is a perennial C4 plant with great potential as a bioenergy source and, thus, a high demand for establishment from seed. This research investigated the effects of ultrasound treatment on germination and seedling growth in switchgrass. Using an orthogonal matrix design, conditions for the ultrasound pretreatment in switchgrass seed, including sonication time (factor A), sonication temperature (factor B) and ultrasound output power (factor C), were optimized for germinating and stimulating seedling growth (indicated as plumular and radicular lengths) through modeling analysis. The results indicate that sonication temperature (B) was the most effective factor for germination, whereas output power (C) had the largest effect on seedling growth when ultrasound treatment was used. Combined with the analyses of range, variance and models, the final optimal ultrasonic treatment conditions were sonication for 22.5 min at 39.7°C and at an output power of 348 W, which provided the greatest germination percentage and best seedling growth. For this study, the orthogonal matrix design was an efficient method for optimizing the conditions of ultrasound seed treatment on switchgrass. The electrical conductivity of seed leachates in three experimental groups (control, soaked in water only, and ultrasound treatment) was determined to investigate the effects of ultrasound on seeds and eliminate the effect of water in the ultrasound treatments. The results showed that the electrical conductivity of seed leachates during either ultrasound treatment or water bath treatment was significantly higher than that of the control, and that the ultrasound treatment had positive effects on switchgrass seeds.

Effect of T6 heat treatment on the microstructural and mechanical properties of Al-Si-Cu-Mg alloys

NASA Astrophysics Data System (ADS)

Patel, Dhruv; Davda, Chintan; Solanki, P. S.; Keshvani, M. J.

2016-05-01

In this communication, it is aimed to optimize the conditions for T6 heat treatment of permanent die cast Al-Si-Cu-Mg alloys. Various solutionizing temperatures, aging treatments and soaking times were used to improve / modify the mechanical properties of presently studied alloys. Formation mechanism of the particles was understood by carrying out optical microscopy and energy dispersive X-ray (EDX) spectroscopy measurements. Spherical particles of alloys were studied for their microstructural properties using scanning electron microscopy (SEM). Microhardness test was performed to investigate their mechanical properties. Dependence of cluster formation and microhardness of the alloys on the adequate solutionizing temperature, aging treatment and soaking time has been discussed in detail.

Adaptive intensity modulated radiotherapy for advanced prostate cancer

NASA Astrophysics Data System (ADS)

Ludlum, Erica Marie

The purpose of this research is to develop and evaluate improvements in intensity modulated radiotherapy (IMRT) for concurrent treatment of prostate and pelvic lymph nodes. The first objective is to decrease delivery time while maintaining treatment quality, and evaluate the effectiveness and efficiency of novel one-step optimization compared to conventional two-step optimization. Both planning methods are examined at multiple levels of complexity by comparing the number of beam apertures, or segments, the amount of radiation delivered as measured by monitor units (MUs), and delivery time. One-step optimization is demonstrated to simplify IMRT planning and reduce segments (from 160 to 40), MUs (from 911 to 746), and delivery time (from 22 to 7 min) with comparable plan quality. The second objective is to examine the capability of three commercial dose calculation engines employing different levels of accuracy and efficiency to handle high--Z materials, such as metallic hip prostheses, included in the treatment field. Pencil beam, convolution superposition, and Monte Carlo dose calculation engines are compared by examining the dose differences for patient plans with unilateral and bilateral hip prostheses, and for phantom plans with a metal insert for comparison with film measurements. Convolution superposition and Monte Carlo methods calculate doses that are 1.3% and 34.5% less than the pencil beam method, respectively. Film results demonstrate that Monte Carlo most closely represents actual radiation delivery, but none of the three engines accurately predict the dose distribution when high-Z heterogeneities exist in the treatment fields. The final objective is to improve the accuracy of IMRT delivery by accounting for independent organ motion during concurrent treatment of the prostate and pelvic lymph nodes. A leaf-shifting algorithm is developed to track daily prostate position without requiring online dose calculation. Compared to conventional methods of adjusting patient position, adjusting the multileaf collimator (MLC) leaves associated with the prostate in each segment significantly improves lymph node dose coverage (maintains 45 Gy compared to 42.7, 38.3, and 34.0 Gy for iso-shifts of 0.5, 1 and 1.5 cm). Altering the MLC portal shape is demonstrated as a new and effective solution to independent prostate movement during concurrent treatment.

Boosting the Supercapacitance of Nitrogen-Doped Carbon by Tuning Surface Functionalities.

PubMed

Biemolt, Jasper; Denekamp, Ilse M; Slot, Thierry K; Rothenberg, Gadi; Eisenberg, David

2017-10-23

The specific capacitance of a highly porous, nitrogen-doped carbon is nearly tripled by orthogonal optimization of the microstructure and surface chemistry. First, the carbons' hierarchical pore structure and specific surface area were tweaked by controlling the temperature and sequence of the thermal treatments. The best process (pyrolysis at 900 °C, washing, and subsequent annealing at 1000 °C) yielded a carbon with a specific capacitance of 117 F g -1 -nearly double that of a carbon made by a typical single-step synthesis at 700 °C. Following the structural optimization, the surface chemistry of the carbons was enriched by applying an oxidation routine based on a mixture of nitric and sulfuric acid in a 1:4 ratio at two different treatment temperatures (0 and 20 °C) and different treatment times. The optimal treatment times were 4 h at 0 °C and only 1 h at 20 °C. Overall, the specific capacitance nearly tripled relative to the original carbon, reaching 168 F g -1 . The inherent nitrogen doping of the carbon comes into interplay with the acid-induced surface functionalization, creating a mixture of oxygen- and nitrogen-oxygen functionalities. The evolution of the surface chemistry was carefully followed by X-ray photoelectron spectroscopy and by N 2 sorption porosimetry, revealing stepwise surface functionalization and simultaneous carbon etching. Overall, these processes are responsible for the peak-shaped capacitance trends in the carbons. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Assessment of Micro-Basin Tillage as a Soil and Water Conservation Practice in the Black Soil Region of Northeast China.

PubMed

Sui, Yuanyuan; Ou, Yang; Yan, Baixing; Xu, Xiaohong; Rousseau, Alain N; Zhang, Yu

2016-01-01

Micro-basin tillage is a soil and water conservation practice that requires building individual earth blocks along furrows. In this study, plot experiments were conducted to assess the efficiency of micro-basin tillage on sloping croplands between 2012 and 2013 (5°and 7°). The conceptual, optimal, block interval model was used to design micro-basins which are meant to capture the maximum amount of water per unit area. Results indicated that when compared to the up-down slope tillage, micro-basin tillage could increase soil water content and maize yield by about 45% and 17%, and reduce runoff, sediment and nutrients loads by about 63%, 96% and 86%, respectively. Meanwhile, micro-basin tillage could reduce the peak runoff rates and delay the initial runoff-yielding time. In addition, micro-basin tillage with the optimal block interval proved to be the best one among all treatments with different intervals. Compared with treatments of other block intervals, the optimal block interval treatments increased soil moisture by around 10% and reduced runoff rate by around 15%. In general, micro-basin tillage with optimal block interval represents an effective soil and water conservation practice for sloping farmland of the black soil region.

Assessment of Micro-Basin Tillage as a Soil and Water Conservation Practice in the Black Soil Region of Northeast China

PubMed Central

Sui, Yuanyuan; Ou, Yang; Yan, Baixing; Xu, Xiaohong; Rousseau, Alain N.; Zhang, Yu

2016-01-01

Micro-basin tillage is a soil and water conservation practice that requires building individual earth blocks along furrows. In this study, plot experiments were conducted to assess the efficiency of micro-basin tillage on sloping croplands between 2012 and 2013 (5°and 7°). The conceptual, optimal, block interval model was used to design micro-basins which are meant to capture the maximum amount of water per unit area. Results indicated that when compared to the up-down slope tillage, micro-basin tillage could increase soil water content and maize yield by about 45% and 17%, and reduce runoff, sediment and nutrients loads by about 63%, 96% and 86%, respectively. Meanwhile, micro-basin tillage could reduce the peak runoff rates and delay the initial runoff-yielding time. In addition, micro-basin tillage with the optimal block interval proved to be the best one among all treatments with different intervals. Compared with treatments of other block intervals, the optimal block interval treatments increased soil moisture by around 10% and reduced runoff rate by around 15%. In general, micro-basin tillage with optimal block interval represents an effective soil and water conservation practice for sloping farmland of the black soil region. PMID:27031339

Optimal intravenous infusion to decrease the haematocrit level in patient of DHF infection

NASA Astrophysics Data System (ADS)

Handayani, D.; Nuraini, N.; Saragih, R.; Wijaya, K. P.; Naiborhu, J.

2014-02-01

The optimal control of infusion model for Dengue Hemorrhagic Fever (DHF) infection is formulated here. The infusion model will be presented in form of haematocrit level. The input control aim to normalize the haematocrit level and is expressed as infusion volume on mL/day. The stability near the equilibrium points will be analyzed. Numerical simulation shows the dynamic of each infection compartments which gives a description of within-host dynamic of dengue virus. These results show particularly that infected compartments tend to be vanished in ±15days after the onset of the virus. In fact, without any control added, the haematocrit level will decrease but not up to the normal level. Therefore the effective haematocrit normalization should be done with the treatment control. Control treatment for a fixed time using a control input can bring haematocrit level to normal range 42-47%. The optimal control in this paper is divided into three cases, i.e. fixed end point, constrained input, and tracking haematocrit state. Each case shows different infection condition in human body. However, all cases require that the haematocrit level to be in normal range in fixed final time.

GPU computing in medical physics: a review.

PubMed

Pratx, Guillem; Xing, Lei

2011-05-01

The graphics processing unit (GPU) has emerged as a competitive platform for computing massively parallel problems. Many computing applications in medical physics can be formulated as data-parallel tasks that exploit the capabilities of the GPU for reducing processing times. The authors review the basic principles of GPU computing as well as the main performance optimization techniques, and survey existing applications in three areas of medical physics, namely image reconstruction, dose calculation and treatment plan optimization, and image processing.

Methods to model and predict the ViewRay treatment deliveries to aid patient scheduling and treatment planning.

PubMed

Liu, Shi; Wu, Yu; Wooten, H Omar; Green, Olga; Archer, Brent; Li, Harold; Yang, Deshan

2016-03-08

A software tool is developed, given a new treatment plan, to predict treatment delivery time for radiation therapy (RT) treatments of patients on ViewRay magnetic resonance image-guided radiation therapy (MR-IGRT) delivery system. This tool is necessary for managing patient treatment scheduling in our clinic. The predicted treatment delivery time and the assessment of plan complexities could also be useful to aid treatment planning. A patient's total treatment delivery time, not including time required for localization, is modeled as the sum of four components: 1) the treatment initialization time; 2) the total beam-on time; 3) the gantry rotation time; and 4) the multileaf collimator (MLC) motion time. Each of the four components is predicted separately. The total beam-on time can be calculated using both the planned beam-on time and the decay-corrected dose rate. To predict the remain-ing components, we retrospectively analyzed the patient treatment delivery record files. The initialization time is demonstrated to be random since it depends on the final gantry angle of the previous treatment. Based on modeling the relationships between the gantry rotation angles and the corresponding rotation time, linear regression is applied to predict the gantry rotation time. The MLC motion time is calculated using the leaves delay modeling method and the leaf motion speed. A quantitative analysis was performed to understand the correlation between the total treatment time and the plan complexity. The proposed algorithm is able to predict the ViewRay treatment delivery time with the average prediction error 0.22min or 1.82%, and the maximal prediction error 0.89 min or 7.88%. The analysis has shown the correlation between the plan modulation (PM) factor and the total treatment delivery time, as well as the treatment delivery duty cycle. A possibility has been identified to significantly reduce MLC motion time by optimizing the positions of closed MLC pairs. The accuracy of the proposed prediction algorithm is sufficient to support patient treatment appointment scheduling. This developed software tool is currently applied in use on a daily basis in our clinic, and could also be used as an important indicator for treatment plan complexity.

Antibiofilm Effect of DNase against Single and Mixed Species Biofilm

PubMed Central

Sharma, Komal

2018-01-01

Biofilms are aggregates of microorganisms that coexist in socially coordinated micro-niche in a self-produced polymeric matrix on pre-conditioned surfaces. The biofilm matrix reduces the efficacy of antibiofilm strategies. DNase degrades the extracellular DNA (e-DNA) present in the matrix, rendering the matrix weak and susceptible to antimicrobials. In the current study, the effect of DNase I was evaluated during biofilm formation (pre-treatment), on preformed biofilms (post-treatment) and both (dual treatment). The DNase I pre-treatment was optimized for P. aeruginosa PAO1 (model biofilm organism) at 10 µg/mL and post-treatment at 10 µg/mL with 15 min of contact duration. Inclusion of Mg2+ alongside DNase I post-treatment resulted in 90% reduction in biofilm within only 5 min of contact time (irrespective of age of biofilm). On extension of these findings, DNase I was found to be less effective against mixed species biofilm than individual biofilms. DNase I can be used as potent antibiofilm agent and with further optimization can be effectively used for biofilm prevention and reduction in situ. PMID:29562719

RARtool: A MATLAB Software Package for Designing Response-Adaptive Randomized Clinical Trials with Time-to-Event Outcomes.

PubMed

Ryeznik, Yevgen; Sverdlov, Oleksandr; Wong, Weng Kee

2015-08-01

Response-adaptive randomization designs are becoming increasingly popular in clinical trial practice. In this paper, we present RARtool , a user interface software developed in MATLAB for designing response-adaptive randomized comparative clinical trials with censored time-to-event outcomes. The RARtool software can compute different types of optimal treatment allocation designs, and it can simulate response-adaptive randomization procedures targeting selected optimal allocations. Through simulations, an investigator can assess design characteristics under a variety of experimental scenarios and select the best procedure for practical implementation. We illustrate the utility of our RARtool software by redesigning a survival trial from the literature.

Preparation of durable hydrophobic cellulose fabric from water glass and mixed organosilanes

NASA Astrophysics Data System (ADS)

Shang, Song-Min; Li, Zhengxiong; Xing, Yanjun; Xin, John H.; Tao, Xiao-Ming

2010-12-01

Durable superhydrophobic cellulose fabric was prepared from water glass and n-octadecyltriethoxysilane (ODTES) with 3-glycidyloxypropyltrimethoxysilane (GPTMS) as crosslinker by sol-gel method. The result showed that the addition of GPTMS could result in a better fixation of silica coating from water glass on cellulose fabric. The silanization of hydrolyzed ODTES at different temperatures and times was studied and optimized. The results showed that silanization time was more important than temperature in forming durable hydrophobic surface. The durability of superhydrophobicity treatment was analyzed by XPS. As a result, the superhydrophobic cotton treated under the optimal condition still remained hydrophobic properties after 50 washing cycles.

Comparison of IMRT planning with two-step and one-step optimization: a strategy for improving therapeutic gain and reducing the integral dose

NASA Astrophysics Data System (ADS)

Abate, A.; Pressello, M. C.; Benassi, M.; Strigari, L.

2009-12-01

The aim of this study was to evaluate the effectiveness and efficiency in inverse IMRT planning of one-step optimization with the step-and-shoot (SS) technique as compared to traditional two-step optimization using the sliding windows (SW) technique. The Pinnacle IMRT TPS allows both one-step and two-step approaches. The same beam setup for five head-and-neck tumor patients and dose-volume constraints were applied for all optimization methods. Two-step plans were produced converting the ideal fluence with or without a smoothing filter into the SW sequence. One-step plans, based on direct machine parameter optimization (DMPO), had the maximum number of segments per beam set at 8, 10, 12, producing a directly deliverable sequence. Moreover, the plans were generated whether a split-beam was used or not. Total monitor units (MUs), overall treatment time, cost function and dose-volume histograms (DVHs) were estimated for each plan. PTV conformality and homogeneity indexes and normal tissue complication probability (NTCP) that are the basis for improving therapeutic gain, as well as non-tumor integral dose (NTID), were evaluated. A two-sided t-test was used to compare quantitative variables. All plans showed similar target coverage. Compared to two-step SW optimization, the DMPO-SS plans resulted in lower MUs (20%), NTID (4%) as well as NTCP values. Differences of about 15-20% in the treatment delivery time were registered. DMPO generates less complex plans with identical PTV coverage, providing lower NTCP and NTID, which is expected to reduce the risk of secondary cancer. It is an effective and efficient method and, if available, it should be favored over the two-step IMRT planning.

Ultrasound Assisted Extraction of Phenolic Compounds from Peaches and Pumpkins

PubMed Central

Altemimi, Ammar; Watson, Dennis G.; Choudhary, Ruplal; Dasari, Mallika R.; Lightfoot, David A.

2016-01-01

The ultrasound-assisted extraction (UAE) method was used to optimize the extraction of phenolic compounds from pumpkins and peaches. The response surface methodology (RSM) was used to study the effects of three independent variables each with three treatments. They included extraction temperatures (30, 40 and 50°C), ultrasonic power levels (30, 50 and 70%) and extraction times (10, 20 and 30 min). The optimal conditions for extractions of total phenolics from pumpkins were inferred to be a temperature of 41.45°C, a power of 44.60% and a time of 25.67 min. However, an extraction temperature of 40.99°C, power of 56.01% and time of 25.71 min was optimal for recovery of free radical scavenging activity (measured by 1, 1-diphenyl-2-picrylhydrazyl (DPPH) reduction). The optimal conditions for peach extracts were an extraction temperature of 41.53°C, power of 43.99% and time of 27.86 min for total phenolics. However, an extraction temperature of 41.60°C, power of 44.88% and time of 27.49 min was optimal for free radical scavenging activity (judged by from DPPH reduction). Further, the UAE processes were significantly better than solvent extractions without ultrasound. By electron microscopy it was concluded that ultrasonic processing caused damage in cells for all treated samples (pumpkin, peach). However, the FTIR spectra did not show any significant changes in chemical structures caused by either ultrasonic processing or solvent extraction. PMID:26885655

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

Impact of Reflex EGFR/ ALK Testing on Time to Treatment of Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer.

PubMed

Cheema, Parneet K; Menjak, Ines B; Winterton-Perks, Zoe; Raphael, Simon; Cheng, Susanna Y; Verma, Sunil; Muinuddin, Ahmad; Freedman, Ryan; Toor, Nevkeet; Perera, Joseph; Anaka, Matthew; Victor, J Charles

2017-02-01

Optimal first-line systemic therapy for patients with advanced nonsquamous (nonsq) non-small-cell lung cancer (NSCLC) requires confirmation of EGFR/ ALK status, which can delay treatment. We evaluated the impact of reflex testing, defined as pathologists initiating EGFR/ ALK testing at the time of diagnosis of nonsq NSCLC, on time to treatment (TTT). We conducted a retrospective review of patients with nonsq NSCLC with medical oncology consultation at Sunnybrook Odette Cancer Centre between March 18, 2010 and April 30, 2014. Data were compared during routine and reflex testing. TTT was defined as the interval between the first medical oncology visit with advanced NSCLC and the initiation of systemic therapy. A total of 306 patients were included (n = 232 for routine testing, n = 74 for reflex testing). There was a trend to improvement in median TTT with reflex testing (36 days [interquartile range {IQR}, 16 to 71 days v 26 days [IQR, 8 to 41 days], P = .071). Omitting patients with intentional delays in systemic therapy for low-volume disease, poor performance status, comorbidity management, and/or radiation therapy, median TTT improved (34 days [IQR, 15 to 67 days] v 22 days [IQR, 8 to 42 days], P = .049). Time to optimal first-line systemic therapy according to published guidelines improved (median, 36 days [IQR, 16 to 91 days] v 24 days [IQR, 8 to 43 days], P = .036). There was no impact on receipt of any first-line systemic therapy (55% v 59%, P = .66). The quality of biomarker testing improved, with fewer unsuccessful tests ( EGFR, 14% v 4%, P = .039; and ALK, 17% v 3%, P = .037). Reflex testing of EGFR/ ALK improved the time to optimal systemic therapy and the quality of biomarker testing for patients with advanced nonsq NSCLC.

Toward a web-based real-time radiation treatment planning system in a cloud computing environment.

PubMed

Na, Yong Hum; Suh, Tae-Suk; Kapp, Daniel S; Xing, Lei

2013-09-21

To exploit the potential dosimetric advantages of intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT), an in-depth approach is required to provide efficient computing methods. This needs to incorporate clinically related organ specific constraints, Monte Carlo (MC) dose calculations, and large-scale plan optimization. This paper describes our first steps toward a web-based real-time radiation treatment planning system in a cloud computing environment (CCE). The Amazon Elastic Compute Cloud (EC2) with a master node (named m2.xlarge containing 17.1 GB of memory, two virtual cores with 3.25 EC2 Compute Units each, 420 GB of instance storage, 64-bit platform) is used as the backbone of cloud computing for dose calculation and plan optimization. The master node is able to scale the workers on an 'on-demand' basis. MC dose calculation is employed to generate accurate beamlet dose kernels by parallel tasks. The intensity modulation optimization uses total-variation regularization (TVR) and generates piecewise constant fluence maps for each initial beam direction in a distributed manner over the CCE. The optimized fluence maps are segmented into deliverable apertures. The shape of each aperture is iteratively rectified to be a sequence of arcs using the manufacture's constraints. The output plan file from the EC2 is sent to the simple storage service. Three de-identified clinical cancer treatment plans have been studied for evaluating the performance of the new planning platform with 6 MV flattening filter free beams (40 × 40 cm(2)) from the Varian TrueBeam(TM) STx linear accelerator. A CCE leads to speed-ups of up to 14-fold for both dose kernel calculations and plan optimizations in the head and neck, lung, and prostate cancer cases considered in this study. The proposed system relies on a CCE that is able to provide an infrastructure for parallel and distributed computing. The resultant plans from the cloud computing are identical to PC-based IMRT and VMAT plans, confirming the reliability of the cloud computing platform. This cloud computing infrastructure has been established for a radiation treatment planning. It substantially improves the speed of inverse planning and makes future on-treatment adaptive re-planning possible.

Toward a web-based real-time radiation treatment planning system in a cloud computing environment

NASA Astrophysics Data System (ADS)

Hum Na, Yong; Suh, Tae-Suk; Kapp, Daniel S.; Xing, Lei

2013-09-01

To exploit the potential dosimetric advantages of intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT), an in-depth approach is required to provide efficient computing methods. This needs to incorporate clinically related organ specific constraints, Monte Carlo (MC) dose calculations, and large-scale plan optimization. This paper describes our first steps toward a web-based real-time radiation treatment planning system in a cloud computing environment (CCE). The Amazon Elastic Compute Cloud (EC2) with a master node (named m2.xlarge containing 17.1 GB of memory, two virtual cores with 3.25 EC2 Compute Units each, 420 GB of instance storage, 64-bit platform) is used as the backbone of cloud computing for dose calculation and plan optimization. The master node is able to scale the workers on an ‘on-demand’ basis. MC dose calculation is employed to generate accurate beamlet dose kernels by parallel tasks. The intensity modulation optimization uses total-variation regularization (TVR) and generates piecewise constant fluence maps for each initial beam direction in a distributed manner over the CCE. The optimized fluence maps are segmented into deliverable apertures. The shape of each aperture is iteratively rectified to be a sequence of arcs using the manufacture’s constraints. The output plan file from the EC2 is sent to the simple storage service. Three de-identified clinical cancer treatment plans have been studied for evaluating the performance of the new planning platform with 6 MV flattening filter free beams (40 × 40 cm2) from the Varian TrueBeamTM STx linear accelerator. A CCE leads to speed-ups of up to 14-fold for both dose kernel calculations and plan optimizations in the head and neck, lung, and prostate cancer cases considered in this study. The proposed system relies on a CCE that is able to provide an infrastructure for parallel and distributed computing. The resultant plans from the cloud computing are identical to PC-based IMRT and VMAT plans, confirming the reliability of the cloud computing platform. This cloud computing infrastructure has been established for a radiation treatment planning. It substantially improves the speed of inverse planning and makes future on-treatment adaptive re-planning possible.

The Utility of a Wireless Implantable Hemodynamic Monitoring System in Patients Requiring Mechanical Circulatory Support.

PubMed

Feldman, David S; Moazami, Nader; Adamson, Philip B; Vierecke, Juliane; Raval, Nir; Shreenivas, Satya; Cabuay, Barry M; Jimenez, Javier; Abraham, William T; O'Connell, John B; Naka, Yoshifumi

Proper timing of left ventricular assist device (LVAD) implantation in advanced heart failure patients is not well established and is an area of intense interest. In addition, optimizing LVAD performance after implantation remains difficult and represents a significant clinical need. Implantable hemodynamic monitoring systems may provide physicians with the physiologic information necessary to improve the timing of LVAD implantation as well as LVAD performance when compared with current methods. The CardioMEMS Heart sensor Allows for Monitoirng of Pressures to Improve Outcomes in NYHA Class III heart failure patients (CHAMPION) Trial enrolled 550 previously hospitalized patients with New York Heart Association (NYHA) class III heart failure. All patients were implanted with a pulmonary artery (PA) pressure monitoring system and randomized to a treatment and control groups. In the treatment group, physicians used the hemodynamic information to make heart failure management decisions. This information was not available to physicians for the control group. During an average of 18 month randomized follow-up, 27 patients required LVAD implantation. At the time of PA pressure sensor implantation, patients ultimately requiring advanced therapy had higher PA pressures, lower systemic pressure, and similar cardiac output measurements. Treatment and control patients in the LVAD subgroup had similar clinical profiles at the time of enrollment. There was a trend toward a shorter length of time to LVAD implantation in the treatment group when hemodynamic information was available. After LVAD implantation, most treatment group patients continued to provide physicians with physiologic information from the hemodynamic monitoring system. As expected PA pressures declined significantly post LVAD implant in all patients, but the magnitude of decline was higher in patients with PA pressure monitoring. Implantable hemodynamic monitoring appeared to improve the timing of LVAD implantation as well as optimize LVAD performance when compared with current methods. Further studies are necessary to evaluate these findings in a prospective manner.

The United States Army Medical Department Journal. July - September 2011

DTIC Science & Technology

2011-09-01

compliance. Figure 1. Functional schematic of the flow path and treatment stages of the water treatment plant. Basin 5  Basin  4  Basin  3  Basin 2...that hindered optimal performance of the WTP. They were the flocculation treatment process and flow distribution through the WTP. Flocculation...designed to simulate the WTP at a flow of 1.5 MGD (the flow through the WTP at the time of jar testing). Jar test samples were collected after

Advances in 4D Treatment Planning for Scanned Particle Beam Therapy — Report of Dedicated Workshops

PubMed Central

Bert, Christoph; Graeff, Christian; Riboldi, Marco; Nill, Simeon; Baroni, Guido; Knopf, Antje-Christin

2014-01-01

We report on recent progress in the field of mobile tumor treatment with scanned particle beams, as discussed in the latest editions of the 4D treatment planning workshop. The workshop series started in 2009, with about 20 people from 4 research institutes involved, all actively working on particle therapy delivery and development. The first workshop resulted in a summary of recommendations for the treatment of mobile targets, along with a list of requirements to apply these guidelines clinically. The increased interest in the treatment of mobile tumors led to a continuously growing number of attendees: the 2012 edition counted more than 60 participants from 20 institutions and commercial vendors. The focus of research discussions among workshop participants progressively moved from 4D treatment planning to complete 4D treatments, aiming at effective and safe treatment delivery. Current research perspectives on 4D treatments include all critical aspects of time resolved delivery, such as in-room imaging, motion detection, beam application, and quality assurance techniques. This was motivated by the start of first clinical treatments of hepato cellular tumors with a scanned particle beam, relying on gating or abdominal compression for motion mitigation. Up to date research activities emphasize significant efforts in investigating advanced motion mitigation techniques, with a specific interest in the development of dedicated tools for experimental validation. Potential improvements will be made possible in the near future through 4D optimized treatment plans that require upgrades of the currently established therapy control systems for time resolved delivery. But since also these novel optimization techniques rely on the validity of the 4DCT, research focusing on alternative 4D imaging technique, such as MRI based 4DCT generation will continue. PMID:24354749

Clinical observation of the application of autologous peripheral blood stem cell transplantation for the treatment of diabetic foot gangrene

PubMed Central

XU, SHI-MIN; LIANG, TING

2016-01-01

The aim of the present study was to investigate the optimal mobilization plan in autologous peripheral blood stem cell transplantation for the treatment of diabetic foot and to observe its clinical curative effect. A total of 127 patients with diabetic foot were treated with different doses of granulocyte colony stimulating factor (G-CSF) to mobilize their hematopoietic stem cells. Subsequently, the extracted stem cell suspension was injected into the ischemic lower extremities along the blood vessels in the areas presenting with pathological changes. Following the treatment, the intermittent claudication distance, skin temperature, ankle brachial index and pain scores of the patients were evaluated. In addition, the associations among the mobilization time, doses and peripheral blood CD34+ level were analyzed. The collection efficiency of the stem cells was associated with the dose of G-CSF and the mobilization time. Following the injection of the autologous peripheral blood stem cell suspension, the ischemic area of the patients was improved significantly. In conclusion, autologous peripheral blood stem cell transplantation can promote the establishment of collateral circulation in patients with diabetic foot, and the optimal time for gathering stem cells is closely correlated with the peripheral blood CD34+ level. PMID:26889255

Evidence-based outcomes following inferior alveolar and lingual nerve injury and repair: a systematic review.

PubMed

Kushnerev, E; Yates, J M

2015-10-01

The inferior alveolar nerve (IAN) and lingual (LN) are susceptible to iatrogenic surgical damage. Systematically review recent clinical evidence regarding IAN/LN repair methods and to develop updated guidelines for managing injury. Recent publications on IAN/LN microsurgical repair from Medline, Embase and Cochrane Library databases were screened by title/abstract. Main texts were appraised for exclusion criteria: no treatment performed or results provided, poor/lacking procedural description, cohort <3 patients. Of 366 retrieved papers, 27 were suitable for final analysis. Treatment type for injured IANs/LNs depended on injury type, injury timing, neurosensory disturbances and intra-operative findings. Best functional nerve recovery occurred after direct apposition and suturing if nerve ending gaps were <10 mm; larger gaps required nerve grafting (sural/greater auricular nerve). Timing of microneurosurgical repair after injury remains debated. Most authors recommend surgery when neurosensory deficit shows no improvement 90 days post-diagnosis. Nerve transection diagnosed intra-operatively should be repaired in situ; minor nerve injury repair can be delayed. No consensus exists regarding optimal methods and timing for IAN/LN repair. We suggest a schematic guideline for treating IAN/LN injury, based on the most current evidence. We acknowledge that additional RCTs are required to provide definitive confirmation of optimal treatment approaches. © 2015 John Wiley & Sons Ltd.

Optimal Design and Operation of In-Situ Chemical Oxidation Using Stochastic Cost Optimization Toolkit

NASA Astrophysics Data System (ADS)

Kim, U.; Parker, J.; Borden, R. C.

2014-12-01

In-situ chemical oxidation (ISCO) has been applied at many dense non-aqueous phase liquid (DNAPL) contaminated sites. A stirred reactor-type model was developed that considers DNAPL dissolution using a field-scale mass transfer function, instantaneous reaction of oxidant with aqueous and adsorbed contaminant and with readily oxidizable natural oxygen demand ("fast NOD"), and second-order kinetic reactions with "slow NOD." DNAPL dissolution enhancement as a function of oxidant concentration and inhibition due to manganese dioxide precipitation during permanganate injection are included in the model. The DNAPL source area is divided into multiple treatment zones with different areas, depths, and contaminant masses based on site characterization data. The performance model is coupled with a cost module that involves a set of unit costs representing specific fixed and operating costs. Monitoring of groundwater and/or soil concentrations in each treatment zone is employed to assess ISCO performance and make real-time decisions on oxidant reinjection or ISCO termination. Key ISCO design variables include the oxidant concentration to be injected, time to begin performance monitoring, groundwater and/or soil contaminant concentrations to trigger reinjection or terminate ISCO, number of monitoring wells or geoprobe locations per treatment zone, number of samples per sampling event and location, and monitoring frequency. Design variables for each treatment zone may be optimized to minimize expected cost over a set of Monte Carlo simulations that consider uncertainty in site parameters. The model is incorporated in the Stochastic Cost Optimization Toolkit (SCOToolkit) program, which couples the ISCO model with a dissolved plume transport model and with modules for other remediation strategies. An example problem is presented that illustrates design tradeoffs required to deal with characterization and monitoring uncertainty. Monitoring soil concentration changes during ISCO was found to be important to avoid decision errors associated with slow rebound of groundwater concentrations.

Generation of a novel phase-space-based cylindrical dose kernel for IMRT optimization.

PubMed

Zhong, Hualiang; Chetty, Indrin J

2012-05-01

Improving dose calculation accuracy is crucial in intensity-modulated radiation therapy (IMRT). We have developed a method for generating a phase-space-based dose kernel for IMRT planning of lung cancer patients. Particle transport in the linear accelerator treatment head of a 21EX, 6 MV photon beam (Varian Medical Systems, Palo Alto, CA) was simulated using the EGSnrc/BEAMnrc code system. The phase space information was recorded under the secondary jaws. Each particle in the phase space file was associated with a beamlet whose index was calculated and saved in the particle's LATCH variable. The DOSXYZnrc code was modified to accumulate the energy deposited by each particle based on its beamlet index. Furthermore, the central axis of each beamlet was calculated from the orientation of all the particles in this beamlet. A cylinder was then defined around the central axis so that only the energy deposited within the cylinder was counted. A look-up table was established for each cylinder during the tallying process. The efficiency and accuracy of the cylindrical beamlet energy deposition approach was evaluated using a treatment plan developed on a simulated lung phantom. Profile and percentage depth doses computed in a water phantom for an open, square field size were within 1.5% of measurements. Dose optimized with the cylindrical dose kernel was found to be within 0.6% of that computed with the nontruncated 3D kernel. The cylindrical truncation reduced optimization time by approximately 80%. A method for generating a phase-space-based dose kernel, using a truncated cylinder for scoring dose, in beamlet-based optimization of lung treatment planning was developed and found to be in good agreement with the standard, nontruncated scoring approach. Compared to previous techniques, our method significantly reduces computational time and memory requirements, which may be useful for Monte-Carlo-based 4D IMRT or IMAT treatment planning.

Adaptation of the CVT algorithm for catheter optimization in high dose rate brachytherapy

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

Poulin, Eric; Fekete, Charles-Antoine Collins; Beaulieu, Luc

2013-11-15

Purpose: An innovative, simple, and fast method to optimize the number and position of catheters is presented for prostate and breast high dose rate (HDR) brachytherapy, both for arbitrary templates or template-free implants (such as robotic templates).Methods: Eight clinical cases were chosen randomly from a bank of patients, previously treated in our clinic to test our method. The 2D Centroidal Voronoi Tessellations (CVT) algorithm was adapted to distribute catheters uniformly in space, within the maximum external contour of the planning target volume. The catheters optimization procedure includes the inverse planning simulated annealing algorithm (IPSA). Complete treatment plans can then bemore » generated from the algorithm for different number of catheters. The best plan is chosen from different dosimetry criteria and will automatically provide the number of catheters and their positions. After the CVT algorithm parameters were optimized for speed and dosimetric results, it was validated against prostate clinical cases, using clinically relevant dose parameters. The robustness to implantation error was also evaluated. Finally, the efficiency of the method was tested in breast interstitial HDR brachytherapy cases.Results: The effect of the number and locations of the catheters on prostate cancer patients was studied. Treatment plans with a better or equivalent dose distributions could be obtained with fewer catheters. A better or equal prostate V100 was obtained down to 12 catheters. Plans with nine or less catheters would not be clinically acceptable in terms of prostate V100 and D90. Implantation errors up to 3 mm were acceptable since no statistical difference was found when compared to 0 mm error (p > 0.05). No significant difference in dosimetric indices was observed for the different combination of parameters within the CVT algorithm. A linear relation was found between the number of random points and the optimization time of the CVT algorithm. Because the computation time decrease with the number of points and that no effects were observed on the dosimetric indices when varying the number of sampling points and the number of iterations, they were respectively fixed to 2500 and to 100. The computation time to obtain ten complete treatments plans ranging from 9 to 18 catheters, with the corresponding dosimetric indices, was 90 s. However, 93% of the computation time is used by a research version of IPSA. For the breast, on average, the Radiation Therapy Oncology Group recommendations would be satisfied down to 12 catheters. Plans with nine or less catheters would not be clinically acceptable in terms of V100, dose homogeneity index, and D90.Conclusions: The authors have devised a simple, fast and efficient method to optimize the number and position of catheters in interstitial HDR brachytherapy. The method was shown to be robust for both prostate and breast HDR brachytherapy. More importantly, the computation time of the algorithm is acceptable for clinical use. Ultimately, this catheter optimization algorithm could be coupled with a 3D ultrasound system to allow real-time guidance and planning in HDR brachytherapy.« less

SU-E-T-502: Initial Results of a Comparison of Treatment Plans Produced From Automated Prioritized Planning Method and a Commercial Treatment Planning System

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

Tiwari, P; Chen, Y; Hong, L

2015-06-15

Purpose We developed an automated treatment planning system based on a hierarchical goal programming approach. To demonstrate the feasibility of our method, we report the comparison of prostate treatment plans produced from the automated treatment planning system with those produced by a commercial treatment planning system. Methods In our approach, we prioritized the goals of the optimization, and solved one goal at a time. The purpose of prioritization is to ensure that higher priority dose-volume planning goals are not sacrificed to improve lower priority goals. The algorithm has four steps. The first step optimizes dose to the target structures, whilemore » sparing key sensitive organs from radiation. In the second step, the algorithm finds the best beamlet weight to reduce toxicity risks to normal tissue while holding the objective function achieved in the first step as a constraint, with a small amount of allowed slip. Likewise, the third and fourth steps introduce lower priority normal tissue goals and beam smoothing. We compared with prostate treatment plans from Memorial Sloan Kettering Cancer Center developed using Eclipse, with a prescription dose of 72 Gy. A combination of liear, quadratic, and gEUD objective functions were used with a modified open source solver code (IPOPT). Results Initial plan results on 3 different cases show that the automated planning system is capable of competing or improving on expert-driven eclipse plans. Compared to the Eclipse planning system, the automated system produced up to 26% less mean dose to rectum and 24% less mean dose to bladder while having the same D95 (after matching) to the target. Conclusion We have demonstrated that Pareto optimal treatment plans can be generated automatically without a trial-and-error process. The solver finds an optimal plan for the given patient, as opposed to database-driven approaches that set parameters based on geometry and population modeling.« less

Particle swarm optimizer for weighting factor selection in intensity-modulated radiation therapy optimization algorithms.

PubMed

Yang, Jie; Zhang, Pengcheng; Zhang, Liyuan; Shu, Huazhong; Li, Baosheng; Gui, Zhiguo

2017-01-01

In inverse treatment planning of intensity-modulated radiation therapy (IMRT), the objective function is typically the sum of the weighted sub-scores, where the weights indicate the importance of the sub-scores. To obtain a high-quality treatment plan, the planner manually adjusts the objective weights using a trial-and-error procedure until an acceptable plan is reached. In this work, a new particle swarm optimization (PSO) method which can adjust the weighting factors automatically was investigated to overcome the requirement of manual adjustment, thereby reducing the workload of the human planner and contributing to the development of a fully automated planning process. The proposed optimization method consists of three steps. (i) First, a swarm of weighting factors (i.e., particles) is initialized randomly in the search space, where each particle corresponds to a global objective function. (ii) Then, a plan optimization solver is employed to obtain the optimal solution for each particle, and the values of the evaluation functions used to determine the particle's location and the population global location for the PSO are calculated based on these results. (iii) Next, the weighting factors are updated based on the particle's location and the population global location. Step (ii) is performed alternately with step (iii) until the termination condition is reached. In this method, the evaluation function is a combination of several key points on the dose volume histograms. Furthermore, a perturbation strategy - the crossover and mutation operator hybrid approach - is employed to enhance the population diversity, and two arguments are applied to the evaluation function to improve the flexibility of the algorithm. In this study, the proposed method was used to develop IMRT treatment plans involving five unequally spaced 6MV photon beams for 10 prostate cancer cases. The proposed optimization algorithm yielded high-quality plans for all of the cases, without human planner intervention. A comparison of the results with the optimized solution obtained using a similar optimization model but with human planner intervention revealed that the proposed algorithm produced optimized plans superior to that developed using the manual plan. The proposed algorithm can generate admissible solutions within reasonable computational times and can be used to develop fully automated IMRT treatment planning methods, thus reducing human planners' workloads during iterative processes. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

High-throughput microplate technique for enzymatic hydrolysis of lignocellulosic biomass.

PubMed

Chundawat, Shishir P S; Balan, Venkatesh; Dale, Bruce E

2008-04-15

Several factors will influence the viability of a biochemical platform for manufacturing lignocellulosic based fuels and chemicals, for example, genetically engineering energy crops, reducing pre-treatment severity, and minimizing enzyme loading. Past research on biomass conversion has focused largely on acid based pre-treatment technologies that fractionate lignin and hemicellulose from cellulose. However, for alkaline based (e.g., AFEX) and other lower severity pre-treatments it becomes critical to co-hydrolyze cellulose and hemicellulose using an optimized enzyme cocktail. Lignocellulosics are appropriate substrates to assess hydrolytic activity of enzyme mixtures compared to conventional unrealistic substrates (e.g., filter paper, chromogenic, and fluorigenic compounds) for studying synergistic hydrolysis. However, there are few, if any, high-throughput lignocellulosic digestibility analytical platforms for optimizing biomass conversion. The 96-well Biomass Conversion Research Lab (BCRL) microplate method is a high-throughput assay to study digestibility of lignocellulosic biomass as a function of biomass composition, pre-treatment severity, and enzyme composition. The most suitable method for delivering milled biomass to the microplate was through multi-pipetting slurry suspensions. A rapid bio-enzymatic, spectrophotometric assay was used to determine fermentable sugars. The entire procedure was automated using a robotic pipetting workstation. Several parameters that affect hydrolysis in the microplate were studied and optimized (i.e., particle size reduction, slurry solids concentration, glucan loading, mass transfer issues, and time period for hydrolysis). The microplate method was optimized for crystalline cellulose (Avicel) and ammonia fiber expansion (AFEX) pre-treated corn stover. Copyright 2008 Wiley Periodicals, Inc.

Optimism bias leads to inconclusive results - an empirical study

PubMed Central

Djulbegovic, Benjamin; Kumar, Ambuj; Magazin, Anja; Schroen, Anneke T.; Soares, Heloisa; Hozo, Iztok; Clarke, Mike; Sargent, Daniel; Schell, Michael J.

2010-01-01

Objective Optimism bias refers to unwarranted belief in the efficacy of new therapies. We assessed the impact of optimism bias on a proportion of trials that did not answer their research question successfully, and explored whether poor accrual or optimism bias is responsible for inconclusive results. Study Design Systematic review Setting Retrospective analysis of a consecutive series phase III randomized controlled trials (RCTs) performed under the aegis of National Cancer Institute Cooperative groups. Results 359 trials (374 comparisons) enrolling 150,232 patients were analyzed. 70% (262/374) of the trials generated conclusive results according to the statistical criteria. Investigators made definitive statements related to the treatment preference in 73% (273/374) of studies. Investigators’ judgments and statistical inferences were concordant in 75% (279/374) of trials. Investigators consistently overestimated their expected treatment effects, but to a significantly larger extent for inconclusive trials. The median ratio of expected over observed hazard ratio or odds ratio was 1.34 (range 0.19 – 15.40) in conclusive trials compared to 1.86 (range 1.09 – 12.00) in inconclusive studies (p<0.0001). Only 17% of the trials had treatment effects that matched original researchers’ expectations. Conclusion Formal statistical inference is sufficient to answer the research question in 75% of RCTs. The answers to the other 25% depend mostly on subjective judgments, which at times are in conflict with statistical inference. Optimism bias significantly contributes to inconclusive results. PMID:21163620

Optimism bias leads to inconclusive results-an empirical study.

PubMed

Djulbegovic, Benjamin; Kumar, Ambuj; Magazin, Anja; Schroen, Anneke T; Soares, Heloisa; Hozo, Iztok; Clarke, Mike; Sargent, Daniel; Schell, Michael J

2011-06-01

Optimism bias refers to unwarranted belief in the efficacy of new therapies. We assessed the impact of optimism bias on a proportion of trials that did not answer their research question successfully and explored whether poor accrual or optimism bias is responsible for inconclusive results. Systematic review. Retrospective analysis of a consecutive-series phase III randomized controlled trials (RCTs) performed under the aegis of National Cancer Institute Cooperative groups. Three hundred fifty-nine trials (374 comparisons) enrolling 150,232 patients were analyzed. Seventy percent (262 of 374) of the trials generated conclusive results according to the statistical criteria. Investigators made definitive statements related to the treatment preference in 73% (273 of 374) of studies. Investigators' judgments and statistical inferences were concordant in 75% (279 of 374) of trials. Investigators consistently overestimated their expected treatment effects but to a significantly larger extent for inconclusive trials. The median ratio of expected and observed hazard ratio or odds ratio was 1.34 (range: 0.19-15.40) in conclusive trials compared with 1.86 (range: 1.09-12.00) in inconclusive studies (P<0.0001). Only 17% of the trials had treatment effects that matched original researchers' expectations. Formal statistical inference is sufficient to answer the research question in 75% of RCTs. The answers to the other 25% depend mostly on subjective judgments, which at times are in conflict with statistical inference. Optimism bias significantly contributes to inconclusive results. Copyright © 2011 Elsevier Inc. All rights reserved.

Multifaceted antibiotic treatment analysis of methicillin-sensitive Staphylococcus aureus bloodstream infections.

PubMed

Weber, Zhanni; Ariano, Robert; Lagacé-Wiens, Philippe; Zelenitsky, Sheryl

2016-12-01

Given the overall prevalence and poor prognosis of Staphylococcus aureus bloodstream infections (BSIs), the study of treatment strategies to improve patient outcomes is important. The aim of this study was to conduct a multifaceted antibiotic treatment analysis of methicillin-sensitive S. aureus (MSSA) BSI and to characterise optimal early antibiotic therapy (within the first 7 days of drawing the index blood culture) for this serious infection. Antibiotic selection was categorised as optimal targeted (intravenous cloxacillin or cefazolin), optimal broad (piperacillin/tazobactam or meropenem), adequate (vancomycin) or inadequate (other antibiotics or oral therapy). A TSE (timing, selection, exposure) score was developed to comprehensively characterise early antibiotic therapy, where higher points corresponded to prompt initiation, optimal antibiotic selection and longer exposure (duration). Amongst 71 cases of complicated MSSA-BSI, end-of-treatment (EOT) response (i.e. clinical cure) was improved when at least adequate antibiotic therapy was initiated within 24 h [71.7% (33/46) vs. 48.0% (12/25); P = 0.047]. Clinical cure was also more likely when therapy included ≥4 days of optimal targeted antibiotics within the first 7 days [74.4% (29/39) vs. 50.0% (16/32); P = 0.03]. The TSE score was an informative index of early antibiotic therapy, with EOT cure documented in 72.0% (36/50) compared with 42.9% (9/21) of cases with scores above and below 15.2, respectively (P = 0.02). In multivariable analysis, lower Charlson comorbidity index, presence of BSI on admission, and optimising early antibiotic therapy, as described above, were associated with clinical cure in patients with MSSA-BSI. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Brain imaging predictors and the international study to predict optimized treatment for depression: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Approximately 50% of patients with major depressive disorder (MDD) do not respond optimally to antidepressant treatments. Given this is a large proportion of the patient population, pretreatment tests that predict which patients will respond to which types of treatment could save time, money and patient burden. Brain imaging offers a means to identify treatment predictors that are grounded in the neurobiology of the treatment and the pathophysiology of MDD. Methods/Design The international Study to Predict Optimized Treatment in Depression is a multi-center, parallel model, randomized clinical trial with an embedded imaging sub-study to identify such predictors. We focus on brain circuits implicated in major depressive disorder and its treatment. In the full trial, depressed participants are randomized to receive escitalopram, sertraline or venlafaxine-XR (open-label). They are assessed using standardized multiple clinical, cognitive-emotional behavioral, electroencephalographic and genetic measures at baseline and at eight weeks post-treatment. Overall, 2,016 depressed participants (18 to 65 years old) will enter the study, of whom a target of 10% will be recruited into the brain imaging sub-study (approximately 67 participants in each treatment arm) and 67 controls. The imaging sub-study is conducted at the University of Sydney and at Stanford University. Structural studies include high-resolution three-dimensional T1-weighted, diffusion tensor and T2/Proton Density scans. Functional studies include standardized functional magnetic resonance imaging (MRI) with three cognitive tasks (auditory oddball, a continuous performance task, and Go-NoGo) and two emotion tasks (unmasked conscious and masked non-conscious emotion processing tasks). After eight weeks of treatment, the functional MRI is repeated with the above tasks. We will establish the methods in the first 30 patients. Then we will identify predictors in the first half (n = 102), test the findings in the second half, and then extend the analyses to the total sample. Trial registration International Study to Predict Optimized Treatment - in Depression (iSPOT-D). ClinicalTrials.gov, NCT00693849. PMID:23866851

Brain imaging predictors and the international study to predict optimized treatment for depression: study protocol for a randomized controlled trial.

PubMed

Grieve, Stuart M; Korgaonkar, Mayuresh S; Etkin, Amit; Harris, Anthony; Koslow, Stephen H; Wisniewski, Stephen; Schatzberg, Alan F; Nemeroff, Charles B; Gordon, Evian; Williams, Leanne M

2013-07-18

Approximately 50% of patients with major depressive disorder (MDD) do not respond optimally to antidepressant treatments. Given this is a large proportion of the patient population, pretreatment tests that predict which patients will respond to which types of treatment could save time, money and patient burden. Brain imaging offers a means to identify treatment predictors that are grounded in the neurobiology of the treatment and the pathophysiology of MDD. The international Study to Predict Optimized Treatment in Depression is a multi-center, parallel model, randomized clinical trial with an embedded imaging sub-study to identify such predictors. We focus on brain circuits implicated in major depressive disorder and its treatment. In the full trial, depressed participants are randomized to receive escitalopram, sertraline or venlafaxine-XR (open-label). They are assessed using standardized multiple clinical, cognitive-emotional behavioral, electroencephalographic and genetic measures at baseline and at eight weeks post-treatment. Overall, 2,016 depressed participants (18 to 65 years old) will enter the study, of whom a target of 10% will be recruited into the brain imaging sub-study (approximately 67 participants in each treatment arm) and 67 controls. The imaging sub-study is conducted at the University of Sydney and at Stanford University. Structural studies include high-resolution three-dimensional T1-weighted, diffusion tensor and T2/Proton Density scans. Functional studies include standardized functional magnetic resonance imaging (MRI) with three cognitive tasks (auditory oddball, a continuous performance task, and Go-NoGo) and two emotion tasks (unmasked conscious and masked non-conscious emotion processing tasks). After eight weeks of treatment, the functional MRI is repeated with the above tasks. We will establish the methods in the first 30 patients. Then we will identify predictors in the first half (n=102), test the findings in the second half, and then extend the analyses to the total sample. International Study to Predict Optimized Treatment--in Depression (iSPOT-D). ClinicalTrials.gov, NCT00693849.

Backward bifurcation and optimal control of Plasmodium Knowlesi malaria

NASA Astrophysics Data System (ADS)

Abdullahi, Mohammed Baba; Hasan, Yahya Abu; Abdullah, Farah Aini

2014-07-01

A deterministic model for the transmission dynamics of Plasmodium Knowlesi malaria with direct transmission is developed. The model is analyzed using dynamical system techniques and it shows that the backward bifurcation occurs for some range of parameters. The model is extended to assess the impact of time dependent preventive (biological and chemical control) against the mosquitoes and vaccination for susceptible humans, while treatment for infected humans. The existence of optimal control is established analytically by the use of optimal control theory. Numerical simulations of the problem, suggest that applying the four control measure can effectively reduce if not eliminate the spread of Plasmodium Knowlesi in a community.

A difference-matrix metaheuristic for intensity map segmentation in step-and-shoot IMRT delivery.

PubMed

Gunawardena, Athula D A; D'Souza, Warren D; Goadrich, Laura D; Meyer, Robert R; Sorensen, Kelly J; Naqvi, Shahid A; Shi, Leyuan

2006-05-21

At an intermediate stage of radiation treatment planning for IMRT, most commercial treatment planning systems for IMRT generate intensity maps that describe the grid of beamlet intensities for each beam angle. Intensity map segmentation of the matrix of individual beamlet intensities into a set of MLC apertures and corresponding intensities is then required in order to produce an actual radiation delivery plan for clinical use. Mathematically, this is a very difficult combinatorial optimization problem, especially when mechanical limitations of the MLC lead to many constraints on aperture shape, and setup times for apertures make the number of apertures an important factor in overall treatment time. We have developed, implemented and tested on clinical cases a metaheuristic (that is, a method that provides a framework to guide the repeated application of another heuristic) that efficiently generates very high-quality (low aperture number) segmentations. Our computational results demonstrate that the number of beam apertures and monitor units in the treatment plans resulting from our approach is significantly smaller than the corresponding values for treatment plans generated by the heuristics embedded in a widely use commercial system. We also contrast the excellent results of our fast and robust metaheuristic with results from an 'exact' method, branch-and-cut, which attempts to construct optimal solutions, but, within clinically acceptable time limits, generally fails to produce good solutions, especially for intensity maps with more than five intensity levels. Finally, we show that in no instance is there a clinically significant change of quality associated with our more efficient plans.

Oxytocin Treatment, Circuitry, and Autism: A Critical Review of the Literature Placing Oxytocin Into the Autism Context.

PubMed

Guastella, Adam J; Hickie, Ian B

2016-02-01

Observed impairment in reciprocal social interaction is a diagnostic hallmark of autism spectrum disorders. There is no effective medical treatment for these problems. Psychological treatments remain costly, time intensive, and developmentally sensitive for efficacy. In this review, we explore the potential of oxytocin-based therapies for social impairments in autism. Evidence shows that acute oxytocin administration improves numerous markers critical to the social circuitry underlying social deficits in autism. Oxytocin may optimize these circuits and enhance reward, motivation, and learning to improve therapeutic outcomes. Despite this, the current evidence of therapeutic benefit from extended oxytocin treatment remains very limited. We highlight complexity in crossing from the laboratory to the autism clinical setting in evaluation of this therapeutic. We discuss a clinical trial approach that provides optimal opportunity for therapeutic response by using personalized methods that better target specific circuitry to define who will obtain benefit, at what stage of development, and the optimal delivery approach for circuitry manipulation. For the autism field, the therapeutic challenges will be resolved by a range of treatment strategies, including greater focus on specific interventions, such as oxytocin, that have a strong basis in the fundamental neurobiology of social behavior. More sophisticated and targeted clinical trials utilizing such approaches are now required, placing oxytocin into the autism context. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Respiratory Plasticity Following Spinal Injury: Role of Chloride-Dependent Inhibitory Neurotransmission

DTIC Science & Technology

2015-10-01

compensation in unanesthetized rats. 15. SUBJECT TERMS Spinal Injury, Treatment , Intermittent hypoxia, rats, spontaneous recovery, induced recovery, rAIH, PKC...After immunofluoresence for KCC1/NKCC2, confocal z-stacks of cholera - toxin back-labeled phrenic motor neurons were made ipsilateral and contralateral...enhanced excitatory neurotransmission) also did not pan out, we suspect that the timing of rAIH treatment in our studies was not optimal. Indeed

Osteochondral injuries of the foot and ankle.

PubMed

Frost, Andrew; Roach, Richard

2009-06-01

Osteochondral injuries commonly affect the ankle joint and involve the dome of the talus. This article describes the etiology and pathogenesis of these injuries. Their clinical presentation is described and advice is given on how to diagnose and investigate suspected osteochondral injuries. The various treatment options currently available are briefly reviewed. There is some attempt made to give consensus on optimal treatment of this condition at the present time.

Group consensus peer review in radiation oncology: commitment to quality.

PubMed

Duggar, W Neil; Bhandari, Rahul; Yang, Chunli Claus; Vijayakumar, Srinivasan

2018-03-27

Peer review, especially prospective peer review, has been supported by professional organizations as an important element in optimal Radiation Oncology practice based on its demonstration of efficacy at detecting and preventing errors prior to patient treatment. Implementation of peer review is not without barriers, but solutions do exist to mitigate or eliminate some of those barriers. Peer review practice at our institution involves three key elements: new patient conference, treatment planning conference, and chart rounds. The treatment planning conference is an adaptation of the group consensus peer review model from radiology which utilizes a group of peers reviewing each treatment plan prior to implementation. The peer group in radiation oncology includes Radiation Oncologists, Physician Residents, Medical Physicists, Dosimetrists, and Therapists. Thus, technical and clinical aspects of each plan are evaluated simultaneously. Though peer review is held in high regard in Radiation Oncology, many barriers commonly exist preventing optimal implementation such as time intensiveness, repetition, and distraction from clinic time with patients. Through the use of automated review tools and commitment by individuals and administration in regards to staffing, scheduling, and responsibilities, these barriers have been mitigated to implement this Group Consensus Peer Review model into a Radiation Oncology Clinic. A Group Consensus Peer Review model has been implemented with strategies to address common barriers to effective and efficient peer review.

Optimization of chitosan treatments for managing microflora in lettuce seeds without affecting germination.

PubMed

Goñi, M G; Moreira, M R; Viacava, G E; Roura, S I

2013-01-30

Many studies have focused on seed decontamination but no one has been capable of eliminating all pathogenic bacteria. Two objectives were followed. First, to assess the in vitro antimicrobial activity of chitosan against: (a) Escherichia coli O157:H7, (b) native microflora of lettuce and (c) native microflora of lettuce seeds. Second, to evaluate the efficiency of chitosan on reducing microflora on lettuce seeds. The overall goal was to find a combination of contact time and chitosan concentration that reduces the microflora of lettuce seeds, without affecting germination. After treatment lettuce seeds presented no detectable microbial counts (<10(2)CFU/50 seeds) for all populations. Moreover, chitosan eliminated E. coli. Regardless of the reduction in the microbial load, a 90% reduction on germination makes imbibition with chitosan, uneconomical. Subsequent treatments identified the optimal treatment as 10 min contact with a 10 g/L chitosan solution, which maintained the highest germination percentage. Copyright © 2012 Elsevier Ltd. All rights reserved.

Biological-based and physical-based optimization for biological evaluation of prostate patient's plans

NASA Astrophysics Data System (ADS)

Sukhikh, E.; Sheino, I.; Vertinsky, A.

2017-09-01

Modern modalities of radiation treatment therapy allow irradiation of the tumor to high dose values and irradiation of organs at risk (OARs) to low dose values at the same time. In this paper we study optimal radiation treatment plans made in Monaco system. The first aim of this study was to evaluate dosimetric features of Monaco treatment planning system using biological versus dose-based cost functions for the OARs and irradiation targets (namely tumors) when the full potential of built-in biological cost functions is utilized. The second aim was to develop criteria for the evaluation of radiation dosimetry plans for patients based on the macroscopic radiobiological criteria - TCP/NTCP. In the framework of the study four dosimetric plans were created utilizing the full extent of biological and physical cost functions using dose calculation-based treatment planning for IMRT Step-and-Shoot delivery of stereotactic body radiation therapy (SBRT) in prostate case (5 fractions per 7 Gy).

Optimization of multi-stage dynamic treatment regimes utilizing accumulated data.

PubMed

Huang, Xuelin; Choi, Sangbum; Wang, Lu; Thall, Peter F

2015-11-20

In medical therapies involving multiple stages, a physician's choice of a subject's treatment at each stage depends on the subject's history of previous treatments and outcomes. The sequence of decisions is known as a dynamic treatment regime or treatment policy. We consider dynamic treatment regimes in settings where each subject's final outcome can be defined as the sum of longitudinally observed values, each corresponding to a stage of the regime. Q-learning, which is a backward induction method, is used to first optimize the last stage treatment then sequentially optimize each previous stage treatment until the first stage treatment is optimized. During this process, model-based expectations of outcomes of late stages are used in the optimization of earlier stages. When the outcome models are misspecified, bias can accumulate from stage to stage and become severe, especially when the number of treatment stages is large. We demonstrate that a modification of standard Q-learning can help reduce the accumulated bias. We provide a computational algorithm, estimators, and closed-form variance formulas. Simulation studies show that the modified Q-learning method has a higher probability of identifying the optimal treatment regime even in settings with misspecified models for outcomes. It is applied to identify optimal treatment regimes in a study for advanced prostate cancer and to estimate and compare the final mean rewards of all the possible discrete two-stage treatment sequences. Copyright © 2015 John Wiley & Sons, Ltd.

Surgical Treatment for Chronic Pancreatitis: Past, Present, and Future

PubMed Central

Welte, Maria; Izbicki, Jakob R.; Bachmann, Kai

2017-01-01

The pancreas was one of the last explored organs in the human body. The first surgical experiences were made before fully understanding the function of the gland. Surgical procedures remained less successful until the discovery of insulin, blood groups, and finally the possibility of blood donation. Throughout the centuries, the surgical approach went from radical resections to minimal resections or only drainage of the gland in comparison to an adequate resection combined with drainage procedures. Today, the well-known and standardized procedures are considered as safe due to the high experience of operating surgeons, the centering of pancreatic surgery in specialized centers, and optimized perioperative treatment. Although surgical procedures have become safer and more efficient than ever, the overall perioperative morbidity after pancreatic surgery remains high and management of postoperative complications stagnates. Current research focuses on the prevention of complications, optimizing the patient's general condition preoperatively and finding the appropriate timing for surgical treatment. PMID:28819358

[Oral thyroxine treatment: towards an individually tailored dose].

PubMed

Centanni, Marco; Franchi, Antonella; Santaguida, Maria Giulia; Virili, Camilla; Nardo, Serena; Gargano, Lucilla

2007-09-01

Sodium levothyroxine is one of the most prescribed drugs all over the world. Oral thyroxine treatment is often used lifelong and the search for optimal daily dose may be a challenge for the physician. Patient age and compliance to prescribed regimen are in fact relevant features to achieve therapeutic goal. Also, the absorption of thyroxine is not a linear function of the ingested dose being sensitive to several interferences. Inaccurate administration modality, thyroxine interaction with different drugs, pregnancy, and malabsorption are all possible causes of increased need for thyroxine. Important and simple evidences are now available to improve the accuracy of drug administration and optimize the treatment. In fact, recent evidence pointed out the role of gastric acid secretion on the subsequent intestinal absorption of thyroxine in relation with the timing of food ingestion as well as with pH impairment associated to frequent gastric disorders like Helicobacter pylori infection and gastric atrophy.

Could Wearable and Mobile Technology Improve the Management of Essential Tremor?

PubMed Central

Daneault, Jean-Francois

2018-01-01

Essential tremor (ET) is the most common movement disorder. Individuals exhibit postural and kinetic tremor that worsens over time and patients may also exhibit other motor and non-motor symptoms. While millions of people are affected by this disorder worldwide, several barriers impede an optimal clinical management of symptoms. In this paper, we discuss the impact of ET on patients and review major issues to the optimal management of ET; from the side-effects and limited efficacy of current medical treatments to the limited number of people who seek treatment for their tremor. Then, we propose seven different areas within which mobile and wearable technology may improve the clinical management of ET and review the current state of research in these areas. PMID:29725318

Effects of hydroformylation treatment on the storage time and blood group antigen expressions of reagent red blood cells.

PubMed

Yu, Yang; Sun, Xiaolin; Guan, Xiaozhen; Zhang, Xiaojuan; Ma, Chunya; Chen, Linfeng; Wang, Deqing

2014-06-01

To evaluate the effects of hydroformylation treatment on the storage time and blood group antigen expressions of reagent red blood cells (RBCs). RBCs from healthy donors were treated by using various final concentrations of paraformaldehyde (0.01%, 0.02%, 0.05%, 0.1%, 0.2%, 0.5% and 1.0%) and glutaraldehyde (0.01%, 0.025%, 0.05%, 0.1%, 0.2%, 0.5% and 1.0%), and one aliquot was used as control (untreated with aldehydes). Supernatant free hemoglobin (FHb) levels in all groups stored at 4 °C were detected every week, and the optimal procedure was selected. Expression of blood group antigens on RBCs treated by the optimal procedure was determined, and the total scores of blood group antigens were calculated. 0.2%, 0.5% and 1.0% Glutaraldehyde groups were ruled out directly due to serious crosslinking and aggregation of RBCs. As the extension of time, FHb levels in other 11 groups gradually increased (p<0.01 or p<0.05). FHb level in 0.025% glutaraldehyde group was significantly lower than that in other groups after 13 weeks (p<0.01), and the antigen strength of Fy(b), Jk(b), and Le(b) decreased slightly compared with those before treatment and storage (p<0.05), and there was no significant change for antigen strength of A, B, D, C, E, c, e, M, N, S, s, k, P1, Fy(a), Jk(a), and Le(a) (p>0.05). 0.025% Glutaraldehyde treatment can provide optimal protection for the membrane of RBCs and keep hemolysis at a low level after 13 weeks storage, and the majority of blood group antigen systems are not significantly affected, and the slight decline of Fy(b), Jk(b), and Le(b) antigen strength was acceptable for classical serological tests. Copyright © 2014 Elsevier Ltd. All rights reserved.

Quantifying pathogen risks associated with potable reuse: A risk assessment case study for Cryptosporidium.

PubMed

Amoueyan, Erfaneh; Ahmad, Sajjad; Eisenberg, Joseph N S; Pecson, Brian; Gerrity, Daniel

2017-08-01

This study evaluated the reliability and equivalency of three different potable reuse paradigms: (1) surface water augmentation via de facto reuse with conventional wastewater treatment; (2) surface water augmentation via planned indirect potable reuse (IPR) with ultrafiltration, pre-ozone, biological activated carbon (BAC), and post-ozone; and (3) direct potable reuse (DPR) with ultrafiltration, ozone, BAC, and UV disinfection. A quantitative microbial risk assessment (QMRA) was performed to (1) quantify the risk of infection from Cryptosporidium oocysts; (2) compare the risks associated with different potable reuse systems under optimal and sub-optimal conditions; and (3) identify critical model/operational parameters based on sensitivity analyses. The annual risks of infection associated with the de facto and planned IPR systems were generally consistent with those of conventional drinking water systems [mean of (9.4 ± 0.3) × 10 -5 to (4.5 ± 0.1) × 10 -4 ], while DPR was clearly superior [mean of (6.1 ± 67) × 10 -9 during sub-optimal operation]. Because the advanced treatment train in the planned IPR system was highly effective in reducing Cryptosporidium concentrations, the associated risks were generally dominated by the pathogen loading already present in the surface water. As a result, risks generally decreased with higher recycled water contributions (RWCs). Advanced treatment failures were generally inconsequential either due to the robustness of the advanced treatment train (i.e., DPR) or resiliency provided by the environmental buffer (i.e., planned IPR). Storage time in the environmental buffer was important for the de facto reuse system, and the model indicated a critical storage time of approximately 105 days. Storage times shorter than the critical value resulted in significant increases in risk. The conclusions from this study can be used to inform regulatory decision making and aid in the development of design or operational criteria for IPR and DPR systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

LINE-1 methylation in plasma DNA as a biomarker of activity of DNA methylation inhibitors in patients with solid tumors.

PubMed

Aparicio, Ana; North, Brittany; Barske, Lindsey; Wang, Xuemei; Bollati, Valentina; Weisenberger, Daniel; Yoo, Christine; Tannir, Nizar; Horne, Erin; Groshen, Susan; Jones, Peter; Yang, Allen; Issa, Jean-Pierre

2009-04-01

Multiple clinical trials are investigating the use of the DNA methylation inhibitors azacitidine and decitabine for the treatment of solid tumors. Clinical trials in hematological malignancies have shown that optimal activity does not occur at their maximum tolerated doses but selection of an optimal biological dose and schedule for use in solid tumor patients is hampered by the difficulty of obtaining tumor tissue to measure their activity. Here we investigate the feasibility of using plasma DNA to measure the demethylating activity of the DNA methylation inhibitors in patients with solid tumors. We compared four methods to measure LINE-1 and MAGE-A1 promoter methylation in T24 and HCT116 cancer cells treated with decitabine treatment and selected Pyrosequencing for its greater reproducibility and higher signal to noise ratio. We then obtained DNA from plasma, peripheral blood mononuclear cells, buccal mucosa cells and saliva from ten patients with metastatic solid tumors at two different time points, without any intervening treatment. DNA methylation measurements were not significantly different between time point 1 and time point 2 in patient samples. We conclude that measurement of LINE-1 methylation in DNA extracted from the plasma of patients with advanced solid tumors, using Pyrosequencing, is feasible and has low within patient variability. Ongoing studies will determine whether changes in LINE-1 methylation in plasma DNA occur as a result of treatment with DNA methylation inhibitors and parallel changes in tumor tissue DNA.

On the importance of prompt oxygen changes for hypofractionated radiation treatments.

PubMed

Kissick, Michael; Campos, David; van der Kogel, Albert; Kimple, Randall

2013-10-21

This discussion is motivated by observations of prompt oxygen changes occurring prior to a significant number of cancer cells dying (permanently stopping their metabolic activity) from therapeutic agents like large doses of ionizing radiation. Such changes must be from changes in the vasculature that supplies the tissue or from the metabolic changes in the tissue itself. An adapted linear-quadratic treatment is used to estimate the cell survival variation magnitudes from repair and reoxygenation from a two-fraction treatment in which the second fraction would happen prior to significant cell death from the first fraction, in the large fraction limit. It is clear the effects of oxygen changes are likely to be the most significant factor for hypofractionation because of large radiation doses. It is a larger effect than repair. Optimal dose timing should be determined by the peak oxygen timing. A call is made to prioritize near real time measurements of oxygen dynamics in tumors undergoing hypofractionated treatments in order to make these treatments adaptable and patient-specific.

Machine Learning Approach to Optimizing Combined Stimulation and Medication Therapies for Parkinson's Disease.

PubMed

Shamir, Reuben R; Dolber, Trygve; Noecker, Angela M; Walter, Benjamin L; McIntyre, Cameron C

2015-01-01

Deep brain stimulation (DBS) of the subthalamic region is an established therapy for advanced Parkinson's disease (PD). However, patients often require time-intensive post-operative management to balance their coupled stimulation and medication treatments. Given the large and complex parameter space associated with this task, we propose that clinical decision support systems (CDSS) based on machine learning algorithms could assist in treatment optimization. Develop a proof-of-concept implementation of a CDSS that incorporates patient-specific details on both stimulation and medication. Clinical data from 10 patients, and 89 post-DBS surgery visits, were used to create a prototype CDSS. The system was designed to provide three key functions: (1) information retrieval; (2) visualization of treatment, and; (3) recommendation on expected effective stimulation and drug dosages, based on three machine learning methods that included support vector machines, Naïve Bayes, and random forest. Measures of medication dosages, time factors, and symptom-specific pre-operative response to levodopa were significantly correlated with post-operative outcomes (P < 0.05) and their effect on outcomes was of similar magnitude to that of DBS. Using those results, the combined machine learning algorithms were able to accurately predict 86% (12/14) of the motor improvement scores at one year after surgery. Using patient-specific details, an appropriately parameterized CDSS could help select theoretically optimal DBS parameter settings and medication dosages that have potential to improve the clinical management of PD patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Optimization of conditions for isolation of high quality chitin from shrimp processing raw byproducts using response surface methodology and its characterization.

PubMed

Nidheesh, T; Suresh, P V

2015-06-01

Chitin is one of the most abundant bioactive biopolymer on earth. It is commercially extracted from seafood processing crustacean shell byproducts by harsh thermochemical treatments. The extraction conditions, the source and pretreatment of raw material significantly affect its quality and bioactivity. In this investigation response surface methodology (RSM) has been applied to optimize and evaluate the interaction of variables for extraction of high quality chitin from shrimp processing raw byproducts. Variables such as, concentration of HCl (%, v/v) 4.5 (for wet) and 4.9 (for dry), reaction time 3 h, solid liquid ratio of HCl (w/v) 1:5.5 (for wet) and 1:7.9 (for dry) with two treatments achieved >98 % demineralization of shrimp byproduct. Variables such as, concentration of NaOH 3.6 % (w/v), reaction time 2.5 h, temperature 69.0 ± 1 °C, solid liquid ratio of NaOH 7.4 (w/v) and two treatments accomplished >98 % deproteinization of demineralized byproducts. Significant (p ≤ 0.05-0.001) interactive effects were observed between different variables. Chitin obtained in these conditions had residual content (%, w/w) of ash <0.4 and protein <0.8 and the degree of N-acetylation was >93 % with purity of >98 %. In conclusion, the optimized conditions by RSM can be applied for large scale preparation of high quality chitin from raw shrimp byproduct.

Origins of timed cancer treatment: early marker rhythm-guided individualized chronochemotherapy*

PubMed Central

Halberg, Franz; Prem, Konald; Halberg, Francine; Norman, Catherine; Cornélissen, Germaine

2008-01-01

A 21-year old patient who presented in 1973 with a rare and highly malignant ovarian endodermal sinus tumor with spillage into the peritoneal cavity is alive and well today after receiving chronochemotherapy. During the first four courses of treatment, medications were given at different circadian stages. Complete blood counts and marker variables such as mood, vigor, nausea, and temperature were monitored around the clock and analyzed by cosinor to seek times of highest tolerance. Remaining treatment courses were administered at a time corresponding to the patient's best drug tolerance, rather than extrapolating the timing of optimal cyclophosphamide administration from also-implemented parallel laboratory studies on mice. Notwithstanding remaining hurdles in bringing chronochemotherapy to the clinic for routine care, merits of marker rhythm-guided chronotherapy documented in this and other case reports have led to the doubling of the two-year disease-free survival of patients with large perioral tumors in a clinical trial. PMID:17228525

A temperature-based feedback control system for electromagnetic phased-array hyperthermia: theory and simulation.

PubMed

Kowalski, M E; Jin, J M

2003-03-07

A hybrid proportional-integral-in-time and cost-minimizing-in-space feedback control system for electromagnetic, deep regional hyperthermia is proposed. The unique features of this controller are that (1) it uses temperature, not specific absorption rate, as the criterion for selecting the relative phases and amplitudes with which to drive the electromagnetic phased-array used for hyperthermia and (2) it requires on-line computations that are all deterministic in duration. The former feature, in addition to optimizing the treatment directly on the basis of a clinically relevant quantity, also allows the controller to sense and react to time- and temperature-dependent changes in local blood perfusion rates and other factors that can significantly impact the temperature distribution quality of the delivered treatment. The latter feature makes it feasible to implement the scheme on-line in a real-time feedback control loop. This is in sharp contrast to other temperature optimization techniques proposed in the literature that generally involve an iterative approximation that cannot be guaranteed to terminate in a fixed amount of computational time. An example of its application is presented to illustrate the properties and demonstrate the capability of the controller to sense and compensate for local, time-dependent changes in blood perfusion rates.

The impact of prostate cancer diagnosis and treatment decision-making on health-related quality of life before treatment onset.

PubMed

Cuypers, Maarten; Lamers, Romy E D; Cornel, Erik B; van de Poll-Franse, Lonneke V; de Vries, Marieke; Kil, Paul J M

2018-04-01

The objective of this study is to test if patients' health-related quality of life (HRQoL) declines after prostate biopsy to detect Pca, and after subsequent treatment decision-making in case Pca is confirmed, and to test whether personality state and traits are associated with these potential changes in HRQoL. Patients who were scheduled for prostate biopsy to detect Pca (N = 377) filled out a baseline questionnaire about HRQoL (EORTC QLQ-C30 and PR25), "big five" personality traits (BFI-10), optimism (LOT-r), and self-efficacy (Decision Self-efficacy Scale) (t0). Patients with confirmed Pca (N = 126) filled out a follow-up questionnaire on HRQoL within 2 weeks after treatment was chosen but had not yet started (t1). HRQoL declined between t0 and t1, reflected in impaired role and cognitive functioning, and elevated fatigue, constipation, and prostate-specific symptoms. Sexual activity and functioning improved. Baseline HRQoL scores were unrelated to the selection of a particular treatment, but for patients who chose a curative treatment, post-decision HRQoL showed a greater decline compared to patients who chose active surveillance. Optimism was associated with HRQoL at baseline; decisional self-efficacy was positively associated with HRQoL at follow-up. No associations between HRQoL and the "big five" personality traits were found. Patients who have undergone prostate biopsy and treatment decision-making for Pca experience a decline in HRQoL. Choosing treatment with a curative intent was associated with greater decline in HRQoL. Interventions aimed at optimism and decision self-efficacy could be helpful to reduce HRQoL impairment around the time of prostate biopsy and treatment decision-making.

Multi-GPU configuration of 4D intensity modulated radiation therapy inverse planning using global optimization

NASA Astrophysics Data System (ADS)

Hagan, Aaron; Sawant, Amit; Folkerts, Michael; Modiri, Arezoo

2018-01-01

We report on the design, implementation and characterization of a multi-graphic processing unit (GPU) computational platform for higher-order optimization in radiotherapy treatment planning. In collaboration with a commercial vendor (Varian Medical Systems, Palo Alto, CA), a research prototype GPU-enabled Eclipse (V13.6) workstation was configured. The hardware consisted of dual 8-core Xeon processors, 256 GB RAM and four NVIDIA Tesla K80 general purpose GPUs. We demonstrate the utility of this platform for large radiotherapy optimization problems through the development and characterization of a parallelized particle swarm optimization (PSO) four dimensional (4D) intensity modulated radiation therapy (IMRT) technique. The PSO engine was coupled to the Eclipse treatment planning system via a vendor-provided scripting interface. Specific challenges addressed in this implementation were (i) data management and (ii) non-uniform memory access (NUMA). For the former, we alternated between parameters over which the computation process was parallelized. For the latter, we reduced the amount of data required to be transferred over the NUMA bridge. The datasets examined in this study were approximately 300 GB in size, including 4D computed tomography images, anatomical structure contours and dose deposition matrices. For evaluation, we created a 4D-IMRT treatment plan for one lung cancer patient and analyzed computation speed while varying several parameters (number of respiratory phases, GPUs, PSO particles, and data matrix sizes). The optimized 4D-IMRT plan enhanced sparing of organs at risk by an average reduction of 26% in maximum dose, compared to the clinical optimized IMRT plan, where the internal target volume was used. We validated our computation time analyses in two additional cases. The computation speed in our implementation did not monotonically increase with the number of GPUs. The optimal number of GPUs (five, in our study) is directly related to the hardware specifications. The optimization process took 35 min using 50 PSO particles, 25 iterations and 5 GPUs.

Multi-GPU configuration of 4D intensity modulated radiation therapy inverse planning using global optimization.

PubMed

Hagan, Aaron; Sawant, Amit; Folkerts, Michael; Modiri, Arezoo

2018-01-16

We report on the design, implementation and characterization of a multi-graphic processing unit (GPU) computational platform for higher-order optimization in radiotherapy treatment planning. In collaboration with a commercial vendor (Varian Medical Systems, Palo Alto, CA), a research prototype GPU-enabled Eclipse (V13.6) workstation was configured. The hardware consisted of dual 8-core Xeon processors, 256 GB RAM and four NVIDIA Tesla K80 general purpose GPUs. We demonstrate the utility of this platform for large radiotherapy optimization problems through the development and characterization of a parallelized particle swarm optimization (PSO) four dimensional (4D) intensity modulated radiation therapy (IMRT) technique. The PSO engine was coupled to the Eclipse treatment planning system via a vendor-provided scripting interface. Specific challenges addressed in this implementation were (i) data management and (ii) non-uniform memory access (NUMA). For the former, we alternated between parameters over which the computation process was parallelized. For the latter, we reduced the amount of data required to be transferred over the NUMA bridge. The datasets examined in this study were approximately 300 GB in size, including 4D computed tomography images, anatomical structure contours and dose deposition matrices. For evaluation, we created a 4D-IMRT treatment plan for one lung cancer patient and analyzed computation speed while varying several parameters (number of respiratory phases, GPUs, PSO particles, and data matrix sizes). The optimized 4D-IMRT plan enhanced sparing of organs at risk by an average reduction of [Formula: see text] in maximum dose, compared to the clinical optimized IMRT plan, where the internal target volume was used. We validated our computation time analyses in two additional cases. The computation speed in our implementation did not monotonically increase with the number of GPUs. The optimal number of GPUs (five, in our study) is directly related to the hardware specifications. The optimization process took 35 min using 50 PSO particles, 25 iterations and 5 GPUs.

Optimal control of HIV/AIDS dynamic: Education and treatment

NASA Astrophysics Data System (ADS)

Sule, Amiru; Abdullah, Farah Aini

2014-07-01

A mathematical model which describes the transmission dynamics of HIV/AIDS is developed. The optimal control representing education and treatment for this model is explored. The existence of optimal Control is established analytically by the use of optimal control theory. Numerical simulations suggest that education and treatment for the infected has a positive impact on HIV/AIDS control.

Optimization of a LSO-Based Detector Module for Time-of-Flight PET

NASA Astrophysics Data System (ADS)

Moses, W. W.; Janecek, M.; Spurrier, M. A.; Szupryczynski, P.; Choong, W.-S.; Melcher, C. L.; Andreaco, M.

2010-06-01

We have explored methods for optimizing the timing resolution of an LSO-based detector module for a single-ring, “demonstration” time-of-flight PET camera. By maximizing the area that couples the scintillator to the PMT and minimizing the average path length that the scintillation photons travel, a single detector timing resolution of 218 ps fwhm is measured, which is considerably better than the 385 ps fwhm obtained by commercial LSO or LYSO TOF detector modules. We explored different surface treatments (saw-cut, mechanically polished, and chemically etched) and reflector materials (Teflon tape, ESR, Lumirror, Melinex, white epoxy, and white paint), and found that for our geometry, a chemically etched surface had 5% better timing resolution than the saw-cut or mechanically polished surfaces, and while there was little dependence on the timing resolution between the various reflectors, white paint and white epoxy were a few percent better. Adding co-dopants to LSO shortened the decay time from 40 ns to 30 ns but maintained the same or higher total light output. This increased the initial photoelectron rate and so improved the timing resolution by 15%. Using photomultiplier tubes with higher quantum efficiency (blue sensitivity index of 13.5 rather than 12) improved the timing resolution by an additional 5%. By choosing the optimum surface treatment (chemically etched), reflector (white paint), LSO composition (co-doped), and PMT (13.5 blue sensitivity index), the coincidence timing resolution of our detector module was reduced from 309 ps to 220 ps fwhm.

Dispositional optimism as predictor of outcome in short- and long-term psychotherapy.

PubMed

Heinonen, Erkki; Heiskanen, Tiia; Lindfors, Olavi; Härkäpää, Kristiina; Knekt, Paul

2017-09-01

Dispositional optimism predicts various beneficial outcomes in somatic health and treatment, but has been little studied in psychotherapy. This study investigated whether an optimistic disposition differentially predicts patients' ability to benefit from short-term versus long-term psychotherapy. A total of 326 adult outpatients with mood and/or anxiety disorder were randomized into short-term (solution-focused or short-term psychodynamic) or long-term psychodynamic therapy and followed up for 3 years. Dispositional optimism was assessed by patients at baseline with the self-rated Life Orientation Test (LOT) questionnaire. Outcome was assessed at baseline and seven times during the follow-up, in terms of depressive (BDI, HDRS), anxiety (SCL-90-ANX, HARS), and general psychiatric symptoms (SCL-90-GSI), all seven follow-up points including patients' self-reports and three including interview-based measures. Lower dispositional optimism predicted faster symptom reduction in short-term than in long-term psychotherapy. Higher optimism predicted equally rapid and eventually greater benefits in long-term, as compared to short-term, psychotherapy. Weaker optimism appeared to predict sustenance of problems early in long-term therapy. Stronger optimism seems to best facilitate engaging in and benefiting from a long-term therapy process. Closer research might clarify the psychological processes responsible for these effects and help fine-tune both briefer and longer interventions to optimize treatment effectiveness for particular patients and their psychological qualities. Weaker dispositional optimism does not appear to inhibit brief therapy from effecting symptomatic recovery. Patients with weaker optimism do not seem to gain added benefits from long-term therapy, but instead may be susceptible to prolonged psychiatric symptoms in the early stages of long-term therapy. © 2016 The British Psychological Society.

[A review of progress of real-time tumor tracking radiotherapy technology based on dynamic multi-leaf collimator].

PubMed

Liu, Fubo; Li, Guangjun; Shen, Jiuling; Li, Ligin; Bai, Sen

2017-02-01

While radiation treatment to patients with tumors in thorax and abdomen is being performed, further improvement of radiation accuracy is restricted by the tumor intra-fractional motion due to respiration. Real-time tumor tracking radiation is an optimal solution to tumor intra-fractional motion. A review of the progress of real-time dynamic multi-leaf collimator(DMLC) tracking is provided in the present review, including DMLC tracking method, time lag of DMLC tracking system, and dosimetric verification.

Density-Functional Theory with Optimized Effective Potential and Self-Interaction Correction for the Double Ionization of He and Be Atoms

NASA Astrophysics Data System (ADS)

Heslar, John; Telnov, Dmitry; Chu, Shih-I.

2012-06-01

We present a self-interaction-free (SIC) time-dependent density-functional theory (TDDFT) for the treatment of double ionization processes of many-electron systems. The method is based on the Krieger-Li-Iafrate (KLI) treatment of the optimized effective potential (OEP) theory and the incorporation of an explicit self-interaction correction (SIC) term. In the framework of the time-dependent density functional theory, we have performed 3D calculations of double ionization of He and Be atoms by strong near-infrared laser fields. We make use of the exchange-correlation potential with the integer discontinuity which improves the description of the double ionization process. We found that proper description of the double ionization requires the TDDFT exchange-correlation potential with the discontinuity with respect to the variation of the spin particle numbers (SPN) only. The results for the intensity-dependent probabilities of single and double ionization are presented and reproduce the famous ``knee'' structure.

[Impact of priming on seed germination and seedling growth of Oldenlandia diffusa under drought stress].

PubMed

Zhu, Zai-Biao; Lu, Wei-Wei; Guo, Qiao-Sheng; Cao, Ya-Yue; Feng, Shan; Ning, Zi-Jun

2014-04-01

Current study was carried out to optimize the priming condition of Oldenlandia diffusa seeds, and improve germination rate and seed vigor of 0. diffusa seeds under drought conditions. Uniform design was used to optimize the concentration and priming time of three priming materials (PEG, KNO3, GA3). Different concentrations of polyethylene glycol (PEG) was used to simulate drought stress. The seedling was cultured in 1/4 Hoagland medium for 30 d. The results showed that seed priming treatment with 366 mg x kg(-1) GA3 for 1h resulted in significant increase in germination rate, germination index, vigor, root length, plant height and biomass of O. diffusa seeds under drought stress (15% PEG), while seed priming with 3.0% KNO3 for 1 h showed little effect on germination and growth of O. diffusa seeds under drought stress. Seed priming treatment with appropriate GA3 concentration and priming time could enhance seed germination and drought resistance of O. diffusa in seedling stage.

Current concepts for chronochemotherapy of cancer.

PubMed

Laerum, O D; Smaaland, R; Abrahamsen, J F

1995-01-01

In this article, a survey on the concepts and scientific basis for applying chemotherapy against malignant tumors on a circadian schedule is given. The idea is to give the cytostatic drugs at times of the day when optimal effect on the tumor is achieved, but at the same time causing minimal toxic side effects. Following a brief description of the complexity of cancer tissue, some aspects of the present status of cancer chemotherapy in general are reviewed. Applications of chronobiology in cancer treatment are then surveyed together with possibilities to increase cytostatic doses and reduce side effects. When optimal tumor cell kill is achieved, the next step is to address the circadian aspects of normal organs, including the proliferative behavior of tissues with rapid cell renewal. Finally, the question of how regulatory mechanisms responsible for normal circadian rhythms can be interfered with is addressed. Cancer chronochemotherapy today combined with modern infusional technology is a promising field for improving cancer treatment in general and reducing side effects and is expected to make important progress in the near future.

The use of a small fenestra technique with the Fisch piston in the surgical treatment of otosclerosis.

PubMed

Pedersen, C B

1987-06-01

The modern surgical treatment of otosclerosis consists of replacement of the sound conducting function of the stapes by a prosthesis. The results obtained in 100 consecutive patients using the small fenestra technique and a 0.4 mm. Teflon and steel wire prosthesis are reported. The surgical technique is described. The hearing was improved in all patients. In 92 per cent of the patients an optimal hearing gain was found after an observation time of 1 to 4 years. Five patients required re-operation during the observation time. The small fenestra technique and the Fisch prosthesis were considered optimal in respect to technical difficulty, hearing improvement and complication rate. There was no sensorineural hearing loss in this series of patients. The absence of serious complications makes it reasonable to operate on both ears in patients with bilateral hearing loss. The results are as good in elderly people as in younger people. Therefore the operation can be offered for patients in all age groups.

Development of independent MU/treatment time verification algorithm for non-IMRT treatment planning: A clinical experience

NASA Astrophysics Data System (ADS)

Tatli, Hamza; Yucel, Derya; Yilmaz, Sercan; Fayda, Merdan

2018-02-01

The aim of this study is to develop an algorithm for independent MU/treatment time (TT) verification for non-IMRT treatment plans, as a part of QA program to ensure treatment delivery accuracy. Two radiotherapy delivery units and their treatment planning systems (TPS) were commissioned in Liv Hospital Radiation Medicine Center, Tbilisi, Georgia. Beam data were collected according to vendors' collection guidelines, and AAPM reports recommendations, and processed by Microsoft Excel during in-house algorithm development. The algorithm is designed and optimized for calculating SSD and SAD treatment plans, based on AAPM TG114 dose calculation recommendations, coded and embedded in MS Excel spreadsheet, as a preliminary verification algorithm (VA). Treatment verification plans were created by TPSs based on IAEA TRS 430 recommendations, also calculated by VA, and point measurements were collected by solid water phantom, and compared. Study showed that, in-house VA can be used for non-IMRT plans MU/TT verifications.

Computational Process Modeling for Additive Manufacturing

NASA Technical Reports Server (NTRS)

Bagg, Stacey; Zhang, Wei

2014-01-01

Computational Process and Material Modeling of Powder Bed additive manufacturing of IN 718. Optimize material build parameters with reduced time and cost through modeling. Increase understanding of build properties. Increase reliability of builds. Decrease time to adoption of process for critical hardware. Potential to decrease post-build heat treatments. Conduct single-track and coupon builds at various build parameters. Record build parameter information and QM Meltpool data. Refine Applied Optimization powder bed AM process model using data. Report thermal modeling results. Conduct metallography of build samples. Calibrate STK models using metallography findings. Run STK models using AO thermal profiles and report STK modeling results. Validate modeling with additional build. Photodiode Intensity measurements highly linear with power input. Melt Pool Intensity highly correlated to Melt Pool Size. Melt Pool size and intensity increase with power. Applied Optimization will use data to develop powder bed additive manufacturing process model.

Evaluation of the clinical usefulness of modulated arc treatment

NASA Astrophysics Data System (ADS)

Lee, Young Kyu; Jang, Hong Seok; Kim, Yeon Sil; Choi, Byung Ock; Kang, Young-Nam; Nam, Sang Hee; Park, Hyeong Wook; Kim, Shin Wook; Shin, Hun Joo; Lee, Jae Choon; Kim, Ji Na; Park, Sung Kwang; Kim, Jin Young

2015-07-01

The purpose of this study is to evaluate the clinical usefulness of modulated arc (mARC) treatment techniques. The mARC treatment plans for non-small-cell lung cancer (NSCLC) patients were made in order to verify the clinical usefulness of mARC. A pre-study was conducted to find the best plan condition for mARC treatment, and the usefulness of the mARC treatment plan was evaluated by comparing it with other Arc treatment plans such as tomotherapy and RapidArc plans. In the case of mARC, the optimal condition for the mARC plan was determined by comparing the dosimetric performance of the mARC plans developed by using various parameters, which included the photon energy (6 MV, 10 MV), the optimization point angle (6°- 10°intervals), and the total number of segments (36 - 59 segments). The best dosimetric performance of mARC was observed at a 10 MV photon energy, a point angle 6 degrees, and 59 segments. The treatment plans for the three different techniques were compared by using the following parameters: the conformity index (CI), homogeneity index (HI), the target coverage, the dose to the OARs, the number of monitor units (MU), the beam on time, and the normal tissue complication probability (NTCP). As a result, the three different treatment techniques showed similar target coverages. The mARC plan had the lowest V20 (volume of lung receiving > 20 Gy) and MU per fraction compared with both the RapidArc and the tomotherapy plans. The mARC plan reduced the beam on time as well. Therefore, the results of this study provide satisfactory evidence that the mARC technique can be considered as a useful clinical technique for radiation treatment.

Low-temperature thermal pre-treatment of municipal wastewater sludge: Process optimization and effects on solubilization and anaerobic degradation.

PubMed

Nazari, Laleh; Yuan, Zhongshun; Santoro, Domenico; Sarathy, Siva; Ho, Dang; Batstone, Damien; Xu, Chunbao Charles; Ray, Madhumita B

2017-04-15

The present study examines the relationship between the degree of solubilization and biodegradability of wastewater sludge in anaerobic digestion as a result of low-temperature thermal pre-treatment. The main effect of thermal pre-treatment is the disintegration of cell membranes and thus solubilization of organic compounds. There is an established correlation between chemical oxygen demand (COD) solubilization and temperature of thermal pre-treatment, but results of thermal pre-treatment in terms of biodegradability are not well understood. Aiming to determine the impact of low temperature treatments on biogas production, the thermal pre-treatment process was first optimized based on an experimental design study on waste activated sludge in batch mode. The optimum temperature, reaction time and pH of the process were determined to be 80 °C, 5 h and pH 10, respectively. All three factors had a strong individual effect (p < 0.001), with a significant interaction effect for temp. pH 2 (p = 0.002). Thermal pre-treatments, carried out on seven different municipal wastewater sludges at the above optimum operating conditions, produced increased COD solubilization of 18.3 ± 7.5% and VSS reduction of 27.7 ± 12.3% compared to the untreated sludges. The solubilization of proteins was significantly higher than carbohydrates. Methane produced in biochemical methane potential (BMP) tests, indicated initial higher rates (p = 0.0013) for the thermally treated samples (k hyd up to 5 times higher), although the ultimate methane yields were not significantly affected by the treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthesis of sodium lignosulphonate from oil palm empty fruit bunches's lignin

NASA Astrophysics Data System (ADS)

Prakoso, Nurcahyo Iman; Purwono, Suryo; Rochmadi

2017-03-01

Synthesis of sodium lignosulphonate have been done by using batch method. Optimation of synthesis method was achieved through this study. The study was conducted on the optimation of mass ratio of lignin to the NaHSO3 solution, the concentration of NaHSO3 solution, reaction temperature, and reaction time. Of all the treatments, it was found that the optimum mass ratio of lignin to the NaHSO3 solution, concentration of NaHSO3 solution, reaction temperature, and reaction time respectively, 0.3 M, 0.1 M 97 °C, and the reaction was carried out for 4 hours. Excellent yields and selective products were obtained (90-92%)

Impact of chronobiology on neuropathic pain treatment.

PubMed

Gilron, Ian

2016-01-01

Inflammatory pain exhibits circadian rhythmicity. Recently, a distinct diurnal pattern has been described for peripheral neuropathic conditions. This diurnal variation has several implications: advancing understanding of chronobiology may facilitate identification of new and improved treatments; developing pain-contingent strategies that maximize treatment at times of the day associated with highest pain intensity may provide optimal pain relief as well as minimize treatment-related adverse effects (e.g., daytime cognitive dysfunction); and consideration of the impact of chronobiology on pain measurement may lead to improvements in analgesic study design that will maximize assay sensitivity of clinical trials. Recent and ongoing chronobiology studies are thus expected to advance knowledge and treatment of neuropathic pain.

Probabilistic objective functions for margin-less IMRT planning

NASA Astrophysics Data System (ADS)

Bohoslavsky, Román; Witte, Marnix G.; Janssen, Tomas M.; van Herk, Marcel

2013-06-01

We present a method to implement probabilistic treatment planning of intensity-modulated radiation therapy using custom software plugins in a commercial treatment planning system. Our method avoids the definition of safety-margins by directly including the effect of geometrical uncertainties during optimization when objective functions are evaluated. Because the shape of the resulting dose distribution implicitly defines the robustness of the plan, the optimizer has much more flexibility than with a margin-based approach. We expect that this added flexibility helps to automatically strike a better balance between target coverage and dose reduction for surrounding healthy tissue, especially for cases where the planning target volume overlaps organs at risk. Prostate cancer treatment planning was chosen to develop our method, including a novel technique to include rotational uncertainties. Based on population statistics, translations and rotations are simulated independently following a marker-based IGRT correction strategy. The effects of random and systematic errors are incorporated by first blurring and then shifting the dose distribution with respect to the clinical target volume. For simplicity and efficiency, dose-shift invariance and a rigid-body approximation are assumed. Three prostate cases were replanned using our probabilistic objective functions. To compare clinical and probabilistic plans, an evaluation tool was used that explicitly incorporates geometric uncertainties using Monte-Carlo methods. The new plans achieved similar or better dose distributions than the original clinical plans in terms of expected target coverage and rectum wall sparing. Plan optimization times were only about a factor of two higher than in the original clinical system. In conclusion, we have developed a practical planning tool that enables margin-less probability-based treatment planning with acceptable planning times, achieving the first system that is feasible for clinical implementation.

O2 Plasma Etching and Antistatic Gun Surface Modifications for CNT Yarn Microelectrode Improve Sensitivity and Antifouling Properties.

PubMed

Yang, Cheng; Wang, Ying; Jacobs, Christopher B; Ivanov, Ilia N; Venton, B Jill

2017-05-16

Carbon nanotube (CNT) based microelectrodes exhibit rapid and selective detection of neurotransmitters. While different fabrication strategies and geometries of CNT microelectrodes have been characterized, relatively little research has investigated ways to selectively enhance their electrochemical properties. In this work, we introduce two simple, reproducible, low-cost, and efficient surface modification methods for carbon nanotube yarn microelectrodes (CNTYMEs): O 2 plasma etching and antistatic gun treatment. O 2 plasma etching was performed by a microwave plasma system with oxygen gas flow and the optimized time for treatment was 1 min. The antistatic gun treatment flows ions by the electrode surface; two triggers of the antistatic gun was the optimized number on the CNTYME surface. Current for dopamine at CNTYMEs increased 3-fold after O 2 plasma etching and 4-fold after antistatic gun treatment. When the two treatments were combined, the current increased 12-fold, showing the two effects are due to independent mechanisms that tune the surface properties. O 2 plasma etching increased the sensitivity due to increased surface oxygen content but did not affect surface roughness while the antistatic gun treatment increased surface roughness but not oxygen content. The effect of tissue fouling on CNT yarns was studied for the first time, and the relatively hydrophilic surface after O 2 plasma etching provided better resistance to fouling than unmodified or antistatic gun treated CNTYMEs. Overall, O 2 plasma etching and antistatic gun treatment improve the sensitivity of CNTYMEs by different mechanisms, providing the possibility to tune the CNTYME surface and enhance sensitivity.

Integrated electrocoagulation-electrooxidation process for the treatment of soluble coffee effluent: Optimization of COD degradation and operation time analysis.

PubMed

Ibarra-Taquez, Harold N; GilPavas, Edison; Blatchley, Ernest R; Gómez-García, Miguel-Ángel; Dobrosz-Gómez, Izabela

2017-09-15

Soluble coffee production generates wastewater containing complex mixtures of organic macromolecules. In this work, a sequential Electrocoagulation-Electrooxidation (EC-EO) process, using aluminum and graphite electrodes, was proposed as an alternative way for the treatment of soluble coffee effluent. Process operational parameters were optimized, achieving total decolorization, as well as 74% and 63.5% of COD and TOC removal, respectively. The integrated EC-EO process yielded a highly oxidized (AOS = 1.629) and biocompatible (BOD 5 /COD ≈ 0.6) effluent. The Molecular Weight Distribution (MWD) analysis showed that during the EC-EO process, EC effectively decomposed contaminants with molecular weight in the range of 10-30 kDa. In contrast, EO was quite efficient in mineralization of contaminants with molecular weight higher than 30 kDa. A kinetic analysis allowed determination of the time required to meet Colombian permissible discharge limits. Finally, a comprehensive operational cost analysis was performed. The integrated EC-EO process was demonstrated as an efficient alternative for the treatment of industrial effluents resulting from soluble coffee production. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of photo-Fenton, O3/H2O2/UV and photocatalytic processes for the treatment of gray water.

PubMed

Hassanshahi, Nahid; Karimi-Jashni, Ayoub

2018-06-21

This research was carried out to compare and optimize the gray water treatment performance by the photo-Fenton, photocatalysis and ozone/H 2 O 2 /UV processes. Experimental design and optimization were carried out using Central Composite Design of Response Surface Methodology. The results of experiments showed that the most effective and influencing factors in photo-Fenton process were H 2 O 2 /Fe 2+ ratio, in ozone/H 2 O 2 /UV experiment were O 3 concentration, H 2 O 2 concentration, reaction time and pH and in photocatalytic process were TiO 2 concentration, pH and reaction time. The highest COD removal in photo-Fenton, ozone/H 2 O 2 /UV and photocatalytic process were 90%, 92% and 55%, respectively. The results were analyzed by design expert software and for all three processes second-order models were proposed to simulate the COD removal efficiency. In conclusion the ozone/H 2 O 2 /UV process is recommended for the treatment of gray water, since it was able to remove both COD and turbidity by 92% and 93%, respectively. Copyright © 2018 Elsevier Inc. All rights reserved.

Methods to model and predict the ViewRay treatment deliveries to aid patient scheduling and treatment planning

PubMed Central

Liu, Shi; Wu, Yu; Wooten, H. Omar; Green, Olga; Archer, Brent; Li, Harold

2016-01-01

A software tool is developed, given a new treatment plan, to predict treatment delivery time for radiation therapy (RT) treatments of patients on ViewRay magnetic resonance image‐guided radiation therapy (MR‐IGRT) delivery system. This tool is necessary for managing patient treatment scheduling in our clinic. The predicted treatment delivery time and the assessment of plan complexities could also be useful to aid treatment planning. A patient's total treatment delivery time, not including time required for localization, is modeled as the sum of four components: 1) the treatment initialization time; 2) the total beam‐on time; 3) the gantry rotation time; and 4) the multileaf collimator (MLC) motion time. Each of the four components is predicted separately. The total beam‐on time can be calculated using both the planned beam‐on time and the decay‐corrected dose rate. To predict the remain‐ing components, we retrospectively analyzed the patient treatment delivery record files. The initialization time is demonstrated to be random since it depends on the final gantry angle of the previous treatment. Based on modeling the relationships between the gantry rotation angles and the corresponding rotation time, linear regression is applied to predict the gantry rotation time. The MLC motion time is calculated using the leaves delay modeling method and the leaf motion speed. A quantitative analysis was performed to understand the correlation between the total treatment time and the plan complexity. The proposed algorithm is able to predict the ViewRay treatment delivery time with the average prediction error 0.22 min or 1.82%, and the maximal prediction error 0.89 min or 7.88%. The analysis has shown the correlation between the plan modulation (PM) factor and the total treatment delivery time, as well as the treatment delivery duty cycle. A possibility has been identified to significantly reduce MLC motion time by optimizing the positions of closed MLC pairs. The accuracy of the proposed prediction algorithm is sufficient to support patient treatment appointment scheduling. This developed software tool is currently applied in use on a daily basis in our clinic, and could also be used as an important indicator for treatment plan complexity. PACS number(s): 87.55.N PMID:27074472

Optimal control on hybrid ode systems with application to a tick disease model.

PubMed

Ding, Wandi

2007-10-01

We are considering an optimal control problem for a type of hybrid system involving ordinary differential equations and a discrete time feature. One state variable has dynamics in only one season of the year and has a jump condition to obtain the initial condition for that corresponding season in the next year. The other state variable has continuous dynamics. Given a general objective functional, existence, necessary conditions and uniqueness for an optimal control are established. We apply our approach to a tick-transmitted disease model with age structure in which the tick dynamics changes seasonally while hosts have continuous dynamics. The goal is to maximize disease-free ticks and minimize infected ticks through an optimal control strategy of treatment with acaricide. Numerical examples are given to illustrate the results.

Optimizing Requirements Decisions with KEYS

NASA Technical Reports Server (NTRS)

Jalali, Omid; Menzies, Tim; Feather, Martin

2008-01-01

Recent work with NASA's Jet Propulsion Laboratory has allowed for external access to five of JPL's real-world requirements models, anonymized to conceal proprietary information, but retaining their computational nature. Experimentation with these models, reported herein, demonstrates a dramatic speedup in the computations performed on them. These models have a well defined goal: select mitigations that retire risks which, in turn, increases the number of attainable requirements. Such a non-linear optimization is a well-studied problem. However identification of not only (a) the optimal solution(s) but also (b) the key factors leading to them is less well studied. Our technique, called KEYS, shows a rapid way of simultaneously identifying the solutions and their key factors. KEYS improves on prior work by several orders of magnitude. Prior experiments with simulated annealing or treatment learning took tens of minutes to hours to terminate. KEYS runs much faster than that; e.g for one model, KEYS ran 13,000 times faster than treatment learning (40 minutes versus 0.18 seconds). Processing these JPL models is a non-linear optimization problem: the fewest mitigations must be selected while achieving the most requirements. Non-linear optimization is a well studied problem. With this paper, we challenge other members of the PROMISE community to improve on our results with other techniques.

Hunger, waiting time and transport costs: time to confront challenges to ART adherence in Africa.

PubMed

Hardon, A P; Akurut, D; Comoro, C; Ekezie, C; Irunde, H F; Gerrits, T; Kglatwane, J; Kinsman, J; Kwasa, R; Maridadi, J; Moroka, T M; Moyo, S; Nakiyemba, A; Nsimba, S; Ogenyi, R; Oyabba, T; Temu, F; Laing, R

2007-05-01

Adherence levels in Africa have been found to be better than those in the US. However around one out of four ART users fail to achieve optimal adherence, risking drug resistance and negative treatment outcomes. A high demand for 2nd line treatments (currently ten times more expensive than 1st line ART) undermines the sustainability of African ART programs. There is an urgent need to identify context-specific constraints to adherence and implement interventions to address them. We used rapid appraisals (involving mainly qualitative methods) to find out why and when people do not adhere to ART in Uganda, Tanzania and Botswana. Multidisciplinary teams of researchers and local health professionals conducted the studies, involving a total of 54 semi-structured interviews with health workers, 73 semi-structured interviews with ARTusers and other key informants, 34 focus group discussions, and 218 exit interviews with ART users. All the facilities studied in Botswana, Tanzania and Uganda provide ARVs free of charge, but ART users report other related costs (e.g. transport expenditures, registration and user fees at the private health facilities, and lost wages due to long waiting times) as main obstacles to optimal adherence. Side effects and hunger in the initial treatment phase are an added concern. We further found that ART users find it hard to take their drugs when they are among people to whom they have not disclosed their HIV status, such as co-workers and friends. The research teams recommend that (i) health care workers inform patients better about adverse effects; (ii) ART programmes provide transport and food support to patients who are too poor to pay; (iii) recurrent costs to users be reduced by providing three-months, rather than the one-month refills once optimal adherence levels have been achieved; and (iv) pharmacists play an important role in this follow-up care.

Performance analysis and optimization of an advanced pharmaceutical wastewater treatment plant through a visual basic software tool (PWWT.VB).

PubMed

Pal, Parimal; Thakura, Ritwik; Chakrabortty, Sankha

2016-05-01

A user-friendly, menu-driven simulation software tool has been developed for the first time to optimize and analyze the system performance of an advanced continuous membrane-integrated pharmaceutical wastewater treatment plant. The software allows pre-analysis and manipulation of input data which helps in optimization and shows the software performance visually on a graphical platform. Moreover, the software helps the user to "visualize" the effects of the operating parameters through its model-predicted output profiles. The software is based on a dynamic mathematical model, developed for a systematically integrated forward osmosis-nanofiltration process for removal of toxic organic compounds from pharmaceutical wastewater. The model-predicted values have been observed to corroborate well with the extensive experimental investigations which were found to be consistent under varying operating conditions like operating pressure, operating flow rate, and draw solute concentration. Low values of the relative error (RE = 0.09) and high values of Willmott-d-index (d will = 0.981) reflected a high degree of accuracy and reliability of the software. This software is likely to be a very efficient tool for system design or simulation of an advanced membrane-integrated treatment plant for hazardous wastewater.

Recovery of Vanadium from Magnetite Ore Using Direct Acid Leaching: Optimization of Parameters by Plackett-Burman and Response Surface Methodologies

NASA Astrophysics Data System (ADS)

Nejad, Davood Ghoddocy; Khanchi, Ali Reza; Taghizadeh, Majid

2018-06-01

Recovery of vanadium from magnetite ore by direct acid leaching is discussed. The proposed process, which employs a mixture of nitric and sulfuric acids, avoids pyrometallurgical treatments since such treatment consumes a high amount of energy. To determine the optimum conditions of vanadium recovery, the leaching process is optimized through Plackett-Burman (P-B) design and response surface methodology (RSM). In this respect, temperature (80-95°C), liquid to solid ratio (L/S) (3-10 mL g-1), sulfuric acid concentration (3-6 M), nitric acid concentration (5-10 vol.%) and time (4-8 h) are considered as the independent variables. According to the P-B approach, temperature and acid concentrations are, respectively, the most effective parameters in the leaching process. These parameters are optimized using RSM to maximize recovery of vanadium by direct acid leaching. In this way, 86.7% of vanadium can be extracted from magnetic ore.

Learning Optimal Individualized Treatment Rules from Electronic Health Record Data

PubMed Central

Wang, Yuanjia; Wu, Peng; Liu, Ying; Weng, Chunhua; Zeng, Donglin

2016-01-01

Medical research is experiencing a paradigm shift from “one-size-fits-all” strategy to a precision medicine approach where the right therapy, for the right patient, and at the right time, will be prescribed. We propose a statistical method to estimate the optimal individualized treatment rules (ITRs) that are tailored according to subject-specific features using electronic health records (EHR) data. Our approach merges statistical modeling and medical domain knowledge with machine learning algorithms to assist personalized medical decision making using EHR. We transform the estimation of optimal ITR into a classification problem and account for the non-experimental features of the EHR data and confounding by clinical indication. We create a broad range of feature variables that reflect both patient health status and healthcare data collection process. Using EHR data collected at Columbia University clinical data warehouse, we construct a decision tree for choosing the best second line therapy for treating type 2 diabetes patients. PMID:28503676

Recovery of Vanadium from Magnetite Ore Using Direct Acid Leaching: Optimization of Parameters by Plackett-Burman and Response Surface Methodologies

NASA Astrophysics Data System (ADS)

Nejad, Davood Ghoddocy; Khanchi, Ali Reza; Taghizadeh, Majid

2018-03-01

Recovery of vanadium from magnetite ore by direct acid leaching is discussed. The proposed process, which employs a mixture of nitric and sulfuric acids, avoids pyrometallurgical treatments since such treatment consumes a high amount of energy. To determine the optimum conditions of vanadium recovery, the leaching process is optimized through Plackett-Burman (P-B) design and response surface methodology (RSM). In this respect, temperature (80-95°C), liquid to solid ratio (L/S) (3-10 mL g-1), sulfuric acid concentration (3-6 M), nitric acid concentration (5-10 vol.%) and time (4-8 h) are considered as the independent variables. According to the P-B approach, temperature and acid concentrations are, respectively, the most effective parameters in the leaching process. These parameters are optimized using RSM to maximize recovery of vanadium by direct acid leaching. In this way, 86.7% of vanadium can be extracted from magnetic ore.

One shot methods for optimal control of distributed parameter systems 1: Finite dimensional control

NASA Technical Reports Server (NTRS)

Taasan, Shlomo

1991-01-01

The efficient numerical treatment of optimal control problems governed by elliptic partial differential equations (PDEs) and systems of elliptic PDEs, where the control is finite dimensional is discussed. Distributed control as well as boundary control cases are discussed. The main characteristic of the new methods is that they are designed to solve the full optimization problem directly, rather than accelerating a descent method by an efficient multigrid solver for the equations involved. The methods use the adjoint state in order to achieve efficient smoother and a robust coarsening strategy. The main idea is the treatment of the control variables on appropriate scales, i.e., control variables that correspond to smooth functions are solved for on coarse grids depending on the smoothness of these functions. Solution of the control problems is achieved with the cost of solving the constraint equations about two to three times (by a multigrid solver). Numerical examples demonstrate the effectiveness of the method proposed in distributed control case, pointwise control and boundary control problems.

Monte Carlo treatment of resonance-radiation imprisonment in fluorescent lamps—revisited

NASA Astrophysics Data System (ADS)

Anderson, James B.

2016-12-01

We reported in 1985 a Monte Carlo treatment of the imprisonment of the 253.7 nm resonance radiation from mercury in the mercury-argon discharge of fluorescent lamps. The calculated spectra of the emitted radiation were found in good agreement with measured spectra. The addition of the isotope mercury-196 to natural mercury was found, also in agreement with experiments, to increase lamp efficiency. In this paper we report the extension of the earlier work with increased accuracy, analysis of photon exit-time distributions, recycling of energy released in quenching, analysis of dynamic similarity for different lamp sizes, variation of Mrozowski transfer rates, prediction and analysis of the hyperfine ultra-violet spectra, and optimization of tailored mercury isotope mixtures for increased lamp efficiency. The spectra were found insensitive to the extent of quenching and recycling. The optimized mixtures were found to increase efficiencies by as much as 5% for several lamp configurations. Optimization without increasing the mercury-196 fraction was found to increase efficiencies by nearly 1% for several configurations.

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

Ureba, A.; Salguero, F. J.; Barbeiro, A. R.

Purpose: The authors present a hybrid direct multileaf collimator (MLC) aperture optimization model exclusively based on sequencing of patient imaging data to be implemented on a Monte Carlo treatment planning system (MC-TPS) to allow the explicit radiation transport simulation of advanced radiotherapy treatments with optimal results in efficient times for clinical practice. Methods: The planning system (called CARMEN) is a full MC-TPS, controlled through aMATLAB interface, which is based on the sequencing of a novel map, called “biophysical” map, which is generated from enhanced image data of patients to achieve a set of segments actually deliverable. In order to reducemore » the required computation time, the conventional fluence map has been replaced by the biophysical map which is sequenced to provide direct apertures that will later be weighted by means of an optimization algorithm based on linear programming. A ray-casting algorithm throughout the patient CT assembles information about the found structures, the mass thickness crossed, as well as PET values. Data are recorded to generate a biophysical map for each gantry angle. These maps are the input files for a home-made sequencer developed to take into account the interactions of photons and electrons with the MLC. For each linac (Axesse of Elekta and Primus of Siemens) and energy beam studied (6, 9, 12, 15 MeV and 6 MV), phase space files were simulated with the EGSnrc/BEAMnrc code. The dose calculation in patient was carried out with the BEAMDOSE code. This code is a modified version of EGSnrc/DOSXYZnrc able to calculate the beamlet dose in order to combine them with different weights during the optimization process. Results: Three complex radiotherapy treatments were selected to check the reliability of CARMEN in situations where the MC calculation can offer an added value: A head-and-neck case (Case I) with three targets delineated on PET/CT images and a demanding dose-escalation; a partial breast irradiation case (Case II) solved with photon and electron modulated beams (IMRT + MERT); and a prostatic bed case (Case III) with a pronounced concave-shaped PTV by using volumetric modulated arc therapy. In the three cases, the required target prescription doses and constraints on organs at risk were fulfilled in a short enough time to allow routine clinical implementation. The quality assurance protocol followed to check CARMEN system showed a high agreement with the experimental measurements. Conclusions: A Monte Carlo treatment planning model exclusively based on maps performed from patient imaging data has been presented. The sequencing of these maps allows obtaining deliverable apertures which are weighted for modulation under a linear programming formulation. The model is able to solve complex radiotherapy treatments with high accuracy in an efficient computation time.« less

[Evaluating an effectiveness of surgical treatment of gastroesophageal reflux disease combined with hiatal hernia].

PubMed

Mozharovskiy, V V; Tsyganov, A A; Mozharovskiy, K V; Tarasov, A A

To assess an effectiveness of surgical treatment of gastroesophageal reflux disease (GERD) combined with hiatal hernia (HH). The trial included 96 patients with GERD and HH who were divided into 2 groups. The principal difference between groups was the use of surgery in the main group and therapeutic treatment in the comparison group. The effectiveness of surgical treatment is superior to therapeutic treatment of GERD by more than 2.5 times. HH combined with GERD is an indication for surgical treatment. Fundoplication cuff should not lead to angular and rotational esophageal deformation. Nissen procedure in Donahue modification (Short Floppy Nissen) simulates optimally the geometry of esophago-gastric junction and His angle.

[Injury of subclavian artery in severe trauma of the shoulder girdle and chest].

PubMed

Samokhvalov, I M; Reva, V A; Pronchenko, A A; Petrov, A N

2013-01-01

The authors consider one of possible variants of surgical treatment of shoulder girdle trauma, which is accompanied by an injury of the main artery. It is based on the application of the principle of staged surgical treatment (damage control orthopedic). The well-timed sufficient diagnostics and treatment of bone-arterial trauma, coordinated work of several surgical teams, the appropriate postoperative management of patients with the using of postponed high-technology intervention allowed obtaining an optimal functional result for extremely severe multitrauma of the chest and limb.

Adaptive treatment-length optimization in spatiobiologically integrated radiotherapy

NASA Astrophysics Data System (ADS)

Ajdari, Ali; Ghate, Archis; Kim, Minsun

2018-04-01

Recent theoretical research on spatiobiologically integrated radiotherapy has focused on optimization models that adapt fluence-maps to the evolution of tumor state, for example, cell densities, as observed in quantitative functional images acquired over the treatment course. We propose an optimization model that adapts the length of the treatment course as well as the fluence-maps to such imaged tumor state. Specifically, after observing the tumor cell densities at the beginning of a session, the treatment planner solves a group of convex optimization problems to determine an optimal number of remaining treatment sessions, and a corresponding optimal fluence-map for each of these sessions. The objective is to minimize the total number of tumor cells remaining (TNTCR) at the end of this proposed treatment course, subject to upper limits on the biologically effective dose delivered to the organs-at-risk. This fluence-map is administered in future sessions until the next image is available, and then the number of sessions and the fluence-map are re-optimized based on the latest cell density information. We demonstrate via computer simulations on five head-and-neck test cases that such adaptive treatment-length and fluence-map planning reduces the TNTCR and increases the biological effect on the tumor while employing shorter treatment courses, as compared to only adapting fluence-maps and using a pre-determined treatment course length based on one-size-fits-all guidelines.

Optimization of antitumor treatment conditions for transcutaneous CO2 application: An in vivo study.

PubMed

Ueha, Takeshi; Kawamoto, Teruya; Onishi, Yasuo; Harada, Risa; Minoda, Masaya; Toda, Mitsunori; Hara, Hitomi; Fukase, Naomasa; Kurosaka, Masahiro; Kuroda, Ryosuke; Akisue, Toshihiro; Sakai, Yoshitada

2017-06-01

Carbon dioxide (CO2) therapy can be applied to treat a variety of disorders. We previously found that transcutaneous application of CO2 with a hydrogel decreased the tumor volume of several types of tumors and induced apoptosis via the mitochondrial pathway. However, only one condition of treatment intensity has been tested. For widespread application in clinical antitumor therapy, the conditions must be optimized. In the present study, we investigated the relationship between the duration, frequency, and treatment interval of transcutaneous CO2 application and antitumor effects in murine xenograft models. Murine xenograft models of three types of human tumors (breast cancer, osteosarcoma, and malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma) were used to assess the antitumor effects of transcutaneous CO2 application of varying durations, frequencies, and treatment intervals. In all human tumor xenografts, apoptosis was significantly induced by CO2 treatment for ≥10 min, and a significant decrease in tumor volume was observed with CO2 treatments of >5 min. The effect on tumor volume was not dependent on the frequency of CO2 application, i.e., twice or five times per week. However, treatment using 3- and 4-day intervals was more effective at decreasing tumor volume than treatment using 2- and 5-day intervals. The optimal conditions of transcutaneous CO2 application to obtain the best antitumor effect in various tumors were as follows: greater than 10 min per application, twice per week, with 3- and 4-day intervals, and application to the site of the tumor. The results suggest that this novel transcutaneous CO2 application might be useful to treat primary tumors, while mitigating some side effects, and therefore could be safe for clinical trials.

Optimal treatment interruptions control of TB transmission model

NASA Astrophysics Data System (ADS)

Nainggolan, Jonner; Suparwati, Titik; Kawuwung, Westy B.

2018-03-01

A tuberculosis model which incorporates treatment interruptions of infectives is established. Optimal control of individuals infected with active TB is given in the model. It is obtained that the control reproduction numbers is smaller than the reproduction number, this means treatment controls could optimize the decrease in the spread of active TB. For this model, controls on treatment of infection individuals to reduce the actively infected individual populations, by application the Pontryagins Maximum Principle for optimal control. The result further emphasized the importance of controlling disease relapse in reducing the number of actively infected and treatment interruptions individuals with tuberculosis.

Optimization of human tendon tissue engineering: peracetic acid oxidation for enhanced reseeding of acellularized intrasynovial tendon.

PubMed

Woon, Colin Y L; Pridgen, Brian C; Kraus, Armin; Bari, Sina; Pham, Hung; Chang, James

2011-03-01

Tissue engineering of human flexor tendons combines tendon scaffolds with recipient cells to create complete cell-tendon constructs. Allogenic acellularized human flexor tendon has been shown to be a useful natural scaffold. However, there is difficulty repopulating acellularized tendon with recipient cells, as cell penetration is restricted by a tightly woven tendon matrix. The authors evaluated peracetic acid treatment in optimizing intratendinous cell penetration. Cadaveric human flexor tendons were harvested, acellularized, and divided into experimental groups. These groups were treated with peracetic acid in varying concentrations (2%, 5%, and 10%) and for varying time periods (4 and 20 hours) to determine the optimal treatment protocol. Experimental tendons were analyzed for differences in tendon microarchitecture. Additional specimens were reseeded by incubation in a fibroblast cell suspension at 1 × 10(6) cells/ml. This group was then analyzed for reseeding efficacy. A final group underwent biomechanical studies for strength. The optimal treatment protocol comprising peracetic acid at 5% concentration for 4 hours produced increased scaffold porosity, improving cell penetration and migration. Treated scaffolds did not show reduced collagen or glycosaminoglycan content compared with controls (p = 0.37 and p = 0.65, respectively). Treated scaffolds were cytotoxic to neither attached cells nor the surrounding cell suspension. Treated scaffolds also did not show inferior ultimate tensile stress or elastic modulus compared with controls (p = 0.26 and p = 0.28, respectively). Peracetic acid treatment of acellularized tendon scaffolds increases matrix porosity, leading to greater reseeding. It may prove to be an important step in tissue engineering of human flexor tendon using natural scaffolds.

Shortening Delivery Times of Intensity Modulated Proton Therapy by Reducing Proton Energy Layers During Treatment Plan Optimization

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

Water, Steven van de, E-mail: s.vandewater@erasmusmc.nl; Kooy, Hanne M.; Heijmen, Ben J.M.

2015-06-01

Purpose: To shorten delivery times of intensity modulated proton therapy by reducing the number of energy layers in the treatment plan. Methods and Materials: We have developed an energy layer reduction method, which was implemented into our in-house-developed multicriteria treatment planning system “Erasmus-iCycle.” The method consisted of 2 components: (1) minimizing the logarithm of the total spot weight per energy layer; and (2) iteratively excluding low-weighted energy layers. The method was benchmarked by comparing a robust “time-efficient plan” (with energy layer reduction) with a robust “standard clinical plan” (without energy layer reduction) for 5 oropharyngeal cases and 5 prostate cases.more » Both plans of each patient had equal robust plan quality, because the worst-case dose parameters of the standard clinical plan were used as dose constraints for the time-efficient plan. Worst-case robust optimization was performed, accounting for setup errors of 3 mm and range errors of 3% + 1 mm. We evaluated the number of energy layers and the expected delivery time per fraction, assuming 30 seconds per beam direction, 10 ms per spot, and 400 Giga-protons per minute. The energy switching time was varied from 0.1 to 5 seconds. Results: The number of energy layers was on average reduced by 45% (range, 30%-56%) for the oropharyngeal cases and by 28% (range, 25%-32%) for the prostate cases. When assuming 1, 2, or 5 seconds energy switching time, the average delivery time was shortened from 3.9 to 3.0 minutes (25%), 6.0 to 4.2 minutes (32%), or 12.3 to 7.7 minutes (38%) for the oropharyngeal cases, and from 3.4 to 2.9 minutes (16%), 5.2 to 4.2 minutes (20%), or 10.6 to 8.0 minutes (24%) for the prostate cases. Conclusions: Delivery times of intensity modulated proton therapy can be reduced substantially without compromising robust plan quality. Shorter delivery times are likely to reduce treatment uncertainties and costs.« less

Evaluation, prediction and optimization the ultrasound-assisted extraction method using response surface methodology: antioxidant and biological properties of Stachys parviflora L.

PubMed

Bashi, Davoud Salar; Dowom, Samaneh Attaran; Bazzaz, Bibi Sedigheh Fazly; Khanzadeh, Farhad; Soheili, Vahid; Mohammadpour, Ali

2016-05-01

To optimize the extraction method using response surface methodology, extract the phenolic compounds, and identify the antioxidant and biological properties of Stachys parviflora L. extracts. Maceration and ultrasound-assisted extraction (UAE) (4, 7, 10 min treatment time, 40, 70, 100 % high-intensity and 60, 80, 100 % (v v-1) methanol purity) were applied to obtain the extracts. SEM was conducted to provide the microstructure of the extracted plant. MICs (colorimetric assay), MFCs (colony diameter), total phenolic content, total flavonoid content, radical scavenging capacity and extraction efficiency were determined. HPLC analysis was applied to measure the existent phenolic compounds. A quadratic model (4 min treatment time, 74.5 % high-intensity and 74.2 % solvent purity) was suggested as the best (TPC: 20.89 mg GAE g-1 d.m., TFC: 6.22 mg QEs g-1 d.m., DPPH IC50: 21.86 µg ml-1 and EE: 113.65 mg g-1 d.m.) UAE extraction model. The optimized UAE extract was generally more effective against Gram-positive microorganisms (MIC: 10-20; MBC: 10-40 (mg ml-1)) than Gram-negative ones (MIC: 40; MBC: >40 (mg ml-1)). Moreover, it (MGI: 2.32-100 %) revealed more anti-mold activity than maceration (MGI: <28.77 %). Explosive disruption of the cell walls, therefore, enhanced extraction yield by acoustic cavitation, was elucidated using SEM. Caffeic acid, tannic acid, quercetin, trans ferulic acid and rosmarinic acid were determined as the phenolic compounds in the optimized extract. RSM optimization was successfully applied for UAE from S. parviflora. The considerable antioxidant and biological properties were attributed to the phenolic compounds.

Evaluation, prediction and optimization the ultrasound-assisted extraction method using response surface methodology: antioxidant and biological properties of Stachys parviflora L.

PubMed Central

Bashi, Davoud Salar; Dowom, Samaneh Attaran; Bazzaz, Bibi Sedigheh Fazly; Khanzadeh, Farhad; Soheili, Vahid; Mohammadpour, Ali

2016-01-01

Objective(s): To optimize the extraction method using response surface methodology, extract the phenolic compounds, and identify the antioxidant and biological properties of Stachys parviflora L. extracts. Materials and Methods: Maceration and ultrasound-assisted extraction (UAE) (4, 7, 10 min treatment time, 40, 70, 100 % high-intensity and 60, 80, 100 % (v v-1) methanol purity) were applied to obtain the extracts. SEM was conducted to provide the microstructure of the extracted plant. MICs (colorimetric assay), MFCs (colony diameter), total phenolic content, total flavonoid content, radical scavenging capacity and extraction efficiency were determined. HPLC analysis was applied to measure the existent phenolic compounds. Results: A quadratic model (4 min treatment time, 74.5 % high-intensity and 74.2 % solvent purity) was suggested as the best (TPC: 20.89 mg GAE g-1 d.m., TFC: 6.22 mg QEs g-1 d.m., DPPH IC50: 21.86 µg ml-1 and EE: 113.65 mg g-1 d.m.) UAE extraction model. The optimized UAE extract was generally more effective against Gram-positive microorganisms (MIC: 10-20; MBC: 10-40 (mg ml-1)) than Gram-negative ones (MIC: 40; MBC: >40 (mg ml-1)). Moreover, it (MGI: 2.32-100 %) revealed more anti-mold activity than maceration (MGI: <28.77 %). Explosive disruption of the cell walls, therefore, enhanced extraction yield by acoustic cavitation, was elucidated using SEM. Caffeic acid, tannic acid, quercetin, trans ferulic acid and rosmarinic acid were determined as the phenolic compounds in the optimized extract. Conclusion: RSM optimization was successfully applied for UAE from S. parviflora. The considerable antioxidant and biological properties were attributed to the phenolic compounds. PMID:27403260

Optimal combinations of control strategies and cost-effective analysis for visceral leishmaniasis disease transmission.

PubMed

Biswas, Santanu; Subramanian, Abhishek; ELMojtaba, Ibrahim M; Chattopadhyay, Joydev; Sarkar, Ram Rup

2017-01-01

Visceral leishmaniasis (VL) is a deadly neglected tropical disease that poses a serious problem in various countries all over the world. Implementation of various intervention strategies fail in controlling the spread of this disease due to issues of parasite drug resistance and resistance of sandfly vectors to insecticide sprays. Due to this, policy makers need to develop novel strategies or resort to a combination of multiple intervention strategies to control the spread of the disease. To address this issue, we propose an extensive SIR-type model for anthroponotic visceral leishmaniasis transmission with seasonal fluctuations modeled in the form of periodic sandfly biting rate. Fitting the model for real data reported in South Sudan, we estimate the model parameters and compare the model predictions with known VL cases. Using optimal control theory, we study the effects of popular control strategies namely, drug-based treatment of symptomatic and PKDL-infected individuals, insecticide treated bednets and spray of insecticides on the dynamics of infected human and vector populations. We propose that the strategies remain ineffective in curbing the disease individually, as opposed to the use of optimal combinations of the mentioned strategies. Testing the model for different optimal combinations while considering periodic seasonal fluctuations, we find that the optimal combination of treatment of individuals and insecticide sprays perform well in controlling the disease for the time period of intervention introduced. Performing a cost-effective analysis we identify that the same strategy also proves to be efficacious and cost-effective. Finally, we suggest that our model would be helpful for policy makers to predict the best intervention strategies for specific time periods and their appropriate implementation for elimination of visceral leishmaniasis.

In-vivo multiphoton microscopy (MPM) of laser-induced optical breakdown (LIOB) in human skin (Conference Presentation)

NASA Astrophysics Data System (ADS)

Balu, Mihaela; Lentsch, Griffin; Korta, Dorota; Konig, Karsten; Kelly, Kristen M.; Tromberg, Bruce J.; Zachary, Christopher B.

2017-02-01

We use a multiphoton microscopy (MPM)-based clinical microscope (MPTflex, JenLab, Germany) to describe changes in human skin following treatment with a fractional non-ablative laser (PicoWay, Candela). The treatment was based on a fractionated picosecond Nd:YAG laser (1064 and 532nm, 3mJ and 1.5mJ (no attenuation), respectively maximum energy/pulse, 100 microbeams/6mmx6mm). Improvements in skin appearance resulting from treatment with this laser have been noted but optimizing the efficacy depends on a thorough understanding of the specific skin response to treatment. MPM is a nonlinear laser scanning microscopy technique that features sub-cellular resolution and label-free molecular contrast. MPM contrast in skin is derived from second-harmonic generation of collagen and two-photon excited fluorescence of NADH/FAD+, elastin, keratin, melanin. In this pilot study, two areas on the arm of a volunteer (skin type II) were treated with the picoWay laser (1064nm, 3mJ; 532nm, 1.5mJ; 1pass). The skin response to treatment was imaged in-vivo at 8 time points over the following 4 weeks. MPM revealed micro-injuries present in epidermis. Damaged individual cells were distinguished after 3h and 24h from treatment with both wavelengths. Pigmented cells were particularly damaged in the process, suggesting that melanin is the main absorber and the primary target for laser induced optical breakdown. At later time points, clusters of cellular necrotic debris were imaged across the treated epidermis. These results represent the groundwork for future longitudinal studies on expanded number of subjects to understand the response to treatment in different skin types at different laser parameters, critical factors in optimizing treatment outcomes.

Optimizing highly noncoplanar VMAT trajectories: the NoVo method.

PubMed

Langhans, Marco; Unkelbach, Jan; Bortfeld, Thomas; Craft, David

2018-01-16

We introduce a new method called NoVo (Noncoplanar VMAT Optimization) to produce volumetric modulated arc therapy (VMAT) treatment plans with noncoplanar trajectories. While the use of noncoplanar beam arrangements for intensity modulated radiation therapy (IMRT), and in particular high fraction stereotactic radiosurgery (SRS), is common, noncoplanar beam trajectories for VMAT are less common as the availability of treatment machines handling these is limited. For both IMRT and VMAT, the beam angle selection problem is highly nonconvex in nature, which is why automated beam angle selection procedures have not entered mainstream clinical usage. NoVo determines a noncoplanar VMAT solution (i.e. the simultaneous trajectories of the gantry and the couch) by first computing a [Formula: see text] solution (beams from every possible direction, suitably discretized) and then eliminating beams by examing fluence contributions. Also all beam angles are scored via geometrical considerations only to find out the usefulness of the whole beam space in a very short time. A custom path finding algorithm is applied to find an optimized, continuous trajectory through the most promising beam angles using the calculated score of the beam space. Finally, using this trajectory a VMAT plan is optimized. For three clinical cases, a lung, brain, and liver case, we compare NoVo to the ideal [Formula: see text] solution, nine beam noncoplanar IMRT, coplanar VMAT, and a recently published noncoplanar VMAT algorithm. NoVo comes closest to the [Formula: see text] solution considering the lung case (brain and liver case: second), as well as improving the solution time by using geometrical considerations, followed by a time effective iterative process reducing the [Formula: see text] solution. Compared to a recently published noncoplanar VMAT algorithm, using NoVo the computation time is reduced by a factor of 2-3 (depending on the case). Compared to coplanar VMAT, NoVo reduces the objective function value by 24%, 49% and 6% for the lung, brain and liver cases, respectively.

Optimizing highly noncoplanar VMAT trajectories: the NoVo method

NASA Astrophysics Data System (ADS)

Langhans, Marco; Unkelbach, Jan; Bortfeld, Thomas; Craft, David

2018-01-01

We introduce a new method called NoVo (Noncoplanar VMAT Optimization) to produce volumetric modulated arc therapy (VMAT) treatment plans with noncoplanar trajectories. While the use of noncoplanar beam arrangements for intensity modulated radiation therapy (IMRT), and in particular high fraction stereotactic radiosurgery (SRS), is common, noncoplanar beam trajectories for VMAT are less common as the availability of treatment machines handling these is limited. For both IMRT and VMAT, the beam angle selection problem is highly nonconvex in nature, which is why automated beam angle selection procedures have not entered mainstream clinical usage. NoVo determines a noncoplanar VMAT solution (i.e. the simultaneous trajectories of the gantry and the couch) by first computing a 4π solution (beams from every possible direction, suitably discretized) and then eliminating beams by examing fluence contributions. Also all beam angles are scored via geometrical considerations only to find out the usefulness of the whole beam space in a very short time. A custom path finding algorithm is applied to find an optimized, continuous trajectory through the most promising beam angles using the calculated score of the beam space. Finally, using this trajectory a VMAT plan is optimized. For three clinical cases, a lung, brain, and liver case, we compare NoVo to the ideal 4π solution, nine beam noncoplanar IMRT, coplanar VMAT, and a recently published noncoplanar VMAT algorithm. NoVo comes closest to the 4π solution considering the lung case (brain and liver case: second), as well as improving the solution time by using geometrical considerations, followed by a time effective iterative process reducing the 4π solution. Compared to a recently published noncoplanar VMAT algorithm, using NoVo the computation time is reduced by a factor of 2-3 (depending on the case). Compared to coplanar VMAT, NoVo reduces the objective function value by 24%, 49% and 6% for the lung, brain and liver cases, respectively.

SU-D-BRC-02: Application of Six Sigma Approach to Improve the Efficiency of Patient-Specific QA in Proton Therapy

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

LAH, J; Shin, D; Manger, R

Purpose: To show how the Six Sigma DMAIC (Define-Measure-Analyze-Improve-Control) can be used for improving and optimizing the efficiency of patient-specific QA process by designing site-specific range tolerances. Methods: The Six Sigma tools (process flow diagram, cause and effect, capability analysis, Pareto chart, and control chart) were utilized to determine the steps that need focus for improving the patient-specific QA process. The patient-specific range QA plans were selected according to 7 treatment site groups, a total of 1437 cases. The process capability index, Cpm was used to guide the tolerance design of patient site-specific range. We also analyzed the financial impactmore » of this project. Results: Our results suggested that the patient range measurements were non-capable at the current tolerance level of ±1 mm in clinical proton plans. The optimized tolerances were calculated for treatment sites. Control charts for the patient QA time were constructed to compare QA time before and after the new tolerances were implemented. It is found that overall processing time was decreased by 24.3% after establishing new site-specific range tolerances. The QA failure for whole process in proton therapy would lead up to a 46% increase in total cost. This result can also predict how costs are affected by changes in adopting the tolerance design. Conclusion: We often believe that the quality and performance of proton therapy can easily be improved by merely tightening some or all of its tolerance requirements. This can become costly, however, and it is not necessarily a guarantee of better performance. The tolerance design is not a task to be undertaken without careful thought. The Six Sigma DMAIC can be used to improve the QA process by setting optimized tolerances. When tolerance design is optimized, the quality is reasonably balanced with time and cost demands.« less

Characteristics of psychiatric patients for whom financial considerations affect optimal treatment provision.

PubMed

West, Joyce C; Pingitore, David; Zarin, Deborah A

2002-12-01

This study assessed characteristics of psychiatric patients for whom financial considerations affected the provision of "optimal" treatment. Psychiatrists reported that for 33.8 percent of 1,228 patients from a national sample, financial considerations such as managed care limitations, the patient's personal finances, and limitations inherent in the public care system adversely affected the provision of optimal treatment. Patients were more likely to have their treatment adversely affected by financial considerations if they were more severely ill, had more than one behavioral health disorder or a psychosocial problem, or were receiving treatment under managed care arrangements. Patients for whom financial considerations affect the provision of optimal treatment represent a population for whom access to treatment may be particularly important.

Patient-specific dosimetric endpoints based treatment plan quality control in radiotherapy.

PubMed

Song, Ting; Staub, David; Chen, Mingli; Lu, Weiguo; Tian, Zhen; Jia, Xun; Li, Yongbao; Zhou, Linghong; Jiang, Steve B; Gu, Xuejun

2015-11-07

In intensity modulated radiotherapy (IMRT), the optimal plan for each patient is specific due to unique patient anatomy. To achieve such a plan, patient-specific dosimetric goals reflecting each patient's unique anatomy should be defined and adopted in the treatment planning procedure for plan quality control. This study is to develop such a personalized treatment plan quality control tool by predicting patient-specific dosimetric endpoints (DEs). The incorporation of patient specific DEs is realized by a multi-OAR geometry-dosimetry model, capable of predicting optimal DEs based on the individual patient's geometry. The overall quality of a treatment plan is then judged with a numerical treatment plan quality indicator and characterized as optimal or suboptimal. Taking advantage of clinically available prostate volumetric modulated arc therapy (VMAT) treatment plans, we built and evaluated our proposed plan quality control tool. Using our developed tool, six of twenty evaluated plans were identified as sub-optimal plans. After plan re-optimization, these suboptimal plans achieved better OAR dose sparing without sacrificing the PTV coverage, and the dosimetric endpoints of the re-optimized plans agreed well with the model predicted values, which validate the predictability of the proposed tool. In conclusion, the developed tool is able to accurately predict optimally achievable DEs of multiple OARs, identify suboptimal plans, and guide plan optimization. It is a useful tool for achieving patient-specific treatment plan quality control.

A novel method to accelerate orthodontic tooth movement

PubMed Central

Buyuk, S. Kutalmış; Yavuz, Mustafa C.; Genc, Esra; Sunar, Oguzhan

2018-01-01

This clinical case report presents fixed orthodontic treatment of a patient with moderately crowded teeth. It was performed with a new technique called ‘discision’. Discision method that was described for the first time by the present authors yielded predictable outcomes, and orthodontic treatment was completed in a short period of time. The total duration of orthodontic treatment was 4 months. Class I molar and canine relationships were established at the end of the treatment. Moreover, crowding in the mandible and maxilla was corrected, and optimal overjet and overbite were established. No scar tissue was observed in any gingival region on which discision was performed. The discision technique was developed as a minimally invasive alternative method to piezocision technique, and the authors suggest that this new method yields good outcomes in achieving rapid tooth movement. PMID:29436571

SU-F-T-618: Evaluation of a Mono-Isocentric Treatment Planning Software for Stereotactic Radiosurgery of Multiple Brain Metastases

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

Sham, E; Sattarivand, M; Mulroy, L

Purpose: To evaluate planning performance of an automated treatment planning software (BrainLAB; Elements) for stereotactic radiosurgery (SRS) of multiple brain metastases. Methods: Brainlab’s Multiple Metastases Elements (MME) uses single isocentric technique to treat up to 10 cranial planning target volumes (PTVs). The planning algorithm of the MME accounts for multiple PTVs overlapping with one another on the beam eyes view (BEV) and automatically selects a subset of all overlapping PTVs on each arc for sparing normal tissues in the brain. The algorithm also optimizes collimator angles, margins between multi-leaf collimators (MLCs) and PTVs, as well as monitor units (MUs) usingmore » minimization of conformity index (CI) for all targets. Planning performance was evaluated by comparing the MME-calculated treatment plan parameters with the same parameters calculated with the Volumetric Modulated Arc Therapy (VMAT) optimization on Varian’s Eclipse platform. Results: Figures 1 to 3 compare several treatment plan outcomes calculated between the MME and VMAT for 5 clinical multi-targets SRS patient plans. Prescribed target dose was volume-dependent and defined based on the RTOG recommendation. For a total number of 18 PTV’s, mean values for the CI, PITV, and GI were comparable between the MME and VMAT within one standard deviation (σ). However, MME-calculated MDPD was larger than the same VMAT-calculated parameter. While both techniques delivered similar maximum point doses to the critical cranial structures and total MU’s for the 5 patient plans, the MME required less treatment planning time by an order of magnitude compared to VMAT. Conclusion: The MME and VMAT produce similar plan qualities in terms of MUs, target dose conformation, and OAR dose sparing. While the selective use of PTVs for arc-optimization with the MME reduces significantly the total planning time in comparison to VMAT, the target dose homogeneity was also compromised due to its simplified inverse planning algorithm used.« less

Optimization of the moving-bed biofilm sequencing batch reactor (MBSBR) to control aeration time by kinetic computational modeling: Simulated sugar-industry wastewater treatment.

PubMed

Faridnasr, Maryam; Ghanbari, Bastam; Sassani, Ardavan

2016-05-01

A novel approach was applied for optimization of a moving-bed biofilm sequencing batch reactor (MBSBR) to treat sugar-industry wastewater (BOD5=500-2500 and COD=750-3750 mg/L) at 2-4 h of cycle time (CT). Although the experimental data showed that MBSBR reached high BOD5 and COD removal performances, it failed to achieve the standard limits at the mentioned CTs. Thus, optimization of the reactor was rendered by kinetic computational modeling and using statistical error indicator normalized root mean square error (NRMSE). The results of NRMSE revealed that Stover-Kincannon (error=6.40%) and Grau (error=6.15%) models provide better fits to the experimental data and may be used for CT optimization in the reactor. The models predicted required CTs of 4.5, 6.5, 7 and 7.5 h for effluent standardization of 500, 1000, 1500 and 2500 mg/L influent BOD5 concentrations, respectively. Similar pattern of the experimental data also confirmed these findings. Copyright © 2016 Elsevier Ltd. All rights reserved.

Technique optimization of orbital atherectomy in calcified peripheral lesions of the lower extremities: the CONFIRM series, a prospective multicenter registry.

PubMed

Das, Tony; Mustapha, Jihad; Indes, Jeffrey; Vorhies, Robert; Beasley, Robert; Doshi, Nilesh; Adams, George L

2014-01-01

The purpose of CONFIRM registry series was to evaluate the use of orbital atherectomy (OA) in peripheral lesions of the lower extremities, as well as optimize the technique of OA. Methods of treating calcified arteries (historically a strong predictor of treatment failure) have improved significantly over the past decade and now include minimally invasive endovascular treatments, such as OA with unique versatility in modifying calcific lesions above and below-the-knee. Patients (3135) undergoing OA by more than 350 physicians at over 200 US institutions were enrolled on an "all-comers" basis, resulting in registries that provided site-reported patient demographics, ABI, Rutherford classification, co-morbidities, lesion characteristics, plaque morphology, device usage parameters, and procedural outcomes. Treatment with OA reduced pre-procedural stenosis from an average of 88-35%. Final residual stenosis after adjunctive treatments, typically low-pressure percutaneous transluminal angioplasty (PTA), averaged 10%. Plaque removal was most effective for severely calcified lesions and least effective for soft plaque. Shorter spin times and smaller crown sizes significantly lowered procedural complications which included slow flow (4.4%), embolism (2.2%), and spasm (6.3%), emphasizing the importance of treatment regimens that focus on plaque modification over maximizing luminal gain. The OA technique optimization, which resulted in a change of device usage across the CONFIRM registry series, corresponded to a lower incidence of adverse events irrespective of calcium burden or co-morbidities. Copyright © 2013 The Authors. Wiley Periodicals, Inc.

Physical reparative treatment in reptiles

PubMed Central

2013-01-01

Background The tissue growth necessary to achieve a complete or partial restitution ad integrum as a result of injury to soft tissue and/or hard times in reptiles is variable and often needs long time in relation to the species, to the habitat and to their intrinsic physiological characteristics. The purpose of this work was to see if the tissue optimization (TO) treatment with radio electric asymmetric conveyer (REAC) provided good results in these animals and whether its use translates into reduced time of tissue repair. This paper describes preliminary results with in promoting the tissue repair in reptiles. Cases presentation A 5 year old male Testudo graeca (Leo) and Trachemys scripta scripta (Mir) and a 15 year old female Testudo hermanni (Juta) were evaluated because of soft tissue injuries. A female 25 year old Trachemys scripta elegans (Ice), a female 2.5 year old Trachemys scripta scripta (Penelope) as well as a 50 year old male Testudo graeca (Margherito) were evaluated because of wounds of the carapace. Following debridement and traditional therapies, Leo, Penelope and Margherito were exposed to the radio electric asymmetric conveyer (REAC) device, with a specific treatment protocol, named tissue optimization-basic (TO-B). Also Ice and Mir were subjected to REAC treatment after wounds debridement. Juta was treated only with REAC treatment. Complete wound healing was evident after 17 days for Leo, 7 days for Penelope, 27 days for Mir, 78 days for Ice and after 14 days for Margherito. Juta showed a considerable tissue activation in 2 days and complete wound healing in 5 days. Conclusion Our findings suggest that REAC TO-B treatment may provide advantages over other traditional methods after complete wound healing in Leo, and also suitable healing in the other patients. Then REAC device with its specific treatment TO-B protocol, which induces tissue repair without causing severe stress to the patient, could be a potential therapy for tissue damage healing in reptiles. Further studies still need to be conducted to support our observations. PMID:23442770

Optimizing molluscicide treatment strategies in different control stages of schistosomiasis in the People's Republic of China.

PubMed

Yang, Guo-Jing; Sun, Le-Ping; Hong, Qing-Biao; Zhu, Hong-Ru; Yang, Kun; Gao, Qi; Zhou, Xiao-Nong

2012-11-14

The application of chemical molluscicides is still one of the most effective measures for schistosomiasis control in P. R. China. By applying diverse molluscicide treatment scenarios on different snail densities in the field, we attempted to understand the cost-effectiveness of molluscicide application so as to prescribe an optimal management approach to control intermediate host snail Oncomelania hupensis under acceptable thresholds based on the goal of the National Schistosomiasis Control Programme. The molluscicidal field trial was carried out in the marshland of an island along the Yangtze River, Jiangsu province, P.R. China in October 2010. Three plots in the island representing low-density, medium-density and high-density groups were identified after the baseline survey on snail density. Each snail density plot was divided into four experimental units in which molluscicide (50% niclosamide ethanolamine salt wettable powder) was applied once, twice, trice and four times, respectively. The logistic regression model to correlate snail mortality rate with the covariates of number of molluscicidal treatment and snail density, and a linear regression model to investigate the relationship between cost-effectiveness and number of molluscicidal treatment as well as snail density were established. The study revealed that increase in the number of molluscicide treatments led to increased snail mortality across all three population density groups. The most cost-effective regimen was seen in the high snail density group with a single molluscicide treatment. For both high and low density groups, the more times molluscicide were applied, the less cost-effectiveness was. However, for the median density group, the level of cost-effectiveness for two applications was slightly higher than that in one time. We concluded that different stages of the national schistosomiasis control/elimination programme, namely morbidity control, transmission control and transmission interruption, should utilize different molluscicide treatment strategies to maximize cost-effectiveness.

A stochastic framework for spot-scanning particle therapy.

PubMed

Robini, Marc; Yuemin Zhu; Wanyu Liu; Magnin, Isabelle

2016-08-01

In spot-scanning particle therapy, inverse treatment planning is usually limited to finding the optimal beam fluences given the beam trajectories and energies. We address the much more challenging problem of jointly optimizing the beam fluences, trajectories and energies. For this purpose, we design a simulated annealing algorithm with an exploration mechanism that balances the conflicting demands of a small mixing time at high temperatures and a reasonable acceptance rate at low temperatures. Numerical experiments substantiate the relevance of our approach and open new horizons to spot-scanning particle therapy.

Optimization of light source parameters in the photodynamic therapy of heterogeneous prostate

NASA Astrophysics Data System (ADS)

Li, Jun; Altschuler, Martin D.; Hahn, Stephen M.; Zhu, Timothy C.

2008-08-01

The three-dimensional (3D) heterogeneous distributions of optical properties in a patient prostate can now be measured in vivo. Such data can be used to obtain a more accurate light-fluence kernel. (For specified sources and points, the kernel gives the fluence delivered to a point by a source of unit strength.) In turn, the kernel can be used to solve the inverse problem that determines the source strengths needed to deliver a prescribed photodynamic therapy (PDT) dose (or light-fluence) distribution within the prostate (assuming uniform drug concentration). We have developed and tested computational procedures to use the new heterogeneous data to optimize delivered light-fluence. New problems arise, however, in quickly obtaining an accurate kernel following the insertion of interstitial light sources and data acquisition. (1) The light-fluence kernel must be calculated in 3D and separately for each light source, which increases kernel size. (2) An accurate kernel for light scattering in a heterogeneous medium requires ray tracing and volume partitioning, thus significant calculation time. To address these problems, two different kernels were examined and compared for speed of creation and accuracy of dose. Kernels derived more quickly involve simpler algorithms. Our goal is to achieve optimal dose planning with patient-specific heterogeneous optical data applied through accurate kernels, all within clinical times. The optimization process is restricted to accepting the given (interstitially inserted) sources, and determining the best source strengths with which to obtain a prescribed dose. The Cimmino feasibility algorithm is used for this purpose. The dose distribution and source weights obtained for each kernel are analyzed. In clinical use, optimization will also be performed prior to source insertion to obtain initial source positions, source lengths and source weights, but with the assumption of homogeneous optical properties. For this reason, we compare the results from heterogeneous optical data with those obtained from average homogeneous optical properties. The optimized treatment plans are also compared with the reference clinical plan, defined as the plan with sources of equal strength, distributed regularly in space, which delivers a mean value of prescribed fluence at detector locations within the treatment region. The study suggests that comprehensive optimization of source parameters (i.e. strengths, lengths and locations) is feasible, thus allowing acceptable dose coverage in a heterogeneous prostate PDT within the time constraints of the PDT procedure.

Optimized Non-Obstructive Particle Damping (NOPD) Treatment for Composite Honeycomb Structures

NASA Technical Reports Server (NTRS)

Panossian, H.

2008-01-01

Non-Obstructive Particle Damping (NOPD) technology is a passive vibration damping approach whereby metallic or non-metallic particles in spherical or irregular shapes, of heavy or light consistency, and even liquid particles are placed inside cavities or attached to structures by an appropriate means at strategic locations, to absorb vibration energy. The objective of the work described herein is the development of a design optimization procedure and discussion of test results for such a NOPD treatment on honeycomb (HC) composite structures, based on finite element modeling (FEM) analyses, optimization and tests. Modeling and predictions were performed and tests were carried out to correlate the test data with the FEM. The optimization procedure consisted of defining a global objective function, using finite difference methods, to determine the optimal values of the design variables through quadratic linear programming. The optimization process was carried out by targeting the highest dynamic displacements of several vibration modes of the structure and finding an optimal treatment configuration that will minimize them. An optimal design was thus derived and laboratory tests were conducted to evaluate its performance under different vibration environments. Three honeycomb composite beams, with Nomex core and aluminum face sheets, empty (untreated), uniformly treated with NOPD, and optimally treated with NOPD, according to the analytically predicted optimal design configuration, were tested in the laboratory. It is shown that the beam with optimal treatment has the lowest response amplitude. Described below are results of modal vibration tests and FEM analyses from predictions of the modal characteristics of honeycomb beams under zero, 50% uniform treatment and an optimal NOPD treatment design configuration and verification with test data.

Optically Based Rapid Screening Method for Proven Optimal Treatment Strategies Before Treatment Begins

DTIC Science & Technology

2015-08-01

lifetime ( t2 ) corresponds to protein- bound NADH (23). Conversely, protein-bound FAD corre- sponds to the short lifetime, whereas free FAD corresponds...single photon counting (TCSPC) electronics (SPC-150, Becker and Hickl). TCSPC uses a fast detector PMT to measure the time between a laser pulse and... Becker and Hickl). A binning of nine surrounding pixels was used. Then, the fluorescence lifetime components were computed for each pixel by deconvolving

Advanced stimulation technology deployment program: Sonat Exploration Company, Haynesville Formation, North Shongaloo, Red Rock Field, Columbia County, Arkansas and Webster Parish, Louisiana. Topical report, August 1995-January 1997

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

Skees, J.L.; Middlebrook, M.L.; Anthony, W.L.

1997-01-01

The objective of this program is to transfer the core GRI advanced stimulation technologies to Sonat Exploration Company for their continued use upon completion of the program. The methodology to accomplish the objective included seminars and training schools, offset well baseline analysis, fracture treatment design optimization, real-time and post-fracture treatment evaluation and documentation of economic benefits.

Dynamic response of C-type natriuretic peptide and its aminoterminal propeptide (NTproCNP) to growth hormone treatment in children with short stature.

PubMed

Olney, Robert C; Salehi, Parisa; Prickett, Timothy C R; Lima, John J; Espiner, Eric A; Sikes, Kaitlin M; Geffner, Mitchell E

2016-10-01

C-type natriuretic peptide (CNP) and its aminoterminal propeptide (NTproCNP) are potential biomarkers of recombinant human growth hormone (rhGH) efficacy. The objective of this study was to describe the pharmacodynamics of plasma CNP and NTproCNP levels in response to rhGH treatment and to identify the optimal time of sampling after starting rhGH. This was a prospective, observational study. Subjects were treated with rhGH for 1 year, with blood sampled at regular intervals. Eighteen prepubertal children, eight with low levels of GH on biochemical testing and ten with idiopathic short stature, completed the study. Blood levels of CNP, NTproCNP, GH, insulin-like growth factor-I, leptin and bone-specific alkaline phosphatase were measured. Anthropometrics were obtained. Plasma levels of both CNP and NTproCNP reached peak levels 7-28 days after starting rhGH treatment and then declined to intermediate levels through the first year. Plasma NTproCNP levels after 14 days trended towards a correlation with height velocity after 6 and 12 months of treatment. Unexpectedly, serum GH levels measured 2 and 28 days after starting rhGH correlated strongly with height velocity after 6 and 12 months of treatment. This study identified 14 days after starting rhGH treatment as the optimal time for assessing CNP and NTproCNP levels as biomarkers of rhGH efficacy. Additionally, we identified GH levels as a potential biomarker. Larger, prospective studies are now needed to test the clinical utility of these biomarkers. © 2016 John Wiley & Sons Ltd.

Effect of hydrothermal pre-treatment (HTP) on poultry slaughterhouse waste (PSW) sludge for the enhancement of the solubilization, physical properties, and biogas production through anaerobic digestion.

PubMed

Park, Seyong; Yoon, Young-Man; Han, Seong Kuk; Kim, Daegi; Kim, Ho

2017-06-01

This study is an assessment of the hydrothermal pre-treatment (HTP) of poultry slaughterhouse waste (PSW) sludge for the enhancement of the solubilization, physical properties, and biogas production through anaerobic digestion. This assessment was carried out to ascertain the optimal HTP temperature. The solubilization and physical properties efficacy was investigated by capillary suction time (CST), time to filter (TTF), and particle size. In addition, the anaerobic digestion was investigated through biochemical methane potential (BMP) tests and subsequent statistical analysis using the modified Gompertz model. HTP was found to have improved the solubilization of the PSW sludge with increasing HTP temperature. In addition, the results of the CST, TTF, and particle size decreased with increasing HTP temperature. These results of the assessment that was conducted in this study confirm that the HTP process indeed modifies the physical properties of PSWs to enhance the solubilization of organic solids. Nevertheless, the results of the BMP tests and the modified Gompertz model analysis show that the optimal HTP temperature of PSWs for anaerobic digestion is 190°C. These findings show that to achieve high conversion efficiency, an accurately designed pre-treatment step must be included in the overall anaerobic digestion process for wastewater treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hydraulic design to optimize the treatment capacity of Multi-Stage Filtration units

NASA Astrophysics Data System (ADS)

Mushila, C. N.; Ochieng, G. M.; Otieno, F. A. O.; Shitote, S. M.; Sitters, C. W.

2016-04-01

Multi-Stage Filtration (MSF) can provide a robust treatment alternative for surface water sources of variable water quality in rural communities at low operation and maintenance costs. MSF is a combination of Slow Sand Filters (SSFs) and Pre-treatment systems. The general objective of this research was to optimize the treatment capacity of MSF. A pilot plant study was undertaken to meet this objective. The pilot plant was monitored for a continuous 98 days from commissioning till the end of the project. Three main stages of MSF namely: The Dynamic Gravel Filter (DGF), Horizontal-flow Roughing Filter (HRF) and SSF were identified, designed and built. The response of the respective MSF units in removal of selected parameters guiding drinking water quality such as microbiological (Faecal and Total coliform), Suspended Solids, Turbidity, PH, Temperature, Iron and Manganese was investigated. The benchmark was the Kenya Bureau (KEBS) and World Health Organization (WHO) Standards for drinking water quality. With respect to microbiological raw water quality improvement, MSF units achieved on average 98% Faecal and 96% Total coliform removal. Results obtained indicate that implementation of MSF in rural communities has the potential to increase access to portable water to the rural populace with a probable consequent decrease in waterborne diseases. With a reduced down time due to illness, more time would be spent in undertaking other economic activities.

Comparison of Conventional and Microwave Treatment on Soymilk for Inactivation of Trypsin Inhibitors and In Vitro Protein Digestibility

PubMed Central

Vagadia, Brinda Harish; Raghavan, Vijaya

2018-01-01

Soymilk is lower in calories compared to cow’s milk, since it is derived from a plant source (no cholesterol) and is an excellent source of protein. Despite the beneficial factors, soymilk is considered as one of the most controversial foods in the world. It contains serine protease inhibitors which lower its nutritional value and digestibility. Processing techniques for the elimination of trypsin inhibitors and lipoxygenase, which have shorter processing time and lower production costs are required for the large-scale manufacturing of soymilk. In this study, the suitable conditions of time and temperature are optimized during microwave processing to obtain soymilk with maximum digestibility with inactivation of trypsin inhibitors, in comparison to the conventional thermal treatment. The microwave processing conditions at a frequency of 2.45 GHz and temperatures of 70 °C, 85 °C and 100 °C for 2, 5 and 8 min were investigated and were compared to conventional thermal treatments at the same temperature for 10, 20 and 30 min. Response surface methodology is used to design and optimize the experimental conditions. Thermal processing was able to increase digestibility by 7% (microwave) and 11% (conventional) compared to control, while trypsin inhibitor activity reduced to 1% in microwave processing and 3% in conventional thermal treatment when compared to 10% in raw soybean. PMID:29316679

Fiber, prebiotics, and diarrhea: what, why, when and how.

PubMed

Generoso, Simone de Vasconcelos; Lages, Priscilla Ceci; Correia, Maria Isabel Toulsson Davisson

2016-07-15

Dietary fiber and prebiotics have been the focus of research and discussion for decades, but there are still pending concepts and definitions, in particular when addressing their use in the prevention and treatment of diarrhea. The purpose of this review is to present the latest advances in the understanding of dietary fiber and prebiotics, to review their proven role in the management of diarrhea, and to postulate the best timings and optimal doses. The use of prebiotics has encompassed not only prevention but also the treatment of distinct types of diarrhea, at different treatment moments, and with regard to various different markers of outcome. Furthermore, the description of soluble fibers claiming to be prebiotics, and vice versa, has too often been the tone in the literature, which has led to misconceptions in classification and, consequently, confusion over the interpretation of results. It remains difficult to establish a consensus about the real impact of fiber and prebiotics on the prevention and therapy of diarrhea. The review highlights the overlapping concepts of fiber and prebiotics, and supports the need for adequate individualization of their use, according to the goal - either prevention or treatment of diarrhea - as well as the optimal timing and dose to be used. Nonetheless, viscous soluble fibers seem to be the best option in treating diarrhea, whereas prebiotics are more important in preventing and avoiding recurrence.

Investigating multi-objective fluence and beam orientation IMRT optimization

NASA Astrophysics Data System (ADS)

Potrebko, Peter S.; Fiege, Jason; Biagioli, Matthew; Poleszczuk, Jan

2017-07-01

Radiation Oncology treatment planning requires compromises to be made between clinical objectives that are invariably in conflict. It would be beneficial to have a ‘bird’s-eye-view’ perspective of the full spectrum of treatment plans that represent the possible trade-offs between delivering the intended dose to the planning target volume (PTV) while optimally sparing the organs-at-risk (OARs). In this work, the authors demonstrate Pareto-aware radiotherapy evolutionary treatment optimization (PARETO), a multi-objective tool featuring such bird’s-eye-view functionality, which optimizes fluence patterns and beam angles for intensity-modulated radiation therapy (IMRT) treatment planning. The problem of IMRT treatment plan optimization is managed as a combined monolithic problem, where all beam fluence and angle parameters are treated equally during the optimization. To achieve this, PARETO is built around a powerful multi-objective evolutionary algorithm, called Ferret, which simultaneously optimizes multiple fitness functions that encode the attributes of the desired dose distribution for the PTV and OARs. The graphical interfaces within PARETO provide useful information such as: the convergence behavior during optimization, trade-off plots between the competing objectives, and a graphical representation of the optimal solution database allowing for the rapid exploration of treatment plan quality through the evaluation of dose-volume histograms and isodose distributions. PARETO was evaluated for two relatively complex clinical cases, a paranasal sinus and a pancreas case. The end result of each PARETO run was a database of optimal (non-dominated) treatment plans that demonstrated trade-offs between the OAR and PTV fitness functions, which were all equally good in the Pareto-optimal sense (where no one objective can be improved without worsening at least one other). Ferret was able to produce high quality solutions even though a large number of parameters, such as beam fluence and beam angles, were included in the optimization.

Iterative dataset optimization in automated planning: Implementation for breast and rectal cancer radiotherapy.

PubMed

Fan, Jiawei; Wang, Jiazhou; Zhang, Zhen; Hu, Weigang

2017-06-01

To develop a new automated treatment planning solution for breast and rectal cancer radiotherapy. The automated treatment planning solution developed in this study includes selection of the iterative optimized training dataset, dose volume histogram (DVH) prediction for the organs at risk (OARs), and automatic generation of clinically acceptable treatment plans. The iterative optimized training dataset is selected by an iterative optimization from 40 treatment plans for left-breast and rectal cancer patients who received radiation therapy. A two-dimensional kernel density estimation algorithm (noted as two parameters KDE) which incorporated two predictive features was implemented to produce the predicted DVHs. Finally, 10 additional new left-breast treatment plans are re-planned using the Pinnacle 3 Auto-Planning (AP) module (version 9.10, Philips Medical Systems) with the objective functions derived from the predicted DVH curves. Automatically generated re-optimized treatment plans are compared with the original manually optimized plans. By combining the iterative optimized training dataset methodology and two parameters KDE prediction algorithm, our proposed automated planning strategy improves the accuracy of the DVH prediction. The automatically generated treatment plans using the dose derived from the predicted DVHs can achieve better dose sparing for some OARs without compromising other metrics of plan quality. The proposed new automated treatment planning solution can be used to efficiently evaluate and improve the quality and consistency of the treatment plans for intensity-modulated breast and rectal cancer radiation therapy. © 2017 American Association of Physicists in Medicine.

Allochthonous bioaugmentation in ex situ treatment of crude oil-polluted sediments in the presence of an effective degrading indigenous microbiome.

PubMed

Fodelianakis, S; Antoniou, E; Mapelli, F; Magagnini, M; Nikolopoulou, M; Marasco, R; Barbato, M; Tsiola, A; Tsikopoulou, I; Giaccaglia, L; Mahjoubi, M; Jaouani, A; Amer, R; Hussein, E; Al-Horani, F A; Benzha, F; Blaghen, M; Malkawi, H I; Abdel-Fattah, Y; Cherif, A; Daffonchio, D; Kalogerakis, N

2015-04-28

Oil-polluted sediment bioremediation depends on both physicochemical and biological parameters, but the effect of the latter cannot be evaluated without the optimization of the former. We aimed in optimizing the physicochemical parameters related to biodegradation by applying an ex-situ landfarming set-up combined with biostimulation to oil-polluted sediment, in order to determine the added effect of bioaugmentation by four allochthonous oil-degrading bacterial consortia in relation to the degradation efficiency of the indigenous community. We monitored hydrocarbon degradation, sediment ecotoxicity and hydrolytic activity, bacterial population sizes and bacterial community dynamics, characterizing the dominant taxa through time and at each treatment. We observed no significant differences in total degradation, but increased ecotoxicity between the different treatments receiving both biostimulation and bioaugmentation and the biostimulated-only control. Moreover, the added allochthonous bacteria quickly perished and were rarely detected, their addition inducing minimal shifts in community structure although it altered the distribution of the residual hydrocarbons in two treatments. Therefore, we concluded that biodegradation was mostly performed by the autochthonous populations while bioaugmentation, in contrast to biostimulation, did not enhance the remediation process. Our results indicate that when environmental conditions are optimized, the indigenous microbiome at a polluted site will likely outperform any allochthonous consortium. Copyright © 2015 Elsevier B.V. All rights reserved.

Problems Experienced by Ovarian Cancer Survivors During Treatment.

PubMed

Keim-Malpass, Jessica; Mihalko, Shannon L; Russell, Greg; Case, Doug; Miller, Brigitte; Avis, Nancy E

To identify problems at different treatment points (early treatment, mid-treatment, early posttreatment, and late posttreatment) among women with ovarian cancer. Longitudinal and cross-sectional study design. An academic and community clinical cancer center in the Southeastern United States. Sixty-eight women with Stage I to IV ovarian cancer. Variables assessed included reported problems (physical, psychosocial, pain, marital, medical interaction), social support, optimism, and responses to open-ended questions. Analysis involved mixed models for longitudinal repeated measures and unpaired t tests and content analysis to describe responses to open-ended questions. Physical and psychosocial problems were greatest during early treatment and decreased throughout the treatment trajectory. Women with greater levels of social support and optimism at baseline had fewer problems over time. Women who did not have trouble paying for basics had fewer problems related to pain and psychological problems. Problems across all domains must be addressed throughout the treatment trajectory, even after chemotherapy has ended. Nurses are well positioned to refer women appropriately to social workers and clinical navigators across all domains of care and should consider systematic assessment of patient-reported problems as a routine form of practice. Copyright © 2017 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.

Technical Note: Improving the VMERGE treatment planning algorithm for rotational radiotherapy

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

Gaddy, Melissa R., E-mail: mrgaddy@ncsu.edu; Papp,

2016-07-15

Purpose: The authors revisit the VMERGE treatment planning algorithm by Craft et al. [“Multicriteria VMAT optimization,” Med. Phys. 39, 686–696 (2012)] for arc therapy planning and propose two changes to the method that are aimed at improving the achieved trade-off between treatment time and plan quality at little additional planning time cost, while retaining other desirable properties of the original algorithm. Methods: The original VMERGE algorithm first computes an “ideal,” high quality but also highly time consuming treatment plan that irradiates the patient from all possible angles in a fine angular grid with a highly modulated beam and then makesmore » this plan deliverable within practical treatment time by an iterative fluence map merging and sequencing algorithm. We propose two changes to this method. First, we regularize the ideal plan obtained in the first step by adding an explicit constraint on treatment time. Second, we propose a different merging criterion that comprises of identifying and merging adjacent maps whose merging results in the least degradation of radiation dose. Results: The effect of both suggested modifications is evaluated individually and jointly on clinical prostate and paraspinal cases. Details of the two cases are reported. Conclusions: In the authors’ computational study they found that both proposed modifications, especially the regularization, yield noticeably improved treatment plans for the same treatment times than what can be obtained using the original VMERGE method. The resulting plans match the quality of 20-beam step-and-shoot IMRT plans with a delivery time of approximately 2 min.« less

The timing and targeting of treatment in influenza pandemics influences the emergence of resistance in structured populations.

PubMed

Althouse, Benjamin M; Patterson-Lomba, Oscar; Goerg, Georg M; Hébert-Dufresne, Laurent

2013-01-01

Antiviral resistance in influenza is rampant and has the possibility of causing major morbidity and mortality. Previous models have identified treatment regimes to minimize total infections and keep resistance low. However, the bulk of these studies have ignored stochasticity and heterogeneous contact structures. Here we develop a network model of influenza transmission with treatment and resistance, and present both standard mean-field approximations as well as simulated dynamics. We find differences in the final epidemic sizes for identical transmission parameters (bistability) leading to different optimal treatment timing depending on the number initially infected. We also find, contrary to previous results, that treatment targeted by number of contacts per individual (node degree) gives rise to more resistance at lower levels of treatment than non-targeted treatment. Finally we highlight important differences between the two methods of analysis (mean-field versus stochastic simulations), and show where traditional mean-field approximations fail. Our results have important implications not only for the timing and distribution of influenza chemotherapy, but also for mathematical epidemiological modeling in general. Antiviral resistance in influenza may carry large consequences for pandemic mitigation efforts, and models ignoring contact heterogeneity and stochasticity may provide misleading policy recommendations.

The duration of hyaluronidase and optimal timing of hyaluronic acid (HA) filler reinjection after hyaluronidase injection.

PubMed

Kim, H J; Kwon, S B; Whang, K U; Lee, J S; Park, Y L; Lee, S Y

2018-02-01

Hyaluronidase injection is a commonly performed treatment for overcorrection or misplacement of hyaluronic acid (HA) filler. Many patients often wants the HA filler reinjection after the use of hyaluronidase, though the optimal timing of reinjection of HA filler still remains unknown. To provide the optimal time interval between hyaluronidase injections and HA filler reinjections. 6 Sprague-Dawley rats were injected with single monophasic HA filler. 1 week after injection, the injected sites were treated with hyaluronidase. Then, HA fillers were reinjected sequentially with differing time intervals from 30 minutes to 14 days. 1 hour after the reinjection of the last HA filler, all injection sites were excised for histologic evaluation. 3 hours after reinjection of HA filler, the appearance of filler material became evident again, retaining its shape and volume. 6 hours after reinjection, the filler materials restored almost its original volume and there were no significant differences from the positive control. Our data suggest that the hyaluronidase loses its effect in dermis and subcutaneous tissue within 3-6 hours after the injection and successful engraftment of reinjected HA filler can be accomplished 6 hours after the injection.

High precision measurement of silicon in naphthas by ICP-OES using isooctane as diluent.

PubMed

Gazulla, M F; Rodrigo, M; Orduña, M; Ventura, M J; Andreu, C

2017-03-01

An analytical protocol for the accurate and precise determination of Si in naphthas is presented by using ICP-OES, optimizing from the sample preparation to the measurement conditions, in order to be able to analyze for the first time silicon contents below 100µgkg -1 in a relatively short time thus being used as a control method. In the petrochemical industry, silicon can be present as a contaminant in different petroleum products such as gasoline, ethanol, or naphthas, forming different silicon compounds during the treatment of these products that are irreversibly adsorbed onto catalyst surfaces decreasing its time life. The complex nature of the organic naphtha sample together with the low detection limits needed make the analysis of silicon quite difficult. The aim of this work is to optimize the measurement of silicon in naphthas by ICP-OES introducing as an improvement the use of isooctane as diluent. The set up was carried out by optimizing the measurement conditions (power, nebulizer flow, pump rate, read time, and viewing mode) and the sample preparation (type of diluent, cleaning process, blanks, and studying various dilution ratios depending on the sample characteristics). Copyright © 2016 Elsevier B.V. All rights reserved.

Antibiotic Cycling and Antibiotic Mixing: Which One Best Mitigates Antibiotic Resistance?

PubMed Central

Peña-Miller, Rafael; Gori, Fabio; Iredell, Jonathan

2017-01-01

Abstract Can we exploit our burgeoning understanding of molecular evolution to slow the progress of drug resistance? One role of an infection clinician is exactly that: to foresee trajectories to resistance during antibiotic treatment and to hinder that evolutionary course. But can this be done at a hospital-wide scale? Clinicians and theoreticians tried to when they proposed two conflicting behavioral strategies that are expected to curb resistance evolution in the clinic, these are known as “antibiotic cycling” and “antibiotic mixing.” However, the accumulated data from clinical trials, now approaching 4 million patient days of treatment, is too variable for cycling or mixing to be deemed successful. The former implements the restriction and prioritization of different antibiotics at different times in hospitals in a manner said to “cycle” between them. In antibiotic mixing, appropriate antibiotics are allocated to patients but randomly. Mixing results in no correlation, in time or across patients, in the drugs used for treatment which is why theorists saw this as an optimal behavioral strategy. So while cycling and mixing were proposed as ways of controlling evolution, we show there is good reason why clinical datasets cannot choose between them: by re-examining the theoretical literature we show prior support for the theoretical optimality of mixing was misplaced. Our analysis is consistent with a pattern emerging in data: neither cycling or mixing is a priori better than the other at mitigating selection for antibiotic resistance in the clinic. Key words: antibiotic cycling, antibiotic mixing, optimal control, stochastic models. PMID:28096304

Antibiotic Cycling and Antibiotic Mixing: Which One Best Mitigates Antibiotic Resistance?

PubMed

Beardmore, Robert Eric; Peña-Miller, Rafael; Gori, Fabio; Iredell, Jonathan

2017-04-01

Can we exploit our burgeoning understanding of molecular evolution to slow the progress of drug resistance? One role of an infection clinician is exactly that: to foresee trajectories to resistance during antibiotic treatment and to hinder that evolutionary course. But can this be done at a hospital-wide scale? Clinicians and theoreticians tried to when they proposed two conflicting behavioral strategies that are expected to curb resistance evolution in the clinic, these are known as "antibiotic cycling" and "antibiotic mixing." However, the accumulated data from clinical trials, now approaching 4 million patient days of treatment, is too variable for cycling or mixing to be deemed successful. The former implements the restriction and prioritization of different antibiotics at different times in hospitals in a manner said to "cycle" between them. In antibiotic mixing, appropriate antibiotics are allocated to patients but randomly. Mixing results in no correlation, in time or across patients, in the drugs used for treatment which is why theorists saw this as an optimal behavioral strategy. So while cycling and mixing were proposed as ways of controlling evolution, we show there is good reason why clinical datasets cannot choose between them: by re-examining the theoretical literature we show prior support for the theoretical optimality of mixing was misplaced. Our analysis is consistent with a pattern emerging in data: neither cycling or mixing is a priori better than the other at mitigating selection for antibiotic resistance in the clinic. : antibiotic cycling, antibiotic mixing, optimal control, stochastic models. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Automatic treatment planning facilitates fast generation of high-quality treatment plans for esophageal cancer.

PubMed

Hansen, Christian Rønn; Nielsen, Morten; Bertelsen, Anders Smedegaard; Hazell, Irene; Holtved, Eva; Zukauskaite, Ruta; Bjerregaard, Jon Kroll; Brink, Carsten; Bernchou, Uffe

2017-11-01

The quality of radiotherapy planning has improved substantially in the last decade with the introduction of intensity modulated radiotherapy. The purpose of this study was to analyze the plan quality and efficacy of automatically (AU) generated VMAT plans for inoperable esophageal cancer patients. Thirty-two consecutive inoperable patients with esophageal cancer originally treated with manually (MA) generated volumetric modulated arc therapy (VMAT) plans were retrospectively replanned using an auto-planning engine. All plans were optimized with one full 6MV VMAT arc giving 60 Gy to the primary target and 50 Gy to the elective target. The planning techniques were blinded before clinical evaluation by three specialized oncologists. To supplement the clinical evaluation, the optimization time for the AU plan was recorded along with DVH parameters for all plans. Upon clinical evaluation, the AU plan was preferred for 31/32 patients, and for one patient, there was no difference in the plans. In terms of DVH parameters, similar target coverage was obtained between the two planning methods. The mean dose for the spinal cord increased by 1.8 Gy using AU (p = .002), whereas the mean lung dose decreased by 1.9 Gy (p < .001). The AU plans were more modulated as seen by the increase of 12% in mean MUs (p = .001). The median optimization time for AU plans was 117 min. The AU plans were in general preferred and showed a lower mean dose to the lungs. The automation of the planning process generated esophageal cancer treatment plans quickly and with high quality.

Using Animated Computer Simulation to Determine the Optimal Resource Support for the Endodontic Specialty Practice at Fort Lewis.

DTIC Science & Technology

1998-03-01

Series Pt Endo Tx 114 Time Series Pt Perio Ex 114 None Pt Perio Tx 114 None Pt Perio Sx 114 None Pt Perio Pot 114 None Pt Exam 114 None Pt Other...prevention, diagnosis, and treatment of diseases and injuries that affect the dental pulp, tooth root, and periapical tissue" (Jablonski, 1982...Time Priority Scheduled Disable Logic Entrance 1 480 99 Yes No wait 180 * Entities * Name Speed (fpm) Stats Pt Endo Ex 114 Time

Effectiveness of internet-supported cognitive behavioral and chronobiological interventions and effect moderation by insomnia subtype: study protocol of a randomized controlled trial.

PubMed

Dekker, Kim; Benjamins, Jeroen S; Van Straten, Annemieke; Hofman, Winni F; Van Someren, Eus J W

2015-07-04

DSM-V criteria for insomnia disorder are met by 6 to 10% of the adult population. Insomnia has severe consequences for health and society. One of the most common treatments provided by primary caregivers is pharmacological treatment, which is far from optimal and has not been recommended since a 2005 consensus report of the National Institutes of Health. The recommended treatment is Cognitive Behavioral Therapy for Insomnia. Effectiveness, however, is still limited. Only a few studies have evaluated the effectiveness of chronobiological treatments, including the timed application of bright light, physical activity and body warming. Another opportunity for optimization of treatment is based on the idea that the people suffering from insomnia most likely represent a heterogeneous mix of subtypes, with different underlying causes and expected treatment responses. The present study aims to evaluate the possibility for optimizing insomnia treatment along the principles of personalized and stratified medicine. It evaluates the following: 1. The relative effectiveness of internet-supported cognitive behavioral therapy, bright light, physical activity and body warming; 2. Whether the effectiveness of internet-supported cognitive behavioral therapy for insomnia can be augmented by simultaneous or prior application of bright light, physical activity and body warming; and 3. Whether the effectiveness of the interventions and their combination are moderated by the insomnia subtype. In a repeated measures, placebo-controlled, randomized clinical trial that included 160 people diagnosed with insomnia disorder, we are evaluating the relative effectiveness of 4 intervention weeks. Primary outcome is subjective sleep efficiency, quantified using a sleep diary. Secondary outcomes include other complaints of sleep and daytime functioning, health-related cost estimates and actigraphic objective sleep estimates. Compliance will be monitored both subjectively and objectively using activity, light and temperature sensors. Insomnia subtypes will be assessed using questionnaires. Mixed effect models will be used to evaluate intervention effects and moderation by insomnia subtype ratings. The current study addresses multiple opportunities to optimize and personalize treatment of insomnia disorder. Netherlands National Trial Register NTR4010, 4 June 2013.

SU-E-T-628: A Cloud Computing Based Multi-Objective Optimization Method for Inverse Treatment Planning.

PubMed

Na, Y; Suh, T; Xing, L

2012-06-01

Multi-objective (MO) plan optimization entails generation of an enormous number of IMRT or VMAT plans constituting the Pareto surface, which presents a computationally challenging task. The purpose of this work is to overcome the hurdle by developing an efficient MO method using emerging cloud computing platform. As a backbone of cloud computing for optimizing inverse treatment planning, Amazon Elastic Compute Cloud with a master node (17.1 GB memory, 2 virtual cores, 420 GB instance storage, 64-bit platform) is used. The master node is able to scale seamlessly a number of working group instances, called workers, based on the user-defined setting account for MO functions in clinical setting. Each worker solved the objective function with an efficient sparse decomposition method. The workers are automatically terminated if there are finished tasks. The optimized plans are archived to the master node to generate the Pareto solution set. Three clinical cases have been planned using the developed MO IMRT and VMAT planning tools to demonstrate the advantages of the proposed method. The target dose coverage and critical structure sparing of plans are comparable obtained using the cloud computing platform are identical to that obtained using desktop PC (Intel Xeon® CPU 2.33GHz, 8GB memory). It is found that the MO planning speeds up the processing of obtaining the Pareto set substantially for both types of plans. The speedup scales approximately linearly with the number of nodes used for computing. With the use of N nodes, the computational time is reduced by the fitting model, 0.2+2.3/N, with r̂2>0.99, on average of the cases making real-time MO planning possible. A cloud computing infrastructure is developed for MO optimization. The algorithm substantially improves the speed of inverse plan optimization. The platform is valuable for both MO planning and future off- or on-line adaptive re-planning. © 2012 American Association of Physicists in Medicine.

Optimal Duration of Conservative Management Prior to Surgery for Cervical and Lumbar Radiculopathy: A Literature Review

PubMed Central

Alentado, Vincent J.; Lubelski, Daniel; Steinmetz, Michael P.; Benzel, Edward C.; Mroz, Thomas E.

2014-01-01

Study Design Literature review. Objective Since the 1970s, spine surgeons have commonly required 6 weeks of failed conservative treatment prior to considering surgical intervention for various spinal pathologies. It is unclear, however, if this standard has been validated in the literature. The authors review the natural history, outcomes, and cost-effectiveness studies relating to the current standard of 6 weeks of nonoperative care prior to surgery for patients with spinal pathologies. Methods A systematic Medline search from 1953 to 2013 was performed to identify natural history, outcomes, and cost-effectiveness studies relating to the optimal period of conservative management prior to surgical intervention for both cervical and lumbar radiculopathy. Demographic information, operative indications, and clinical outcomes are reviewed for each study. Results A total of 5,719 studies were identified; of these, 13 studies were selected for inclusion. Natural history studies demonstrated that 88% of patients with cervical radiculopathy and 70% of patients with lumbar radiculopathy showed improvement within 4 weeks following onset of symptoms. Outcomes and cost-effectiveness studies supported surgical intervention within 8 weeks of symptom onset for both cervical and lumbar radiculopathy. Conclusions There are limited studies supporting any optimal duration of conservative treatment prior to surgery for cervical and lumbar radiculopathy. Therefore, evidence-based conclusions cannot be made. Based on the available literature, we suggest that an optimal timing for surgery following cervical radiculopathy is within 8 weeks of onset of symptoms. A shorter period of 4 weeks may be appropriate based on natural history studies. Additionally, we found that optimal timing for surgery following lumbar radiculopathy is between 4 and 8 weeks. A prospective study is needed to explicitly identify the optimal duration of conservative therapy prior to surgery so that costs may be reduced and patient outcomes improved. PMID:25396110

Posttreatment Lyme disease syndrome.

PubMed

Aucott, John N

2015-06-01

The prognosis following appropriate antibiotic treatment of early or late Lyme disease is favorable but can be complicated by persistent symptoms of unknown cause termed posttreatment Lyme disease syndrome (PTLDS), characterized by fatigue, musculoskeletal pain, and cognitive complaints that persist for 6 months or longer after completion of antibiotic therapy. Risk factors include delayed diagnosis, increased severity of symptoms, and presence of neurologic symptoms at time of initial treatment. Two-tier serologic testing is neither sensitive nor specific for diagnosis of PTLDS because of variability in convalescent serologic responses after treatment of early Lyme disease. Optimal treatment of PTLDS awaits more precise understanding of the pathophysiologic mechanisms involved in this illness and future treatment trials. Copyright © 2015 Elsevier Inc. All rights reserved.

Advanced Exploration Systems Logistics Reduction and Repurposing Trash-to-Gas and Heat Melt Compactor KSC

NASA Technical Reports Server (NTRS)

Caraccio, Anne J.; Layne, Andrew; Hummerick, Mary

2013-01-01

Topics covered: 1. Project Structure 2. "Trash to Gas" 3. "Smashing Trash! The Heat Melt Compactor" 4. "Heat Melt Compaction as an Effective Treatment for Eliminating Microorganisms from Solid Waste" Thermal degradation of trash reduces volume while creating water, carbon dioxide and ash. CO2 can be fed to Sabatier reactor for CH4 production to fuel LOX/LCH4 ascent vehicle. Optimal performance: HFWS, full temperature ramp to 500-600 C. Tar challenges exist. Catalysis: Dolomag did eliminate allene byproducts from the product stream. 2nd Gen Reactor Studies. Targeting power, mass, time efficiency. Gas separation, Catalysis to reduce tar formation. Microgravity effects. Downselect in August will determine where we should spend time optimizing the technology.

Timing of Surgery in Rasmussen Syndrome: Is Patience a Virtue?

PubMed Central

Hartman, Adam L.; Cross, J. Helen

2014-01-01

Rasmussen syndrome affects previously normal people and forever changes their lives and the lives of their families. Although understood as a probable autoimmune condition, medical treatment remains limited and surgery remains the only cure, although with inevitable functional consequences. Difficulties remain in deciding on the optimal timing of surgery. Here, we review data available to aid clinicians faced with making the decision of when to recommend hemispherectomy. Not all patients have rapidly progressive disease, however, and such patients may benefit from immunomodulatory treatment. Thus, a patient's clinical course requires careful evaluation in order to identify those who would benefit most from early surgery. PMID:24955069

EUD-based biological optimization for carbon ion therapy

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

Brüningk, Sarah C., E-mail: sarah.brueningk@icr.ac.uk; Kamp, Florian; Wilkens, Jan J.

2015-11-15

Purpose: Treatment planning for carbon ion therapy requires an accurate modeling of the biological response of each tissue to estimate the clinical outcome of a treatment. The relative biological effectiveness (RBE) accounts for this biological response on a cellular level but does not refer to the actual impact on the organ as a whole. For photon therapy, the concept of equivalent uniform dose (EUD) represents a simple model to take the organ response into account, yet so far no formulation of EUD has been reported that is suitable to carbon ion therapy. The authors introduce the concept of an equivalentmore » uniform effect (EUE) that is directly applicable to both ion and photon therapies and exemplarily implemented it as a basis for biological treatment plan optimization for carbon ion therapy. Methods: In addition to a classical EUD concept, which calculates a generalized mean over the RBE-weighted dose distribution, the authors propose the EUE to simplify the optimization process of carbon ion therapy plans. The EUE is defined as the biologically equivalent uniform effect that yields the same probability of injury as the inhomogeneous effect distribution in an organ. Its mathematical formulation is based on the generalized mean effect using an effect-volume parameter to account for different organ architectures and is thus independent of a reference radiation. For both EUD concepts, quadratic and logistic objective functions are implemented into a research treatment planning system. A flexible implementation allows choosing for each structure between biological effect constraints per voxel and EUD constraints per structure. Exemplary treatment plans are calculated for a head-and-neck patient for multiple combinations of objective functions and optimization parameters. Results: Treatment plans optimized using an EUE-based objective function were comparable to those optimized with an RBE-weighted EUD-based approach. In agreement with previous results from photon therapy, the optimization by biological objective functions resulted in slightly superior treatment plans in terms of final EUD for the organs at risk (OARs) compared to voxel-based optimization approaches. This observation was made independent of the underlying objective function metric. An absolute gain in OAR sparing was observed for quadratic objective functions, whereas intersecting DVHs were found for logistic approaches. Even for considerable under- or overestimations of the used effect- or dose–volume parameters during the optimization, treatment plans were obtained that were of similar quality as the results of a voxel-based optimization. Conclusions: EUD-based optimization with either of the presented concepts can successfully be applied to treatment plan optimization. This makes EUE-based optimization for carbon ion therapy a useful tool to optimize more specifically in the sense of biological outcome while voxel-to-voxel variations of the biological effectiveness are still properly accounted for. This may be advantageous in terms of computational cost during treatment plan optimization but also enables a straight forward comparison of different fractionation schemes or treatment modalities.« less

Patient-Reported Health-Related Quality of Life Is a Predictor of Outcomes in Ambulatory Heart Failure Patients Treated With Left Ventricular Assist Device Compared With Medical Management: Results From the ROADMAP Study (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management).

PubMed

Stehlik, Josef; Estep, Jerry D; Selzman, Craig H; Rogers, Joseph G; Spertus, John A; Shah, Keyur B; Chuang, Joyce; Farrar, David J; Starling, Randall C

2017-06-01

The prospective observational ROADMAP study (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management) demonstrated that ambulatory advanced heart failure patients selected for left ventricular assist device (LVAD) were more likely to be alive at 1 year on original therapy with ≥75-m improvement in 6-minute walk distance compared with patients assigned to optimal medical management. Whether baseline health-related quality of life (hrQoL) resulted in a heterogeneity of this treatment benefit is unknown. Patient-reported hrQoL was assessed with EuroQol questionnaire and visual analogue scale (VAS). We aimed to identify predictors of event-free survival and survival with acceptable hrQoL (VAS≥60). LVAD patients had significant improvement in 3 of 5 EuroQol dimensions ( P <0.05), but no significant changes were observed with optimal medical management. Among patients with baseline VAS<55, survival on original treatment was lower for optimal medical management patients compared with those assigned to LVAD (58±7% versus 82±5%; P =0.004). No such difference was seen if baseline VAS was ≥55 (70±7% versus 75±9%; P =0.79). Survival on original therapy with acceptable quality of life was also more likely with LVAD versus optimal medical management if baseline VAS was <55, whereas outcomes in patients with higher baseline VAS scores were similar regardless of treatment assignment ( P =0.046 for treatment arm and baseline VAS interaction). LVAD therapy resulted in improvement of patient health status in heart failure patients with low self-reported hrQoL, but not in patients with acceptable quality of life at the time of LVAD implantation. Patient-reported hrQoL should be integrated into decision making concerning the use and timing of LVAD therapy in heart failure patients who are symptom limited but remain ambulatory. URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01452802. © 2017 American Heart Association, Inc.

Automated treatment planning for a dedicated multi-source intra-cranial radiosurgery treatment unit accounting for overlapping structures and dose homogeneity

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

Ghobadi, Kimia; Ghaffari, Hamid R.; Aleman, Dionne M.

2013-09-15

Purpose: The purpose of this work is to advance the two-step approach for Gamma Knife{sup ®} Perfexion™ (PFX) optimization to account for dose homogeneity and overlap between the planning target volume (PTV) and organs-at-risk (OARs).Methods: In the first step, a geometry-based algorithm is used to quickly select isocentre locations while explicitly accounting for PTV-OARs overlaps. In this approach, the PTV is divided into subvolumes based on the PTV-OARs overlaps and the distance of voxels to the overlaps. Only a few isocentres are selected in the overlap volume, and a higher number of isocentres are carefully selected among voxels that aremore » immediately close to the overlap volume. In the second step, a convex optimization is solved to find the optimal combination of collimator sizes and their radiation duration for each isocentre location.Results: This two-step approach is tested on seven clinical cases (comprising 11 targets) for which the authors assess coverage, OARs dose, and homogeneity index and relate these parameters to the overlap fraction for each case. In terms of coverage, the mean V{sub 99} for the gross target volume (GTV) was 99.8% while the V{sub 95} for the PTV averaged at 94.6%, thus satisfying the clinical objectives of 99% for GTV and 95% for PTV, respectively. The mean relative dose to the brainstem was 87.7% of the prescription dose (with maximum 108%), while on average, 11.3% of the PTV overlapped with the brainstem. The mean beam-on time per fraction per dose was 8.6 min with calibration dose rate of 3.5 Gy/min, and the computational time averaged at 205 min. Compared with previous work involving single-fraction radiosurgery, the resulting plans were more homogeneous with average homogeneity index of 1.18 compared to 1.47.Conclusions: PFX treatment plans with homogeneous dose distribution can be achieved by inverse planning using geometric isocentre selection and mathematical modeling and optimization techniques. The quality of the obtained treatment plans are clinically satisfactory while the homogeneity index is improved compared to conventional PFX plans.« less

Optimization of radiation treatment of ginger ( Zingiber officinale) rhizomes using response surface methodology

NASA Astrophysics Data System (ADS)

Nketsia-Tabiri, Josephine

1998-06-01

The effects of pre-irradiation storage time (7-21 days), radiation dose (0-75 Gy) and post-irradiation storage time (2-20 weeks) on sprouting, wrinkling and weight loss of ginger was investigated using a central composite rotatable design. Predictive models developed for all three responses were highly significant. Weight loss and wrinkling decreased as pre-irradiation storage time increased. Dose and post-irradiation storage time had significant interactive effects on weight loss and sprouting. Processing conditions for achieving minimal sprouting resulted in maximum weight loss and wrinkling.

An Optimized Analytical Method for the Simultaneous Detection of Iodoform, Iodoacetic Acid, and Other Trihalomethanes and Haloacetic Acids in Drinking Water

PubMed Central

Jiang, Songhui; Templeton, Michael R.; He, Gengsheng; Qu, Weidong

2013-01-01

An optimized method is presented using liquid-liquid extraction and derivatization for the extraction of iodoacetic acid (IAA) and other haloacetic acids (HAA9) and direct extraction of iodoform (IF) and other trihalomethanes (THM4) from drinking water, followed by detection by gas chromatography with electron capture detection (GC-ECD). A Doehlert experimental design was performed to determine the optimum conditions for the five most significant factors in the derivatization step: namely, the volume and concentration of acidic methanol (optimized values  = 15%, 1 mL), the volume and concentration of Na2SO4 solution (129 g/L, 8.5 mL), and the volume of saturated NaHCO3 solution (1 mL). Also, derivatization time and temperature were optimized by a two-variable Doehlert design, resulting in the following optimized parameters: an extraction time of 11 minutes for IF and THM4 and 14 minutes for IAA and HAA9; mass of anhydrous Na2SO4 of 4 g for IF and THM4 and 16 g for IAA and HAA9; derivatization time of 160 min and temperature at 40°C. Under optimal conditions, the optimized procedure achieves excellent linearity (R2 ranges 0.9990–0.9998), low detection limits (0.0008–0.2 µg/L), low quantification limits (0.008–0.4 µg/L), and good recovery (86.6%–106.3%). Intra- and inter-day precision were less than 8.9% and 8.8%, respectively. The method was validated by applying it to the analysis of raw, flocculated, settled, and finished waters collected from a water treatment plant in China. PMID:23613747

TU-AB-303-01: A Feasibility Study for Dynamic Adaptive Therapy of Non-Small Cell Lung Cancer

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

Kim, M; Phillips, M

2015-06-15

Purpose: To compare plans for NSCLC optimized using Dynamic Adaptive Therapy (DAT) with conventional IMRT optimization. DAT adapts plans based on changes in the target volume by using dynamic programing techniques to consider expected changes into the optimization process. Information gathered during treatment, e.g. from CBCT, is incorporated into the optimization. Methods and materials: DAT is formulated using stochastic control formalism, which minimizes the total expected number of tumor cells at the end of a treatment course subject to uncertainty inherent in the tumor response and organs-at-risk (OAR) dose constraints. This formulation allows for non-stationary dose distribution as well asmore » non-stationary fractional dose as needed to achieve a series of optimal plans that are conformal to tumor over time. Sixteen phantom cases with various sizes and locations of tumors, and OAR geometries were generated. Each case was planned with DAT and conventional IMRT (60Gy/30fx). Tumor volume change over time was obtained by using, daily MVCT-based, two-level cell population model. Monte Carlo simulations have been performed for each treatment course to account for uncertainty in tumor response. Same OAR dose constraints were applied for both methods. The frequency of plan modification was varied to 1, 2, 5 (weekly), and 29 (daily). The final average tumor dose and OAR doses have been compared to quantify the potential benefit of DAT. Results: The average tumor max, min, mean, and D95 resulted from DAT were 124.0–125.2%, 102.1–114.7%, 113.7–123.4%, and 102.0–115.9% (range dependent on the frequency of plan modification) of those from conventional IMRT. Cord max, esophagus max, lung mean, heart mean, and unspecified tissue D05 resulted from AT were 84–102.4%, 99.8–106.9%, 66.9–85.6%, 58.2–78.8%, and 85.2–94.0% of those from conventional IMRT. Conclusions: Significant tumor dose increase and OAR dose reduction, especially with parallel OAR with mean or dose-volume constraints, can be achieved using DAT.« less

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

Guida, K; Qamar, K; Thompson, M

Purpose: The RTOG 1005 trial offered a hypofractionated arm in delivering WBRT+SIB. Traditionally, treatments were planned at our institution using field-in-field (FiF) tangents with a concurrent 3D conformal boost. With the availability of VMAT, it is possible that a hybrid VMAT-3D planning technique could provide another avenue in treating WBRT+SIB. Methods: A retrospective study of nine patients previously treated using RTOG 1005 guidelines was performed to compare FiF+3D plans with the hybrid technique. A combination of static tangents and partial VMAT arcs were used in base-dose optimization. The hybrid plans were optimized to deliver 4005cGy to the breast PTVeval andmore » 4800cGy to the lumpectomy PTVeval over 15 fractions. Plans were optimized to meet the planning goals dictated by RTOG 1005. Results: Hybrid plans yielded similar coverage of breast and lumpectomy PTVs (average D95 of 4013cGy compared to 3990cGy for conventional), while reducing the volume of high dose within the breast; the average D30 and D50 for the hybrid technique were 4517cGy and 4288cGy, compared to 4704cGy and 4377cGy for conventional planning. Hybrid plans increased conformity as well, yielding CI95% values of 1.22 and 1.54 for breast and lumpectomy PTVeval volumes; in contrast, conventional plans averaged 1.49 and 2.27, respectively. The nearby organs at risk (OARs) received more low dose with the hybrid plans due to low dose spray from the partial arcs, but all hybrid plans did meet the acceptable constraints, at a minimum, from the protocol. Treatment planning time was also reduced, as plans were inversely optimized (VMAT) rather than forward optimized. Conclusion: Hybrid-VMAT could be a solution in delivering WB+SIB, as plans yield very conformal treatment plans and maintain clinical standards in OAR sparing. For treating breast cancer patients with a simultaneously-integrated boost, Hybrid-VMAT offers superiority in dosimetric conformity and planning time as compared to FIF techniques.« less

Optimal routes of administration, vehicles and timing of progesterone treatment for inhibition of delivery during pregnancy.

PubMed

Fang, Dajun; Moreno, Mario; Garfield, Robert E; Kuon, Ruben; Xia, Huimin

2017-09-01

Progestins, notably progesterone (P4) and 17 alpha hydroxyprogesterone caproate, are presently used to treat pregnant women at risk of preterm birth. The aim of this study was to assess the optimal treatment options for progesterone (P4) to delay delivery using a sensitive bioassay for progesterone. Pregnant rats, known to be highly sensitive to progestins, were treated with P4, including Prochieve ® (also known as Crinone ® ), in various vehicles from day 13 of gestation and in late gestation, days 19 to 22, and delivery times noted. Various routes of administration of P4 and various treatment periods were studied. Use of micronized P4 by rectal, subcutaneous injection (sc) and topical (transdermal) administration in various oils all significantly (P<0.05-<0.001) delay delivery, but vaginal Prochieve ® did not. Administration of P4 in late gestation also prevented (P<0.001) delivery even when given 8h before delivery. Prochieve ® possesses little biological activity to suppress delivery in a sensitive bioassay system and suggests that this preparation may be of little value in prevention and inhibition of preterm birth. Further, this study shows: 1) Inhibition of delivery is increased with P4 treatments when given subcutaneously or topically. 2) P4 in fish oil provides the best vehicle for topical treatment and may be an effective treatment of preterm birth. 3) P4 in fish oil also delays delivery even when treatment begins just prior to normal delivery. 4) To prevent preterm birth in pregnant women, randomized controlled studies are needed with a potent progestin using better formulations and routes of administration. Copyright © 2017. Published by Elsevier B.V.

Maximizing the potential of direct aperture optimization through collimator rotation

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

Milette, Marie-Pierre; Otto, Karl; Medical Physics, BC Cancer Agency-Vancouver Centre, Vancouver, British Columbia

Intensity-modulated radiation therapy (IMRT) treatment plans are conventionally produced by the optimization of fluence maps followed by a leaf sequencing step. An alternative to fluence based inverse planning is to optimize directly the leaf positions and field weights of multileaf collimator (MLC) apertures. This approach is typically referred to as direct aperture optimization (DAO). It has been shown that equivalent dose distributions may be generated that have substantially fewer monitor units (MU) and number of apertures compared to fluence based optimization techniques. Here we introduce a DAO technique with rotated apertures that we call rotating aperture optimization (RAO). The advantagesmore » of collimator rotation in IMRT have been shown previously and include higher fluence spatial resolution, increased flexibility in the generation of aperture shapes and less interleaf effects. We have tested our RAO algorithm on a complex C-shaped target, seven nasopharynx cancer recurrences, and one multitarget nasopharynx carcinoma patient. A study was performed in order to assess the capabilities of RAO as compared to fixed collimator angle DAO. The accuracy of fixed and rotated collimator aperture delivery was also verified. An analysis of the optimized treatment plans indicates that plans generated with RAO are as good as or better than DAO while maintaining a smaller number of apertures and MU than fluence based IMRT. Delivery verification results show that RAO is less sensitive to tongue and groove effects than DAO. Delivery time is currently increased due to the collimator rotation speed although this is a mechanical limitation that can be eliminated in the future.« less

Development of a protocol to optimize electric power consumption and life cycle environmental impacts for operation of wastewater treatment plant.

PubMed

Piao, Wenhua; Kim, Changwon; Cho, Sunja; Kim, Hyosoo; Kim, Minsoo; Kim, Yejin

2016-12-01

In wastewater treatment plants (WWTPs), the portion of operating costs related to electric power consumption is increasing. If the electric power consumption decreased, however, it would be difficult to comply with the effluent water quality requirements. A protocol was proposed to minimize the environmental impacts as well as to optimize the electric power consumption under the conditions needed to meet the effluent water quality standards in this study. This protocol was comprised of six phases of procedure and was tested using operating data from S-WWTP to prove its applicability. The 11 major operating variables were categorized into three groups using principal component analysis and K-mean cluster analysis. Life cycle assessment (LCA) was conducted for each group to deduce the optimal operating conditions for each operating state. Then, employing mathematical modeling, six improvement plans to reduce electric power consumption were deduced. The electric power consumptions for suggested plans were estimated using an artificial neural network. This was followed by a second round of LCA conducted on the plans. As a result, a set of optimized improvement plans were derived for each group that were able to optimize the electric power consumption and life cycle environmental impact, at the same time. Based on these test results, the WWTP operating management protocol presented in this study is deemed able to suggest optimal operating conditions under which power consumption can be optimized with minimal life cycle environmental impact, while allowing the plant to meet water quality requirements.

Cost analysis of biologic drugs in rheumatoid arthritis first line treatment after methotrexate failure according to patients' body weight.

PubMed

Román Ivorra, José Andrés; Ivorra, José; Monte-Boquet, Emilio; Canal, Cristina; Oyagüez, Itziar; Gómez-Barrera, Manuel

2016-01-01

The objective was to assess the influence of patients' weight in the cost of rheumatoid arthritis treatment with biologic drugs used in first line after non-adequate response to methotrexate. Pharmaceutical and administration costs were calculated in two scenarios: non-optimization and optimization of intravenous (IV) vials. The retrospective analysis of 66 patients from a Spanish 1,000 beds-hospital Rheumatology Clinic Service was used to obtain posology and weight data. The study time horizon was two years. Costs were expressed in 2013 euros. For an average 69kg-weighted patient the lowest cost corresponded to abatacept subcutaneous (SC ABA) (€21,028.09) in the scenario without IV vials optimization and infliximab (IFX) (€20,779.29) with optimization. Considering patients' weight in the scenario without IV vials optimization infliximab (IFX) was the least expensive drug in patients ranged 45-49kg, IV ABA in 50-59kg and SC ABA in patients over 60kg. With IV vials optimization IFX was the least expensive drug in patients under 69kg and SC ABA over 70kg. Assuming comparable effectiveness of biological drugs, patient's weight is a variable to consider, potentials savings could reach €20,000 in two years. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Withdrawal-oriented therapy for smokers.

PubMed

Hajek, P

1989-06-01

The treatment approach of the Maudsley Hospital Smokers Clinic is described. It stems from the notion that smokers seeking help are dependent on nicotine, and that withdrawal discomfort is a major block to their success in quitting. Accordingly, therapy focuses on helping clients overcome nicotine deprivation. It uses nicotine replacement and a special format of group treatment. Details are given of preparation of clients, use of nicotine chewing gum, use of group-oriented groupwork, use of information about withdrawal, and training in withdrawal-oriented therapy. Data are presented concerning characteristics of the clientele, treatment adherence, and treatment results. A number of controversial issues are addressed, such as the optimal duration of treatment, timing of the quit date, the value of educational input, and the value of individualization of treatment goals.

Hydraulic Fracturing Treatment Controls on Induced Microseismicity Attributes

NASA Astrophysics Data System (ADS)

Reyes-Montes, J. M.; Kelly, C.; Huang, J.; Zhao, X.; Young, R. P.

2014-12-01

Hydraulic fracturing imposes stress changes in the treated rock through the injection of a mix of fluid and proppant at variable rates and can result in stimulated microseismicity (induced or triggered) with a wide range of magnitudes associated to the opening of new cracks or the mobilisation of pre-existing fractures. Optimizing the treatment is vital for the economic and sustainable development of hydrocarbon reservoir and for the minimization of potential environmental impacts. The analysis of the induced seismicity and of event parameters provide an estimate of the effect of the treatment and the extent of the changes in the rock reservoir properties affecting fluid conductivity. This gives critical feedback for the optimization of the treatment, especially during real-time monitoring. In this study, we correlate microseismic attributes such as the fracture dimensions, event distribution and b-values with the fluid treatment parameters such as the pumping pressure and the slurry rate across different reservoir treatments. Although the microseismic attributes are influenced by many different factors such as the reservoir elastic properties, the stress regime and in-situ fracturing, we consistently observed positive correlations between the slurry rate, plateau treatment pressure and the fracture dimensions. In addition, the variation and systematic deviation of b-value from the natural average of 1.0 gives an insight into the geomechanical behavior of the reservoir. Similar to b-value, another fractal dimension, D-value, indicates the fracture spatial propagation from linear advancement (D=1.0) to planar distribution (D=2.0) to full space occurrence (D=3.0). By merging microseismic events from multiple treatment stages, we statistically analyzed magnitude distribution and spatial and temporal structure of the microseismic cloud induced during the stimulation of a range of different reservoirs with a total population of ~20,000 MS events. Analysis on multiple treatment projects can provide a first order guidance on selecting optimal treatment parameters.

Optimizing Quality of Life in Patients with Hormone Receptor-Positive Metastatic Breast Cancer: Treatment Options and Considerations.

PubMed

Chalasani, Pavani

2017-01-01

The treatment landscape for hormone receptor-positive metastatic breast cancer continues to evolve as the molecular mechanisms of this heterogeneous disease are better understood and targeted treatment strategies are developed. Patients are now living for extended periods of time with this disease as they progress through sequential lines of treatment. With a rapidly expanding therapeutic armamentarium, the prevalence of metastatic breast cancer patients with prolonged survival is expected to increase, as is the duration of survival. Practice guidelines recommend endocrine therapy alone as first-line therapy for the majority of patients with metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. The approval of new agents and expanded combination options has extended their use beyond first line, but endocrine therapy is not used as widely in clinical practice as recommended. As all treatments are palliative, even as survival is prolonged, optimizing and maintaining patient quality of life is crucial. This article surveys data relevant to the use of endocrine therapy in the setting of hormone receptor-positive metastatic breast cancer, including key clinical evidence regarding approved therapies and the impact of these therapies on patient quality of life. © 2017 S. Karger AG, Basel.

Maximizing the probability of satisfying the clinical goals in radiation therapy treatment planning under setup uncertainty

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

Fredriksson, Albin, E-mail: albin.fredriksson@raysearchlabs.com; Hårdemark, Björn; Forsgren, Anders

2015-07-15

Purpose: This paper introduces a method that maximizes the probability of satisfying the clinical goals in intensity-modulated radiation therapy treatments subject to setup uncertainty. Methods: The authors perform robust optimization in which the clinical goals are constrained to be satisfied whenever the setup error falls within an uncertainty set. The shape of the uncertainty set is included as a variable in the optimization. The goal of the optimization is to modify the shape of the uncertainty set in order to maximize the probability that the setup error will fall within the modified set. Because the constraints enforce the clinical goalsmore » to be satisfied under all setup errors within the uncertainty set, this is equivalent to maximizing the probability of satisfying the clinical goals. This type of robust optimization is studied with respect to photon and proton therapy applied to a prostate case and compared to robust optimization using an a priori defined uncertainty set. Results: Slight reductions of the uncertainty sets resulted in plans that satisfied a larger number of clinical goals than optimization with respect to a priori defined uncertainty sets, both within the reduced uncertainty sets and within the a priori, nonreduced, uncertainty sets. For the prostate case, the plans taking reduced uncertainty sets into account satisfied 1.4 (photons) and 1.5 (protons) times as many clinical goals over the scenarios as the method taking a priori uncertainty sets into account. Conclusions: Reducing the uncertainty sets enabled the optimization to find better solutions with respect to the errors within the reduced as well as the nonreduced uncertainty sets and thereby achieve higher probability of satisfying the clinical goals. This shows that asking for a little less in the optimization sometimes leads to better overall plan quality.« less

Methodologies in the modeling of combined chemo-radiation treatments

NASA Astrophysics Data System (ADS)

Grassberger, C.; Paganetti, H.

2016-11-01

The variety of treatment options for cancer patients has increased significantly in recent years. Not only do we combine radiation with surgery and chemotherapy, new therapeutic approaches such as immunotherapy and targeted therapies are starting to play a bigger role. Physics has made significant contributions to radiation therapy treatment planning and delivery. In particular, treatment plan optimization using inverse planning techniques has improved dose conformity considerably. Furthermore, medical physics is often the driving force behind tumor control and normal tissue complication modeling. While treatment optimization and outcome modeling does focus mainly on the effects of radiation, treatment modalities such as chemotherapy are treated independently or are even neglected entirely. This review summarizes the published efforts to model combined modality treatments combining radiation and chemotherapy. These models will play an increasing role in optimizing cancer therapy not only from a radiation and drug dosage standpoint, but also in terms of spatial and temporal optimization of treatment schedules.

A Fluorescent Tile DNA Diagnocode System for In Situ Rapid and Selective Diagnosis of Cytosolic RNA Cancer Markers

PubMed Central

Park, Kyung Soo; Shin, Seung Won; Jang, Min Su; Shin, Woojung; Yang, Kisuk; Min, Junhong; Cho, Seung-Woo; Oh, Byung-Keun; Bae, Jong Wook; Jung, Sunghwan; Choi, Jeong-Woo; Um, Soong Ho

2015-01-01

Accurate cancer diagnosis often requires extraction and purification of genetic materials from cells, and sophisticated instrumentations that follow. Otherwise in order to directly treat the diagnostic materials to cells, multiple steps to optimize dose concentration and treatment time are necessary due to diversity in cellular behaviors. These processes may offer high precision but hinder fast analysis of cancer, especially in clinical situations that need rapid detection and characterization of cancer. Here we present a novel fluorescent tile DNA nanostructure delivered to cancer cytosol by employing nanoparticle technology. Its structural anisotropicity offers easy manipulation for multifunctionalities, enabling the novel DNA nanostructure to detect intracellular cancer RNA markers with high specificity within 30 minutes post treatment, while the nanoparticle property bypasses the requirement of treatment optimization, effectively reducing the complexity of applying the system for cancer diagnosis. Altogether, the system offers a precise and rapid detection of cancer, suggesting the future use in the clinical fields. PMID:26678430

[Subcutaneous bortezomib as a new promising way to successful maintenance therapy in multiple myeloma].

PubMed

Grosicki, Sebastian

2012-01-01

Multiple myeloma (MM) despite the introduction to clinical practice of a new drugs in the last years, and still searching of new points of the handle for targeting treatment, remaining incurable disease. Even most intensive and most modern induction-consolidation regimens is not in the state to eradicate of the clone of myeloma, and even complete remission in immunofixation the most often after some time ends progression. Optimal way of maintenance treatment is still searching, which would be maximally effective near acceptable toxicity. Now hypothesis about possible successful maintenance therapy, which may prolong survival of MM patients became more actual in the face of the introduction to the studies with maintenance of a new drugs as: thalidomide, lenalidomide and bortesomib. The expectations on the essential progress to establish the optimal bortesomib-based regimen of the maintenance treatment in MM cause the results of the studies with its subcutaneous administration, which proved comparable efficacy with advantage in toxicity profile, especially neurological in comparison to classic intravenous way.

Comparison between DCA - SSO - VDR and VMAT dose delivery techniques for 15 SRS/SRT patients

NASA Astrophysics Data System (ADS)

Tas, B.; Durmus, I. F.

2018-02-01

To evaluate dose delivery between Dynamic Conformal Arc (DCA) - Segment Shape Optimization (SSO) - Variation Dose Rate (VDR) and Volumetric Modulated Arc Therapy (VMAT) techniques for fifteen SRS patients using Versa HD® lineer accelerator. Fifteen SRS / SRT patient's optimum treatment planning were performed using Monaco5.11® treatment planning system (TPS) with 1 coplanar and 3 non-coplanar fields for VMAT technique, then the plans were reoptimized with the same optimization parameters for DCA - SSO - VDR technique. The advantage of DCA - SSO - VDR technique were determined less MUs and beam on time, also larger segments decrease dosimetric uncertainities of small fields quality assurance. The advantage of VMAT technique were determined a little better GI, CI, PCI, brain V12Gy and brain mean dose. The results show that the clinical objectives and plans for both techniques satisfied all organs at risks (OARs) dose constraints. Depends on the shape and localization of target, we could choose one of these techniques for linear accelerator based SRS / SRT treatment.

Regional process redesign of lung cancer care: a learning health system pilot project.

PubMed

Fung-Kee-Fung, M; Maziak, D E; Pantarotto, J R; Smylie, J; Taylor, L; Timlin, T; Cacciotti, T; Villeneuve, P J; Dennie, C; Bornais, C; Madore, S; Aquino, J; Wheatley-Price, P; Ozer, R S; Stewart, D J

2018-02-01

The Ottawa Hospital (toh) defined delay to timely lung cancer care as a system design problem. Recognizing the patient need for an integrated journey and the need for dynamic alignment of providers, toh used a learning health system (lhs) vision to redesign regional diagnostic processes. A lhs is driven by feedback utilizing operational and clinical information to drive system optimization and innovation. An essential component of a lhs is a collaborative platform that provides connectivity across silos, organizations, and professions. To operationalize a lhs, we developed the Ottawa Health Transformation Model (ohtm) as a consensus approach that addresses process barriers, resistance to change, and conflicting priorities. A regional Community of Practice (cop) was established to engage stakeholders, and a dedicated transformation team supported process improvements and implementation. The project operationalized the lung cancer diagnostic pathway and optimized patient flow from referral to initiation of treatment. Twelve major processes in referral, review, diagnostics, assessment, triage, and consult were redesigned. The Ottawa Hospital now provides a diagnosis to 80% of referrals within the provincial target of 28 days. The median patient journey from referral to initial treatment decreased by 48% from 92 to 47 days. The initiative optimized regional integration from referral to initial treatment. Use of a lhs lens enabled the creation of a system that is standardized to best practice and open to ongoing innovation. Continued transformation initiatives across the continuum of care are needed to incorporate best practice and optimize delivery systems for regional populations.

Cost-Effectiveness Analysis of Systemic Therapies in Advanced Pancreatic Cancer in the Canadian Health Care System.

PubMed

Coyle, Doug; Ko, Yoo-Joung; Coyle, Kathryn; Saluja, Ronak; Shah, Keya; Lien, Kelly; Lam, Henry; Chan, Kelvin K W

2017-04-01

To assess the cost-effectiveness of gemcitabine (G), G + 5-fluorouracil, G + capecitabine, G + cisplatin, G + oxaliplatin, G + erlotinib, G + nab-paclitaxel (GnP), and FOLFIRINOX in the treatment of advanced pancreatic cancer from a Canadian public health payer's perspective, using data from a recently published Bayesian network meta-analysis. Analysis was conducted through a three-state Markov model and used data on the progression of disease with treatment from the gemcitabine arms of randomized controlled trials combined with estimates from the network meta-analysis for the newer regimens. Estimates of health care costs were obtained from local providers, and utilities were derived from the literature. The model estimates the effect of treatment regimens on costs and quality-adjusted life-years (QALYs) discounted at 5% per annum. At a willingness-to-pay (WTP) threshold of greater than $30,666 per QALY, FOLFIRINOX would be the most optimal regimen. For a WTP threshold of $50,000 per QALY, the probability that FOLFIRINOX would be optimal was 57.8%. There was no price reduction for nab-paclitaxel when GnP was optimal. From a Canadian public health payer's perspective at the present time and drug prices, FOLFIRINOX is the optimal regimen on the basis of the cost-effectiveness criterion. GnP is not cost-effective regardless of the WTP threshold. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

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.

Effect of optimal daily fertigation on migration of water and salt in soil, root growth and fruit yield of cucumber (Cucumis sativus L.) in solar-greenhouse.

PubMed

Liang, Xinshu; Gao, Yinan; Zhang, Xiaoying; Tian, Yongqiang; Zhang, Zhenxian; Gao, Lihong

2014-01-01

Inappropriate and excessive irrigation and fertilization have led to the predominant decline of crop yields, and water and fertilizer use efficiency in intensive vegetable production systems in China. For many vegetables, fertigation can be applied daily according to the actual water and nutrient requirement of crops. A greenhouse study was therefore conducted to investigate the effect of daily fertigation on migration of water and salt in soil, and root growth and fruit yield of cucumber. The treatments included conventional interval fertigation, optimal interval fertigation and optimal daily fertigation. Generally, although soil under the treatment optimal interval fertigation received much lower fertilizers than soil under conventional interval fertigation, the treatment optimal interval fertigation did not statistically decrease the economic yield and fruit nutrition quality of cucumber when compare to conventional interval fertigation. In addition, the treatment optimal interval fertigation effectively avoided inorganic nitrogen accumulation in soil and significantly (P<0.05) increased the partial factor productivity of applied nitrogen by 88% and 209% in the early-spring and autumn-winter seasons, respectively, when compared to conventional interval fertigation. Although soils under the treatments optimal interval fertigation and optimal daily fertigation received the same amount of fertilizers, the treatment optimal daily fertigation maintained the relatively stable water, electrical conductivity and mineral nitrogen levels in surface soils, promoted fine root (<1.5 mm diameter) growth of cucumber, and eventually increased cucumber economic yield by 6.2% and 8.3% and partial factor productivity of applied nitrogen by 55% and 75% in the early-spring and autumn-winter seasons, respectively, when compared to the treatment optimal interval fertigation. These results suggested that optimal daily fertigation is a beneficial practice for improving crop yield and the water and fertilizers use efficiency in solar greenhouse.

Effect of Optimal Daily Fertigation on Migration of Water and Salt in Soil, Root Growth and Fruit Yield of Cucumber (Cucumis sativus L.) in Solar-Greenhouse

PubMed Central

Liang, Xinshu; Gao, Yinan; Zhang, Xiaoying; Tian, Yongqiang; Zhang, Zhenxian; Gao, Lihong

2014-01-01

Inappropriate and excessive irrigation and fertilization have led to the predominant decline of crop yields, and water and fertilizer use efficiency in intensive vegetable production systems in China. For many vegetables, fertigation can be applied daily according to the actual water and nutrient requirement of crops. A greenhouse study was therefore conducted to investigate the effect of daily fertigation on migration of water and salt in soil, and root growth and fruit yield of cucumber. The treatments included conventional interval fertigation, optimal interval fertigation and optimal daily fertigation. Generally, although soil under the treatment optimal interval fertigation received much lower fertilizers than soil under conventional interval fertigation, the treatment optimal interval fertigation did not statistically decrease the economic yield and fruit nutrition quality of cucumber when compare to conventional interval fertigation. In addition, the treatment optimal interval fertigation effectively avoided inorganic nitrogen accumulation in soil and significantly (P<0.05) increased the partial factor productivity of applied nitrogen by 88% and 209% in the early-spring and autumn-winter seasons, respectively, when compared to conventional interval fertigation. Although soils under the treatments optimal interval fertigation and optimal daily fertigation received the same amount of fertilizers, the treatment optimal daily fertigation maintained the relatively stable water, electrical conductivity and mineral nitrogen levels in surface soils, promoted fine root (<1.5 mm diameter) growth of cucumber, and eventually increased cucumber economic yield by 6.2% and 8.3% and partial factor productivity of applied nitrogen by 55% and 75% in the early-spring and autumn-winter seasons, respectively, when compared to the treatment optimal interval fertigation. These results suggested that optimal daily fertigation is a beneficial practice for improving crop yield and the water and fertilizers use efficiency in solar greenhouse. PMID:24475204

Effect of acetylation treatment and soaking time to bending strength of sugar palm fiber composite

NASA Astrophysics Data System (ADS)

Diharjo, Kuncoro; Permana, Andy; Arsada, Robbi; Asmoro, Gundhi; Budiono, Herru Santosa; Firdaus, Yohanes

2017-01-01

The objective of this experiment is to investigate the maximum bending strength of sugar palm composite by optimizing acetylation treatment and soaking time of the fiber. In this research, the acetylation treatments were varied in acetic acid content (0-10%, in weight) and soaking time (30-150 minutes). The composite specimens were produced using a press mold method for 40% of fiber and 60% of bisphenolic matrix composition in weight. The bending testing was conducted using three point bending method according to ASTM D790. The composite with the treated fiber of 4% acetyl acid has maximum bending strength and modulus due to the effect of removing lignin and other polluters without degrading the fiber strength. The longer of soaking time in the acid solution can significantly enhance the bending strength and modulus. The composite with low strength has an opening fracture, and there is no opening fracture on the composite with high strength.

Antipsychotic treatment in schizophrenia: the role of computerized neuropsychological assessment.

PubMed

Kertzman, Semion; Reznik, Ilya; Grinspan, Haim; Weizman, Abraham; Kotler, Moshe

2008-01-01

The present study analyzes the role of neurocognitive assessment instruments in the detection of the contribution of antipsychotic treatment to cognitive functioning. Recently, a panel of experts suggested six main domains (working memory; attention/vigilance; verbal/visual learning and memory; reasoning and problem solving; speed of processing) implicated in schizophrenia-related cognitive deficits, which serve as a theoretical base for creation of real-time computerized neurocognitive batteries. The high sensitivity of computerized neuropsychological testing is based on their ability to adopt the reaction time (RT) paradigm for the assessment of brain function in a real-time regime. This testing is highly relevant for the monitoring of the cognitive effects of antipsychotics. Computerized assessment assists in the identification of state- and trait-related cognitive impairments. The optimal real-time computerized neurocognitive battery should composite balance between broad and narrow coverage of cognitive domains relevant to the beneficial effects of antipsychotics and will enable better planning of treatment and rehabilitation programs.

Segmental osteotomies of the maxilla.

PubMed

Rosen, H M

1989-10-01

Multiple segment Le Fort I osteotomies provide the maxillofacial surgeon with the capabilities to treat complex dentofacial deformities existing in all three planes of space. Sagittal, vertical, and transverse maxillomandibular discrepancies as well as three-dimensional abnormalities within the maxillary arch can be corrected simultaneously. Accordingly, optimal aesthetic enhancement of the facial skeleton and a functional, healthy occlusion can be realized. What may be perceived as elaborate treatment plans are in reality conservative in terms of osseous stability and treatment time required. The close cooperation of an orthodontist well-versed in segmental orthodontics and orthognathic surgery is critical to the success of such surgery. With close attention to surgical detail, the complication rate inherent in such surgery can be minimized and the treatment goals achieved in a timely and predictable fashion.

[Modern concepts of trauma care and multiple trauma management in oral and maxillofacial region].

PubMed

Tan, Yinghui

2015-06-01

Multiple trauma management requires the application of modem trauma care theories. Optimal treatment results can be achieved by reinforcing cooperation and stipulating a treatment plan together with other disciplines. Based on modem theories in trauma care and our understanding of the theoretical points, this paper analyzes the injury assessment strategies and methods in oral and maxillofacial multiple trauma management. Moreover, this paper discusses operating time and other influencing factors as well as proposed definitive surgical timing and indications in comprehensive management of oral and maxillofacial multiple trauma patients associated with injuries in other body parts. We hope that this paper can help stomatological physicians deepen their understanding of modem trauma care theories and improve their capacity and results in the treatment of oral and maxillofacial multiple trauma.

Fraction-variant beam orientation optimization for non-coplanar IMRT

NASA Astrophysics Data System (ADS)

O'Connor, Daniel; Yu, Victoria; Nguyen, Dan; Ruan, Dan; Sheng, Ke

2018-02-01

Conventional beam orientation optimization (BOO) algorithms for IMRT assume that the same set of beam angles is used for all treatment fractions. In this paper we present a BOO formulation based on group sparsity that simultaneously optimizes non-coplanar beam angles for all fractions, yielding a fraction-variant (FV) treatment plan. Beam angles are selected by solving a multi-fraction fluence map optimization problem involving 500-700 candidate beams per fraction, with an additional group sparsity term that encourages most candidate beams to be inactive. The optimization problem is solved using the fast iterative shrinkage-thresholding algorithm. Our FV BOO algorithm is used to create five-fraction treatment plans for digital phantom, prostate, and lung cases as well as a 30-fraction plan for a head and neck case. A homogeneous PTV dose coverage is maintained in all fractions. The treatment plans are compared with fraction-invariant plans that use a fixed set of beam angles for all fractions. The FV plans reduced OAR mean dose and D 2 values on average by 3.3% and 3.8% of the prescription dose, respectively. Notably, mean OAR dose was reduced by 14.3% of prescription dose (rectum), 11.6% (penile bulb), 10.7% (seminal vesicle), 5.5% (right femur), 3.5% (bladder), 4.0% (normal left lung), 15.5% (cochleas), and 5.2% (chiasm). D 2 was reduced by 14.9% of prescription dose (right femur), 8.2% (penile bulb), 12.7% (proximal bronchus), 4.1% (normal left lung), 15.2% (cochleas), 10.1% (orbits), 9.1% (chiasm), 8.7% (brainstem), and 7.1% (parotids). Meanwhile, PTV homogeneity defined as D 95/D 5 improved from .92 to .95 (digital phantom), from .95 to .98 (prostate case), and from .94 to .97 (lung case), and remained constant for the head and neck case. Moreover, the FV plans are dosimetrically similar to conventional plans that use twice as many beams per fraction. Thus, FV BOO offers the potential to reduce delivery time for non-coplanar IMRT.

Optimizing Tactics for Use of the U.S. Antiviral Strategic National Stockpile for Pandemic Influenza

PubMed Central

Dimitrov, Nedialko B.; Goll, Sebastian; Hupert, Nathaniel; Pourbohloul, Babak; Meyers, Lauren Ancel

2011-01-01

In 2009, public health agencies across the globe worked to mitigate the impact of the swine-origin influenza A (pH1N1) virus. These efforts included intensified surveillance, social distancing, hygiene measures, and the targeted use of antiviral medications to prevent infection (prophylaxis). In addition, aggressive antiviral treatment was recommended for certain patient subgroups to reduce the severity and duration of symptoms. To assist States and other localities meet these needs, the U.S. Government distributed a quarter of the antiviral medications in the Strategic National Stockpile within weeks of the pandemic's start. However, there are no quantitative models guiding the geo-temporal distribution of the remainder of the Stockpile in relation to pandemic spread or severity. We present a tactical optimization model for distributing this stockpile for treatment of infected cases during the early stages of a pandemic like 2009 pH1N1, prior to the wide availability of a strain-specific vaccine. Our optimization method efficiently searches large sets of intervention strategies applied to a stochastic network model of pandemic influenza transmission within and among U.S. cities. The resulting optimized strategies depend on the transmissability of the virus and postulated rates of antiviral uptake and wastage (through misallocation or loss). Our results suggest that an aggressive community-based antiviral treatment strategy involving early, widespread, pro-rata distribution of antivirals to States can contribute to slowing the transmission of mildly transmissible strains, like pH1N1. For more highly transmissible strains, outcomes of antiviral use are more heavily impacted by choice of distribution intervals, quantities per shipment, and timing of shipments in relation to pandemic spread. This study supports previous modeling results suggesting that appropriate antiviral treatment may be an effective mitigation strategy during the early stages of future influenza pandemics, increasing the need for systematic efforts to optimize distribution strategies and provide tactical guidance for public health policy-makers. PMID:21283514

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

PubMed

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

2013-12-21

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

WE-AB-209-10: Optimizing the Delivery of Sequential Fluence Maps for Efficient VMAT Delivery

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

Craft, D; Balvert, M

2016-06-15

Purpose: To develop an optimization model and solution approach for computing MLC leaf trajectories and dose rates for high quality matching of a set of optimized fluence maps to be delivered sequentially around a patient in a VMAT treatment. Methods: We formulate the fluence map matching problem as a nonlinear optimization problem where time is discretized but dose rates and leaf positions are continuous variables. For a given allotted time, which is allocated across the fluence maps based on the complexity of each fluence map, the optimization problem searches for the best leaf trajectories and dose rates such that themore » original fluence maps are closely recreated. Constraints include maximum leaf speed, maximum dose rate, and leaf collision avoidance, as well as the constraint that the ending leaf positions for one map are the starting leaf positions for the next map. The resulting model is non-convex but smooth, and therefore we solve it by local searches from a variety of starting positions. We improve solution time by a custom decomposition approach which allows us to decouple the rows of the fluence maps and solve each leaf pair individually. This decomposition also makes the problem easily parallelized. Results: We demonstrate method on a prostate case and a head-and-neck case and show that one can recreate fluence maps to high degree of fidelity in modest total delivery time (minutes). Conclusion: We present a VMAT sequencing method that reproduces optimal fluence maps by searching over a vast number of possible leaf trajectories. By varying the total allotted time given, this approach is the first of its kind to allow users to produce VMAT solutions that span the range of wide-field coarse VMAT deliveries to narrow-field high-MU sliding window-like approaches.« less

Principles of management of thoracolumbar fractures.

PubMed

Dai, Li-yang

2012-05-01

There is little consensus on treatment of thoracolumbar fractures, which are one of the most controversial areas in spine surgery. The great variations in clinical decision making may come from differences in evaluation of spine stability with these fractures. Few high-quality studies concerning optimal treatment of thoracolumbar fractures have been conducted. This article reviews the conflicting results and recommendations for management of thoracolumbar fractures of currently published reports. Specifically, it addresses issues regarding evaluation of stability, indications for operative treatment, timing of surgery, surgical approach, and fusion length. © 2012 Tianjin Hospital and Blackwell Publishing Asia Pty Ltd.

Deposition of SiC x H y O z thin film on epoxy resin by nanosecond pulsed APPJ for improving the surface insulating performance

NASA Astrophysics Data System (ADS)

Qing, XIE; Haofan, LIN; Shuai, ZHANG; Ruixue, WANG; Fei, KONG; Tao, SHAO

2018-02-01

Non-thermal plasma surface modification for epoxy resin (EP) to improve the insulation properties has wide application prospects in gas insulated switchgear and gas insulated transmission line. In this paper, a pulsed Ar dual dielectrics atmospheric-pressure plasma jet (APPJ) was used for SiC x H y O z thin film deposition on EP samples. The film deposition was optimized by varying the treatment time while other parameters were kept at constants (treatment distance: 10 mm, precursor flow rate: 0.6 l min-1, maximum instantaneous power: 3.08 kW and single pulse energy: 0.18 mJ). It was found that the maximum value of flashover voltages for negative and positive voltage were improved by 18% and 13% when the deposition time was 3 min, respectively. The flashover voltage reduced as treatment time increased. Moreover, all the surface conductivity, surface charge dissipation rate and surface trap level distribution reached an optimal value when thin film deposition time was 3 min. Other measurements, such as atomic force microscopy and scanning electron microscope for EP surface morphology, Fourier transform infrared spectroscopy and x-ray photoelectron spectroscopy for EP surface compositions, optical emission spectra for APPJ deposition process were carried out to better understand the deposition processes and mechanisms. The results indicated that the original organic groups (C-H, C-C, C=O, C=C) were gradually replaced by the Si containing inorganic groups (Si-O-Si and Si-OH). The reduction of C=O in ester group and C=C in p-substituted benzene of the EP samples might be responsible for shallowing the trap level and then enhancing the flashover voltage. However, when the plasma treatment time was longer than 3 min, the significant increase of the surface roughness might increase the trap level depth and then deteriorate the flashover performance.

Computational Modeling and Real-Time Control of Patient-Specific Laser Treatment of Cancer

PubMed Central

Fuentes, D.; Oden, J. T.; Diller, K. R.; Hazle, J. D.; Elliott, A.; Shetty, A.; Stafford, R. J.

2014-01-01

An adaptive feedback control system is presented which employs a computational model of bioheat transfer in living tissue to guide, in real-time, laser treatments of prostate cancer monitored by magnetic resonance thermal imaging (MRTI). The system is built on what can be referred to as cyberinfrastructure - a complex structure of high-speed network, large-scale parallel computing devices, laser optics, imaging, visualizations, inverse-analysis algorithms, mesh generation, and control systems that guide laser therapy to optimally control the ablation of cancerous tissue. The computational system has been successfully tested on in-vivo, canine prostate. Over the course of an 18 minute laser induced thermal therapy (LITT) performed at M.D. Anderson Cancer Center (MDACC) in Houston, Texas, the computational models were calibrated to intra-operative real time thermal imaging treatment data and the calibrated models controlled the bioheat transfer to within 5°C of the predetermined treatment plan. The computational arena is in Austin, Texas and managed at the Institute for Computational Engineering and Sciences (ICES). The system is designed to control the bioheat transfer remotely while simultaneously providing real-time remote visualization of the on-going treatment. Post operative histology of the canine prostate reveal that the damage region was within the targeted 1.2cm diameter treatment objective. PMID:19148754

Computational modeling and real-time control of patient-specific laser treatment of cancer.

PubMed

Fuentes, D; Oden, J T; Diller, K R; Hazle, J D; Elliott, A; Shetty, A; Stafford, R J

2009-04-01

An adaptive feedback control system is presented which employs a computational model of bioheat transfer in living tissue to guide, in real-time, laser treatments of prostate cancer monitored by magnetic resonance thermal imaging. The system is built on what can be referred to as cyberinfrastructure-a complex structure of high-speed network, large-scale parallel computing devices, laser optics, imaging, visualizations, inverse-analysis algorithms, mesh generation, and control systems that guide laser therapy to optimally control the ablation of cancerous tissue. The computational system has been successfully tested on in vivo, canine prostate. Over the course of an 18 min laser-induced thermal therapy performed at M.D. Anderson Cancer Center (MDACC) in Houston, Texas, the computational models were calibrated to intra-operative real-time thermal imaging treatment data and the calibrated models controlled the bioheat transfer to within 5 degrees C of the predetermined treatment plan. The computational arena is in Austin, Texas and managed at the Institute for Computational Engineering and Sciences (ICES). The system is designed to control the bioheat transfer remotely while simultaneously providing real-time remote visualization of the on-going treatment. Post-operative histology of the canine prostate reveal that the damage region was within the targeted 1.2 cm diameter treatment objective.

Optimizing Soft Tissue Management and Spacer Design in Segmental Bone Defects

DTIC Science & Technology

2014-10-01

the time of the “Pre-Procedure”. Autogenous Cancellous Bone Graft (ACBG harvested from the sternum at the time of the treatment surgery is used as...will receive more specialized training and orientation to microCT analysis, both on a theoretical and practical level. He will work with raw CT...adjacent to the PMMA) composed of mononuclear cells and exhibited extensive, diffuse fibrous connective tissue.  Performed histology on goat autogenous

Optimal Transport Destination for Ischemic Stroke Patients With Unknown Vessel Status: Use of Prehospital Triage Scores.

PubMed

Schlemm, Eckhard; Ebinger, Martin; Nolte, Christian H; Endres, Matthias; Schlemm, Ludwig

2017-08-01

Patients with acute ischemic stroke (AIS) and large vessel occlusion may benefit from direct transportation to an endovascular capable comprehensive stroke center (mothership approach) as opposed to direct transportation to the nearest stroke unit without endovascular therapy (drip and ship approach). The optimal transport strategy for patients with AIS and unknown vessel status is uncertain. The rapid arterial occlusion evaluation scale (RACE, scores ranging from 0 to 9, with higher scores indicating higher stroke severity) correlates with the National Institutes of Health Stroke Scale and was developed to identify patients with large vessel occlusion in a prehospital setting. We evaluate how the RACE scale can help to inform prehospital triage decisions for AIS patients. In a model-based approach, we estimate probabilities of good outcome (modified Rankin Scale score of ≤2 at 3 months) as a function of severity of stroke symptoms and transport times for the mothership approach and the drip and ship approach. We use these probabilities to obtain optimal RACE cutoff scores for different transfer time settings and combinations of treatment options (time-based eligibility for secondary transfer under the drip and ship approach, time-based eligibility for thrombolysis at the comprehensive stroke center under the mothership approach). In our model, patients with AIS are more likely to benefit from direct transportation to the comprehensive stroke center if they have more severe strokes. Values of the optimal RACE cutoff scores range from 0 (mothership for all patients) to >9 (drip and ship for all patients). Shorter transfer times and longer door-to-needle and needle-to-transfer (door out) times are associated with lower optimal RACE cutoff scores. Use of RACE cutoff scores that take into account transport times to triage AIS patients to the nearest appropriate hospital may lead to improved outcomes. Further studies should examine the feasibility of translation into clinical practice. © 2017 American Heart Association, Inc.

Effects of Ultrasonic Parameters on the Crystallization Behavior of Virgin Coconut Oil.

PubMed

Wu, Linhe; Cao, Jun; Bai, Xinpeng; Chen, Haiming; Zhang, Yuxiang; Wu, Qian

2016-12-01

Crystallization behavior of virgin coconut oil (VCO) in the absence and presence of ultrasonic treatment under a temperature gradient field was investigated. The effects of ultrasonic parameters on the crystallization behavior of VCO were studied by differential scanning calorimetry, ultraviolet/visible spectrophotometry and polarized light microscopy. The thermal effect of the ultrasonic treatment was also increased at higher power levels. Therefore, the optimal power level was determined at approximately 36 W. Induction time reduced evidently and the crystallization rate was accelerated under ultrasonic treatment at crystallization temperature (T c ) above 15°C. However, no significant difference in induction time was noted at 13°C. The result of morphological studies showed that the growth mechanism of crystals was significantly changed. Meanwhile, smaller and uniform crystals were produced by the ultrasonic treatment. This study shows a novel technique to accelerate the crystallization rate and alter the growth mechanism of VCO crystals.

THE EFFECTS OF INSTRUMENT ASSISTED SOFT TISSUE MOBILIZATION ON LOWER EXTREMITY MUSCLE PERFORMANCE: A RANDOMIZED CONTROLLED TRIAL.

PubMed

MacDonald, Nicole; Baker, Russell; Cheatham, Scott W

2016-12-01

Instrument-Assisted Soft Tissue Mobilization (IASTM) is a non-invasive therapeutic technique used to theoretically aid in scar tissue breakdown and absorption, fascial mobilization, and improved tissue healing. Researchers have hypothesized that utilizing IASTM will improve muscular efficiency and performance; yet previous Investigations has been focused on treating injury. The purpose of this investigation was to explore the effects of IASTM on muscle performance to assess if typical treatment application affected measures of muscular performance. A pretest-posttest randomized control design. A convenience sample of 48 physically active adults (mean age 24 ± 4 years), randomly assigned to one of three groups: quadriceps treatment group, triceps surae treatment group, or control group. Participants performed a five-minute warm-up on a Monark bicycle ergometer before performing three countermovement vertical jumps (CMJ). Immediately after, the IASTM treatment was applied by one researcher for three minutes on each leg at the specified site (e.g., quadriceps) for those assigned to the treatment groups, while the control group rested for six minutes. Immediately following treatment, participants performed three additional CMJs. Pre- and post-testing included measures of vertical jump height (JH), peak power (PP) and peak velocity (PV). There were no statistically significant differences found between treatment groups in JH, PP, or PV or across pre- and post-test trials. These preliminary findings suggest that standard treatment times of IASTM do not produce an immediate effect in muscular performance in healthy participants. This may help clinicians determine the optimal sequencing of IASTM when it is part of a pre-performance warm-up program. Future research should be conducted to determine the muscle performance effects of IASTM in individuals with known myofascial restriction and to determine optimal treatment parameters, such as instrument type, amount of pressure, and treatment time necessary to affect muscular performance. 1b.

Pre-hospital treatment of STEMI patients. A scientific statement of the Working Group Acute Cardiac Care of the European Society of Cardiology.

PubMed

Tubaro, M; Danchin, N; Goldstein, P; Filippatos, G; Hasin, Y; Heras, M; Jansky, P; Norekval, T M; Swahn, E; Thygesen, K; Vrints, C; Zahger, D; Arntz, H R; Bellou, A; De La Coussaye, J E; De Luca, L; Huber, K; Lambert, Y; Lettino, M; Lindahl, B; McLean, S; Nibbe, L; Peacock, W F; Price, S; Quinn, T; Spaulding, C; Tatu-Chitoiu, G; Van De Werf, F

2011-06-01

In ST-elevation myocardial infarction (STEMI) the pre-hospital phase is the most critical, as the administration of the most appropriate treatment in a timely manner is instrumental for mortality reduction. STEMI systems of care based on networks of medical institutions connected by an efficient emergency medical service are pivotal. The first steps are devoted to minimize the patient's delay in seeking care, rapidly dispatch a properly staffed and equipped ambulance to make the diagnosis on scene, deliver initial drug therapy and transport the patient to the most appropriate (not necessarily the closest) cardiac facility. Primary PCI is the treatment of choice, but thrombolysis followed by coronary angiography and possibly PCI is a valid alternative, according to patient's baseline risk, time from symptoms onset and primary PCI-related delay. Paramedics and nurses have an important role in pre-hospital STEMI care and their empowerment is essential to increase the effectiveness of the system. Strong cooperation between cardiologists and emergency medicine doctors is mandatory for optimal pre-hospital STEMI care. Scientific societies have an important role in guideline implementation as well as in developing quality indicators and performance measures; health care professionals must overcome existing barriers to optimal care together with political and administrative decision makers.

New clinical trial to study long-term progression of brain and spine cancers | Center for Cancer Research

Cancer.gov

Dr. Mark Gilbert, Chief, Neuro-Oncology Branch, describes an ambitious new clinical trial that, for the first time, will study the long-term progression of brain and spine cancers. The 10,000 patient trial is the largest of its kind and will follow patients throughout the course of their disease. In addition to identifying optimal treatments for common brain and spine cancers, the study focuses on treatment discovery for rare, overlooked cancers.

Optimization of process parameters for pilot-scale liquid-state bioconversion of sewage sludge by mixed fungal inoculation.

PubMed

Rahman, Roshanida A; Molla, Abul Hossain; Barghash, Hind F A; Fakhru'l-Razi, Ahmadun

2016-01-01

Liquid-state bioconversion (LSB) technique has great potential for application in bioremediation of sewage sludge. The purpose of this study is to determine the optimum level of LSB process of sewage sludge treatment by mixed fungal (Aspergillus niger and Penicillium corylophilum) inoculation in a pilot-scale bioreactor. The optimization of process factors was investigated using response surface methodology based on Box-Behnken design considering hydraulic retention time (HRT) and substrate influent concentration (S0) on nine responses for optimizing and fitted to the regression model. The optimum region was successfully depicted by optimized conditions, which was identified as the best fit for convenient multiple responses. The results from process verification were in close agreement with those obtained through predictions. Considering five runs of different conditions of HRT (low, medium and high 3.62, 6.13 and 8.27 days, respectively) with the range of S0 value (the highest 12.56 and the lowest 7.85 g L(-1)), it was monitored as the lower HRT was considered as the best option because it required minimum days of treatment than the others with influent concentration around 10 g L(-1). Therefore, optimum process factors of 3.62 days for HRT and 10.12 g L(-1) for S0 were identified as the best fit for LSB process and its performance was deviated by less than 5% in most of the cases compared to the predicted values. The recorded optimized results address a dynamic development in commercial-scale biological treatment of wastewater for safe and environment-friendly disposal in near future.

Model-Based Individualized Treatment of Chemotherapeutics: Bayesian Population Modeling and Dose Optimization

PubMed Central

Jayachandran, Devaraj; Laínez-Aguirre, José; Rundell, Ann; Vik, Terry; Hannemann, Robert; Reklaitis, Gintaras; Ramkrishna, Doraiswami

2015-01-01

6-Mercaptopurine (6-MP) is one of the key drugs in the treatment of many pediatric cancers, auto immune diseases and inflammatory bowel disease. 6-MP is a prodrug, converted to an active metabolite 6-thioguanine nucleotide (6-TGN) through enzymatic reaction involving thiopurine methyltransferase (TPMT). Pharmacogenomic variation observed in the TPMT enzyme produces a significant variation in drug response among the patient population. Despite 6-MP’s widespread use and observed variation in treatment response, efforts at quantitative optimization of dose regimens for individual patients are limited. In addition, research efforts devoted on pharmacogenomics to predict clinical responses are proving far from ideal. In this work, we present a Bayesian population modeling approach to develop a pharmacological model for 6-MP metabolism in humans. In the face of scarcity of data in clinical settings, a global sensitivity analysis based model reduction approach is used to minimize the parameter space. For accurate estimation of sensitive parameters, robust optimal experimental design based on D-optimality criteria was exploited. With the patient-specific model, a model predictive control algorithm is used to optimize the dose scheduling with the objective of maintaining the 6-TGN concentration within its therapeutic window. More importantly, for the first time, we show how the incorporation of information from different levels of biological chain-of response (i.e. gene expression-enzyme phenotype-drug phenotype) plays a critical role in determining the uncertainty in predicting therapeutic target. The model and the control approach can be utilized in the clinical setting to individualize 6-MP dosing based on the patient’s ability to metabolize the drug instead of the traditional standard-dose-for-all approach. PMID:26226448

Effects of temperature on the life history parameters of Anoplophora Glabripennis (Coleoptera: Cerambycidae)

Treesearch

Melody A. Keena; Paul M. Moore; Steve M. Ulanecki

2003-01-01

There is a critical need for information on the basic biology of the Asian longhorned beetle, Anoplophora glabripennis (Motschulsky), to provide the biological basis for predicting developmental phenology in order to optimize the timing of exclusion and eradication treatments and to predict attack rates under different environmental conditions. In...

Electrochemical degradation and mineralization of glyphosate herbicide.

PubMed

Tran, Nam; Drogui, Patrick; Doan, Tuan Linh; Le, Thanh Son; Nguyen, Hoai Chau

2017-12-01

The presence of herbicide is a concern for both human and ecological health. Glyphosate is occasionally detected as water contaminants in agriculture areas where the herbicide is used extensively. The removal of glyphosate in synthetic solution using advanced oxidation process is a possible approach for remediation of contaminated waters. The ability of electrochemical oxidation for the degradation and mineralization of glyphosate herbicide was investigated using Ti/PbO 2 anode. The current intensity, treatment time, initial concentration and pH of solution are the influent parameters on the degradation efficiency. An experimental design methodology was applied to determine the optimal condition (in terms of cost/effectiveness) based on response surface methodology. Glyphosate concentration (C 0  = 16.9 mg L -1 ) decreased up to 0.6 mg L -1 when the optimal conditions were imposed (current intensity of 4.77 A and treatment time of 173 min). The removal efficiencies of glyphosate and total organic carbon were 95 ± 16% and 90.31%, respectively. This work demonstrates that electrochemical oxidation is a promising process for degradation and mineralization of glyphosate.

[Establishing the idea of holistic integrative medicine, optimizing the quality of health care service in prevention and treatment].

PubMed

Sun, Xing-guo

2015-07-01

Under background of reductionism in the modern science, physiology and medicine are stepwise refined into system, organ, disease, cell and gene etc. Although clinical medicine, only service in whole human object, obviously brought tremendous progress, it also appeared obvious defects and limits at the same time. Professionalized and specialized medicine not only needs to be integrated from basics to clinical fields, but also from prevention, health management, clinical treatment and functional rehabilitation medicine. People are indivisible organic whole. Professionalization, translation and integration must be combined. In order to provide the best quality and optimized medical service for the Chinese people and to lead in the world, we have to strengthen professional and technical knowledge, and have to establish the holistic integrative medical philosophy for physiology and medicine too.

Magnetic hyperthermia performance of magnetite nanoparticle assemblies under different driving fields

NASA Astrophysics Data System (ADS)

Wu, Kai; Wang, Jian-Ping

2017-05-01

The heating performance of magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF) is dependent on several factors. Optimizing these factors improves the heating efficiency for cancer therapy and meanwhile lowers the MNP treatment dosage. AMF is one of the most easily controllable variables to enhance the efficiency of heat generation. This paper investigated the optimal magnetic field strength and frequency for an assembly of magnetite nanoparticles. For hyperthermia treatment in clinical applications, monodispersed NPs are forming nanoclusters in target regions where a strong magnetically interactive environment is anticipated, which leads to a completely different situation than MNPs in ferrofluids. Herein, the energy barrier model is revisited and Néel relaxation time is tailored for high MNP packing densities. AMF strength and frequency are customized for different magnetite NPs to achieve the highest power generation and the best hyperthermia performance.

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

A surrogate-based metaheuristic global search method for beam angle selection in radiation treatment planning.

PubMed

Zhang, H H; Gao, S; Chen, W; Shi, L; D'Souza, W D; Meyer, R R

2013-03-21

An important element of radiation treatment planning for cancer therapy is the selection of beam angles (out of all possible coplanar and non-coplanar angles in relation to the patient) in order to maximize the delivery of radiation to the tumor site and minimize radiation damage to nearby organs-at-risk. This category of combinatorial optimization problem is particularly difficult because direct evaluation of the quality of treatment corresponding to any proposed selection of beams requires the solution of a large-scale dose optimization problem involving many thousands of variables that represent doses delivered to volume elements (voxels) in the patient. However, if the quality of angle sets can be accurately estimated without expensive computation, a large number of angle sets can be considered, increasing the likelihood of identifying a very high quality set. Using a computationally efficient surrogate beam set evaluation procedure based on single-beam data extracted from plans employing equallyspaced beams (eplans), we have developed a global search metaheuristic process based on the nested partitions framework for this combinatorial optimization problem. The surrogate scoring mechanism allows us to assess thousands of beam set samples within a clinically acceptable time frame. Tests on difficult clinical cases demonstrate that the beam sets obtained via our method are of superior quality.

A surrogate-based metaheuristic global search method for beam angle selection in radiation treatment planning

PubMed Central

Zhang, H H; Gao, S; Chen, W; Shi, L; D’Souza, W D; Meyer, R R

2013-01-01

An important element of radiation treatment planning for cancer therapy is the selection of beam angles (out of all possible coplanar and non-coplanar angles in relation to the patient) in order to maximize the delivery of radiation to the tumor site and minimize radiation damage to nearby organs-at-risk. This category of combinatorial optimization problem is particularly difficult because direct evaluation of the quality of treatment corresponding to any proposed selection of beams requires the solution of a large-scale dose optimization problem involving many thousands of variables that represent doses delivered to volume elements (voxels) in the patient. However, if the quality of angle sets can be accurately estimated without expensive computation, a large number of angle sets can be considered, increasing the likelihood of identifying a very high quality set. Using a computationally efficient surrogate beam set evaluation procedure based on single-beam data extracted from plans employing equally-spaced beams (eplans), we have developed a global search metaheuristic process based on the Nested Partitions framework for this combinatorial optimization problem. The surrogate scoring mechanism allows us to assess thousands of beam set samples within a clinically acceptable time frame. Tests on difficult clinical cases demonstrate that the beam sets obtained via our method are superior quality. PMID:23459411

Inducing optimal substitution between antibiotics under open access to the resource of antibiotic susceptibility.

PubMed

Herrmann, Markus; Nkuiya, Bruno

2017-06-01

This paper designs a bio-economic model to examine the use of substitute antibiotic drugs (analogs) sold by an industry that has open access to the resource of the antibiotic class's susceptibility (treatment effectiveness). Antibiotics are characterized by different expected recovery rates and production costs, which in conjunction with the class's treatment susceptibility determines their relative effectiveness. Our analysis reveals that the high-quality antibiotic drug loses its comparative advantage over time making the low-quality drug the treatment of last resort in the market equilibrium and the social optimum when antibiotic susceptibility cannot replenish. However, when antibiotic susceptibility is renewable, both antibiotics may be used in the long run, and the comparative advantage of the high-quality drug may be restored in the social optimum that allows lowering infection in the long run. We develop the optimal tax/subsidy scheme that would induce antibiotic producers under open access to behave optimally and account for the social cost of infection and value of antibiotic susceptibility. We show that the welfare loss associated with the uncorrected open-access allocation is highest; when the resource of antibiotic susceptibility is non-renewable, high morbidity costs are incurred by individuals, and low social discount rates apply. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Modeling and Control of a Delayed Hepatitis B Virus Model with Incubation Period and Combination Treatment.

PubMed

Sun, Deshun; Liu, Fei

2018-06-01

In this paper, a hepatitis B virus (HBV) model with an incubation period and delayed state and control variables is firstly proposed. Furthermore, the combination treatment is adopted to have a longer-lasting effect than mono-therapy. The equilibrium points and basic reproduction number are calculated, and then the local stability is analyzed on this model. We then present optimal control strategies based on the Pontryagin's minimum principle with an objective function not only to reduce the levels of exposed cells, infected cells and free viruses nearly to zero at the end of therapy, but also to minimize the drug side-effect and the cost of treatment. What's more, we develop a numerical simulation algorithm for solving our HBV model based on the combination of forward and backward difference approximations. The state dynamics of uninfected cells, exposed cells, infected cells, free viruses, CTL and ALT are simulated with or without optimal control, which show that HBV is reduced nearly to zero based on the time-varying optimal control strategies whereas the disease would break out without control. At last, by the simulations, we prove that strategy A is the best among the three kinds of strategies we adopt and further comparisons have been done between model (1) and model (2).

SU-G-TeP1-05: Development and Clinical Introduction of Automated Radiotherapy Treatment Planning for Prostate Cancer

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

Winkel, D; Bol, GH; Asselen, B van

Purpose: To develop an automated radiotherapy treatment planning and optimization workflow for prostate cancer in order to generate clinical treatment plans. Methods: A fully automated radiotherapy treatment planning and optimization workflow was developed based on the treatment planning system Monaco (Elekta AB, Stockholm, Sweden). To evaluate our method, a retrospective planning study (n=100) was performed on patients treated for prostate cancer with 5 field intensity modulated radiotherapy, receiving a dose of 35×2Gy to the prostate and vesicles and a simultaneous integrated boost of 35×0.2Gy to the prostate only. A comparison was made between the dosimetric values of the automatically andmore » manually generated plans. Operator time to generate a plan and plan efficiency was measured. Results: A comparison of the dosimetric values show that automatically generated plans yield more beneficial dosimetric values. In automatic plans reductions of 43% in the V72Gy of the rectum and 13% in the V72Gy of the bladder are observed when compared to the manually generated plans. Smaller variance in dosimetric values is seen, i.e. the intra- and interplanner variability is decreased. For 97% of the automatically generated plans and 86% of the clinical plans all criteria for target coverage and organs at risk constraints are met. The amount of plan segments and monitor units is reduced by 13% and 9% respectively. Automated planning requires less than one minute of operator time compared to over an hour for manual planning. Conclusion: The automatically generated plans are highly suitable for clinical use. The plans have less variance and a large gain in time efficiency has been achieved. Currently, a pilot study is performed, comparing the preference of the clinician and clinical physicist for the automatic versus manual plan. Future work will include expanding our automated treatment planning method to other tumor sites and develop other automated radiotherapy workflows.« less

Expression and Secretion of Endostar Protein by Escherichia Coli: Optimization of Culture Conditions Using the Response Surface Methodology.

PubMed

Mohajeri, Abbas; Abdolalizadeh, Jalal; Pilehvar-Soltanahmadi, Younes; Kiafar, Farhad; Zarghami, Nosratollah

2016-10-01

Endostar as a specific drug in treatment of the nonsmall cell lung cancer is produced using Escherichia coli expression system. Plackett-Burman design (PBD) and response surface methodology (RSM) are statistical tools for experimental design and optimization of biotechnological processes. This investigation aimed to predict and develop the optimal culture condition and its components for expression and secretion of endostar into the culture medium of E. coli. The synthetic endostar coding sequence was fused with PhoA signal peptide. The nine factors involved in the production of recombinant protein-postinduction temperature, cell density, rotation speed, postinduction time, concentration of glycerol, IPTG, peptone, glycine, and triton X-100-were evaluated using PBD. Four significant factors were selected based on PBD results for optimizing culture condition using RSM. Endostar was purified using cation exchange chromatography and size exclusion chromatography. The maximum level of endostar was obtained under the following condition: 13.57-h postinduction time, 0.76 % glycine, 0.7 % triton X-100, and 4.87 % glycerol. The predicted levels of endostar was significantly correlated with experimental levels (R 2 = 0.982, P = 0.00). The obtained results indicated that PBD and RSM are effective tools for optimization of culture condition and its components for endostar production in E. coli. The most important factors in the enhancement of the protein production are glycerol, glycine, and postinduction time.

Optimal conditions for preparation of banana peels, sugarcane bagasse and watermelon rind in removing copper from water.

PubMed

Liu, Cong; Ngo, Huu Hao; Guo, Wenshan; Tung, Kuo-Lun

2012-09-01

In this study, three agro-waste materials were used as biosorbents for removal of copper (Cu) from water. This work aims to optimise conditions for preparation of these materials to obtain maximum Cu adsorption capacity. The optimal conditions were determined in terms of Cu removal efficiency and/or energy consumption. The results indicate that banana peels dried at 120°C for 2h and ground into powder form led to a better performance in terms of both copper removal efficiency and energy consumption. For sugarcane bagasse and watermelon rind, 120°C was the suitable drying temperature. However, the best drying time was 1h for sugarcane bagasse and 3h for watermelon rind. The powder form with size of <150 μm was optimal for all biosorbents in terms of removal efficiency and equilibration time. The findings are beneficial to the application of these agro-waste materials for Cu removal from water and wastewater treatment. Copyright © 2012. Published by Elsevier Ltd.

An Innovative Design of a Clay-Zeolite Medium for the Adsorption of Total Phosphorus from Wastewater.

PubMed

Ciosek, Amanda Lidia; Luk, Grace K; Warner, Michèle; Warner, R Anthony

2016-02-01

Phosphorus significantly influences the eutrophication process, modifying the quality of waterways and habitat, especially in stagnant waterbodies exposed to septic tank effluent at high nutrient levels. This research explores the development of a cost-effective, efficient, and affordable on-site wastewater treatment system targeted as total phosphorus (TP) removal technology. The research objective is to demonstrate the TP removal efficiency of an optimized clay-zeolite medium by chemical adsorption. The study observes the effects of pellet medium design and modifications, influent concentrations, and contact time. Following various stages of optimization, the preliminary testing achieves a 45 ± 1.8% removal after 45 minutes of contact time. The optimized pellets are contained within a five-layer bench-scale model, achieving equilibrium TP removal of 72 ± 2.9% after 3 hours. Theoretical extrapolation to 12 contact hours indicates an achievement of 88% removal is possible. The results show a positive correlation with the linearized Langmuir and Freundlich adsorption isotherms.

Dynamic trajectory-based couch motion for improvement of radiation therapy trajectories in cranial SRT

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

MacDonald, R. Lee; Thomas, Christopher G., E-mail: Chris.Thomas@cdha.nshealth.ca; Department of Medical Physics, Nova Scotia Cancer Centre, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia B3H 1V7

2015-05-15

Purpose: To investigate potential improvement in external beam stereotactic radiation therapy plan quality for cranial cases using an optimized dynamic gantry and patient support couch motion trajectory, which could minimize exposure to sensitive healthy tissue. Methods: Anonymized patient anatomy and treatment plans of cranial cancer patients were used to quantify the geometric overlap between planning target volumes and organs-at-risk (OARs) based on their two-dimensional projection from source to a plane at isocenter as a function of gantry and couch angle. Published dose constraints were then used as weighting factors for the OARs to generate a map of couch-gantry coordinate space,more » indicating degree of overlap at each point in space. A couch-gantry collision space was generated by direct measurement on a linear accelerator and couch using an anthropomorphic solid-water phantom. A dynamic, fully customizable algorithm was written to generate a navigable ideal trajectory for the patient specific couch-gantry space. The advanced algorithm can be used to balance the implementation of absolute minimum values of overlap with the clinical practicality of large-scale couch motion and delivery time. Optimized cranial cancer treatment trajectories were compared to conventional treatment trajectories. Results: Comparison of optimized treatment trajectories with conventional treatment trajectories indicated an average decrease in mean dose to the OARs of 19% and an average decrease in maximum dose to the OARs of 12%. Degradation was seen for homogeneity index (6.14% ± 0.67%–5.48% ± 0.76%) and conformation number (0.82 ± 0.02–0.79 ± 0.02), but neither was statistically significant. Removal of OAR constraints from volumetric modulated arc therapy optimization reveals that reduction in dose to OARs is almost exclusively due to the optimized trajectory and not the OAR constraints. Conclusions: The authors’ study indicated that simultaneous couch and gantry motion during radiation therapy to minimize the geometrical overlap in the beams-eye-view of target volumes and the organs-at-risk can have an appreciable dose reduction to organs-at-risk.« less

Trigeminal neuralgia--a coherent cross-specialty management program.

PubMed

Heinskou, Tone; Maarbjerg, Stine; Rochat, Per; Wolfram, Frauke; Jensen, Rigmor Højland; Bendtsen, Lars

2015-01-01

Optimal management of patients with classical trigeminal neuralgia (TN) requires specific treatment programs and close collaboration between medical, radiological and surgical specialties. Organization of such treatment programs has never been described before. With this paper we aim to describe the implementation and feasibility of an accelerated cross-speciality management program, to describe the collaboration between the involved specialties and to report the patient flow during the first 2 years after implementation. Finally, we aim to stimulate discussions about optimal management of TN. Based on collaboration between neurologists, neuroradiologists and neurosurgeons a standardized program for TN was implemented in May 2012 at the Danish Headache Center (DHC). First out-patient visit and subsequent 3.0 Tesla MRI scan was booked in an accelerated manner. The MRI scan was performed according to a special TN protocol developed for this program. Patients initially referred to neurosurgery were re-directed to DHC for pre-surgical evaluation of diagnosis and optimization of medical treatment. Follow-up was 2 years with fixed visits where medical treatment and indication for neurosurgery was continuously evaluated. Scientific data was collected in a structured and prospective manner. From May 2012 to April 2014, 130 patients entered the accelerated program. Waiting time for the first out-patient visit was 42 days. Ninety-four percent of the patients had a MRI performed according to the special protocol after a mean of 37 days. Within 2 years follow-up 35% of the patients were referred to neurosurgery after a median time of 65 days. Five scientific papers describing demographics, clinical characteristics and neuroanatomical abnormalities were published. The described cross-speciality management program proved to be feasible and to have acceptable waiting times for referral and highly specialized work-up of TN patients in a public tertiary referral centre for headache and facial pain. Early high quality MRI ensured correct diagnosis and that the neurosurgeons had a standardized basis before decision-making on impending surgery. The program ensured that referral of the subgroup of patients in need for surgery was standardized, ensured continuous evaluation of the need for adjustments in pharmacological management and formed the basis for scientific research.

Survival Impact of Increasing Time to Treatment Initiation for Patients With Head and Neck Cancer in the United States.

PubMed

Murphy, Colin T; Galloway, Thomas J; Handorf, Elizabeth A; Egleston, Brian L; Wang, Lora S; Mehra, Ranee; Flieder, Douglas B; Ridge, John A

2016-01-10

To estimate the overall survival (OS) impact from increasing time to treatment initiation (TTI) for patients with head and neck squamous cell carcinoma (HNSCC). Using the National Cancer Data Base (NCDB), we examined patients who received curative therapy for the following sites: oral tongue, oropharynx, larynx, and hypopharynx. TTI was the number of days from diagnosis to initiation of curative treatment. The effect of TTI on OS was determined by using Cox regression models (MVA). Recursive partitioning analysis (RPA) identified TTI thresholds via conditional inference trees to estimate the greatest differences in OS on the basis of randomly selected training and validation sets, and repeated this 1,000 times to ensure robustness of TTI thresholds. A total of 51,655 patients were included. On MVA, TTI of 61 to 90 days versus less than 30 days (hazard ratio [HR], 1.13; 95% CI, 1.08 to 1.19) independently increased mortality risk. TTI of 67 days appeared as the optimal threshold on the training RPA, statistical significance was confirmed in the validation set (P < .001), and the 67-day TTI was the optimal threshold in 54% of repeated simulations. Overall, 96% of simulations validated two optimal TTI thresholds, with ranges of 46 to 52 days and 62 to 67 days. The median OS for TTI of 46 to 52 days or fewer versus 53 to 67 days versus greater than 67 days was 71.9 months (95% CI, 70.3 to 73.5 months) versus 61 months (95% CI, 57 to 66.1 months) versus 46.6 months (95% CI, 42.8 to 50.7 months), respectively (P < .001). In the most recent year with available data (2011), 25% of patients had TTI of greater than 46 days. TTI independently affects survival. One in four patients experienced treatment delay. TTI of greater than 46 to 52 days introduced an increased risk of death that was most consistently detrimental beyond 60 days. Prolonged TTI is currently affecting survival. © 2015 by American Society of Clinical Oncology.

Survival Impact of Increasing Time to Treatment Initiation for Patients With Head and Neck Cancer in the United States

PubMed Central

Murphy, Colin T.; Handorf, Elizabeth A.; Egleston, Brian L.; Wang, Lora S.; Mehra, Ranee; Flieder, Douglas B.; Ridge, John A.

2016-01-01

Purpose To estimate the overall survival (OS) impact from increasing time to treatment initiation (TTI) for patients with head and neck squamous cell carcinoma (HNSCC). Methods Using the National Cancer Data Base (NCDB), we examined patients who received curative therapy for the following sites: oral tongue, oropharynx, larynx, and hypopharynx. TTI was the number of days from diagnosis to initiation of curative treatment. The effect of TTI on OS was determined by using Cox regression models (MVA). Recursive partitioning analysis (RPA) identified TTI thresholds via conditional inference trees to estimate the greatest differences in OS on the basis of randomly selected training and validation sets, and repeated this 1,000 times to ensure robustness of TTI thresholds. Results A total of 51,655 patients were included. On MVA, TTI of 61 to 90 days versus less than 30 days (hazard ratio [HR], 1.13; 95% CI, 1.08 to 1.19) independently increased mortality risk. TTI of 67 days appeared as the optimal threshold on the training RPA, statistical significance was confirmed in the validation set (P < .001), and the 67-day TTI was the optimal threshold in 54% of repeated simulations. Overall, 96% of simulations validated two optimal TTI thresholds, with ranges of 46 to 52 days and 62 to 67 days. The median OS for TTI of 46 to 52 days or fewer versus 53 to 67 days versus greater than 67 days was 71.9 months (95% CI, 70.3 to 73.5 months) versus 61 months (95% CI, 57 to 66.1 months) versus 46.6 months (95% CI, 42.8 to 50.7 months), respectively (P < .001). In the most recent year with available data (2011), 25% of patients had TTI of greater than 46 days. Conclusion TTI independently affects survival. One in four patients experienced treatment delay. TTI of greater than 46 to 52 days introduced an increased risk of death that was most consistently detrimental beyond 60 days. Prolonged TTI is currently affecting survival. PMID:26628469

SU-F-T-501: Dosimetric Comparison of Single Arc-Per-Beam and Two Arc-Per-Beam VMAT Optimization in the Monaco Treatment Planning System

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

Kalet, A; Cao, N; Meyer, J

Purpose: The purpose of this study was to evaluate the dosimetric and practical effects of the Monaco treatment planning system “max arcs-per-beam” optimization parameter in pelvic radiotherapy treatments. Methods: A total of 17 previously treated patients were selected for this study with a range of pelvic disease site including prostate(9), bladder(1), uterus(3), rectum(3), and cervix(1). For each patient, two plans were generated, one using a arc-per-beam setting of ‘1’ and another with setting of ‘2’. The setting allows the optimizer to add a gantry direction change, creating multiple arc passes per beam sequence. Volumes and constraints established from the initialmore » clinical treatments were used for planning. All constraints and dose coverage objects were kept the same between plans, and all plans were normalized to 99.7% to ensure 100% of the PTV received 95% of the prescription dose. We evaluated the PTV conformity index, homogeneity index, total monitor units, number of control points, and various dose volume histogram (DVH) points for statistical comparison (alpha=0.05). Results: We found for the 10 complex shaped target volumes (small central volumes with extending bilateral ‘arms’ to cover nodal regions) that the use of 2 arcs-per-beam achieved significantly lower average DVH values for the bladder V20 (p=0.036) and rectum V30 (p=0.001) while still meeting the high dose target constraints. DVH values for the simpler, more spherical PTVs were not found significantly different. Additionally, we found a beam delivery time reduction of approximately 25%. Conclusion: In summary, the dosimetric benefit, while moderate, was improved over a 1 arc-per-beam setting for complex PTVs, and equivalent in other cases. The overall reduced delivery time suggests that the use of multiple arcs-per-beam could lead to reduced patient on table time, increased clinical throughput, and reduced medical physics quality assurance effort.« less

Optimization of conditions for cadmium selenide quantum dot biosynthesis in Saccharomyces cerevisiae.

PubMed

Brooks, Jordan; Lefebvre, Daniel D

2017-04-01

The biosynthesis of quantum dots has been explored as an alternative to traditional physicochemical methods; however, relatively few studies have determined optimal synthesis parameters. Saccharomyces cerevisiae sequentially treated with sodium selenite and cadmium chloride synthesized CdSe quantum dots in the cytoplasm. These nanoparticles displayed a prominent yellow fluorescence, with an emission maximum of approximately 540 nm. The requirement for glutathione in the biosynthetic mechanism was explored by depleting its intracellular content through cellular treatments with 1-chloro-2,4-dinitrobenzene and buthionine sulfoximine. Synthesis was significantly inhibited by both of these reagents when they were applied after selenite treatment prior to the addition of cadmium, thereby indicating that glutathione contributes to the biosynthetic process. Determining the optimum conditions for biosynthesis revealed that quantum dots were produced most efficiently at entry into stationary phase followed by direct addition of 1 mM selenite for only 6 h and then immediately incubating these cells in fresh growth medium containing 3 mM Cd (II). Synthesis of quantum dots reached a maximum at 84 h of reaction time. Biosynthesis of 800-μg g -1 fresh weight cells was achieved. For the first time, significant efforts have been undertaken to optimize each aspect of the CdSe biosynthetic procedure in S. cerevisiae, resulting in a 70% increased production.

Investigation of Optimal Time for Starting Betamethasone Using Fatigue Scores and Prognostic Nutritional Index in Terminally Ill Patients With Cancer-Related Fatigue.

PubMed

Koyama, Nanako; Matsumura, Chikako; Morii, Hiroaki; Hasegawa, Chiaki; Hira, Daiki; Daigo, Yataro; Terada, Tomohiro; Yano, Yoshitaka

2017-06-01

Corticosteroids are frequently used to treat cancer-related fatigue (CRF), but it is yet to be established as standard care, and few reports have defined the appropriate time to start treatment. We investigated the optimal time for starting betamethasone and evaluated the clinical validity of using the prognostic nutritional index (PNI) for this purpose. Data were retrospectively collected for patients with terminal cancer receiving betamethasone for palliative care. Fatigue strength was evaluated by the daily occurrence of fatigue, using proportion of adequate fatigue, AF(%), defined as the average of the daily score for all treatment days, AF(%) all , the initial 5 days, AF(%) initi5 , or the last 5 days, AF(%) last5 . We examined (1) the relationship between survival time and adequate fatigue for CRF and (2) the correlation between survival time and PNI (based on serum albumin and lymphocytes). Data from 24 patients were included. The AF(%) all was approximately 50% at 42 days before death and gradually decreased as the survival time shortened ( R 2 =.41, P <.001). There was a clear positive correlation between AF(%) all and AF(%) initi5 ( R 2 =.84, P <.001). At 42 days before death, PNI was approximately 30 and significantly correlated with the survival time ( R 2 = .873, P <.001). The adequate fatigue appears to be dependent on survival time, and PNI might be useful for identifying patients that will benefit from betamethasone use. It is hoped that these results will contribute to individualized pharmacotherapy of terminally ill patients with CRF.

A Longitudinal Analysis of Treatment Optimism and HIV Acquisition and Transmission Risk Behaviors Among Black Men Who Have Sex with Men in HPTN 061.

PubMed

Levy, Matthew E; Phillips, Gregory; Magnus, Manya; Kuo, Irene; Beauchamp, Geetha; Emel, Lynda; Hucks-Ortiz, Christopher; Hamilton, Erica L; Wilton, Leo; Chen, Iris; Mannheimer, Sharon; Tieu, Hong-Van; Scott, Hyman; Fields, Sheldon D; Del Rio, Carlos; Shoptaw, Steven; Mayer, Kenneth

2017-10-01

Little is known about HIV treatment optimism and risk behaviors among Black men who have sex with men (BMSM). Using longitudinal data from BMSM in the HPTN 061 study, we examined participants' self-reported comfort with having condomless sex due to optimistic beliefs regarding HIV treatment. We assessed correlates of treatment optimism and its association with subsequent risk behaviors for HIV acquisition or transmission using multivariable logistic regression with generalized estimating equations. Independent correlates of treatment optimism included age ≥35 years, annual household income <$20,000, depressive symptoms, high HIV conspiracy beliefs, problematic alcohol use, and previous HIV diagnosis. Treatment optimism was independently associated with subsequent condomless anal sex with a male partner of serodiscordant/unknown HIV status among HIV-infected men, but this association was not statistically significant among HIV-uninfected men. HIV providers should engage men in counseling conversations to assess and minimize willingness to have condomless sex that is rooted in optimistic treatment beliefs without knowledge of viral suppression.

Effect of ultrasound and centrifugal force on carambola (Averrhoa carambola L.) slices during osmotic dehydration.

PubMed

Barman, Nirmali; Badwaik, Laxmikant S

2017-01-01

Osmotic dehydration (OD) of carambola slices were carried out using glucose, sucrose, fructose and glycerol as osmotic agents with 70°Bx solute concentration, 50°C of temperature and for time of 180min. Glycerol and sucrose were selected on the basis of their higher water loss, weight reduction and lowers solid gain. Further the optimization of OD of carambola slices (5mm thick) were carried out under different process conditions of temperature (40-60°C), concentration of sucrose and glycerol (50-70°Bx), time (180min) and fruit to solution ratio (1:10) against various responses viz. water loss, solid gain, texture, rehydration ratio and sensory score according to a composite design. The optimized value for temperature, concentration of sucrose and glycerol has been found to be 50°C, 66°Bx and 66°Bx respectively. Under optimized conditions the effect of ultrasound for 10, 20, 30min and centrifugal force (2800rpm) for 15, 30, 45 and 60min on OD of carambola slices were checked. The controlled samples showed 68.14% water loss and 13.05% solid gain in carambola slices. While, the sample having 30min ultrasonic treatment showed 73.76% water loss and 9.79% solid gain; and the sample treated with centrifugal force for 60min showed 75.65% water loss and 6.76% solid gain. The results showed that with increasing in treatment time the water loss, rehydration ratio were increased and solid gain, texture were decreased. Copyright © 2016 Elsevier B.V. All rights reserved.

Discovery and safety profiling of a potent preclinical candidate, (4-[4-[[(3R)-3-(hydroxycarbamoyl)-8-azaspiro[4.5]decan-3-yl]sulfonyl]phenoxy]-N-methylbenzamide) (CM-352), for the prevention and treatment of hemorrhage.

PubMed

Orbe, Josune; Rodríguez, José A; Sánchez-Arias, Juan A; Salicio, Agustina; Belzunce, Miriam; Ugarte, Ana; Chang, Haisul C Y; Rabal, Obdulia; Oyarzabal, Julen; Páramo, José A

2015-04-09

Discovery of potent and safe therapeutics that improve upon currently available antifibrinolytics, e.g., tranexamic acid (TXA, 1) and aprotinin, has been challenging. Matrix metalloproteinases (MMPs) participate in thrombus dissolution. Then we designed a novel series of optimized MMP inhibitors that went through phenotypic screening consisting of thromboelastometry and mouse tail bleeding. Our optimized lead compound, CM-352 (2), inhibited fibrinolysis in human whole blood functional assays and was more effective than the current standard of care, 1, in the tail-bleeding model using a 30 000 times lower dose. Moreover, 2 reduced blood loss during liver hepatectomy, while 1 and aprotinin had no effect. Molecule 2 displayed optimal pharmacokinetic and safety profiles with no evidence of thrombosis or coagulation impairment. This novel mechanism of action, targeting MMP, defines a new class of antihemorrhagic agents without interfering with normal hemostatic function. Furthermore, 2 represents a preclinical candidate for the acute treatment of bleeding.

Induced bioelectrochemical metabolism for bioremediation of petroleum refinery wastewater: Optimization of applied potential and flow of wastewater.

PubMed

Mohanakrishna, Gunda; Al-Raoush, Riyadh I; Abu-Reesh, Ibrahim M

2018-07-01

Hybrid based bioelectrochemical system (BES) configured with embedded anode and cathode electrodes in soil was tested for the bioelectrochemical degradation of petroleum refinery wastewater (PRW). Four applied potentials were studied to optimize under batch mode operation, among which 2 V resulted in higher COD degradation (69.2%) and power density (725 mW/m 2 ) during 7 days of operation. Further studies with continuous mode of operation at optimized potential (2 V) showed that hydraulic retention time (HRT) of 19 h achieved the highest COD removal (37%) and highest power density (561 mW/m 2 ). BES function with respect to treatment efficiencies of other pollutants of PRW was also identified with respect to oil and grease (batch mode, 91%; continuous mode, 34%), total dissolved salts (batch mode, 53%; continuous mode, 24%) and sulfates (batch mode, 59%; continuous mode, 42%). Soil microenvironment in association with BES forms complex processes, providing suitable conditions for efficient treatment of PRW. Copyright © 2018 Elsevier Ltd. All rights reserved.

Optimization of the cleaning process on a pilot filtration setup for waste water treatment accompanied by flow visualization

NASA Astrophysics Data System (ADS)

Bílek, Petr; Hrůza, Jakub

2018-06-01

This paper deals with an optimization of the cleaning process on a liquid flat-sheet filter accompanied by visualization of the inlet side of a filter. The cleaning process has a crucial impact on the hydrodynamic properties of flat-sheet filters. Cleaning methods avoid depositing of particles on the filter surface and forming a filtration cake. Visualization significantly helps to optimize the cleaning methods, because it brings new overall view on the filtration process in time. The optical method, described in the article, enables to see flow behaviour in a thin laser sheet on the inlet side of a tested filter during the cleaning process. Visualization is a strong tool for investigation of the processes on filters in details and it is also possible to determine concentration of particles after an image analysis. The impact of air flow rate, inverse pressure drop and duration on the cleaning mechanism is investigated in the article. Images of the cleaning process are compared to the hydrodynamic data. The tests are carried out on a pilot filtration setup for waste water treatment.

Intraprocedural yttrium-90 positron emission tomography/CT for treatment optimization of yttrium-90 radioembolization.

PubMed

Bourgeois, Austin C; Chang, Ted T; Bradley, Yong C; Acuff, Shelley N; Pasciak, Alexander S

2014-02-01

Radioembolization with yttrium-90 ((90)Y) microspheres relies on delivery of appropriate treatment activity to ensure patient safety and optimize treatment efficacy. We report a case in which (90)Y positron emission tomography (PET)/computed tomography (CT) was performed to optimize treatment planning during a same-day, three-part treatment session. This treatment consisted of (i) an initial (90)Y infusion with a dosage determined using an empiric treatment planning model, (ii) quantitative (90)Y PET/CT imaging, and (iii) a secondary infusion with treatment planning based on quantitative imaging data with the goal of delivering a specific total tumor absorbed dose. © 2014 SIR Published by SIR All rights reserved.

Technique Optimization of Orbital Atherectomy in Calcified Peripheral Lesions of the Lower Extremities: The CONFIRM Series, A Prospective Multicenter Registry

PubMed Central

Das, Tony; Mustapha, Jihad; Indes, Jeffrey; Vorhies, Robert; Beasley, Robert; Doshi, Nilesh; Adams, George L

2014-01-01

Objectives The purpose of CONFIRM registry series was to evaluate the use of orbital atherectomy (OA) in peripheral lesions of the lower extremities, as well as optimize the technique of OA. Background Methods of treating calcified arteries (historically a strong predictor of treatment failure) have improved significantly over the past decade and now include minimally invasive endovascular treatments, such as OA with unique versatility in modifying calcific lesions above and below-the-knee. Methods Patients (3135) undergoing OA by more than 350 physicians at over 200 US institutions were enrolled on an “all-comers” basis, resulting in registries that provided site-reported patient demographics, ABI, Rutherford classification, co-morbidities, lesion characteristics, plaque morphology, device usage parameters, and procedural outcomes. Results Treatment with OA reduced pre-procedural stenosis from an average of 88–35%. Final residual stenosis after adjunctive treatments, typically low-pressure percutaneous transluminal angioplasty (PTA), averaged 10%. Plaque removal was most effective for severely calcified lesions and least effective for soft plaque. Shorter spin times and smaller crown sizes significantly lowered procedural complications which included slow flow (4.4%), embolism (2.2%), and spasm (6.3%), emphasizing the importance of treatment regimens that focus on plaque modification over maximizing luminal gain. Conclusion The OA technique optimization, which resulted in a change of device usage across the CONFIRM registry series, corresponded to a lower incidence of adverse events irrespective of calcium burden or co-morbidities. © 2013 The Authors. Wiley Periodicals, Inc. PMID:23737432

Roadmap to control HBV and HDV epidemics in China

DOE PAGES

Goyal, Ashish; Murray, John M.

2017-04-23

Hepatitis B virus (HBV) is endemic in China. Almost 10% of HBV infected individuals are also infected with hepatitis D virus (HDV) which has a 5–10 times higher mortality rate than HBV mono-infection. The aim of this manuscript is to devise strategies that can not only control HBV infections but also HDV infections in China under the current health care budget in an optimal manner. Furthermore, using a mathematical model, an annual budget of 10 billion dollars was optimally allocated among five interventions namely, testing and HBV adult vaccination, treatment for mono-infected and dually-infected individuals, second line treatment for HBVmore » mono-infections, and awareness programs. As a result, we determine that the optimal strategy is to test and treat both infections as early as possible while applying awareness programs at full intensity. Under this strategy, an additional 19.8 million HBV, 1.9 million HDV infections and 0.25 million lives will be saved over the next 10 years at a cost-savings of 79 billion dollars than performing no intervention. Introduction of second line treatment does not add a significant economic burden yet prevents 1.4 million new HBV infections and 15,000 new HDV infections. In conclusion, test and treatment programs are highly efficient in reducing HBV and HDV prevalence in the population. Under the current health budget in China, not only test and treat programs but awareness programs and second line treatment can also be implemented that minimizes prevalence and mortality, and maximizes economic benefits.« less

Roadmap to control HBV and HDV epidemics in China

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

Goyal, Ashish; Murray, John M.

Hepatitis B virus (HBV) is endemic in China. Almost 10% of HBV infected individuals are also infected with hepatitis D virus (HDV) which has a 5–10 times higher mortality rate than HBV mono-infection. The aim of this manuscript is to devise strategies that can not only control HBV infections but also HDV infections in China under the current health care budget in an optimal manner. Furthermore, using a mathematical model, an annual budget of 10 billion dollars was optimally allocated among five interventions namely, testing and HBV adult vaccination, treatment for mono-infected and dually-infected individuals, second line treatment for HBVmore » mono-infections, and awareness programs. As a result, we determine that the optimal strategy is to test and treat both infections as early as possible while applying awareness programs at full intensity. Under this strategy, an additional 19.8 million HBV, 1.9 million HDV infections and 0.25 million lives will be saved over the next 10 years at a cost-savings of 79 billion dollars than performing no intervention. Introduction of second line treatment does not add a significant economic burden yet prevents 1.4 million new HBV infections and 15,000 new HDV infections. In conclusion, test and treatment programs are highly efficient in reducing HBV and HDV prevalence in the population. Under the current health budget in China, not only test and treat programs but awareness programs and second line treatment can also be implemented that minimizes prevalence and mortality, and maximizes economic benefits.« less

A review of the efficacy of transcranial magnetic stimulation (TMS) treatment for depression, and current and future strategies to optimize efficacy.

PubMed

Loo, Colleen K; Mitchell, Philip B

2005-11-01

There is a growing interest in extending the use of repetitive transcranial magnetic stimulation (rTMS) beyond research centres to the widespread clinical treatment of depression. Thus it is timely to critically review the evidence for the efficacy of rTMS as an antidepressant treatment. Factors relevant to the efficacy of rTMS are discussed along with the implications of these for the further optimization of rTMS. Clinical trials of the efficacy of rTMS in depressed subjects are summarized and reviewed, focusing mainly on sham-controlled studies and meta-analyses published to date. There is a fairly consistent statistical evidence for the superiority of rTMS over a sham control, though the degree of clinical improvement is not large. However, this data is derived mainly from two-week comparisons of rTMS versus sham, and evidence suggests greater efficacy with longer treatment courses. Studies so far have also varied greatly in approaches to rTMS stimulation (with respect to stimulation site, stimulus parameters etc) with little empirical evidence to inform on the relative merits of these approaches. Only studies published in English were reviewed. Many of the studies in the literature had small sample sizes and different methodologies, making comparisons between studies difficult. Current published studies and meta-analyses have evaluated the efficacy of rTMS as given in treatment paradigms that are almost certainly suboptimal (e.g of two weeks' duration). While the data nevertheless supports positive outcomes for rTMS, there is much scope for the further refinement and development of rTMS as an antidepressant treatment. Ongoing research is critical for optimizing the efficacy of rTMS.

Treatment of oilfield wastewater by combined process of micro-electrolysis, Fenton oxidation and coagulation.

PubMed

Zhang, Zhenchao

2017-12-01

In this study, a combined process was developed that included micro-electrolysis, Fenton oxidation and coagulation to treat oilfield fracturing wastewater. Micro-electrolysis and Fenton oxidation were applied to reduce chemical oxygen demand (COD) organic load and to enhance organic components gradability, respectively. Orthogonal experiment were employed to investigate the influence factors of micro-electrolysis and Fenton oxidation on COD removal efficiency. For micro-electrolysis, the optimum conditions were: pH, 3; iron-carbon dosage, 50 mg/L; mass ratio of iron-carbon, 2:3; reaction time, 60 min. For Fenton oxidation, a total reaction time of 90 min, a H 2 O 2 dosage of 12 mg/L, with a H 2 O 2 /Fe 2+ mole ratio of 30, pH of 3 were selected to achieve optimum oxidation. The optimum conditions in coagulation process: pH, cationic polyacrylamide dosage, mixing speed and time is 4.3, 2 mg/L, 150 rpm and 30 s, respectively. In the continuous treatment process under optimized conditions, the COD of oily wastewater fell 56.95%, 46.23%, 30.67%, respectively, from last stage and the total COD removal efficiency reached 83.94% (from 4,314 to 693 mg/L). In the overall treatment process under optimized conditions, the COD of oily wastewater was reduced from 4,314 to 637 mg/L, and the COD removal efficiency reached 85.23%. The contribution of each stage is 68.45% (micro-electrolysis), 24.07% (Fenton oxidation), 7.48% (coagulation), respectively. Micro-electrolysis is the uppermost influencing process on COD removal. Compared with the COD removal efficiency of three processes on raw wastewater under optimized conditions: the COD removal efficiency of single micro-electrolysis, single Fenton oxidation, single coagulation is 58.34%, 44.88% and 39.72%, respectively. Experiments proved the effect of combined process is marvelous and the overall water quality of the final effluent could meet the class III national wastewater discharge standard of petrochemical industry of China (GB8978-1996).

Optimizing basin-scale coupled water quantity and water quality man-agement with stochastic dynamic programming

NASA Astrophysics Data System (ADS)

Davidsen, Claus; Liu, Suxia; Mo, Xingguo; Engelund Holm, Peter; Trapp, Stefan; Rosbjerg, Dan; Bauer-Gottwein, Peter

2015-04-01

Few studies address water quality in hydro-economic models, which often focus primarily on optimal allocation of water quantities. Water quality and water quantity are closely coupled, and optimal management with focus solely on either quantity or quality may cause large costs in terms of the oth-er component. In this study, we couple water quality and water quantity in a joint hydro-economic catchment-scale optimization problem. Stochastic dynamic programming (SDP) is used to minimize the basin-wide total costs arising from water allocation, water curtailment and water treatment. The simple water quality module can handle conservative pollutants, first order depletion and non-linear reactions. For demonstration purposes, we model pollutant releases as biochemical oxygen demand (BOD) and use the Streeter-Phelps equation for oxygen deficit to compute the resulting min-imum dissolved oxygen concentrations. Inelastic water demands, fixed water allocation curtailment costs and fixed wastewater treatment costs (before and after use) are estimated for the water users (agriculture, industry and domestic). If the BOD concentration exceeds a given user pollution thresh-old, the user will need to pay for pre-treatment of the water before use. Similarly, treatment of the return flow can reduce the BOD load to the river. A traditional SDP approach is used to solve one-step-ahead sub-problems for all combinations of discrete reservoir storage, Markov Chain inflow clas-ses and monthly time steps. Pollution concentration nodes are introduced for each user group and untreated return flow from the users contribute to increased BOD concentrations in the river. The pollutant concentrations in each node depend on multiple decision variables (allocation and wastewater treatment) rendering the objective function non-linear. Therefore, the pollution concen-tration decisions are outsourced to a genetic algorithm, which calls a linear program to determine the remainder of the decision variables. This hybrid formulation keeps the optimization problem computationally feasible and represents a flexible and customizable method. The method has been applied to the Ziya River basin, an economic hotspot located on the North China Plain in Northern China. The basin is subject to severe water scarcity, and the rivers are heavily polluted with wastewater and nutrients from diffuse sources. The coupled hydro-economic optimiza-tion model can be used to assess costs of meeting additional constraints such as minimum water qual-ity or to economically prioritize investments in waste water treatment facilities based on economic criteria.

A fast optimization algorithm for multicriteria intensity modulated proton therapy planning.

PubMed

Chen, Wei; Craft, David; Madden, Thomas M; Zhang, Kewu; Kooy, Hanne M; Herman, Gabor T

2010-09-01

To describe a fast projection algorithm for optimizing intensity modulated proton therapy (IMPT) plans and to describe and demonstrate the use of this algorithm in multicriteria IMPT planning. The authors develop a projection-based solver for a class of convex optimization problems and apply it to IMPT treatment planning. The speed of the solver permits its use in multicriteria optimization, where several optimizations are performed which span the space of possible treatment plans. The authors describe a plan database generation procedure which is customized to the requirements of the solver. The optimality precision of the solver can be specified by the user. The authors apply the algorithm to three clinical cases: A pancreas case, an esophagus case, and a tumor along the rib cage case. Detailed analysis of the pancreas case shows that the algorithm is orders of magnitude faster than industry-standard general purpose algorithms (MOSEK'S interior point optimizer, primal simplex optimizer, and dual simplex optimizer). Additionally, the projection solver has almost no memory overhead. The speed and guaranteed accuracy of the algorithm make it suitable for use in multicriteria treatment planning, which requires the computation of several diverse treatment plans. Additionally, given the low memory overhead of the algorithm, the method can be extended to include multiple geometric instances and proton range possibilities, for robust optimization.

Extraction of gelatin from salmon (Salmo salar) fish skin using trypsin-aided process: optimization by Plackett-Burman and response surface methodological approaches.

PubMed

Fan, HuiYin; Dumont, Marie-Josée; Simpson, Benjamin K

2017-11-01

Gelatin from salmon ( Salmo salar ) skin with high molecular weight protein chains ( α -chains) was extracted using trypsin-aided process. Response surface methodology was used to optimise the extraction parameters. Yield, hydroxyproline content and protein electrophoretic profile via sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of gelatin were used as responses in the optimization study. The optimum conditions were determined as: trypsin concentration at 1.49 U/g; extraction temperature at 45 °C; and extraction time at 6 h 16 min. This response surface optimized model was significant and produced an experimental value (202.04 ± 8.64%) in good agreement with the predicted value (204.19%). Twofold higher yields of gelatin with high molecular weight protein chains were achieved in the optimized process with trypsin treatment when compared to the process without trypsin.

Time-lapse analysis of potential cellular responsiveness to Johrei, a Japanese healing technique

PubMed Central

Taft, Ryan; Moore, Dan; Yount, Garret

2005-01-01

Background Johrei is an alternative healing practice which involves the channeling of a purported universal healing energy to influence the health of another person. Despite little evidence to support the efficacy of such practices the use of such treatments is on the rise. Methods We assessed cultured human cancer cells for potential responsiveness to Johrei treatment from a short distance. Johrei treatment was delivered by practitioners who participated in teams of two, alternating every half hour for a total of four hours of treatment. The practitioners followed a defined set of mental procedures to minimize variability in mental states between experiments. An environmental chamber maintained optimal growth conditions for cells throughout the experiments. Computerized time-lapse microscopy allowed documentation of cancer cell proliferation and cell death before, during and after Johrei treatments. Results Comparing eight control experiments with eight Johrei intervention experiments, we found no evidence of a reproducible cellular response to Johrei treatment. Conclusion Cell death and proliferation rates of cultured human cancer cells do not appear responsive to Johrei treatment from a short distance. PMID:15667653

iCycle: Integrated, multicriterial beam angle, and profile optimization for generation of coplanar and noncoplanar IMRT plans

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

Breedveld, Sebastiaan; Storchi, Pascal R. M.; Voet, Peter W. J.

2012-02-15

Purpose: To introduce iCycle, a novel algorithm for integrated, multicriterial optimization of beam angles, and intensity modulated radiotherapy (IMRT) profiles. Methods: A multicriterial plan optimization with iCycle is based on a prescription called wish-list, containing hard constraints and objectives with ascribed priorities. Priorities are ordinal parameters used for relative importance ranking of the objectives. The higher an objective priority is, the higher the probability that the corresponding objective will be met. Beam directions are selected from an input set of candidate directions. Input sets can be restricted, e.g., to allow only generation of coplanar plans, or to avoid collisions betweenmore » patient/couch and the gantry in a noncoplanar setup. Obtaining clinically feasible calculation times was an important design criterium for development of iCycle. This could be realized by sequentially adding beams to the treatment plan in an iterative procedure. Each iteration loop starts with selection of the optimal direction to be added. Then, a Pareto-optimal IMRT plan is generated for the (fixed) beam setup that includes all so far selected directions, using a previously published algorithm for multicriterial optimization of fluence profiles for a fixed beam arrangement Breedveld et al.[Phys. Med. Biol. 54, 7199-7209 (2009)]. To select the next direction, each not yet selected candidate direction is temporarily added to the plan and an optimization problem, derived from the Lagrangian obtained from the just performed optimization for establishing the Pareto-optimal plan, is solved. For each patient, a single one-beam, two-beam, three-beam, etc. Pareto-optimal plan is generated until addition of beams does no longer result in significant plan quality improvement. Plan generation with iCycle is fully automated. Results: Performance and characteristics of iCycle are demonstrated by generating plans for a maxillary sinus case, a cervical cancer patient, and a liver patient treated with SBRT. Plans generated with beam angle optimization did better meet the clinical goals than equiangular or manually selected configurations. For the maxillary sinus and liver cases, significant improvements for noncoplanar setups were seen. The cervix case showed that also in IMRT with coplanar setups, beam angle optimization with iCycle may improve plan quality. Computation times for coplanar plans were around 1-2 h and for noncoplanar plans 4-7 h, depending on the number of beams and the complexity of the site. Conclusions: Integrated beam angle and profile optimization with iCycle may result in significant improvements in treatment plan quality. Due to automation, the plan generation workload is minimal. Clinical application has started.« less

Interactive Dose Shaping - efficient strategies for CPU-based real-time treatment planning

NASA Astrophysics Data System (ADS)

Ziegenhein, P.; Kamerling, C. P.; Oelfke, U.

2014-03-01

Conventional intensity modulated radiation therapy (IMRT) treatment planning is based on the traditional concept of iterative optimization using an objective function specified by dose volume histogram constraints for pre-segmented VOIs. This indirect approach suffers from unavoidable shortcomings: i) The control of local dose features is limited to segmented VOIs. ii) Any objective function is a mathematical measure of the plan quality, i.e., is not able to define the clinically optimal treatment plan. iii) Adapting an existing plan to changed patient anatomy as detected by IGRT procedures is difficult. To overcome these shortcomings, we introduce the method of Interactive Dose Shaping (IDS) as a new paradigm for IMRT treatment planning. IDS allows for a direct and interactive manipulation of local dose features in real-time. The key element driving the IDS process is a two-step Dose Modification and Recovery (DMR) strategy: A local dose modification is initiated by the user which translates into modified fluence patterns. This also affects existing desired dose features elsewhere which is compensated by a heuristic recovery process. The IDS paradigm was implemented together with a CPU-based ultra-fast dose calculation and a 3D GUI for dose manipulation and visualization. A local dose feature can be implemented via the DMR strategy within 1-2 seconds. By imposing a series of local dose features, equal plan qualities could be achieved compared to conventional planning for prostate and head and neck cases within 1-2 minutes. The idea of Interactive Dose Shaping for treatment planning has been introduced and first applications of this concept have been realized.

SU-F-T-163: Improve Proton Therapy Efficiency: Report of a Workshop

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

Zheng, Y; Flanz, J; Mah, D

Purpose: The technology of proton therapy, especially the pencil beam scanning technique, is evolving very quickly. However, the efficiency of proton therapy seems to lag behind conventional photon therapy. The purpose of the abstract is to report on the findings of a workshop on improvement of QA, planning and treatment efficiency in proton therapy. Methods: A panel of physicists, clinicians, and vendor representatives from over 18 institutions in the United States and internationally were convened in Knoxville, Tennessee in November, 2015. The panel discussed several topics on how to improve proton therapy efficiency, including 1) lean principle and failure modemore » and effects analysis, 2) commissioning and machine QA, 3) treatment planning, optimization and evaluation, 4) patient positioning and IGRT, 5) vendor liaison and machine availability, and 6) staffing, education and training. Results: The relative time needed for machine QA, treatment planning & check in proton therapy was found to range from 1 to 2.5 times of that in photon therapy. Current status in proton QA, planning and treatment was assessed. Key areas for efficiency improvement, such as elimination of unnecessary QA items or steps and development of efficient software or hardware tools, were identified. A white paper to summarize our findings is being written. Conclusion: It is critical to improve efficiency by developing reliable proton beam lines, efficient software tools on treatment planning, optimization and evaluation, and dedicated proton QA device. Conscious efforts and collaborations from both industry leaders and proton therapy centers are needed to achieve this goal and further advance the technology of proton therapy.« less

Automated geometric optimization for robotic HIFU treatment of liver tumors.

PubMed

Williamson, Tom; Everitt, Scott; Chauhan, Sunita

2018-05-01

High intensity focused ultrasound (HIFU) represents a non-invasive method for the destruction of cancerous tissue within the body. Heating of targeted tissue by focused ultrasound transducers results in the creation of ellipsoidal lesions at the target site, the locations of which can have a significant impact on treatment outcomes. Towards this end, this work describes a method for the optimization of lesion positions within arbitrary tumors, with specific anatomical constraints. A force-based optimization framework was extended to the case of arbitrary tumor position and constrained orientation. Analysis of the approximate reachable treatment volume for the specific case of treatment of liver tumors was performed based on four transducer configurations and constraint conditions derived. Evaluation was completed utilizing simplified spherical and ellipsoidal tumor models and randomly generated tumor volumes. The total volume treated, lesion overlap and healthy tissue ablated was evaluated. Two evaluation scenarios were defined and optimized treatment plans assessed. The optimization framework resulted in improvements of up to 10% in tumor volume treated, and reductions of up to 20% in healthy tissue ablated as compared to the standard lesion rastering approach. Generation of optimized plans proved feasible for both sub- and intercostally located tumors. This work describes an optimized method for the planning of lesion positions during HIFU treatment of liver tumors. The approach allows the determination of optimal lesion locations and orientations, and can be applied to arbitrary tumor shapes and sizes. Copyright © 2018 Elsevier Ltd. All rights reserved.

A business case for quality improvement in addiction treatment: evidence from the NIATx collaborative.

PubMed

Quanbeck, Andrew R; Madden, Lynn; Edmundson, Eldon; Ford, James H; McConnell, K John; McCarty, Dennis; Gustafson, David H

2012-01-01

The Network for the Improvement of Addiction Treatment (NIATx) promotes treatment access and retention through a customer-focused quality improvement model. This paper explores the issue of the "business case" for quality improvement in addiction treatment from the provider's perspective. The business case model developed in this paper is based on case examples of early NIATx participants coupled with a review of the literature. Process inefficiencies indicated by long waiting times, high no-show rates, and low continuation rates cause underutilization of capacity and prevent optimal financial performance. By adopting customer-focused practices aimed at removing barriers to treatment access and retention, providers may be able to improve financial performance, increase staff retention, and gain long-term strategic advantage.

The prognostic value of functional and anatomical parameters for the selection of patients receiving yttrium-90 microspheres for the treatment of liver cancer

NASA Astrophysics Data System (ADS)

Mesoloras, Geraldine

Yttrium-90 (90Y) microsphere therapy is being utilized as a treatment option for patients with primary and metastatic liver cancer due to its ability to target tumors within the liver. The success of this treatment is dependent on many factors, including the extent and type of disease and the nature of prior treatments received. Metabolic activity, as determined by PET imaging, may correlate with the number of viable cancer cells and reflect changes in viable cancer cell volume. However, contouring of PET images by hand is labor intensive and introduces an element of irreproducibility into the determination of functional target/tumor volume (FTV). A computer-assisted method to aid in the automatic contouring of FTV has the potential to substantially improve treatment individualization and outcome assessment. Commercial software to determine FTV in FDG-avid primary and metastatic liver tumors has been evaluated and optimized. Volumes determined using the automated technique were compared to those from manually drawn contours identified using the same cutoff in the standard uptake value (SUV). The reproducibility of FTV is improved through the introduction of an optimal threshold value determined from phantom experiments. Application of the optimal threshold value from the phantom experiments to patient scans was in good agreement with hand-drawn determinations of the FTV. It is concluded that computer-assisted contouring of the FTV for primary and metastatic liver tumors improves reproducibility and increases accuracy, especially when combined with the selection of an optimal SUV threshold determined from phantom experiments. A method to link the pre-treatment assessment of functional (PET based) and anatomical (CT based) parameters to post-treatment survival and time to progression was evaluated in 22 patients with colorectal cancer liver metastases treated using 90Y microspheres and chemotherapy. The values for pre-treatment parameters that were the best predictors of response were determined for FTV, anatomical tumor volume, total lesion glycolysis, and the tumor marker, CEA. Of the parameters considered, the best predictors of response were found to be pre-treatment FTV ≤153 cm3, ATV ≤163 cm3, TLG ≤144 g in the chemo-SIRT treated field, and CEA ≤11.6 ng/mL.

Effect of Aptensio XR (Methylphenidate HCl Extended-Release) Capsules on Sleep in Children with Attention-Deficit/Hyperactivity Disorder.

PubMed

Owens, Judith; Weiss, Margaret; Nordbrock, Earl; Mattingly, Greg; Wigal, Sharon; Greenhill, Laurence L; Chang, Wei-Wei; Childress, Ann; Kupper, Robert J; Adjei, Akwete

2016-12-01

To evaluate measures of sleep (exploratory endpoints) in two pivotal studies of a multilayer bead extended-release methylphenidate (MPH-MLR) treatment of attention-deficit/hyperactivity disorder in children. Study 1 evaluated the time course of response to MPH-MLR (n = 26) patients in an analog classroom setting through four phases: screening (≤28 days), open label (OL) dose optimization (4 weeks), double-blind (DB) crossover (2 weeks; placebo vs. optimized dose), and follow-up call. Study 2 was a forced-dose parallel evaluation of MPH-MLR (n = 230) in four phases: screening (≤28 days), DB (1 week; placebo or MPH-MLR 10, 15, 20, or 40 mg/day), OL dose optimization (11 weeks), and follow-up call. Sleep was evaluated by parents using the Children's or Adolescent Sleep Habits Questionnaire (CSHQ or ASHQ) during the DB and OL phases. DB analysis: Study 1 (crossover), analysis of variance; Study 2, analysis of covariance. OL analysis: paired t-test. DB: treatments were significantly different in Study 1 only for CSHQ Sleep Onset Delay (MPH-MLR, 1.90 vs. placebo, 1.34; p = 0.0046, placebo was better), and Study 2 for CSHQ Parasomnias (treatment, p = 0.0295), but no MPH-MLR treatment was different from placebo (pairwise MPH-MLR treatment to placebo, all p ≥ 0.170). OL: CSHQ total and Bedtime Resistance, Sleep Duration, Sleep Anxiety, Night Wakings, Parasomnias, and Sleep-disordered Breathing subscales decreased (improved, Study 1) significant only for CSHQ Night Wakings (p < 0.05); in Study 2 CSHQ total and Bedtime Resistance, Sleep Duration, Night Wakings, Parasomnias, and Daytime Sleepiness, and ASHQ total, Bedtime, Sleep Behavior, and Morning Waking all significantly improved (p < 0.05). In both studies, there was minimal negative impact of MPH-MLR on sleep during the brief DB phase and none during the longer duration OL phase. Some measures of sleep improved with optimized MPH-MLR dose.

The Optimal Timing of Hepatitis C Therapy in Transplant Eligible Patients With Child B and C Cirrhosis: A Cost-Effectiveness Analysis.

PubMed

Tapper, Elliot B; Hughes, Michael S; Buti, Maria; Dufour, Jean-Francois; Flamm, Steve; Firdoos, Saima; Curry, Michael P; Afdhal, Nezam H

2017-05-01

Ledipasvir (LDV)/sofosbuvir (SOF) has demonstrated high efficacy, safety, and tolerability in hepatitis C virus (HCV)-infected patients. There is limited data, however, regarding the optimal timing of therapy in the context of possible liver transplantation (LT). We compared the cost-effectiveness of 12 weeks of HCV therapy before or after LT or nontreatment using a decision analytical microsimulation state-transition model for a simulated cohort of 10 000 patients with HCV Genotype 1 or 4 with Child B or C cirrhosis. All model parameters regarding the efficacy of therapy, adverse events and the effect of therapy on changes in model for end-stage liver disease (MELD) scores were derived from the SOLAR-1 and 2 trials. The simulations were repeated with 10 000 samples from the parameter distributions. The primary outcome was cost (2014 US dollars) per quality adjusted life year. Treatment before LT yielded more quality-adjusted life year for less money than treatment after LT or nontreatment. Treatment before LT was cost-effective in 100% of samples at a willingness-to-pay threshold of US $100 000 in the base-case and when the analysis was restricted to Child B alone, Child C, or MELD > 15. Treatment before transplant was not cost-effective when MELD was 6-10. In sensitivity analyses, the MELD after which treatment before transplant was cost-effective was 13 and the maximum cost of LDV/SOF therapy at which treatment before LT is cost-effective is US $177 381. From a societal perspective, HCV therapy using LDV/SOF with ribavirin before LT is the most cost-effective strategy for patients with decompensated cirrhosis and MELD score greater than 13.

Influence of patient mispositioning on SAR distribution and simulated temperature in regional deep hyperthermia

NASA Astrophysics Data System (ADS)

Aklan, Bassim; Gierse, Pia; Hartmann, Josefin; Ott, Oliver J.; Fietkau, Rainer; Bert, Christoph

2017-06-01

Patient positioning plays an important role in regional deep hyperthermia to obtain a successful hyperthermia treatment. In this study, the influence of possible patient mispositioning was systematically assessed on specific absorption rate (SAR) and temperature distribution. With a finite difference time domain approach, the SAR and temperature distributions were predicted for six patients at 312 positions. Patient displacements and rotations as well as the combination of both were considered inside the Sigma-Eye applicator. Position sensitivity is assessed for hyperthermia treatment planning -guided steering, which relies on model-based optimization of the SAR and temperature distribution. The evaluation of the patient mispositioning was done with and without optimization. The evaluation without optimization was made by creating a treatment plan for the patient reference position in the center of the applicator and applied for all other positions, while the evaluation with optimization was based on creating an individual plan for each position. The parameter T90 was used for the temperature evaluation, which was defined as the temperature that covers 90% of the gross tumor volume (GTV). Furthermore, the hotspot tumor quotient (HTQ) was used as a goal function to assess the quality of the SAR and temperature distribution. The T90 was shown considerably dependent on the position within the applicator. Without optimization, the T90 was clearly decreased below 40 °C by patient shifts and the combination of shifts and rotations. However, the application of optimization for each positon led to an increase of T90 in the GTV. Position inaccuracies of less than 1 cm in the X-and Y-directions and 2 cm in the Z-direction, resulted in an increase of HTQ of less than 5%, which does not significantly affect the SAR and temperature distribution. Current positioning precision is sufficient in the X (right-left)-direction, but position accuracy is required in the Y-and Z-directions.

Heat transfer simulation and retort program adjustment for thermal processing of wheat based Haleem in semi-rigid aluminum containers.

PubMed

Vatankhah, Hamed; Zamindar, Nafiseh; Shahedi Baghekhandan, Mohammad

2015-10-01

A mixed computational strategy was used to simulate and optimize the thermal processing of Haleem, an ancient eastern food, in semi-rigid aluminum containers. Average temperature values of the experiments showed no significant difference (α = 0.05) in contrast to the predicted temperatures at the same positions. According to the model, the slowest heating zone was located in geometrical center of the container. The container geometrical center F0 was estimated to be 23.8 min. A 19 min processing time interval decrease in holding time of the treatment was estimated to optimize the heating operation since the preferred F0 of some starch or meat based fluid foods is about 4.8-7.5 min.

Increasing the antioxidant activity, total phenolic and flavonoid contents by optimizing the germination conditions of amaranth seeds.

PubMed

Perales-Sánchez, Janitzio X K; Reyes-Moreno, Cuauhtémoc; Gómez-Favela, Mario A; Milán-Carrillo, Jorge; Cuevas-Rodríguez, Edith O; Valdez-Ortiz, Angel; Gutiérrez-Dorado, Roberto

2014-09-01

The aim of this study was to optimize the germination conditions of amaranth seeds that would maximize the antioxidant activity (AoxA), total phenolic (TPC), and flavonoid (TFC) contents. To optimize the germination bioprocess, response surface methodology was applied over three response variables (AoxA, TPC, TFC). A central composite rotable experimental design with two factors [germination temperature (GT), 20-45 ºC; germination time (Gt), 14-120 h] in five levels was used; 13 treatments were generated. The amaranth seeds were soaked in distilled water (25 °C/6 h) before germination. The sprouts from each treatment were dried (50 °C/8 h), cooled, and ground to obtain germinated amaranth flours (GAF). The best combination of germination bioprocess variables for producing optimized GAF with the highest AoxA [21.56 mmol trolox equivalent (TE)/100 g sample, dw], TPC [247.63 mg gallic acid equivalent (GAE)/100 g sample, dw], and TFC [81.39 mg catechin equivalent (CAE)/100 g sample, dw] was GT = 30 ºC/Gt = 78 h. The germination bioprocess increased AoxA, TPC, and TFC in 300-470, 829, and 213%, respectively. The germination is an effective strategy to increase the TPC and TFC of amaranth seeds for enhancing functionality with improved antioxidant activity.

Mechanical valve obstruction: Review of diagnostic and treatment strategies

PubMed Central

Salamon, Jason; Munoz-Mendoza, Jerson; Liebelt, Jared J; Taub, Cynthia C

2015-01-01

Prosthetic valve obstruction (PVO) is a rare but feared complication of mechanical valve replacement. Diagnostic evaluation should focus on differentiating prosthetic valve thrombosis (PVT) from pannus formation, as their treatment options differ. History of sub-optimal anti-coagulation and post-op time course to development of PVO are useful clinical characteristics in differentiating thrombus from pannus formation. Treatment of PVT is influenced by the patient’s symptoms, valve location, degree of obstruction and thrombus size and may include thrombolysis or surgical intervention. Alternatively, pannus formation requires surgical intervention. The purpose of this article is to review the pathophysiology, epidemiology, diagnostic approach and treatment options for aortic and mitral valve PVO. PMID:26730292

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

Thomas, D; O’Connell, D; Lamb, J

Purpose: To demonstrate real-time dose calculation of free-breathing MRI guided Co−60 treatments, using a motion model and Monte-Carlo dose calculation to accurately account for the interplay between irregular breathing motion and an IMRT delivery. Methods: ViewRay Co-60 dose distributions were optimized on ITVs contoured from free-breathing CT images of lung cancer patients. Each treatment plan was separated into 0.25s segments, accounting for the MLC positions and beam angles at each time point. A voxel-specific motion model derived from multiple fast-helical free-breathing CTs and deformable registration was calculated for each patient. 3D images for every 0.25s of a simulated treatment weremore » generated in real time, here using a bellows signal as a surrogate to accurately account for breathing irregularities. Monte-Carlo dose calculation was performed every 0.25s of the treatment, with the number of histories in each calculation scaled to give an overall 1% statistical uncertainty. Each dose calculation was deformed back to the reference image using the motion model and accumulated. The static and real-time dose calculations were compared. Results: Image generation was performed in real time at 4 frames per second (GPU). Monte-Carlo dose calculation was performed at approximately 1frame per second (CPU), giving a total calculation time of approximately 30 minutes per treatment. Results show both cold- and hot-spots in and around the ITV, and increased dose to contralateral lung as the tumor moves in and out of the beam during treatment. Conclusion: An accurate motion model combined with a fast Monte-Carlo dose calculation allows almost real-time dose calculation of a free-breathing treatment. When combined with sagittal 2D-cine-mode MRI during treatment to update the motion model in real time, this will allow the true delivered dose of a treatment to be calculated, providing a useful tool for adaptive planning and assessing the effectiveness of gated treatments.« less

Pathfinding to an optimal strategy of revascularization in primary coronary intervention in patients with multivessel disease: a network meta-analysis of randomized trials.

PubMed

Komócsi, András; Kehl, Dániel; d'Ascenso, Fabrizio; DiNicolantonio, James; Vorobcsuk, András

2017-03-01

In ST-segment elevation myocardial infarction (STEMI), current guidelines discourage treatment of the non-culprit lesions at the time of the primary intervention. Latest trials have challenged this strategy suggesting benefit of early complete revascularization. We performed a Bayesian multiple treatment network meta-analysis of randomized clinical trials (RCTs) in STEMI on culprit-only intervention (CO) versus different timing multivessel revascularization, including immediate (IM), same hospitalization (SH) or later staged (ST). Outcome parameters were pooled with a random-effects model. For multiple-treatment meta-analysis, a Bayesian Markov chain Monte Carlo method was used. Eight RCTs involving 2077 patients were identified. ST and IM revascularization was associated with a decrease in major adverse cardiac events (MACEs) compared to culprit-only approach (risk ratio [RR]: 0.43 credible interval [CrI]: 0.22-0.77 and RR: 0.36 CrI: 0.24-0.54, respectively). IM was superior to SH (RR: 0.49 CrI: 0.29-0.80). With regards to myocardial infarction IM was superior to SH (RR: 0.18 CrI: 0.02-0.99). The posterior probability of being the best choice of treatment regarding the frequency of MACEs was 71.2% for IM, 28.5% for ST, 0.3% for SH and 0.05% for culprit-only approach. Results from RCTs indicate that immediate or staged revascularization of non-culprit lesions reduces major adverse events in patients after primary percutaneous coronary intervention. Differences in MACEs suggest superiority of the immediate or staged intervention; however, further randomized trials are needed to determine the optimal timing of revascularization of the non-culprit lesions.

Preclinical evaluation of 18F-ML-10 to determine timing of apoptotic response to chemotherapy in solid tumors

DOE PAGES

Demirci, Emre; Ahmed, Rafay; Ocak, Meltem; ...

2017-01-10

Here, we investigated 2-(5-fluoro-pentyl)-2-methyl-malonic acid ( 18F-ML-10) positron emission tomography (PET) imaging of apoptosis posttherapy to determine optimal timing for predicting chemotherapy response in a mouse head/neck xenograft cancer model. BALB/c nude mice (4-8 weeks old) were implanted with UM-SCC-22B tumors. The treatment group received 2 doses of doxorubicin (10 mg/kg, days 0, 2). Small animal 18F-ML-10 PET/computed tomography was performed before and on days 1, 3, and 7 postchemotherapy. Using regions of interest around tumors, 18F-ML-10 uptake change was measured as %ID/g and uptake relative to liver. Terminal Uridine Nick-End Labeling (TUNEL) immunohistochemistry assay was performed using tumor samplesmore » of baseline and on days 1, 3, and 7 posttreatment. As a result, treated mice demonstrated increased 18F-ML-10 uptake compared to baseline and controls, and 10 of 13 mice showed tumor volume decreases. All control mice showed tumor volume increases. Tumor-to-liver (T/L) ratios from the control group mice did not show significant change from baseline ( P > .05); however, T/L ratios of the treatment group showed significant 18F-ML-10 uptake differences from baseline compared to days 3 and 7 posttreatment ( P < .05), but no significant difference at 1 day posttreatment. In conclusion, 2-(5-Fluoro-pentyl)-2-methyl-malonic acid PET imaging has the potential for early assessment of treatment-induced apoptosis. Timing and image analysis strategies may require optimization, depending on the type of tumor and cancer treatment.« less