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Sample records for optimal chronomodulated treatment

  1. Tumor growth rate determines the timing of optimal chronomodulated treatment schedules.

    Directory of Open Access Journals (Sweden)

    Samuel Bernard

    2010-03-01

    Full Text Available In host and cancer tissues, drug metabolism and susceptibility to drugs vary in a circadian (24 h manner. In particular, the efficacy of a cell cycle specific (CCS cytotoxic agent is affected by the daily modulation of cell cycle activity in the target tissues. Anti-cancer chronotherapy, in which treatments are administered at a particular time each day, aims at exploiting these biological rhythms to reduce toxicity and improve efficacy of the treatment. The circadian status, which is the timing of physiological and behavioral activity relative to daily environmental cues, largely determines the best timing of treatments. However, the influence of variations in tumor kinetics has not been considered in determining appropriate treatment schedules. We used a simple model for cell populations under chronomodulated treatment to identify which biological parameters are important for the successful design of a chronotherapy strategy. We show that the duration of the phase of the cell cycle targeted by the treatment and the cell proliferation rate are crucial in determining the best times to administer CCS drugs. Thus, optimal treatment times depend not only on the circadian status of the patient but also on the cell cycle kinetics of the tumor. Then, we developed a theoretical analysis of treatment outcome (TATO to relate the circadian status and cell cycle kinetic parameters to the treatment outcomes. We show that the best and the worst CCS drug administration schedules are those with 24 h intervals, implying that 24 h chronomodulated treatments can be ineffective or even harmful if administered at wrong circadian times. We show that for certain tumors, administration times at intervals different from 24 h may reduce these risks without compromising overall efficacy.

  2. Formulation and optimization of chronomodulated press-coated tablet of carvedilol by Box–Behnken statistical design

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    Satwara RS

    2012-08-01

    Full Text Available Rohan S Satwara, Parul K PatelDepartment of Pharmaceutics, Babaria Institute of Pharmacy, Vadodara, Gujarat, IndiaObjective: The primary objective of the present investigation was to formulate and optimize chronomodulated press-coated tablets to deliver the antihypertensive carvedilol at an effective quantity predawn, when a blood pressure spike is typically observed in most hypertensive patients.Experimental work: Preformulation studies and drug excipient compatibility studies were carried out for carvedilol and excipients. Core tablets (6 mm containing carvedilol and 10-mm press-coated tablets were prepared by direct compression. The Box–Behnken experimental design was applied to these press-coated tablets (F1–F15 formula with differing concentrations of rate-controlling polymers. Hydroxypropyl methyl cellulose K4M, ethyl cellulose, and K-carrageenan were used as rate-controlling polymers in the outer layer. These tablets were subjected to various precompression and postcompression tests. The optimized batch was derived both by statistically (using desirability function and graphically (using Design Expert® 8; Stat-Ease Inc. Tablets formulated using the optimized formulas were then evaluated for lag time and in vitro dissolution.Results and discussion: Results of preformulation studies were satisfactory. No interaction was observed between carvedilol and excipients by ultraviolet, Fourier transform infrared spectroscopy, and dynamic light scattering analysis. The results of precompression studies and postcompression studies were within limits. The varying lag time and percent cumulative carvedilol release after 8 h was optimized to obtain a formulation that offered a release profile with 6 h lag time, followed by complete carvedilol release after 8 h. The results showed no significant bias between predicted response and actual response for the optimized formula.Conclusion: Bedtime dosing of chronomodulated press-coated tablets may offer a

  3. Development of time controlled chronomodulated tablet with swelling and rupturable layers: Optimization of factors influencing lag-time and drug release

    OpenAIRE

    Desai, Mayur; Rishad R. Jivani; Patel, Laxman D; Jivani, Noordin P; Sonagara, Bhavin

    2012-01-01

    Introduction: A tablet system consisting of cores coated with two layers of swelling and rupturable coatings was prepared and evaluated as time controlled chronomodulated tablet. Materials and Methods: Cores containing Montelukast sodium as model drug were prepared by direct compression and then coated sequentially with an inner swelling layer containing a HPMC E 5 and an outer rupturable layer of Eudragit RL/RS (1:1). A three-factor, two-level, full factorial design was used to investigate t...

  4. Design and Evaluation of Chronomodulated Drug Delivery of Tramadol Hydrochloride.

    Science.gov (United States)

    Alekya, Thota; Narendar, Dudhipala; Mahipal, Donthi; Arjun, Narala; Nagaraj, Banala

    2017-09-26

    Rheumatoid arthritis is an auto immune disease which requires chronotherapy as it occurs during early morning. Tramadol hydrochloride (TH) is an analgesic drug, used to treat rheumatoid arthritis. The aim of the present investigation was to develop chronomodulated drug delivery system of tramadol hydrochloride such that it releases the drug early in the morning, during which the symptoms of rheumatoid arthritis worsen. To develop chronomodulated drug delivery system of TH, initially core tablets of TH were prepared using three different supradisintegrants followed by coating with pH dependent polymer of Eudragit S100. The prepared core tablets are evaluated for physical parameters and an optimal system was identified. Further, coating composition of Eudragit S100 was optimized and coating tablets of TH was prepared. The prepared coated tablets were evaluated for weight variation, hardness, drug content and in vitro release studies in 0.1N HCl, pH 6.8 phosphate buffer and pH 7.4 phosphate buffer. Formulation with 7.5% of coating solution (ES2) had shown a significant drug release after a lag time of 3 h (in pH 6.8 medium), 6 h (in pH 6.8 medium) and 8 h (in pH 7.4 medium), respectively. DSC studies revealed that no interaction between core and coated materials with drug was observed. Thus, chronomodulated drug delivery system of TH was formulated and assuming that if a tablet is administered around 9 pm to 10 pm, the drug release starts after a lag time of 6 h i. e., around 3am to 4 am. © Georg Thieme Verlag KG Stuttgart · New York.

  5. [Modeling 5-FU clearance during a chronomodulated infusion].

    Science.gov (United States)

    Kwiatkowski, F; Chevalier, V; Chevrier, R; Richard, D; Cure, H; Chollet, P

    2003-06-01

    Drugs pharmacokinetic control is a usual practice in case of flat continuous infusions. It enables among others, to modulate delivered doses when drug concentrations in blood appear too high. With chronotherapy, this possibility becomes more difficult because of sinusoidal outflows of infusion. We propose here a method that enables this follow-up, established through the study of 21 metastatic colorectal cancer patients, treated with a chronomodulated infusion of high dose 5-fluoro-uracil (5-FU) and folinic acid. This pharmacokinetic follow-up permitted the modelisation of 5-FU clearance and the calculation of an index, which was, in our study, correlated to the treatment response and also to main encountered toxicities.

  6. Synergistic Effect of Combination Topotecan and Chronomodulated Radiation Therapy on Xenografted Human Nasopharyngeal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, YanLing; Chen, Xin; Ren, PeiRong; Su, Zhou; Cao, HongYing; Zhou, Jie; Zou, XiaoYan; Fu, ShaoZhi; Lin, Sheng; Fan, Juan; Yang, Bo; Sun, XiaoYang [Department of Oncology, Affiliated Hospital of Luzhou Medical College, Luzhou (China); Zhou, Yan; Chen, Yue [Department of Medical Imaging, Luzhou Medical College, Luzhou (China); Yang, LingLin, E-mail: yanglinglin2003@tom.com [Department of Oncology, Affiliated Hospital of Luzhou Medical College, Luzhou (China); Wu, JingBo, E-mail: wjb6147@163.com [Department of Oncology, Affiliated Hospital of Luzhou Medical College, Luzhou (China)

    2013-10-01

    Purpose: To investigate the in vivo chronomodulated radiosensitizing effect of topotecan (TPT) on human nasopharyngeal carcinoma (NPC) and its possible mechanisms. Methods and Materials: Xenografted BALB/c (nu/nu) NPC mice were synchronized with an alternation of 12 hours of light from 0 to 12 hours after light onset (HALO) and 12 hours of darkness to establish a unified biological rhythm. Chronomodulated radiosensitization of TPT was investigated by analysis of tumor regrowth delay (TGD), pimonidazole hydrochloride, histone H2AX phosphorylation, (γ-H2AX) topoisomerase I (Top I), cell cycle, and apoptosis after treatment with (1) TPT (10 mg/kg) alone; (2) radiation therapy alone (RT); and (3) TPT+RT at 3, 9, 15, and 21 HALO. The tumor-loaded mice without any treatment were used as controls. Results: The TPT+RT combination was more effective than TPT or RT as single agents. The TPT+RT combination at 15 HALO was best (TGD = 58.0 ± 3.6 days), and TPT+RT at 3 HALO was worst (TGD = 35.0 ± 1.5 days) among the 4 TPT+RT groups (P<.05). Immunohistochemistry analysis revealed a significantly increased histone H2AX phosphorylation expression and decreased pimonidazole hydrochloride expression in the TPT+RT group at the same time point. The results suggested that the level of tumor hypoxia and DNA damage varied in a time-dependent manner. The expression of Top I in the TPT+RT group was also significantly different from the control tumors at 15 HALO (P<.05). Cell apoptosis index was increased and the proportion of cells in S phase was decreased (P<.05) with the highest value in 15 HALO and the lowest in 3 HALO. Conclusions: This study suggested that TPT combined with chronoradiotherapy could enhance the radiosensitivity of xenografted NPC. The TPT+RT group at 15 HALO had the best therapeutic effect. The chronomodulated radiosensitization mechanisms of TPT might be related to circadian rhythm of tumor hypoxia, cell cycle redistribution, DNA damage, and expression of Top I.

  7. Optimizing clozapine treatment

    DEFF Research Database (Denmark)

    Damkier, P; Lublin, H; Taylor, D

    2011-01-01

    Clozapine treatment remains the gold standard for treatment-resistant schizophrenia, but treatment with clozapine is associated with several side-effects that complicate the use of the drug. This clinical overview aims to provide psychiatrists with knowledge about how to optimize clozapine...... treatment. Relevant strategies for reducing side-effects and increasing the likelihood of response are discussed....

  8. Does chronomodulated radiotherapy improve pathological response in locally advanced rectal cancer?

    Science.gov (United States)

    Squire, Tim; Buchanan, Grant; Rangiah, David; Davis, Ian; Yip, Desmond; Chua, Yu Jo; Rich, Tyvin; Elsaleh, Hany

    2017-01-01

    The predominant mode of radiation-induced cell death for solid tumours is mitotic catastrophe, which is in part dependent on sublethal damage repair being complete at around 6 h. Circadian variation appears to play a role in normal cellular division, and this could influence tumour response of radiation treatment depending on the time of treatment delivery. We tested the hypothesis that radiation treatment later in the day may improve tumour response and nodal downstaging in rectal cancer patients treated neoadjuvantly with radiation therapy. Recruitment was by retrospective review of 267 rectal cancer patients treated neoadjuvantly in the Department of Radiation Oncology at the Canberra Hospital between January 2010 and November 2015. One hundred and fifty-five patients met the inclusion criteria for which demographic, pathological and imaging data were collected, as well as the time of day patients received treatment with each fraction of radiotherapy. Data analysis was performed using the Statistical Package R with nonparametric methods of significance for all tests set at p < 0.05. Of the 45 female and 110 male patients, the median age was 64. Seventy-three percent had cT3 disease and there was a mean tumour distance from the anal verge of 7 cm. Time to surgical resection following radiotherapy ranged from 4 to 162 days with a median of 50 days, with a complete pathological response seen in 21% of patients. Patients exhibiting a favourable pathological response had smaller median pre- and postradiotherapy tumour size and had a greater change in tumour size following treatment (p < 0.01). Patients who received the majority of their radiotherapy fractions after 12:00 pm were more likely to show a complete or moderate pathological response (p = 0.035) and improved nodal downstaging. There were also more favourable responses amongst patients with longer time to surgical resection postradiotherapy (p < 0.004), although no relationship was seen between response and

  9. Optimal Antihypertensive Combination Treatments

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    Massimo Volpe

    2012-03-01

    Full Text Available Over the past three decades it has been consistently shown that optimal blood pressure (BP control significantly reduced cardiovascular (CV morbidity and mortality [1]. Despite solid evidence in favour of benefits derived from BP reductions, however, hypertension control in treated hypertensive patients remains suboptimal worldwide [2, 3]. In addition, proportions of diagnosed and treated hypertensive patients remain largely unchanged over the last two decades[4]. Multiple factors may be advocated to explain this observation, including variation in healthcare access and availability [5, 6], attitudes amongst clinicians towards hypertension [7, 8], inaccuracy in BP measurements [9] and underuse or under dosage of antihypertensive drugs in both monotherapy and in combination therapy [10, 11].On the basis of these considerations, it is beyond the aim of this article to discuss the socioeconomic impact on healthcare and BP measurement techniques. Instead it will seek to explain the importance of attaining early optimal BP control and the use of combination therapy as a new paradigm for the modern clinical management of hypertension.

  10. Design of Chronomodulated Drug Delivery System of Valsartan: In Vitro Characterization

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    Sokar, M.; Hanafy, A.; Elkamel, A.; El-Gamal, S.

    2015-01-01

    The aim of the present study was to design and evaluate a chronomodulated time-clock pulsatile tablets of valsartan to release it after a certain lag time, independent of the gastrointestinal pH, in its absorption window to cope with the circadian rhythm of human body for blood pressure elevation. Core tablets were prepared by direct compression of a homogenous mixture of valsartan, Avicel PH101, croscarmellose sodium, magnesium stearate and Aerosil. The core tablets were then sprayed coated with a sealing layer formed of ethyl cellulose that was subsequently coated with a release-controlling layer. Three different aqueous dispersions namely; carnauba wax or beeswax or a mixture in a ratio of 2.5:1, respectively, were used to form five time-clock tablet formulations having the release controlling layer with different thickness {B5, B10, B20, BW5 and CW5}. Quality control testing were carried out to the core tablets. Differential scanning calorimetry was also performed to detect the possible drug excipient interaction in the core tablet formulation. The release was carried out, for the prepared time-clock tablet formulations, in 0.1 N hydrochloric acid for the first 2 h, followed by phosphate buffer (pH 6.8) for 4.5 h. The effect of pH on valsartan release was studied through a release study in 0.1 N hydrochloric acid for 6.5 h. Two phase dissolution study was performed to the selected time-clock tablet formulation to predict the drug permeation through the gastrointestinal tract. Stability study of the selected formula was performed at 25°/60% RH and at 40°/75% RH for 3 months. Results showed that a release-controlling layer composed of a mixture of carnauba wax and beeswax in a ratio of 2.5:1 showed a reasonable release lag time. The release lag time of the tablets increased with the increase of the coat thickness, thus B20>B10>B5 with corresponding lag time values of 4.5, 3 and 2.5 h, respectively. Selected B5 tablet formula exhibited a reasonable lag time

  11. Design of chronomodulated drug delivery system of valsartan: in vitro characterization

    Directory of Open Access Journals (Sweden)

    M Sokar

    2015-01-01

    Full Text Available The aim of the present study was to design and evaluate a chronomodulated time-clock pulsatile tablets of valsartan to release it after a certain lag time, independent of the gastrointestinal pH, in its absorption window to cope with the circadian rhythm of human body for blood pressure elevation. Core tablets were prepared by direct compression of a homogenous mixture of valsartan, Avicel PH101, croscarmellose sodium, magnesium stearate and Aerosil. The core tablets were then sprayed coated with a sealing layer formed of ethyl cellulose that was subsequently coated with a release-controlling layer. Three different aqueous dispersions namely; carnauba wax or beeswax or a mixture in a ratio of 2.5:1, respectively, were used to form five time-clock tablet formulations having the release controlling layer with different thickness {B5, B10, B20, BW5 and CW5}. Quality control testing were carried out to the core tablets. Differential scanning calorimetry was also performed to detect the possible drug excipient interaction in the core tablet formulation. The release was carried out, for the prepared time-clock tablet formulations, in 0.1 N hydrochloric acid for the first 2 h, followed by phosphate buffer (pH 6.8 for 4.5 h. The effect of pH on valsartan release was studied through a release study in 0.1 N hydrochloric acid for 6.5 h. Two phase dissolution study was performed to the selected time-clock tablet formulation to predict the drug permeation through the gastrointestinal tract. Stability study of the selected formula was performed at 25°/60% RH and at 40°/75% RH for 3 months. Results showed that a release-controlling layer composed of a mixture of carnauba wax and beeswax in a ratio of 2.5:1 showed a reasonable release lag time. The release lag time of the tablets increased with the increase of the coat thickness, thus B20>B10>B5 with corresponding lag time values of 4.5, 3 and 2.5 h, respectively. Selected B5 tablet formula exhibited a

  12. Design of Chronomodulated Drug Delivery System of Valsartan: In Vitro Characterization.

    Science.gov (United States)

    Sokar, M; Hanafy, A; Elkamel, A; El-Gamal, S

    2015-01-01

    The aim of the present study was to design and evaluate a chronomodulated time-clock pulsatile tablets of valsartan to release it after a certain lag time, independent of the gastrointestinal pH, in its absorption window to cope with the circadian rhythm of human body for blood pressure elevation. Core tablets were prepared by direct compression of a homogenous mixture of valsartan, Avicel PH101, croscarmellose sodium, magnesium stearate and Aerosil. The core tablets were then sprayed coated with a sealing layer formed of ethyl cellulose that was subsequently coated with a release-controlling layer. Three different aqueous dispersions namely; carnauba wax or beeswax or a mixture in a ratio of 2.5:1, respectively, were used to form five time-clock tablet formulations having the release controlling layer with different thickness {B5, B10, B20, BW5 and CW5}. Quality control testing were carried out to the core tablets. Differential scanning calorimetry was also performed to detect the possible drug excipient interaction in the core tablet formulation. The release was carried out, for the prepared time-clock tablet formulations, in 0.1 N hydrochloric acid for the first 2 h, followed by phosphate buffer (pH 6.8) for 4.5 h. The effect of pH on valsartan release was studied through a release study in 0.1 N hydrochloric acid for 6.5 h. Two phase dissolution study was performed to the selected time-clock tablet formulation to predict the drug permeation through the gastrointestinal tract. Stability study of the selected formula was performed at 25°/60% RH and at 40°/75% RH for 3 months. Results showed that a release-controlling layer composed of a mixture of carnauba wax and beeswax in a ratio of 2.5:1 showed a reasonable release lag time. The release lag time of the tablets increased with the increase of the coat thickness, thus B20>B10>B5 with corresponding lag time values of 4.5, 3 and 2.5 h, respectively. Selected B5 tablet formula exhibited a reasonable lag time

  13. Phase I study of intermittent and chronomodulated oral therapy with capecitabine in patients with advanced and/or metastatic cancer

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    Gasparro Simona

    2006-02-01

    Full Text Available Abstract Background The combination of capecitabine and gemcitabine at Fixed Dose Rate (FDR has been demonstrated to be well tolerated, with apparent efficacy in patients with advanced cancers. FDR gemcitabine infusion leads to enhanced intracellular accumulation of drug and possible augmented clinical effect. The goals of this phase I study were to determine the maximum-tolerated dose (MTD of chronomodulated capecitabine in patients with advanced cancer and to describe the dose-limiting toxicities (DLT, the safety profile of this way of administration. Methods Patients with advanced solid tumours who had failed to response to standard therapy or for whom no standard therapy was available were elegible for this study. Capecitabine was administered orally according to following schedule: 1/4 of dose at 8:00 a.m.; 1/4 of dose at 6:00 p.m. and 1/2 of dose at 11:00 p.m. each day for 14 consecutive days, followed by a 7-day rest period. Results All 27 patients enrolled onto the study were assessable for toxicity. The most common toxicities during the first two cycles of chemotherapy were fatigue, diarrhoea and hand foot syndrome (HFS. Only one out of the nine patients treated at capecitabine dose of 2,750 mg/m2 met protocol-specified DLT criteria (fatigue grade 4. However, at these doses the majority of cycles of therapy were delivered without dose reduction or delay. No other episodes of DLT were observed at the same dose steps and at the lower dose steps of capecitabine (1,500/1,750/2,000/2,250/2,500 mg/m2. The dose of 2,750 mg/m2 is recommended for further study. Tumor responses were observed in patients with metastatic breast and colorectal cancer. Conclusion High doses of chronomodulated capecitabine can be administered with acceptable toxicity. The evidence of antitumor activity deserves further investigation in phase II combination chemotherapy studies.

  14. Chronomodulated drug delivery system of salbutamol sulphate for the treatment of nocturnal asthma

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    Qureshi J

    2008-01-01

    Full Text Available A time dependent pulsed release system consisting of an effervescent core surrounded by consecutive layers of swelling and rupturable polymers was prepared and evaluated. The cores containing salbutamol sulphate as bioactive agent were prepared by direct compression method using different ratios of microcrystalline cellulose and effervescent agent and then coated sequentially with an inner swelling layer containing a hydrocolloid, hydroxypropylmethylcellulose E5 and an outer rupturable layer having Eudragit RL/RS (1:1. The effects of various processing and formulative parameters on the performance of system were studied. The rupture and dissolution tests were studied using the USP paddle method at 50 rpm in 0.1 N HCl and phosphate buffer pH 6.8. The lag time of the drug release decreased by increasing the inner swelling layer and increased by increasing the rupturing layer level. All the results obtained in the present study suggest that osmotic pumping effect was involved which eventually lead to the drug release.

  15. A randomized study comparing short-time infusion of oxaliplatin in combination with capecitabine XELOX(30) and chronomodulated XELOX(30) as first-line therapy in patients with advanced colorectal cancer

    DEFF Research Database (Denmark)

    Qvortrup, C; Jensen, Benny Vittrup; Fokstuen, T;

    2010-01-01

    Chronotherapy is one of the several approaches to increase efficacy and reduce toxicity of chemotherapy. In a phase II study in the second-line in patients with metastatic colorectal cancer (mCRC), we found that chronomodulated XELOX (XELOX(30Chron)) was a well-tolerated regimen with potentially ...

  16. Economic and environmental optimization of waste treatment

    Energy Technology Data Exchange (ETDEWEB)

    Münster, M. [System Analysis Department, DTU Management Engineering, Technical University of Denmark, Frederiksborgvej 399, 4000 Roskilde (Denmark); Ravn, H. [RAM-løse edb, Æblevangen 55, 2765 Smørum (Denmark); Hedegaard, K.; Juul, N. [System Analysis Department, DTU Management Engineering, Technical University of Denmark, Frederiksborgvej 399, 4000 Roskilde (Denmark); Ljunggren Söderman, M. [IVL Swedish Environmental Research Institute, Box 53021, SE-40014 Gothenburg (Sweden); Chalmers University of Technology, SE-412 96 Gothenburg (Sweden)

    2015-04-15

    Highlights: • Optimizing waste treatment by incorporating LCA methodology. • Applying different objectives (minimizing costs or GHG emissions). • Prioritizing multiple objectives given different weights. • Optimum depends on objective and assumed displaced electricity production. - Abstract: This article presents the new systems engineering optimization model, OptiWaste, which incorporates a life cycle assessment (LCA) methodology and captures important characteristics of waste management systems. As part of the optimization, the model identifies the most attractive waste management options. The model renders it possible to apply different optimization objectives such as minimizing costs or greenhouse gas emissions or to prioritize several objectives given different weights. A simple illustrative case is analysed, covering alternative treatments of one tonne of residual household waste: incineration of the full amount or sorting out organic waste for biogas production for either combined heat and power generation or as fuel in vehicles. The case study illustrates that the optimal solution depends on the objective and assumptions regarding the background system – illustrated with different assumptions regarding displaced electricity production. The article shows that it is feasible to combine LCA methodology with optimization. Furthermore, it highlights the need for including the integrated waste and energy system into the model.

  17. Imaging TMS: antidepressant mechanisms and treatment optimization.

    Science.gov (United States)

    Dubin, Marc

    2017-04-01

    With the antidepressant efficacy of Transcranial Magnetic Stimulation well-established by several meta-analyses, there is growing interest in its mechanism of action. TMS has been shown to engage, and in some cases, normalize functional connectivity and neurotransmitter levels within networks dysfunctional in the depressed state. In this review, I will suggest candidate biomarkers, based on neuroimaging, that may be predictive of response to TMS. I will then review the effects of TMS on networks and neurotransmitter systems involved in depression. Throughout, I will also discuss how our current understanding of response predication and network engagement may be used to personalize treatment and optimize its efficacy.

  18. Optimizing the treatment of rhegmatogenous retinal detachment

    DEFF Research Database (Denmark)

    Hajari, Javad Nouri

    2016-01-01

    within one year after initial surgery with pneumatic retinopexy, scleral buckling and VTX with gas, and one and a half years after surgery with VTX with oil. Also lack of oil removal within the first year is a failed operation. It is widely accepted that RRD is an acute disease but when should surgery...... as an acute eye disease that needs immediate treatment. With the increasing number of cataract surgeries and an increased elderly population, the numbers of RRD occurrences are increasing. The aim of this thesis is to create knowledge on how treatment and care of RRD patients can be optimized. In the first...... of cataract surgeries and an increased elderly population. Using data from the NPR, we estimated that the risk of a RRD occurring on the fellow eye is 100 times larger than on the first eye and that middle aged men have the highest risk. Having an increase in the incidence of RRD we need to ensure...

  19. Mathematical Optimization Techniques for Multi-Phase Radiation Treatment Design

    OpenAIRE

    Sonderman, David

    1983-01-01

    A mathematical model for optimal external beam radiotherapy treatment design over multiple treatment phases is presented. The solution procedure is discussed and illustrated on a case of boost treatment for lung cancer. The models are integrated with current radiobiological software to produce an optimal design over both phases of treatment displayed by means of computer graphics.

  20. Formulation and Evaluation of Chronomodulated Pulsatile Drug Delivery System of Salbutamol Sulphate

    Directory of Open Access Journals (Sweden)

    Anusha V

    2015-12-01

    Full Text Available Chronotherapy denotes the therapy in which the release of the drug in the body is allowed to match with the circadian rhythm of the disease, such that the required action of the drug is shown with minimal side effects. The main interesting fact of chronotherapy is its ability to deliver the drug in required concentrations during the time of its greatest need such that synchronizing circadian rhythm of diseases or symptoms. Pulsatile drug delivery system for Salbutamol sulphate was formulated initially as core tablets followed by formulation of pulsatile tablets using press-coated technology. Core tablets were formulated using various concentrations of superdisintegrant (Sodium starch glycolate, cross povidone and diluents (MCC & Dicalcium phosphate. The core tablets were then compressed into pulsatile tablets using combinations of HPMC K 100M and Eudragit L 100, Eudragit S 100 in various concentrations. Core tablets were evaluated and based on the dissolution studies trial T3was optimized as it shows lower disintegration time and faster drug release. Then the pulsatile tablets were evaluated for various tests and drug release studies were conducted for 2 hours in 0.1N HCl followed by pH 6.8 buffer and the trial S6 was optimized which showed satisfactory greater lag time of about 6 hours with satisfactory drug release which contains a combination of HPMC K15M (20mg, Eudragit L 100 (50mg, Eudragit S100 (60mg. Pulsatile tablets were formulated utilizing press coated technology and the combination of polymers provided required lag time with satisfactory dissolution profile.

  1. Optimal control of HIV/AIDS dynamic: Education and treatment

    Science.gov (United States)

    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.

  2. Childhood cancer treatment optimization: In rhabdomyosarcoma and supportive care

    NARCIS (Netherlands)

    Schoot, R.A.

    2015-01-01

    This thesis covers two subjects investigating optimization of cancer cure: prevention and treatment of central venous catheter related complications and improvement of local treatment in head and neck rhabdomyosarcoma survivors. Central venous catheters are indispensable in the modern day treatment

  3. Childhood cancer treatment optimization: In rhabdomyosarcoma and supportive care

    NARCIS (Netherlands)

    Schoot, R.A.

    2015-01-01

    This thesis covers two subjects investigating optimization of cancer cure: prevention and treatment of central venous catheter related complications and improvement of local treatment in head and neck rhabdomyosarcoma survivors. Central venous catheters are indispensable in the modern day treatment

  4. Integrated modeling of ozonation for optimization of drinking water treatment

    NARCIS (Netherlands)

    van der Helm, A.W.C.

    2007-01-01

    Drinking water treatment plants automation becomes more sophisticated, more on-line monitoring systems become available and integration of modeling environments with control systems becomes easier. This gives possibilities for model-based optimization. In operation of drinking water treatment

  5. Aortic stenosis: From diagnosis to optimal treatment

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    Tavčiovski Dragan

    2008-01-01

    Full Text Available Aortic stenosis is the most frequent valvular heart disease. Aortic sclerosis is the first characteristic lesion of the cusps, which is considered today as the process similar to atherosclerosis. Progression of the disease is an active process leading to forming of bone matrix and heavily calcified stiff cusps by inflammatory cells and osteopontin. It is a chronic, progressive disease which can remain asymptomatic for a long time even in the presence of severe aortic stenosis. Proper physical examination remains an essential diagnostic tool in aortic stenosis. Recognition of characteristic systolic murmur draws attention and guides further diagnosis in the right direction. Doppler echocardiography is an ideal tool to confirm diagnosis. It is well known that exercise tests help in stratification risk of asymptomatic aortic stenosis. Serial measurements of brain natriuretic peptide during a follow-up period may help to identify the optimal time for surgery. Heart catheterization is mostly restricted to preoperative evaluation of coronary arteries rather than to evaluation of the valve lesion itself. Currently, there is no ideal medical treatment for slowing down the disease progression. The first results about the effect of ACE inhibitors and statins in aortic sclerosis and stenosis are encouraging, but there is still not enough evidence. Onset symptoms based on current ACC/AHA/ESC recommendations are I class indication for aortic valve replacement. Aortic valve can be replaced with a biological or prosthetic valve. There is a possibility of percutaneous aortic valve implantation and transapical operation for patients that are contraindicated for standard cardiac surgery.

  6. Optimizing municipal wastewater treatment plants using an improved multi-objective optimization method.

    Science.gov (United States)

    Zhang, Rui; Xie, Wen-Ming; Yu, Han-Qing; Li, Wen-Wei

    2014-04-01

    An improved multi-objective optimization (MOO) model was established and used for simultaneously optimizing the treatment cost and multiple effluent quality indexes (including effluent COD, NH4(+)-N, NO3(-)-N) of a municipal wastewater treatment plant (WWTP). Compared with previous models that were mainly based on the use of fixed decision factors and did not taken into account the treatment cost, this model introduces a relationship model based on back propagation algorithm to determine the set of decision factors according to the expected optimization targets. Thus, a more flexible and precise optimization of the treatment process was allowed. Moreover, a MOO of conflicting objectives (i.e., treatment cost and effluent quality) was achieved. Applying this method, an optimal balance between operating cost and effluent quality of a WWTP can be found. This model may offer a useful tool for optimized design and control of practical WWTPs.

  7. Economic and environmental optimization of waste treatment

    DEFF Research Database (Denmark)

    Münster, Marie; Ravn, Hans; Hedegaard, Karsten;

    2015-01-01

    waste: incineration of the full amount or sorting out organic waste for biogas production for either combined heat and power generation or as fuel in vehicles. The case study illustrates that the optimal solution depends on the objective and assumptions regarding the background system - illustrated......This article presents the new systems engineering optimization model, OptiWaste, which incorporates a life cycle assessment (LCA) methodology and captures important characteristics of waste management systems. As part of the optimization, the model identifies the most attractive waste management...... with different assumptions regarding displaced electricity production. The article shows that it is feasible to combine LCA methodology with optimization. Furthermore, it highlights the need for including the integrated waste and energy system into the model. © 2014 Elsevier Ltd. All rights reserved....

  8. Economic and environmental optimization of waste treatment

    DEFF Research Database (Denmark)

    Münster, Marie; Ravn, Hans; Hedegaard, Karsten

    2015-01-01

    with different assumptions regarding displaced electricity production. The article shows that it is feasible to combine LCA methodology with optimization. Furthermore, it highlights the need for including the integrated waste and energy system into the model. © 2014 Elsevier Ltd. All rights reserved.......This article presents the new systems engineering optimization model, OptiWaste, which incorporates a life cycle assessment (LCA) methodology and captures important characteristics of waste management systems. As part of the optimization, the model identifies the most attractive waste management...... waste: incineration of the full amount or sorting out organic waste for biogas production for either combined heat and power generation or as fuel in vehicles. The case study illustrates that the optimal solution depends on the objective and assumptions regarding the background system - illustrated...

  9. Optimization model for the design of distributed wastewater treatment networks

    Directory of Open Access Journals (Sweden)

    Ibrić Nidret

    2012-01-01

    Full Text Available In this paper we address the synthesis problem of distributed wastewater networks using mathematical programming approach based on the superstructure optimization. We present a generalized superstructure and optimization model for the design of the distributed wastewater treatment networks. The superstructure includes splitters, treatment units, mixers, with all feasible interconnections including water recirculation. Based on the superstructure the optimization model is presented. The optimization model is given as a nonlinear programming (NLP problem where the objective function can be defined to minimize the total amount of wastewater treated in treatment operations or to minimize the total treatment costs. The NLP model is extended to a mixed integer nonlinear programming (MINLP problem where binary variables are used for the selection of the wastewater treatment technologies. The bounds for all flowrates and concentrations in the wastewater network are specified as general equations. The proposed models are solved using the global optimization solvers (BARON and LINDOGlobal. The application of the proposed models is illustrated on the two wastewater network problems of different complexity. First one is formulated as the NLP and the second one as the MINLP. For the second one the parametric and structural optimization is performed at the same time where optimal flowrates, concentrations as well as optimal technologies for the wastewater treatment are selected. Using the proposed model both problems are solved to global optimality.

  10. New ways to optimize breast cancer treatment

    NARCIS (Netherlands)

    Schröder, Carolina Pia

    2001-01-01

    Breast cancer patients without apparent distant metastases at the time of primary tumor removal, may later suffer from a distant relapse, indicating the presence of occult micrometastases at the time of diagnosis. Sensitive methods to detect micrometastatic breast cancer may be helpful in optimizing

  11. [Clinical laboratory approaches to parodontitis treatment optimization].

    Science.gov (United States)

    Soboleva, L A; Shul'diakov, A A; Oseeva, A O; Aleksandrova, E A

    2010-01-01

    In order to determine cycloferon liniment clinical-pathogenetic efficacy in comprehensive parodontitis therapy examination and treatment of 80 patients was done. It was determined that the cycloferon liniment use in comprehensive treatment of patients with parodontitis let to reduce infectious load in parodontal pockets and local inflammation intensity, to normalize the secretory immunoglobulin level and immune status indices that provided speed up of healing process and reduction relapse frequency.

  12. Economic optimization of waste treatment and energy production in Denmark

    DEFF Research Database (Denmark)

    Münster, Marie; Ravn, Hans; Hedegaard, Karsten

    2013-01-01

    This article presents an optimization model that incorporates LCA methodology and captures important characteristics of waste management systems. The most attractive waste management options are in the model identified as part the optimization. The model renders it possible to apply different...... optimization objectives such as minimizing costs or greenhouse gas emissions or to prioritise several objectives given different weights. An illustrative case is analyzed, covering alternative treatments of 1 tonne residual household waste: incineration of the full amount or sorting out organic waste...... shows that it is feasible to combine LCA approaches with optimization and highlights the need for including the integrated waste and energy system into the model....

  13. Optimal vaccination and treatment of an epidemic network model

    Science.gov (United States)

    Chen, Lijuan; Sun, Jitao

    2014-08-01

    In this Letter, we firstly propose an epidemic network model incorporating two controls which are vaccination and treatment. For the constant controls, by using Lyapunov function, global stability of the disease-free equilibrium and the endemic equilibrium of the model is investigated. For the non-constant controls, by using the optimal control strategy, we discuss an optimal strategy to minimize the total number of the infected and the cost associated with vaccination and treatment. Table 1 and Figs. 1-5 are presented to show the global stability and the efficiency of this optimal control.

  14. Optimal treatment of anaphylaxis: antihistamines versus epinephrine.

    Science.gov (United States)

    Fineman, Stanley M

    2014-07-01

    Anaphylaxis is a rapid, systemic, often unanticipated, and potentially life-threatening immune reaction occurring after exposure to certain foreign substances. The main immunologic triggers include food, insect venom, and medications. Multiple immunologic pathways underlie anaphylaxis, but most involve immune activation and release of immunomodulators. Anaphylaxis can be difficult to recognize clinically, making differential diagnosis key. The incidence of anaphylaxis has at least doubled during the past few decades, and in the United States alone, an estimated 1500 fatalities are attributed to anaphylaxis annually. The increasing incidence and potentially life-threatening nature of anaphylaxis coupled with diagnostic challenges make appropriate and timely treatment critical. Epinephrine is universally recommended as the first-line therapy for anaphylaxis, and early treatment is critical to prevent a potentially fatal outcome. Despite the evidence and guideline recommendations supporting its use for anaphylaxis, epinephrine remains underused. Data indicate that antihistamines are more commonly used to treat patients with anaphylaxis. Although histamine is involved in anaphylaxis, treatment with antihistamines does not relieve or prevent all of the pathophysiological symptoms of anaphylaxis, including the more serious complications such as airway obstruction, hypotension, and shock. Additionally, antihistamines do not act as rapidly as epinephrine; maximal plasma concentrations are reached between 1 and 3 hours for antihistamines compared with < 10 minutes for intramuscular epinephrine injection. This demonstrates the need for improved approaches to educate physicians and patients regarding the appropriate treatment of anaphylaxis.

  15. Optimal vaccination and treatment of an epidemic network model

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Lijuan [Department of Mathematics, Tongji University, Shanghai 200092 (China); College of Mathematics and Computer Science, Fuzhou University, Fuzhou, Fujian 350002 (China); Sun, Jitao, E-mail: sunjt@sh163.net [Department of Mathematics, Tongji University, Shanghai 200092 (China)

    2014-08-22

    In this Letter, we firstly propose an epidemic network model incorporating two controls which are vaccination and treatment. For the constant controls, by using Lyapunov function, global stability of the disease-free equilibrium and the endemic equilibrium of the model is investigated. For the non-constant controls, by using the optimal control strategy, we discuss an optimal strategy to minimize the total number of the infected and the cost associated with vaccination and treatment. Table 1 and Figs. 1–5 are presented to show the global stability and the efficiency of this optimal control. - Highlights: • Propose an optimally controlled SIRS epidemic model on heterogeneous networks. • Obtain criteria of global stability of the disease-free equilibrium and the endemic equilibrium. • Investigate existence of optimal control for the control problem. • The results be illustrated by some numerical simulations.

  16. Optimization of wastewater treatment plant operation for greenhouse gas mitigation.

    Science.gov (United States)

    Kim, Dongwook; Bowen, James D; Ozelkan, Ertunga C

    2015-11-01

    This study deals with the determination of optimal operation of a wastewater treatment system for minimizing greenhouse gas emissions, operating costs, and pollution loads in the effluent. To do this, an integrated performance index that includes three objectives was established to assess system performance. The ASMN_G model was used to perform system optimization aimed at determining a set of operational parameters that can satisfy three different objectives. The complex nonlinear optimization problem was simulated using the Nelder-Mead Simplex optimization algorithm. A sensitivity analysis was performed to identify influential operational parameters on system performance. The results obtained from the optimization simulations for six scenarios demonstrated that there are apparent trade-offs among the three conflicting objectives. The best optimized system simultaneously reduced greenhouse gas emissions by 31%, reduced operating cost by 11%, and improved effluent quality by 2% compared to the base case operation.

  17. Integrated modeling of ozonation for optimization of drinking water treatment

    NARCIS (Netherlands)

    van der Helm, A.W.C.

    2007-01-01

    Drinking water treatment plants automation becomes more sophisticated, more on-line monitoring systems become available and integration of modeling environments with control systems becomes easier. This gives possibilities for model-based optimization. In operation of drinking water treatment plants

  18. Integrated modeling of ozonation for optimization of drinking water treatment

    NARCIS (Netherlands)

    van der Helm, A.W.C.

    2007-01-01

    Drinking water treatment plants automation becomes more sophisticated, more on-line monitoring systems become available and integration of modeling environments with control systems becomes easier. This gives possibilities for model-based optimization. In operation of drinking water treatment plants

  19. Optimal Heating in Heat-Treatment Process Based on Grey Asynchronous Particle Swarm Optimization

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    To ensure plate heating quality and reduce energy consumption in heat-treatment process, optimal heating for plates in a roller hearth furnace was investigated and a new strategy for heating procedure optimization was developed. During solving process, plate temperature forecast model based on heat transfer mechanics was established to calculate plate temperature with the assumed heating procedure. In addition, multi-objective feature of optimal heating was analyzed. And the method, which is composed of asynchronous particle swarm optimization and grey relational analysis, was adopted for solving the multi-objective problem. The developed strategy for optimizing heating has been applied to the mass production. The result indicates that the absolute plate discharging temperature deviation between measured value and target value does not exceed ± 8 ℃, and the relative deviation is less than ± 0.77%.

  20. Modeling Vertical Flow Treatment Wetland Hydraulics to Optimize Treatment Efficiency

    Science.gov (United States)

    2011-03-24

    Shelley (Member) Date //signed// 10 Mar 2011 Robert Ritzi (Member) Wright State University Date iv AFIT/GES/ENV/11-M03...members; Dr. Michael Shelley, for his invaluable insights into past research of the treatment wetland at Wright Patterson AFB; and Dr. Robert Ritzi, for...Amon, J.P., A. Agrawal, M.L. Shelley, B.C. Opperman, M.P. Enright , N.D. Clemmer, T. Slusser, J. Lach, T. Sobolewski, W. Gruner, and A.C. Entingh

  1. Challenges when performing economic optimization of waste treatment: A review

    DEFF Research Database (Denmark)

    Juul, Nina; Münster, Marie; Ravn, H.

    2013-01-01

    Strategic and operational decisions in waste management, in particular with respect to investments in new treatment facilities, are needed due to a number of factors, including continuously increasing amounts of waste, political demands for efficient utilization of waste resources......, and the decommissioning of existing waste treatment facilities. Optimization models can assist in ensuring that these investment strategies are economically feasible.Various economic optimization models for waste treatment have been developed which focus on different parameters. Models focusing on transport are one...... example, but models focusing on energy production have also been developed, as well as models which take into account a plant’s economies of scale, environmental impact, material recovery and social costs. Finally, models combining different criteria for the selection of waste treatment methods in multi...

  2. Challenges when Performing Economic Optimization of Waste Treatment

    DEFF Research Database (Denmark)

    Juul, Nina; Münster, Marie; Ravn, Hans

    2011-01-01

    New investments in waste treatment facilities are needed due to a number of factors including continuously increasing waste amounts, political demands for efficient utilization of the waste resources in terms of recycling or energy production, and decommissioning of existing waste treatment...... facilities due to age and stricter environmental regulation. Optimization models can assist in ensuring that these investment strategies will be economically feasible. Various economic optimization models for waste treatment have been developed which focus on different parameters. Models focusing...... in multi criteria analysis have been developed. A thorough updated review of the existing models is presented and the main challenges and the crucial parameters to take into account when assessing the economic performance of waste treatment alternatives are identified. The review article will assist both...

  3. Combining clinical variables to optimize prediction of antidepressant treatment outcomes

    OpenAIRE

    Iniesta, R.; Malki, K.; Maier, W; Rietschel, M.; Mors, O; Hauser, J; Henigsberg, N.; Dernovsek, M. Z.; Souery, D.; Stahl, D.; Dobson, R.; Aitchison, K. J.; Farmer, A; Lewis, C.M.; McGuffin, P.

    2016-01-01

    The outcome of treatment with antidepressants varies markedly across people with the same diagnosis. A clinically significant prediction of outcomes could spare the frustration of trial and error approach and improve the outcomes of major depressive disorder through individualized treatment selection. It is likely that a combination of multiple predictors is needed to achieve such prediction. We used elastic net regularized regression to optimize prediction of symptom improvement and remissio...

  4. Economic optimization of waste treatment and energy production in Denmark

    DEFF Research Database (Denmark)

    Münster, Marie; Ravn, Hans; Hedegaard, Karsten

    2013-01-01

    optimization objectives such as minimizing costs or greenhouse gas emissions or to prioritise several objectives given different weights. An illustrative case is analyzed, covering alternative treatments of 1 tonne residual household waste: incineration of the full amount or sorting out organic waste...

  5. Fighting the Hydra: Optimizing treatment for type 2 diabetes

    NARCIS (Netherlands)

    Simon, A.C.R.

    2014-01-01

    This thesis focused on optimizing treatment for type 2 diabetes. We evaluated short-term risk (hypoglycaemia) and long-term risk (cancer) of sulfonylurea derivatives and insulin and reviewed the (dis)advantages of the long-acting insulin analogues, insulin glargine and insulin detemir. Furthermore,

  6. Optimizing stormwater treatment practices a handbook of assessment and maintenance

    CERN Document Server

    Erickson, Andrew J; Gulliver, John S

    2013-01-01

    Optimizing Stormwater Treatment Practices: A Handbook of Assessment and Maintenance provides the information necessary for developing and operating an effective maintenance program for stormwater treatment. The book offers instructions on how to measure the level of performance of stormwater treatment practices directly and bases proposed maintenance schedules on actual performance and historical maintenance efforts and costs. The inspection methods, which are proven in the field and have been implemented successfully, are necessary as regulatory agencies are demanding evaluations of the performance of stormwater treatment practices. The authors have developed a three-tiered approach that offers readers a standard protocol for how to determine the effectiveness of stormwater treatment practices currently in place. This book also: Provides a standard protocol for how to determine the effectiveness of stormwater treatment practices Assists readers with identifying which assessment techniques to use for stormwa...

  7. Selection of an optimal treatment method for acute periodontitis disease.

    Science.gov (United States)

    Aliev, Rafik A; Aliyev, B F; Gardashova, Latafat A; Huseynov, Oleg H

    2012-04-01

    The present paper is devoted to selection of an optimal treatment method for acute periodontitis by using fuzzy Choquet integral-based approach. We consider application of different treatment methods depending on development stages and symptoms of the disease. The effectiveness of application of different treatment methods in each stage of the disease is linguistically evaluated by a dentist. The stages of the disease are also linguistically described by a dentist. Dentist's linguistic evaluations are represented by fuzzy sets. The total effectiveness of the each considered treatment method is calculated by using fuzzy Choquet integral with fuzzy number-valued integrand and fuzzy number-valued fuzzy measure. The most effective treatment method is determined by using fuzzy ranking method.

  8. Optimal treatment increased the seed germination of Salvia verticillata L.

    Directory of Open Access Journals (Sweden)

    ALALEH KHAKPOOR

    2015-12-01

    Full Text Available Most seeds of the medicinal species are variable regarding their ecological compatibility with environmental conditions. Therefore, identifying the ecophysiological factors that affect dormancy and create optimal conditions for seed germination of medicinal plants is necessary for their culture and production. To evaluate the effect of different treatments on seed germination of medicinal species of Salvia verticillata, collected in the summer of 2010 in Eastern Azarbaijan, we have performed completely randomized experimental tests with 4 replications. The experimental design of treatment prior to growth included: scrape the skin with sandpaper, treatment with 500 ppm gibberellic acid for 24 and 48 h, treatment with citric acid for 10, 20 and 30 minutes, chilling for 2 and 4 weeks, treatment with warm water at 70°C and control treatment. Results showed that the effect of different treatments was significant on seed germination percent of the medicinal plant Salvia verticillata. Scrape the skin with sandpaper, citric acid treatment for 10, 20 and 30 minutes, and gibberellic acid treatment for 24 hours, increased the germination percentage compared to the control treatment. The most positive impact was observed on the dormancy breaking and germination of medicinal species Salvia verticillata.

  9. Optimization of stereotactic body radiotherapy treatment planning using a multicriteria optimization algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Ghandour, Sarah; Cosinschi, Adrien; Mazouni, Zohra; Pachoud, Marc; Matzinger, Oscar [Riviera-Chablais Hospital, Vevey (Switzerland). Cancer Center, Radiotherapy Dept.

    2016-07-01

    To provide high-quality and efficient dosimetric planning for various types of stereotactic body radiotherapy (SBRT) for tumor treatment using a multicriteria optimization (MCO) technique fine-tuned with direct machine parameter optimization (DMPO). Eighteen patients with lung (n = 11), liver (n = 5) or adrenal cell cancer (n = 2) were treated using SBRT in our clinic between December 2014 and June 2015. Plans were generated using the RayStation trademark Treatment Planning System (TPS) with the VMAT technique. Optimal deliverable SBRT plans were first generated using an MCO algorithm to find a well-balanced tradeoff between tumor control and normal tissue sparing in an efficient treatment planning time. Then, the deliverable plan was post-processed using the MCO solution as the starting point for the DMPO algorithm to improve the dose gradient around the planning target volume (PTV) while maintaining the clinician's priorities. The dosimetric quality of the plans was evaluated using dose-volume histogram (DVH) parameters, which account for target coverage and the sparing of healthy tissue, as well as the CI100 and CI50 conformity indexes. Using a combination of the MCO and DMPO algorithms showed that the treatment plans were clinically optimal and conformed to all organ risk dose volume constraints reported in the literature, with a computation time of approximately one hour. The coverage of the PTV (D99% and D95%) and sparing of organs at risk (OAR) were similar between the MCO and MCO + DMPO plans, with no significant differences (p > 0.05) for all the SBRT plans. The average CI100 and CI50 values using MCO + DMPO were significantly better than those with MCO alone (p < 0.05). The MCO technique allows for convergence on an optimal solution for SBRT within an efficient planning time. The combination of the MCO and DMPO techniques yields a better dose gradient, especially for lung tumors.

  10. Optimizing global liver function in radiation therapy treatment planning

    Science.gov (United States)

    Wu, Victor W.; Epelman, Marina A.; Wang, Hesheng; Romeijn, H. Edwin; Feng, Mary; Cao, Yue; Ten Haken, Randall K.; Matuszak, Martha M.

    2016-09-01

    Liver stereotactic body radiation therapy (SBRT) patients differ in both pre-treatment liver function (e.g. due to degree of cirrhosis and/or prior treatment) and radiosensitivity, leading to high variability in potential liver toxicity with similar doses. This work investigates three treatment planning optimization models that minimize risk of toxicity: two consider both voxel-based pre-treatment liver function and local-function-based radiosensitivity with dose; one considers only dose. Each model optimizes different objective functions (varying in complexity of capturing the influence of dose on liver function) subject to the same dose constraints and are tested on 2D synthesized and 3D clinical cases. The normal-liver-based objective functions are the linearized equivalent uniform dose (\\ell \\text{EUD} ) (conventional ‘\\ell \\text{EUD} model’), the so-called perfusion-weighted \\ell \\text{EUD} (\\text{fEUD} ) (proposed ‘fEUD model’), and post-treatment global liver function (GLF) (proposed ‘GLF model’), predicted by a new liver-perfusion-based dose-response model. The resulting \\ell \\text{EUD} , fEUD, and GLF plans delivering the same target \\ell \\text{EUD} are compared with respect to their post-treatment function and various dose-based metrics. Voxel-based portal venous liver perfusion, used as a measure of local function, is computed using DCE-MRI. In cases used in our experiments, the GLF plan preserves up to 4.6 % ≤ft(7.5 % \\right) more liver function than the fEUD (\\ell \\text{EUD} ) plan does in 2D cases, and up to 4.5 % ≤ft(5.6 % \\right) in 3D cases. The GLF and fEUD plans worsen in \\ell \\text{EUD} of functional liver on average by 1.0 Gy and 0.5 Gy in 2D and 3D cases, respectively. Liver perfusion information can be used during treatment planning to minimize the risk of toxicity by improving expected GLF; the degree of benefit varies with perfusion pattern. Although fEUD model optimization is computationally inexpensive and

  11. Optimizing global liver function in radiation therapy treatment planning

    Science.gov (United States)

    Wu, Victor W; Epelman, Marina A; Wang, Hesheng; Romeijn, H Edwin; Feng, Mary; Cao, Yue; Haken, Randall K Ten; Matuszak, Martha M

    2017-01-01

    Liver stereotactic body radiation therapy (SBRT) patients differ in both pre-treatment liver function (e.g. due to degree of cirrhosis and/or prior treatment) and radiosensitivity, leading to high variability in potential liver toxicity with similar doses. This work investigates three treatment planning optimization models that minimize risk of toxicity: two consider both voxel-based pre-treatment liver function and local-function-based radiosensitivity with dose; one considers only dose. Each model optimizes different objective functions (varying in complexity of capturing the influence of dose on liver function) subject to the same dose constraints and are tested on 2D synthesized and 3D clinical cases. The normal-liver-based objective functions are the linearized equivalent uniform dose (ℓEUD) (conventional ‘ℓEUD model’), the so-called perfusion-weighted ℓEUD (fEUD) (proposed ‘fEUD model’), and post-treatment global liver function (GLF) (proposed ‘GLF model’), predicted by a new liver-perfusion-based dose-response model. The resulting ℓEUD, fEUD, and GLF plans delivering the same target ℓEUD are compared with respect to their post-treatment function and various dose-based metrics. Voxel-based portal venous liver perfusion, used as a measure of local function, is computed using DCE-MRI. In cases used in our experiments, the GLF plan preserves up to 4.6%(7.5%) more liver function than the fEUD (ℓEUD) plan does in 2D cases, and up to 4.5%(5.6%) in 3D cases. The GLF and fEUD plans worsen in ℓEUD of functional liver on average by 1.0 Gy and 0.5 Gy in 2D and 3D cases, respectively. Liver perfusion information can be used during treatment planning to minimize the risk of toxicity by improving expected GLF; the degree of benefit varies with perfusion pattern. Although fEUD model optimization is computationally inexpensive and often achieves better GLF than ℓEUD model optimization does, the GLF model directly optimizes a more clinically

  12. MO-B-BRB-00: Optimizing the Treatment Planning Process

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2015-06-15

    The radiotherapy treatment planning process has evolved over the years with innovations in treatment planning, treatment delivery and imaging systems. Treatment modality and simulation technologies are also rapidly improving and affecting the planning process. For example, Image-guided-radiation-therapy has been widely adopted for patient setup, leading to margin reduction and isocenter repositioning after simulation. Stereotactic Body radiation therapy (SBRT) and Radiosurgery (SRS) have gradually become the standard of care for many treatment sites, which demand a higher throughput for the treatment plans even if the number of treatments per day remains the same. Finally, simulation, planning and treatment are traditionally sequential events. However, with emerging adaptive radiotherapy, they are becoming more tightly intertwined, leading to iterative processes. Enhanced efficiency of planning is therefore becoming more critical and poses serious challenge to the treatment planning process; Lean Six Sigma approaches are being utilized increasingly to balance the competing needs for speed and quality. In this symposium we will discuss the treatment planning process and illustrate effective techniques for managing workflow. Topics will include: Planning techniques: (a) beam placement, (b) dose optimization, (c) plan evaluation (d) export to RVS. Planning workflow: (a) import images, (b) Image fusion, (c) contouring, (d) plan approval (e) plan check (f) chart check, (g) sequential and iterative process Influence of upstream and downstream operations: (a) simulation, (b) immobilization, (c) motion management, (d) QA, (e) IGRT, (f) Treatment delivery, (g) SBRT/SRS (h) adaptive planning Reduction of delay between planning steps with Lean systems due to (a) communication, (b) limited resource, (b) contour, (c) plan approval, (d) treatment. Optimizing planning processes: (a) contour validation (b) consistent planning protocol, (c) protocol/template sharing, (d) semi

  13. Tool Steel Heat Treatment Optimization Using Neural Network Modeling

    Science.gov (United States)

    Podgornik, Bojan; Belič, Igor; Leskovšek, Vojteh; Godec, Matjaz

    2016-11-01

    Optimization of tool steel properties and corresponding heat treatment is mainly based on trial and error approach, which requires tremendous experimental work and resources. Therefore, there is a huge need for tools allowing prediction of mechanical properties of tool steels as a function of composition and heat treatment process variables. The aim of the present work was to explore the potential and possibilities of artificial neural network-based modeling to select and optimize vacuum heat treatment conditions depending on the hot work tool steel composition and required properties. In the current case training of the feedforward neural network with error backpropagation training scheme and four layers of neurons (8-20-20-2) scheme was based on the experimentally obtained tempering diagrams for ten different hot work tool steel compositions and at least two austenitizing temperatures. Results show that this type of modeling can be successfully used for detailed and multifunctional analysis of different influential parameters as well as to optimize heat treatment process of hot work tool steels depending on the composition. In terms of composition, V was found as the most beneficial alloying element increasing hardness and fracture toughness of hot work tool steel; Si, Mn, and Cr increase hardness but lead to reduced fracture toughness, while Mo has the opposite effect. Optimum concentration providing high KIc/HRC ratios would include 0.75 pct Si, 0.4 pct Mn, 5.1 pct Cr, 1.5 pct Mo, and 0.5 pct V, with the optimum heat treatment performed at lower austenitizing and intermediate tempering temperatures.

  14. Speed optimized influence matrix processing in inverse treatment planning tools

    Energy Technology Data Exchange (ETDEWEB)

    Ziegenhein, Peter; Wilkens, Jan J; Nill, Simeon; Oelfke, Uwe [German Cancer Research Center (DKFZ), Department of Medical Physics in Radiation Oncology, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Ludwig, Thomas [University of Heidelberg, Institute of Computer Science, Research Group Parallel and Distributed Systems, Im Neuenheimer Feld 348, 69120 Heidelberg (Germany)], E-mail: p.ziegenhein@dkfz.de, E-mail: u.oelfke@dkfz.de

    2008-05-07

    An optimal plan in modern treatment planning tools is found through the use of an iterative optimization algorithm, which deals with a high amount of patient-related data and number of treatment parameters to be optimized. Thus, calculating a good plan is a very time-consuming process which limits the application for patients in clinics and for research activities aiming for more accuracy. A common technique to handle the vast amount of radiation dose data is the concept of the influence matrix (DIJ), which stores the dose contribution of each bixel to the patient in the main memory of the computer. This study revealed that a bottleneck for the optimization time arises from the data transfer of the dose data between the memory and the CPU. In this note, we introduce a new method which speeds up the data transportation from stored dose data to the CPU. As an example we used the DIJ approach as is implemented in our treatment planning tool KonRad, developed at the German Cancer Research Center (DKFZ) in Heidelberg. A data cycle reordering method is proposed to take the advantage of modern memory hardware. This induces a minimal eviction policy which results in a memory behaviour exhibiting a 2.6 times faster algorithm compared to the naive implementation. Although our method is described for the DIJ approach implemented in KonRad, we believe that any other planning tool which uses a similar approach to store the dose data will also benefit from the described methods. (note)

  15. [Optimal Treatment for Rheumatoid Arthritis with Companion Diagnostics].

    Science.gov (United States)

    Kumagai, Shunichi

    2015-11-01

    The medical strategy for rheumatoid arthritis (RA) has markedly advanced in recent years. The introduction of biologics in addition to methotrexate, an anchor drug, has made it possible to not only suppress pain and inflammation (clinical remission), but also inhibit joint destruction (structural remission), leading to cure from the disease. Since the condition and pathology are heterogeneous among individual patients, optimal treatment for each patient based on the use of companion diagnostics is desired (precision medicine). ACPA is important to diagnose RA, but also to assess the prognosis. ACPA is also a part of companion diagnostics for preclinical RA because it has been found to be positive before the onset. Treatment should be performed under consideration of the disease state such as activity, prognosis regarding joint destruction, and complications. It is also important to clarify the patient characteristics, such as responsiveness to the drugs and risk of adverse effects. Biomarkers, such as proteomics and pharmacogenomics, have been reported as companion diagnostics for optimal treatment of RA. RA is a multifactorial disorder with clinically heterogeneous features. Gene-environment interaction is closely involved in the production of ACPA, and then secondary stimuli to joints may lead to symptoms of RA. Joint injury, emotional stress, and infections often trigger the onset of RA. It is possible to cure RA, achieving complete remission, by early aggressive treatment and returning to the pre-clinical state with environmental improvement. [Review

  16. Optimal partial-arcs in VMAT treatment planning

    CERN Document Server

    Wala, Jeremiah; Chen, Wei; Craft, David

    2012-01-01

    Purpose: To improve the delivery efficiency of VMAT by extending the recently published VMAT treatment planning algorithm vmerge to automatically generate optimal partial-arc plans. Methods and materials: A high-quality initial plan is created by solving a convex multicriteria optimization problem using 180 equi-spaced beams. This initial plan is used to form a set of dose constraints, and a set of partial-arc plans is created by searching the space of all possible partial-arc plans that satisfy these constraints. For each partial-arc, an iterative fluence map merging and sequencing algorithm (vmerge) is used to improve the delivery efficiency. Merging continues as long as the dose quality is maintained above a user-defined threshold. The final plan is selected as the partial arc with the lowest treatment time. The complete algorithm is called pmerge. Results: Partial-arc plans are created using pmerge for a lung, liver and prostate case, with final treatment times of 127, 245 and 147 seconds. Treatment times...

  17. Optimal flow sensor placement on wastewater treatment plants.

    Science.gov (United States)

    Villez, Kris; Vanrolleghem, Peter A; Corominas, Lluís

    2016-09-15

    Obtaining high quality data collected on wastewater treatment plants is gaining increasing attention in the wastewater engineering literature. Typical studies focus on recognition of faulty data with a given set of installed sensors on a wastewater treatment plant. Little attention is however given to how one can install sensors in such a way that fault detection and identification can be improved. In this work, we develop a method to obtain Pareto optimal sensor layouts in terms of cost, observability, and redundancy. Most importantly, the resulting method allows reducing the large set of possibilities to a minimal set of sensor layouts efficiently for any wastewater treatment plant on the basis of structural criteria only, with limited sensor information, and without prior data collection. In addition, the developed optimization scheme is fast. Practically important is that the number of sensors needed for both observability of all flows and redundancy of all flow sensors is only one more compared to the number of sensors needed for observability of all flows in the studied wastewater treatment plant configurations.

  18. Optimal treatment sequence in COPD: Can a consensus be found?

    Science.gov (United States)

    Ferreira, J; Drummond, M; Pires, N; Reis, G; Alves, C; Robalo-Cordeiro, C

    2016-01-01

    There is currently no consensus on the treatment sequence in chronic obstructive pulmonary disease (COPD), although it is recognized that early diagnosis is of paramount importance to start treatment in the early stages of the disease. Although it is fairly consensual that initial treatment should be with an inhaled short-acting beta agonist, a short-acting muscarinic antagonist, a long-acting beta-agonist or a long-acting muscarinic antagonist. As the disease progresses, several therapeutic options are available, and which to choose at each disease stage remains controversial. When and in which patients to use dual bronchodilation? When to use inhaled corticosteroids? And triple therapy? Are the existing non-inhaled therapies, such as mucolytic agents, antibiotics, phosphodiesterase-4 inhibitors, methylxanthines and immunostimulating agents, useful? If so, which patients would benefit? Should co-morbidities be taken into account when choosing COPD therapy for a patient? This paper reviews current guidelines and available evidence and proposes a therapeutic scheme for COPD patients. We also propose a treatment algorithm in the hope that it will help physicians to decide the best approach for their patients. The authors conclude that, at present, a full consensus on optimal treatment sequence in COPD cannot be found, mainly due to disease heterogeneity and lack of biomarkers to guide treatment. For the time being, and although some therapeutic approaches are consensual, treatment of COPD should be patient-oriented.

  19. Using Chemical Reaction Kinetics to Predict Optimal Antibiotic Treatment Strategies

    Science.gov (United States)

    Abel zur Wiesch, Pia; Cohen, Ted

    2017-01-01

    Identifying optimal dosing of antibiotics has proven challenging—some antibiotics are most effective when they are administered periodically at high doses, while others work best when minimizing concentration fluctuations. Mechanistic explanations for why antibiotics differ in their optimal dosing are lacking, limiting our ability to predict optimal therapy and leading to long and costly experiments. We use mathematical models that describe both bacterial growth and intracellular antibiotic-target binding to investigate the effects of fluctuating antibiotic concentrations on individual bacterial cells and bacterial populations. We show that physicochemical parameters, e.g. the rate of drug transmembrane diffusion and the antibiotic-target complex half-life are sufficient to explain which treatment strategy is most effective. If the drug-target complex dissociates rapidly, the antibiotic must be kept constantly at a concentration that prevents bacterial replication. If antibiotics cross bacterial cell envelopes slowly to reach their target, there is a delay in the onset of action that may be reduced by increasing initial antibiotic concentration. Finally, slow drug-target dissociation and slow diffusion out of cells act to prolong antibiotic effects, thereby allowing for less frequent dosing. Our model can be used as a tool in the rational design of treatment for bacterial infections. It is easily adaptable to other biological systems, e.g. HIV, malaria and cancer, where the effects of physiological fluctuations of drug concentration are also poorly understood. PMID:28060813

  20. Using Chemical Reaction Kinetics to Predict Optimal Antibiotic Treatment Strategies.

    Science.gov (United States)

    Abel Zur Wiesch, Pia; Clarelli, Fabrizio; Cohen, Ted

    2017-01-01

    Identifying optimal dosing of antibiotics has proven challenging-some antibiotics are most effective when they are administered periodically at high doses, while others work best when minimizing concentration fluctuations. Mechanistic explanations for why antibiotics differ in their optimal dosing are lacking, limiting our ability to predict optimal therapy and leading to long and costly experiments. We use mathematical models that describe both bacterial growth and intracellular antibiotic-target binding to investigate the effects of fluctuating antibiotic concentrations on individual bacterial cells and bacterial populations. We show that physicochemical parameters, e.g. the rate of drug transmembrane diffusion and the antibiotic-target complex half-life are sufficient to explain which treatment strategy is most effective. If the drug-target complex dissociates rapidly, the antibiotic must be kept constantly at a concentration that prevents bacterial replication. If antibiotics cross bacterial cell envelopes slowly to reach their target, there is a delay in the onset of action that may be reduced by increasing initial antibiotic concentration. Finally, slow drug-target dissociation and slow diffusion out of cells act to prolong antibiotic effects, thereby allowing for less frequent dosing. Our model can be used as a tool in the rational design of treatment for bacterial infections. It is easily adaptable to other biological systems, e.g. HIV, malaria and cancer, where the effects of physiological fluctuations of drug concentration are also poorly understood.

  1. Treatment optimization in MS: Canadian MS Working Group updated recommendations.

    Science.gov (United States)

    Freedman, Mark S; Selchen, Daniel; Arnold, Douglas L; Prat, Alexandre; Banwell, Brenda; Yeung, Michael; Morgenthau, David; Lapierre, Yves

    2013-05-01

    The Canadian Multiple Sclerosis Working Group (CMSWG) developed practical recommendations in 2004 to assist clinicians in optimizing the use of disease-modifying therapies (DMT) in patients with relapsing multiple sclerosis. The CMSWG convened to review how disease activity is assessed, propose a more current approach for assessing suboptimal response, and to suggest a scheme for switching or escalating treatment. Practical criteria for relapses, Expanded Disability Status Scale (EDSS) progression and MRI were developed to classify the clinical level of concern as Low, Medium and High. The group concluded that a change in treatment may be considered in any RRMS patient if there is a high level of concern in any one domain (relapses, progression or MRI), a medium level of concern in any two domains, or a low level of concern in all three domains. These recommendations for assessing treatment response should assist clinicians in making more rational choices in their management of relapsing MS patients.

  2. Age-related macular degeneration: epidemiology and optimal treatment

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    (exudative cases); the remainder has only geographic atrophy. In cross-sectional population-based studies about 45% of eyes with AMD have visual acuity reduced to 20/200 or worse. This is true both for exudative AMD and pure geographic atrophy. Age and genetic predisposition are known risk factors for AMD...... a fluorescein angiographic study and a physician capable of interpreting it. For CNV not involving the foveal centre, the only evidence-based treatment is laser photocoagulation. For AMD cases with subfoveal CNV, good visual acuity, and predominantly classic fluorescence pattern on fluorescein angiography....... Smoking is probably also a risk factor. Preventive strategies using macular laser photocoagulation are under investigation, but their efficacy in preventing visual loss is as yet unproven. There is no treatment with proven efficacy for geographic atrophy. Optimal treatment for exudative AMD requires...

  3. Moisture-heating Treatment and Processing Optimization of Parboiled Rice

    Institute of Scientific and Technical Information of China (English)

    Zhao Siming; Xiong Shanbai

    2001-01-01

    Effect of moisture-heating treatment on the quality of parboiled rice and processing optimization were studied. Results indicated that the riboflavine content of parboiled rice is higher, and the color is light, aroma is strong and the head yield ratio is higher by soaking with acid and ethanol, cooking at high-pressure and then drying with high temperature-high moisture. Optimal processing parameters are soaking paddy with citrate acid for 2h, then with 1.5% ethanol for 1.5h, high pressure cooking for 30min, and then drying under 55%RH, 90℃ for 30min, cooling slowly for 2.5h, and shelling and milling immediately. Head yield ratio and whole rice ratio was 67.3% and 87.0% respectively, the color of finished product is light, rice aroma is strong, and the content of riboflavine is 2.47mg/100g.

  4. Moisture-heating Treatment and Processing Optimization of Parboiled Rice

    Institute of Scientific and Technical Information of China (English)

    ZhaoSiming; XiongShanbai

    2001-01-01

    Abstract: Effect of moisture-heating treatment on the quality ofparboiled rice and processing optimization were studied. Resultsindicated that the riboflavine content of parboiled rice is higher, and thecolor is light, aroma is strong and the head yield ratio is higher bysoaking with acid and ethanol, cooking at high-pressure and thendrying with high temperature-high moisture. Optimal processingparameters are soaking paddy with citrate acid for 2h, then with 1.5%ethanol for 1.5h, high pressure cooking for 30min, and then dryingunder 55%RH, 90~C for 30min, cooling slowly for 2.5h, and shelling andmilling immediately. Head yield ratio and whole rice ratio was 67.3%and 87.0% respectively, the color of finished product is light, ricearoma is strong, and the content of riboflavine is 2.47mg/100g.

  5. Recommendations for optimizing methotrexate treatment for patients with rheumatoid arthritis

    Science.gov (United States)

    Bello, Alfonso E; Perkins, Elizabeth L; Jay, Randy; Efthimiou, Petros

    2017-01-01

    Methotrexate (MTX) remains the cornerstone therapy for patients with rheumatoid arthritis (RA), with well-established safety and efficacy profiles and support in international guidelines. Clinical and radiologic results indicate benefits of MTX monotherapy and combination with other agents, yet patients may not receive optimal dosing, duration, or route of administration to maximize their response to this drug. This review highlights best practices for MTX use in RA patients. First, to improve the response to oral MTX, a high initial dose should be administered followed by rapid titration. Importantly, this approach does not appear to compromise safety or tolerability for patients. Treatment with oral MTX, with appropriate dose titration, then should be continued for at least 6 months (as long as the patient experiences some response to treatment within 3 months) to achieve an accurate assessment of treatment efficacy. If oral MTX treatment fails due to intolerability or inadequate response, the patient may be “rescued” by switching to subcutaneous delivery of MTX. Consideration should also be given to starting with subcutaneous MTX given its favorable bioavailability and pharmacodynamic profile over oral delivery. Either initiation of subcutaneous MTX therapy or switching from oral to subcutaneous administration improves persistence with treatment. Upon transition from oral to subcutaneous delivery, MTX dosage should be maintained, rather than increased, and titration should be performed as needed. Similarly, if another RA treatment is necessary to control the disease, the MTX dosage and route of administration should be maintained, with titration as needed. PMID:28435338

  6. Sustainable Optimization for Wastewater Treatment System Using PSF-HS

    Directory of Open Access Journals (Sweden)

    Zong Woo Geem

    2016-03-01

    Full Text Available The sustainability in a river with respect to water quality is critical because it is highly related with environmental pollution, economic expenditure, and public health. This study proposes a sustainability problem of wastewater treatment system for river ecosystem conservation which helps the healthy survival of the aquatic biota and human beings. This study optimizes the design of a wastewater treatment system using the parameter-setting-free harmony search algorithm, which does not require the existing tedious value-setting process for algorithm parameters. The real-scale system has three different options of wastewater treatment, such as filtration, nitrification, and diverted irrigation (fertilization, as well as two existing treatment processes (settling and biological oxidation. The objective of this system design is to minimize life cycle costs, including initial construction costs of those treatment options, while satisfying minimal dissolved oxygen requirements in the river, maximal nitrate-nitrogen concentration in groundwater, and a minimal nitrogen requirement for crop farming. Results show that the proposed technique could successfully find solutions without requiring a tedious setting process.

  7. Inclusion variations and calcium treatment optimization in pipeline steel production

    Science.gov (United States)

    Liu, Jian-Hua; Wu, Hua-Jie; Bao, Yan-Ping; Wang, Min

    2011-10-01

    SiCa line and SiCaBaFe alloy were injected into liquid pipeline steel at the end of LF refining as calcium treatment, and samples were taken from the ladles, mould, and slabs. Analysis of Ca content and inclusions shows that Ca content in steel decreases obviously in the following process after calcium treatment; the compositions, morphology, and sizes of inclusions also vary much in the production; primary inclusions in the ladles prior to calcium treatment are mainly Al2O3 inclusions, but they turn to fine irregular CaS-CaO-Al2O3 compound inclusions after the treatment, then become fine globular CaO-Al2O3 inclusions in the mould, and finally change to a few larger irregular CaS-CaO-Al2O3 complex inclusions in the slabs. Thermodynamic study reveals that inclusion variations are related with the preferential reactions among Ca, Al2O3, and S and the precipitation of S in CaO-Al2O3 inclusions with high sulfur capacity. New evaluation standards for calcium treatment in high-grade pipeline steel were put forward according to the inclusion variations and requirements of pipeline steel on inclusion controlling, and the calcium process was studied and optimized.

  8. [Optimization of acupuncture treatment programs for facial paralysis].

    Science.gov (United States)

    Luo, He-Ping; Lin, Tian-dong; Cai, Min; Huang, Xian-xun; Wang, Bang-bo; Gao, Wei-keng

    2010-02-01

    To optimize the acupuncture treatment programs for facial paralysis. Sixty-three patients of facial paralysis were randomly divided and treated according to the table of L9 (3)4 in orthogonal test. They were treated with different combined programs of 4 factors and 3 levels, including factor A (acupuncture op portunity), B (acupoints prescription), C (quantity of stimulus) and D (time of electroacupuncture). The change of facial nerve function score was observed to choose the best acupuncture treatment program for facial paralysis from factor A (acupuncture opportunity), B (acupoints prescription), C (quantity of stimulus), D (time of electroacupuncture) and their 3 levels in each factor. B (acupoints prescription) and D (time of electroacupuncture) were significant factors (P facial paralysis.

  9. Pharmacokinetic characteristics of antimicrobials and optimal treatment of urosepsis.

    Science.gov (United States)

    Wagenlehner, Florian M E; Weidner, Wolfgang; Naber, Kurt G

    2007-01-01

    Urosepsis accounts for approximately 25% of all sepsis cases and may develop from a community-acquired or nosocomial urinary tract infection (UTI). Nevertheless, the underlying UTI is almost exclusively a complicated one with involvement of the parenchymatous urogenital organs (e.g. kidneys, prostate) and mostly associated with any kind of obstructive uropathy. If urosepsis originates from a nosocomial infection, a broad spectrum of Gram-negative and Gram-positive pathogens have to be expected, which are often multiresistant. In urosepsis, as in other types of sepsis, the severity of sepsis depends mostly upon the host response. The treatment of urosepsis follows the generally accepted rules of the 'Surviving Sepsis' campaign guidelines. Early normalisation of blood pressure and early adequate empirical antibacterial therapy with optimised dosing are equally important to meet the requirements of early goal-directed therapy. In most cases of urosepsis, early control of the infectious focus is possible and as important. Optimal supportive measures need to follow the early phase of resuscitation. To lower mortality from urosepsis, an optimal interdisciplinary approach between intensive care, anti-infective therapy and urology is essential, assisted by easy access to the necessary laboratory and imaging diagnostic procedures. Although most antibacterials achieve high urinary concentrations, there are several unique features of complicated UTI, and thus urosepsis, that influence the activity of antibacterial substances: (i) renal pharmacokinetics differ in unilateral and bilateral renal impairment and in unilateral and bilateral renal obstruction; (ii) variations in pH may influence the activity of certain antibacterials; and (iii) biofilm infection is frequently found under these conditions, which may increase the minimal inhibitory concentrations (MIC) of the antibacterials at the site of infection by several hundred folds. Assessment of antibacterial pharmacodynamic

  10. Treatment optimization in low- and middle-income countries

    Directory of Open Access Journals (Sweden)

    Cooper D

    2012-11-01

    Full Text Available The unprecedented, successful collaborative international effort to provide universal access to HIV care, including effective antiretroviral therapy (ART, has reached a critical time point. The global economic downturn, changing donor priorities and competing priorities in the health sector threaten the capacity of various agencies to maintain support for the continued scale-up of access toward the UN General Assembly-agreed target of 15 million people with HIV/AIDS receiving ART by 2015. This aspiration has recently received added impetus as we have come to understand that treatment acts as prevention by reducing the infectiousness of treated individuals. It is now necessary to review the elements of the success to date, in order to be able to do more with less. These elements include efforts to optimize delivery of HIV care, including ART, in low- and middle-income countries (LMIC; the emergence of new agents and drug classes which have simplified HIV treatment and made broader successful management more achievable; and changes to commencement protocols. Recent studies have indicated that earlier commencement of HIV therapy is beneficial, leading to changes in the recommended ART initiation threshold in LMIC to <350 CD4 T cells/µL. Studies currently underway are investigating approaches to second-line ART in LMIC. The results from these studies will better inform the rollout of effective second-line therapy. In addition, the financial cost of ART makes optimization of dosing an important consideration in LMIC, in order to maximize effectiveness while limiting costs. ART monitoring is also an important priority in LMIC. Efforts to develop simple and reliable technologies that can provide rapid results in the field are underway. The final priority is operational optimization, to ensure service delivery through initiatives such as exploiting economies of scale and the training and retention of health professionals. Although the challenges in

  11. Growth hormone for optimization of refractory heart failure treatment

    Directory of Open Access Journals (Sweden)

    Bocchi Edimar Alcides

    1999-01-01

    Full Text Available It has been reported that growth hormone may benefit selected patients with congestive heart failure. A 63-year-old man with refractory congestive heart failure waiting for heart transplantation, depending on intravenous drugs (dobutamine and presenting with progressive worsening of the clinical status and cachexia, despite standard treatment, received growth hormone replacement (8 units per day for optimization of congestive heart failure management. Increase in both serum growth hormone levels (from 0.3 to 0.8 mg/l and serum IGF-1 levels (from 130 to 300ng/ml was noted, in association with clinical status improvement, better optimization of heart failure treatment and discontinuation of dobutamine infusion. Left ventricular ejection fraction (by MUGA increased from 13 % to 18 % and to 28 % later, in association with reduction of pulmonary pressures and increase in exercise capacity (rise in peak VO2 to 13.4 and to 16.2ml/kg/min later. The patient was "de-listed" for heart transplantation. Growth hormone may benefit selected patients with refractory heart failure.

  12. Combining clinical variables to optimize prediction of antidepressant treatment outcomes.

    Science.gov (United States)

    Iniesta, Raquel; Malki, Karim; Maier, Wolfgang; Rietschel, Marcella; Mors, Ole; Hauser, Joanna; Henigsberg, Neven; Dernovsek, Mojca Zvezdana; Souery, Daniel; Stahl, Daniel; Dobson, Richard; Aitchison, Katherine J; Farmer, Anne; Lewis, Cathryn M; McGuffin, Peter; Uher, Rudolf

    2016-07-01

    The outcome of treatment with antidepressants varies markedly across people with the same diagnosis. A clinically significant prediction of outcomes could spare the frustration of trial and error approach and improve the outcomes of major depressive disorder through individualized treatment selection. It is likely that a combination of multiple predictors is needed to achieve such prediction. We used elastic net regularized regression to optimize prediction of symptom improvement and remission during treatment with escitalopram or nortriptyline and to identify contributing predictors from a range of demographic and clinical variables in 793 adults with major depressive disorder. A combination of demographic and clinical variables, with strong contributions from symptoms of depressed mood, reduced interest, decreased activity, indecisiveness, pessimism and anxiety significantly predicted treatment outcomes, explaining 5-10% of variance in symptom improvement with escitalopram. Similar combinations of variables predicted remission with area under the curve 0.72, explaining approximately 15% of variance (pseudo R(2)) in who achieves remission, with strong contributions from body mass index, appetite, interest-activity symptom dimension and anxious-somatizing depression subtype. Escitalopram-specific outcome prediction was more accurate than generic outcome prediction, and reached effect sizes that were near or above a previously established benchmark for clinical significance. Outcome prediction on the nortriptyline arm did not significantly differ from chance. These results suggest that easily obtained demographic and clinical variables can predict therapeutic response to escitalopram with clinically meaningful accuracy, suggesting a potential for individualized prescription of this antidepressant drug.

  13. Optimal Pharmacologic Treatment Strategies in Obesity and Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Gayotri Goswami

    2014-06-01

    Full Text Available The prevalence of obesity has increased to pandemic levels worldwide and is related to increased risk of morbidity and mortality. Metabolic comorbidities are commonly associated with obesity and include metabolic syndrome, pre-diabetes, and type 2 diabetes. Even if the prevalence of obesity remains stable until 2030, the anticipated numbers of people with diabetes will more than double as a consequence of population aging and urbanization. Weight reduction is integral in the prevention of diabetes among obese adults with pre-diabetes. Lifestyle intervention and weight reduction are also key in the management of type 2 diabetes. Weight loss is challenging for most obese patients, but for those with diabetes, it can pose an even greater challenge due to the weight gain associated with many treatment regimens. This article will review optimal treatment strategies for patients with comorbid obesity and type 2 diabetes. The role of anti-obesity agents in diabetes will also be reviewed. This literature review will provide readers with current strategies for the pharmacologic treatment of obesity and diabetes with a focus on the weight outcomes related to diabetes treatments.

  14. Impedance cardiography – optimization and efficacy evaluation of antihypertensive treatment

    Directory of Open Access Journals (Sweden)

    Katarzyna Panasiuk-Kamińska

    2016-09-01

    Full Text Available Background . Hypertension is a civilization disease which currently affects about 10.5 m people in Poland. The number of patients with diagnosed, untreated hypertension amounts to 18%, and as many as 45% of patients are treated ineffectively whereas only 26% are treated effectively. Impedance cardiography (IC is an important tool both in diagnostics and the treatment of hypertensive patients, particularly in the case of antihypertensive treatment resistance. This method allows for the individualized treatment of each patient on the basis of hemodynamic parameters, monitoring of hypertensive patients in the outpatient care setting, and the assessment of cardiovascular risk factors. Objectives . The aim of the study was to evaluate the efficacy of hypotensive medications in patients with hypertension using impedance cardiography. Material and methods. The study involved 60 hypertensive patients, treated with antihypertensives, who failed to achieve the required blood pressure values. The modification of hypertension therapy was based on EBM (evidence-based medicine and on hemodynamic parameters obtained using impedance cardiography. Results . It was found that high blood pressure therapy based on impedance cardiography parameters has a significant influence on blood pressure reduction compared to EM B-based therapy: below 140/90: 66.8 vs. 55.1% and below 130/80: 23.5 vs. 18.9%. Conclusions . On the basis of this study it was confirmed that impedance cardiography allows for a significant reduction of hypertension and the selection of the most effective therapeutic strategy, providing for the optimization and efficacy of hypertension treatment.

  15. Noninfectious uveitis: strategies to optimize treatment compliance and adherence

    Directory of Open Access Journals (Sweden)

    Dolz-Marco R

    2015-08-01

    Full Text Available Rosa Dolz-Marco,1 Roberto Gallego-Pinazo,1 Manuel Díaz-Llopis,2 Emmett T Cunningham Jr,3–6 J Fernando Arévalo7,8 1Unit of Macula, Department of Ophthalmology, University and Polytechnic Hospital La Fe, 2Faculty of Medicine, University of Valencia, Spain; 3Department of Ophthalmology, California Pacific Medical Center, San Francisco, 4Department of Ophthalmology, Stanford University School of Medicine, Stanford, 5The Francis I Proctor Foundation, University of California San Francisco Medical Center, 6West Coast Retina Medical Group, San Francisco, CA, USA; 7Vitreoretina Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; 8Retina Division, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA Abstract: Noninfectious uveitis includes a heterogenous group of sight-threatening ocular and systemic disorders. Significant progress has been made in the treatment of noninfectious uveitis in recent years, particularly with regard to the effective use of corticosteroids and non-corticosteroid immunosuppressive drugs, including biologic agents. All of these therapeutic approaches are limited, however, by any given patient’s ability to comply with and adhere to their prescribed treatment. In fact, compliance and adherence are among the most important patient-related determinants of treatment success. We discuss strategies to optimize compliance and adherence. Keywords: noninfectious uveitis, intraocular inflammation, immunosuppressive treatment, adherence, compliance, therapeutic failure

  16. Optimization of conventional water treatment plant using dynamic programming.

    Science.gov (United States)

    Mostafa, Khezri Seyed; Bahareh, Ghafari; Elahe, Dadvar; Pegah, Dadras

    2015-12-01

    In this research, the mathematical models, indicating the capability of various units, such as rapid mixing, coagulation and flocculation, sedimentation, and the rapid sand filtration are used. Moreover, cost functions were used for the formulation of conventional water and wastewater treatment plant by applying Clark's formula (Clark, 1982). Also, by applying dynamic programming algorithm, it is easy to design a conventional treatment system with minimal cost. The application of the model for a case reduced the annual cost. This reduction was approximately in the range of 4.5-9.5% considering variable limitations. Sensitivity analysis and prediction of system's feedbacks were performed for different alterations in proportion from parameters optimized amounts. The results indicated (1) that the objective function is more sensitive to design flow rate (Q), (2) the variations in the alum dosage (A), and (3) the sand filter head loss (H). Increasing the inflow by 20%, the total annual cost would increase to about 12.6%, while 20% reduction in inflow leads to 15.2% decrease in the total annual cost. Similarly, 20% increase in alum dosage causes 7.1% increase in the total annual cost, while 20% decrease results in 7.9% decrease in the total annual cost. Furthermore, the pressure decrease causes 2.95 and 3.39% increase and decrease in total annual cost of treatment plants.

  17. Optimized evaporation technique for leachate treatment: Small scale implementation.

    Science.gov (United States)

    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.

  18. Electrochemical treatment of deproteinated whey wastewater and optimization of treatment conditions with response surface methodology.

    Science.gov (United States)

    Güven, Güray; Perendeci, Altunay; Tanyolaç, Abdurrahman

    2008-08-30

    Electrochemical treatment of deproteinated whey wastewater produced during cheese manufacture was studied as an alternative treatment method for the first time in literature. Through the preliminary batch runs, appropriate electrode material was determined as iron due to high removal efficiency of chemical oxygen demand (COD), and turbidity. The electrochemical treatment conditions were optimized through response surface methodology (RSM), where applied voltage was kept in the range, electrolyte concentration was minimized, waste concentration and COD removal percent were maximized at 25 degrees C. Optimum conditions at 25 degrees C were estimated through RSM as 11.29 V applied voltage, 100% waste concentration (containing 40 g/L lactose) and 19.87 g/L electrolyte concentration to achieve 29.27% COD removal. However, highest COD removal through the set of runs was found as 53.32% within 8h. These results reveal the applicability of electrochemical treatment to the deproteinated whey wastewater as an alternative advanced wastewater treatment method.

  19. Optimization of electrocoagulation process for the treatment of landfill leachate

    Science.gov (United States)

    Huda, N.; Raman, A. A.; Ramesh, S.

    2017-06-01

    The main problem of landfill leachate is its diverse composition comprising of persistent organic pollutants (POPs) which must be removed before being discharge into the environment. In this study, the treatment of leachate using electrocoagulation (EC) was investigated. Iron was used as both the anode and cathode. Response surface methodology was used for experimental design and to study the effects of operational parameters. Central Composite Design was used to study the effects of initial pH, inter-electrode distance, and electrolyte concentration on color, and COD removals. The process could remove up to 84 % color and 49.5 % COD. The experimental data was fitted onto second order polynomial equations. All three factors were found to be significantly affect the color removal. On the other hand, electrolyte concentration was the most significant parameter affecting the COD removal. Numerical optimization was conducted to obtain the optimum process performance. Further work will be conducted towards integrating EC with other wastewater treatment processes such as electro-Fenton.

  20. A randomized study comparing short-time infusion of oxaliplatin in combination with capecitabine XELOX(30) and chronomodulated XELOX(30) as first-line therapy in patients with advanced colorectal cancer.

    Science.gov (United States)

    Qvortrup, C; Jensen, B V; Fokstuen, T; Nielsen, S E; Keldsen, N; Glimelius, B; Bjerregaard, B; Mejer, J; Larsen, F O; Pfeiffer, P

    2010-01-01

    Chronotherapy is one of the several approaches to increase efficacy and reduce toxicity of chemotherapy. In a phase II study in the second-line in patients with metastatic colorectal cancer (mCRC), we found that chronomodulated XELOX (XELOX(30Chron)) was a well-tolerated regimen with potentially reduced toxicity. One hundred and forty-one patients with unresectable mCRC were enrolled in a randomized study comparing standard XELOX (XELOX(30)), arm A, and XELOX(30Chron), arm B-both with short-time infusion of oxaliplatin-with the primary aim of reducing overall toxicity. Overall toxicity grade 2-4 was 90% versus 85%, P = 0.47 and grade 3-4 was 31% versus 37%, P = 0.6 in arm A and B, respectively. We found no significant differences in median overall survival (17.6 versus 15.5 months; P = 0.068) and median progression-free survival (8.9 versus 8.8 months; P = 0.7). The incidence of grade 3 neuropathy was 16% in arm A and 19% in arm B (P = 0.7) after a cumulative dose of oxaliplatin of 1000 mg/m(2). XELOX(30Chron) does not reduce toxicity or improve efficacy. A 30-min infusion of oxaliplatin is safe and does not increase the severity of chronic neuropathy.

  1. Optimization of epilepsy treatment with vagus nerve stimulation

    Science.gov (United States)

    Uthman, Basim; Bewernitz, Michael; Liu, Chang-Chia; Ghacibeh, Georges

    2007-11-01

    Epilepsy is one of the most common chronic neurological disorders that affects close to 50 million people worldwide. Antiepilepsy drugs (AEDs), the main stay of epilepsy treatment, control seizures in two thirds of patients only. Other therapies include the ketogenic diet, ablative surgery, hormonal treatments and neurostimulation. While other approaches to stimulation of the brain are currently in the experimental phase vagus nerve stimulation (VNS) has been approved by the FDA since July 1997 for the adjunctive treatment of intractable partial onset epilepsy with and without secondary generalization in patients twelve years of age or older. The safety and efficacy of VNS have been proven and duplicated in two subsequent double-blinded controlled studies after two pilot studies demonstrated the feasibility of VNS in man. Long term observational studies confirmed the safety of VNS and that its effectiveness is sustained over time. While AEDs influence seizure thresholds via blockade or modulation of ionic channels, inhibit excitatory neurotransmitters or enhance inhibitory neurotransmitters the exact mechanism of action of VNS is not known. Neuroimaging studies revealed that VNS increases blood flow in certain regions of the brain such as the thalamus. Chemical lesions in the rat brains showed that norepinephrine is an important link in the anticonvulsant effect of VNS. Analysis of cerebrospinal fluid obtained from patients before and after treatment with VNS showed modest decreases in excitatory neurotransmitters. Although Hammond et al. reported no effect of VNS on scalp EEG by visual analysis and Salinsky et al. found no effect of VNS on scalp EEG by spectral analysis, Kuba et al. suggested that VNS reduces interictal epileptiform activity. Further, nonlinear dynamical analysis of the electroencephalogram in the rat and man have reportedly shown predictable changes (decrease in the short term Lyapunov exponent STLmax and T-index) more than an hour prior to the

  2. How to study optimal timing of PET/CT for monitoring of cancer treatment

    DEFF Research Database (Denmark)

    Vach, Werner; Høilund-Carlsen, Poul Flemming; Fischer, Barbara Malene Bjerregaard

    2011-01-01

    Purpose: The use of PET/CT for monitoring treatment response in cancer patients after chemo- or radiotherapy is a very promising approach to optimize cancer treatment. However, the timing of the PET/CT-based evaluation of reduction in viable tumor tissue is a crucial question. We investigated how...... to plan and analyze studies to optimize this timing. Methods: General considerations about studying the optimal timing are given and four fundamental steps are illustrated using data from a published study. Results: The optimal timing should be examined by optimizing the schedule with respect...... to predicting the overall individual time course we can observe in the case of dense measurements. The optimal timing needs not to and should not be studied by optimizing the association with the prognosis of the patient. Conclusions: The optimal timing should be examined in specific ‘schedule optimizing...

  3. OPTIMIZATION OF TETRANDRINE TREATMENT IN RAT HEPATIC FIBROSIS MODEL

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To optimize the therapeutic dosage of tetrandrine (Tet) in rat hepatic fibrosis model. Methods 50 Wistar rats were divided into 5 groups at random including normal control, model control, Tettreated model groups of l0mg·kg-1 ·d-1, 5mg·kg-1 ·d-1 and 2.5mg·kg-1 ·d-1 ( n =10 in each group). All rats,except for the normal controls, were injected with axenic porcine serum (0. 5ml each time, twice a week) intraperitoneally for 8 weeks to establish hepatic fibrosis. After the 8th week, rats of Tet-treated model groups were given by gavage once a day with different doses of Tet for another 8 weeks. Then the liver function, serum levels of hyaluronic acid (HA) , laminin ( LM) , and procollagen type Ⅲ (PCⅢ) were tested. Collagen type Ⅰ and Ⅲ, pathological changes in liver tissue were also assessed. Results Most indices of liver function including alanine minotransferase (ALT), aspartate aminotransferase ( AST), albumin (ALB), albumin/globulin ratio (A/G) and alkaline phosphatase (ALP) improved significantly in Tet-treated groups with the exception of γ-glutamyl transpeptidase (γ-GT) and total bilirubin (TBIL). Secondly, markedly lowered levels of HA, LM and collagen type Ⅰ, Ⅲ were also detected by radioimmunology and immunohistochemistry in the 5 mg · kg- 1 · d- 1 Tet-treated model group. Moreover, pathological findings confirmed the statistically significant improvement in hepatofibrotic degree resulted from the treatment of 5mg · kg- 1 · d-1 rather than other doses of Tet. Conclusion For experimental Wistar rats, Tet exhibited an anti-hepatofibrotic action in doses within the range of 2.5mg·kg-1 ·d-1 to 10mg·kg 1 ·d-1, and 5mg·kg-1 ·d-1 may be theoptimum one among all doses.

  4. Impedance cardiography – optimization and efficacy evaluation of antihypertensive treatment

    National Research Council Canada - National Science Library

    Panasiuk-Kamińska, Katarzyna; Szeliga-Król, Jolanta; Zubilewicz, Renata; Jaroszyński, Andrzej

    2016-01-01

    ...% are treated effectively. Impedance cardiography (IC) is an important tool both in diagnostics and the treatment of hypertensive patients, particularly in the case of antihypertensive treatment resistance...

  5. Optimizing patient treatment decisions in an era of rapid technological advances: the case of hepatitis C treatment.

    Science.gov (United States)

    Liu, Shan; Brandeau, Margaret L; Goldhaber-Fiebert, Jeremy D

    2017-03-01

    How long should a patient with a treatable chronic disease wait for more effective treatments before accepting the best available treatment? We develop a framework to guide optimal treatment decisions for a deteriorating chronic disease when treatment technologies are improving over time. We formulate an optimal stopping problem using a discrete-time, finite-horizon Markov decision process. The goal is to maximize a patient's quality-adjusted life expectancy. We derive structural properties of the model and analytically solve a three-period treatment decision problem. We illustrate the model with the example of treatment for chronic hepatitis C virus (HCV). Chronic HCV affects 3-4 million Americans and has been historically difficult to treat, but increasingly effective treatments have been commercialized in the past few years. We show that the optimal treatment decision is more likely to be to accept currently available treatment-despite expectations for future treatment improvement-for patients who have high-risk history, who are older, or who have more comorbidities. Insights from this study can guide HCV treatment decisions for individual patients. More broadly, our model can guide treatment decisions for curable chronic diseases by finding the optimal treatment policy for individual patients in a heterogeneous population.

  6. Optimalization Of Port-Wine Stain Treatment With Lasers

    Science.gov (United States)

    Lahaye, C. T.; van Gemert, M. J.; Henning, J. P. H.

    1985-03-01

    To optimalize laser-parameters for therapy of port-wine stains temperature calculations have been performed on a skin model. The optimal values of these numerically evaluated variables are: wavelength λ= 415,577 or 540 nm., pulse-time t1 a few milliseconds and beam radius wi> 0.1 mm. Based on these theoretical results some experiments have been carried out which confirm the calculations. Thus laser-therapy for port-wine stains can be ameliorated.

  7. Nonalcoholic steatohepatitis: emerging targeted therapies to optimize treatment options

    Directory of Open Access Journals (Sweden)

    Milic S

    2015-08-01

    Full Text Available Sandra Milic,1 Ivana Mikolasevic,1,2 Irena Krznaric-Zrnic,1 Marija Stanic,3 Goran Poropat,1 Davor Stimac,1 Vera Vlahovic-Palcevski,4 Lidija Orlic2 1Department of Gastroenterology, UHC Rijeka, Rijeka, Croatia; 2Department of Nephrology, Dialysis and Kidney Transplantation, UHC Rijeka, Rijeka, Croatia; 3Department of Hematology, UHC Rijeka, Rijeka, Croatia; 4Department for Clinical Pharmacology, University of Rijeka Medical School, UHC Rijeka, Rijeka, Croatia Abstract: Diet and lifestyle changes have led to worldwide increases in the prevalences of obesity and metabolic syndrome, resulting in substantially greater incidence of nonalcoholic fatty liver disease (NAFLD. NAFLD is considered a hepatic manifestation of metabolic syndrome and is related to diabetes, insulin resistance, central obesity, hyperlipidemia, and hypertension. Nonalcoholic steatohepatitis (NASH is an entity that describes liver inflammation due to NAFLD. Growing evidence suggests that NAFLD is a multisystem disease with a clinical burden that is not only confined to liver-related morbidity and mortality, but that also affects several extra-hepatic organs and regulatory pathways. Thus, NAFLD is considered an important public health issue, but there is currently no effective therapy for all NAFLD patients in the general population. Studies seeking optimal therapy for NAFLD and NASH have not yet led to development of a universal protocol for treating this growing problem. Several pharmacological agents have been studied in an effort to improve insulin resistance and the proinflammatory mediators that may be responsible for NASH progression. Cardiovascular risk factors are highly prevalent among NASH patients, and the backbone of treatment regimens for these patients still comprises general lifestyle interventions, including dietary changes and increased physical activity. Vitamin E and thiazolidinedione derivatives are currently the most evidence-based therapeutic options, but only

  8. Determination of an optimal control strategy for drug administration in tumor treatment using multi-objective optimization differential evolution.

    Science.gov (United States)

    Lobato, Fran Sérgio; Machado, Vinicius Silvério; Steffen, Valder

    2016-07-01

    The mathematical modeling of physical and biologic systems represents an interesting alternative to study the behavior of these phenomena. In this context, the development of mathematical models to simulate the dynamic behavior of tumors is configured as an important theme in the current days. Among the advantages resulting from using these models is their application to optimization and inverse problem approaches. Traditionally, the formulated Optimal Control Problem (OCP) has the objective of minimizing the size of tumor cells by the end of the treatment. In this case an important aspect is not considered, namely, the optimal concentrations of drugs may affect the patients' health significantly. In this sense, the present work has the objective of obtaining an optimal protocol for drug administration to patients with cancer, through the minimization of both the cancerous cells concentration and the prescribed drug concentration. The resolution of this multi-objective problem is obtained through the Multi-objective Optimization Differential Evolution (MODE) algorithm. The Pareto's Curve obtained supplies a set of optimal protocols from which an optimal strategy for drug administration can be chosen, according to a given criterion.

  9. Using qualitative evidence to optimize child PTSD treatment guidelines.

    NARCIS (Netherlands)

    Wesel, F. van; Alisic, E.; Boeije, H.

    2014-01-01

    The importance of patients’ perspectives in the treatment of posttraumatic stress disorder (PTSD) is increasingly emphasized in recent years. However, qualitative evidence regarding these perspectives, is not systematically included in treatment guidelines. The possibilities of adding systematically

  10. ANOXIA, Treatment by Oxygen Deprivation, Optimizing Treatment Time of Museum Objects

    CERN Document Server

    Gunn, M; Naffah, C; Ziaeepour, H; Gunn, Michele; Merizzi, Fabrice; Naffah, Christitiane; Ziaeepour, Houri

    2006-01-01

    ANOXIA, treatment by oxygen deprivation is largely used for decontamination and disinfestation of cellulose and protein-based organic materials. More specifically this method is applied to more than one hundred thousand of objects destinated for a new museum in Paris, "Musee du Quai Branly". We describe the anoxia installation in this museum and report the result of a study regarding the efficiency of this method and the optimum treatment time, crucial for treating a large collection. We show that the standard 21 days of exposure is not always the optimal choice. Temperature plays a crucial role for hastening the death of insects found within objects. At a temperature of 25C, it is entirely possible to reduce exposure times to 10 or 15 days for the insect species commonly found in museums. The oxygen drop times is between 1 and 2 days for most objects, depending on type and porosity of materials. This corresponds to a treatment time between 15 and 16 days. The effect of humidity is less clear. It can increase...

  11. [Optimization of complex treatment of patients with severe oral leukoplakia].

    Science.gov (United States)

    Rabinovich, O F; Rabinovich, I M; Abramova, E S

    2015-01-01

    The aim of the study was to prove the rationale for antiviral therapy combined with surgical procedures for treatment of severe oral leukoplakia. Complex clinical and laboratory evaluation and treatment was performed in 56 patients divided in 2 groups. Control group was presented by 13 patients receiving dental treatment, local and systemic keratoplastic formulations. Main group involved 43 patients in which conventional treatment protocol was completed by antiviral therapy and surgical procedures. Leukoplakia diagnosis was based on clinical findings, histological and immunohistochemical studies as well as optic coherent tomography data. The obtained results evidently prove the necessity for including antiviral therapy and surgical procedures in treatment scheme of severe oral leukoplakia.

  12. Parameter Identification of Anaerobic Wastewater Treatment Bioprocesses Using Particle Swarm Optimization

    Directory of Open Access Journals (Sweden)

    Dorin Sendrescu

    2013-01-01

    Full Text Available This paper deals with the offline parameters identification for a class of wastewater treatment bioprocesses using particle swarm optimization (PSO techniques. Particle swarm optimization is a relatively new heuristic method that has produced promising results for solving complex optimization problems. In this paper one uses some variants of the PSO algorithm for parameter estimation of an anaerobic wastewater treatment process that is a complex biotechnological system. The identification scheme is based on a multimodal numerical optimization problem with high dimension. The performances of the method are analyzed by numerical simulations.

  13. Treatment of pilonidal sinuses in Denmark is not optimal

    DEFF Research Database (Denmark)

    Fabricius, Rasmus; Petersen, Linda Wiuff; Bertelsen, Claus Anders

    2010-01-01

    The standard treatments of chronic pilonidal sinuses (PS) were previously wide excision with primary midline closure or open treatment by non-specialist surgeons resulting in high rates of unhealed wounds and recurrences. An evidence-based shift from the now obsolete midline procedures towards off...

  14. Doubly Robust Estimation of Optimal Dynamic Treatment Regimes

    DEFF Research Database (Denmark)

    Barrett, Jessica K; Henderson, Robin; Rosthøj, Susanne

    2014-01-01

    We compare methods for estimating optimal dynamic decision rules from observational data, with particular focus on estimating the regret functions defined by Murphy (in J. R. Stat. Soc., Ser. B, Stat. Methodol. 65:331-355, 2003). We formulate a doubly robust version of the regret-regression appro......We compare methods for estimating optimal dynamic decision rules from observational data, with particular focus on estimating the regret functions defined by Murphy (in J. R. Stat. Soc., Ser. B, Stat. Methodol. 65:331-355, 2003). We formulate a doubly robust version of the regret....... 189-326, 2004). Simulation studies suggest that while the regret-regression approach is most efficient when there is no model misspecification, in the presence of misspecification the efficient g-estimation procedure is more robust. The g-estimation method can be difficult to apply in complex...

  15. Optimal price subsidies for appropriate malaria testing and treatment behaviour

    DEFF Research Database (Denmark)

    Hansen, K. S.; Lesner, T. H.; Østerdal, L. P.

    2016-01-01

    of presumptive diagnosis. A global subsidy on artemisinin-based combination therapy (ACT) has recently been suggested to increase access to the most effective malaria treatment. Methods: Following the recommendation by World Health Organization that parasitological testing should be performed before treatment......, ACT medicines, and cheap, less effective anti-malarials are sold. Assuming that the individual has certain beliefs of the accuracy of the RDT and the probability that the fever is malaria, the model predicts the diagnosis-treatment behaviour of the individual. Subsidies on RDTs and ACT are introduced...... to incentivize appropriate behaviour: choose an RDT before treatment and purchase ACT only if the test is positive. Results: Solving the model numerically suggests that a combined subsidy on both RDT and ACT is cost minimizing and improves diagnosis-treatment behaviour of individuals. For certain beliefs...

  16. Optimized Non-Obstructive Particle Damping (NOPD) Treatment for Composite Honeycomb Structures

    Science.gov (United States)

    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.

  17. Gout: optimizing treatment to achieve a disease cure

    Science.gov (United States)

    Bernal, José Antonio; Quilis, Neus; Andrés, Mariano; Sivera, Francisca; Pascual, Eliseo

    2016-01-01

    Gout is one of the most common inflammatory arthritides. The disease is due to the deposition of monosodium urate crystals. These deposits are reversible with proper treatment, suggesting that gout is a curable disease. The main aim in gout is to lower serum uric acid levels to a pre-established target; there are different urate-lowering drugs (xanthine oxidase inhibitors, uricosurics and uricases) through which this can be achieved. Proper treatment of gout also involves correct management of acute flares and their prevention. To ensure treatment adherence it is necessary to explain to the patient what the objectives are. PMID:26977282

  18. Superstructure development and optimization under uncertainty for design and retrofit of municipal wastewater treatment plants

    DEFF Research Database (Denmark)

    Bozkurt, Hande; Quaglia, Alberto; Gernaey, Krist

    2014-01-01

    n this contribution, an optimization - based approach is presented for optimal process selec tion and design for domestic wastewater treatment plant s (WWTP s ). In particular, we address the issue of uncertainties by formulating the WWTP design problem as a Stochastic Mixed Integer (Non) Linear...

  19. HIV treatment optimism and its predictors among young adults in southern Malawi.

    Science.gov (United States)

    Yeatman, Sara; Dovel, Kathryn; Conroy, Amy; Namadingo, Hazel

    2013-08-01

    This study measures HIV treatment optimism and its predictors in a representative sample of young adults in southern Malawi. In 2010, 1275 women and 470 men between the ages of 16 and 26 were asked about their exposure to people on antiretroviral therapy (ART), sexual risk behavior, HIV status, and beliefs about ART. We used confirmatory factor analysis to develop a 4-item scale of the belief that HIV is a less serious health threat due to ART (reduced-severity optimism) and used a single measure to capture belief in the reduced infectivity of HIV due to ART (reduced-susceptibility optimism). Overall, respondents reported low levels of HIV treatment optimism. Being female and using ART were the largest predictors of both types of treatment optimism. We found a nonlinear relationship between exposure to people on ART and reduced-severity optimism. People who knew someone on ART but did not discuss it with them had lower levels of reduced-severity optimism than people who did not know anyone on ART and people who regularly discussed treatment with someone on ART. In multivariate regression models, HIV treatment optimism was positively associated with all measures of sexual risk behavior among men, but negatively associated with unprotected sex with a nonprimary partner among women. Our findings suggest that the spread of ART in Malawi has not led to widespread HIV treatment optimism. This may reflect the relatively recent spread of ART, the generalized nature of the HIV epidemic, or the fact that access to ART is complicated by structural limitations that delay treatment and limited availability of second-line medicines.

  20. Optimizing the treatment of mood disorders in the perinatal period

    Science.gov (United States)

    Meltzer-Brody, Samantha; Jones, Ian

    2015-01-01

    The perinatal period is a time of high risk for women with unipolar and bipolar mood disorders. We discuss treatment considerations for perinatal mood disorders, including unipolar and bipolar depression as well as postpartum psychosis. We further explore the unique issues faced by women and their families across the full trajectory of the perinatal period from preconception planning through pregnancy and following childbirth. Treatment of perinatal mood disorders requires a collaborative care approach between obstetrics practitioners and mental health providers, to ensure that a thoughtful risk : benefit analysis is conducted. It is vital to consider the risks of the underlying illness versus risks of medication exposure during pregnancy or lactation. When considering medication treatment, attention must be paid to prior medication trials that were most efficacious and best tolerated. Lastly, it is important to assess the impact of individual psychosocial stressors and lifestyle factors on treatment response. PMID:26246794

  1. Optimizing Treatment of Familial Hypercholesterolemia in Children and Adolescents.

    Science.gov (United States)

    Luirink, Ilse K; Hutten, Barbara A; Wiegman, Albert

    2015-09-01

    Cardiovascular disease (CVD) is still the most prominent cause of death and morbidity in the world, and one of the major risk factors for developing CVD is hypercholesterolemia. Familial hypercholesterolemia (FH) is a dominantly inherited disorder characterized by markedly elevated plasma low-density lipoprotein cholesterol and premature coronary heart disease. Currently, several treatment options are available for children with FH. Lifestyle adjustments are the first step in treatment. If this is not sufficient, statins are the preferred initial pharmacological therapy and they have been proven effective and safe. However, treatment goals are often not achieved and, hence, there is a need for novel treatment options. Currently, several options are being studied in adults and first results are promising. However, studies in children are still to be awaited.

  2. Optimal price subsidies for appropriate malaria testing and treatment behaviour

    DEFF Research Database (Denmark)

    Hansen, Kristian Schultz; Lesner, Tine Hjernø; Østerdal, Lars Peter

    2016-01-01

    , ACT medicines, and cheap, less effective anti-malarials are sold. Assuming that the individual has certain beliefs of the accuracy of the RDT and the probability that the fever is malaria, the model predicts the diagnosis-treatment behaviour of the individual. Subsidies on RDTs and ACT are introduced...... to incentivize appropriate behaviour: choose an RDT before treatment and purchase ACT only if the test is positive. RESULTS: Solving the model numerically suggests that a combined subsidy on both RDT and ACT is cost minimizing and improves diagnosis-treatment behaviour of individuals. For certain beliefs......BACKGROUND: Malaria continues to be a serious public health problem particularly in Africa. Many people infected with malaria do not access effective treatment due to high price. At the same time many individuals receiving malaria drugs do not suffer from malaria because of the common practice...

  3. Optimizing Treatment of Familial Hypercholesterolemia in Children and Adolescents

    OpenAIRE

    Luirink, Ilse K.; Hutten, Barbara A; Wiegman, Albert

    2015-01-01

    Cardiovascular disease (CVD) is still the most prominent cause of death and morbidity in the world, and one of the major risk factors for developing CVD is hypercholesterolemia. Familial hypercholesterolemia (FH) is a dominantly inherited disorder characterized by markedly elevated plasma low-density lipoprotein cholesterol and premature coronary heart disease. Currently, several treatment options are available for children with FH. Lifestyle adjustments are the first step in treatment. If th...

  4. Optimal price subsidies for appropriate malaria testing and treatment behaviour.

    Science.gov (United States)

    Hansen, Kristian Schultz; Lesner, Tine Hjernø; Østerdal, Lars Peter

    2016-11-04

    Malaria continues to be a serious public health problem particularly in Africa. Many people infected with malaria do not access effective treatment due to high price. At the same time many individuals receiving malaria drugs do not suffer from malaria because of the common practice of presumptive diagnosis. A global subsidy on artemisinin-based combination therapy (ACT) has recently been suggested to increase access to the most effective malaria treatment. Following the recommendation by World Health Organization that parasitological testing should be performed before treatment and ACT prescribed to confirmed cases only, it is investigated in this paper if a subsidy on malaria rapid diagnostic tests (RDTs) should be incorporated. A model is developed consisting of a representative individual with fever suspected to be malaria, seeking care at a specialized drug shop where RDTs, ACT medicines, and cheap, less effective anti-malarials are sold. Assuming that the individual has certain beliefs of the accuracy of the RDT and the probability that the fever is malaria, the model predicts the diagnosis-treatment behaviour of the individual. Subsidies on RDTs and ACT are introduced to incentivize appropriate behaviour: choose an RDT before treatment and purchase ACT only if the test is positive. Solving the model numerically suggests that a combined subsidy on both RDT and ACT is cost minimizing and improves diagnosis-treatment behaviour of individuals. For certain beliefs, such as low trust in RDT accuracy and strong belief that a fever is malaria, subsidization is not sufficient to incentivize appropriate behaviour. A combined subsidy on both RDT and ACT rather than a single subsidy is likely required to improve diagnosis-treatment behaviour among individuals seeking care for malaria in the private sector.

  5. Optimizing settling conditions for treatment of liquid hog manure.

    Science.gov (United States)

    Trias, M; Mortula, M M; Hu, Z; Gagnon, G A

    2004-08-01

    Sedimentation is a widely used separation method for treating agricultural waste. There are several chemical and biological characteristics, which can affect the settling behavior and liquid waste. The optimization of cation balances and potential for nitrification are among these processes. In addition to sedimentation, it can also affect the dewaterability of the samples. Liquid hog manure was used during the laboratory based experiments to investigate the effects of Ca2+ and Mg2+ ions and nitrification inhibition on the overall settling and dewatering characteristics. The results indicated that settling and dewatering characteristics improved during the course of the experiments. However, the improvement in settling and dewatering characteristics was inconsistent and not statistically significant. Cation addition in aerated reactor increased the highest settling velocity (94%). The improvement in dewaterability, as quantified by capillary suction time, was also not consistent. The greatest filterability observed in the supernatant was a capillary suction time of 40 s for a M:D ratio of 2:1. Initial NH 4 + concentration was more important than the nitrification inhibitor, as the presence of nitrification inhibitor increased the nitrification rate by over 300% because of the high initial NH 4 + concentration and low volatile suspended solid. The results from these experiments provide the basis for further field evaluation of cation optimization.

  6. [Optimization of parodontitis treatment of patients with tuberculosis].

    Science.gov (United States)

    Aleksandrova, E A; Lepilin, A V; Kazimirova, N E; Shul'diakov, A A

    2010-01-01

    For the purpose to determine the clinic-pathogenetic efficacy of Cycloferon liniment in the combined therapy of parodontitis of patients with focal tuberculosis medical examination and treatment of 40 patients is carried out. It is established, that use of liniment Cycloferon in the combined treatment of patients with focal tuberculosis allows to accelerate process of normalization of lipid peroxidation parameters and antioxidant potential of blood, to decrease infection load (Herpes symplex virus I, Candida albicans, Staphylococcus aureus) in parodontal recess and evidence of local inflammation with reduction of activity of the tumours necrosis factor and interleukin 1beta, that provides acceleration of recuperation processes, lowering the frequency of parodontitis relapses.

  7. Optimizing prophylactic treatment of migraine: Subtypes and patient matching

    Directory of Open Access Journals (Sweden)

    Michel Dib

    2008-09-01

    Full Text Available Michel DibFédération du système nerveux central, Hôpital de la Salpêtrière, Assistance Publique- Hôpitaux de Paris, FranceAbstract: Advances in our understanding of the pathophysiology of migraine have resulted in important breakthroughs in treatment. For example, understanding of the role of serotonin in the cerebrovascular circulation has led to the development of triptans for the acute relief of migraine headaches, and the identification of cortical spreading depression as an early central event associated wih migraine has brought renewed interest in antiepileptic drugs for migraine prophylaxis. However, migraine still remains inadequately treated. Indeed, it is apparent that migraine is not a single disease but rather a syndrome that can manifest itself in a variety of pathological conditions. The consequences of this may be that treatment needs to be matched to particular patients. Clinical research needs to be devoted to identifying which sort of patients benefit best from which treatments, particularly in the field of prophylaxis. We propose four patterns of precipitating factors (adrenergic, serotoninergic, menstrual, and muscular which may be used to structure migraine prophylaxis. Finally, little is known about long-term outcome in treated migraine. It is possible that appropriate early prophylaxis may modify the long-term course of the disease and avoid late complications.Keywords: migraine, diagnosis, treatment, prophylaxis, subtypes

  8. Plasma drug activity assay for treatment optimization in tuberculosis patients

    NARCIS (Netherlands)

    Heysell, S.K.; Mtabho, C.; Mpagama, S.; Mwaigwisya, S.; Pholwat, S.; Ndusilo, N.; Gratz, J.; Aarnoutse, R.E.; Kibiki, G.S.; Houpt, E.R.

    2011-01-01

    Low antituberculosis (TB) drug levels are common, but their clinical significance remains unclear, and methods of measurement are resource intensive. Subjects initiating treatment for sputum smear-positive pulmonary TB were enrolled from Kibong'oto National TB Hospital, Tanzania, and levels of isoni

  9. Clinical pharmacology in leishmaniasis: treatment optimization of a neglected disease

    NARCIS (Netherlands)

    Dorlo, T.P.C.

    2013-01-01

    This thesis presents various novel applications of clinical pharmacokinetics and pharmacodynamics in the treatment of leishmaniasis, by which diverse clinically relevant issues, mainly related to the efficacy and safety of miltefosine, could be elucidated. Throughout this thesis, the added value of

  10. A Multi-Criteria Framework with Voxel-Dependent Parameters for Radiotherapy Treatment Plan Optimization

    CERN Document Server

    Zarepisheh, Masoud; Li, Nan; Jia, Xun; Jiang, Steve B

    2012-01-01

    In a treatment plan optimization problem for radiotherapy, a clinically acceptable plan is usually generated by an optimization process with weighting factors or reference doses adjusted for organs. Recent discoveries indicate that adjusting parameters associated with each voxel may lead to better plan quality. However, it is still unclear regarding the mathematical reasons behind it. To answer questions related to this problem, we establish in this work a new mathematical framework equipped with two theorems. The new framework clarifies the different consequences of adjusting organ-dependent and voxel-dependent parameters for the treatment plan optimization of radiation therapy, as well as the different effects of adjusting weighting factors versus reference doses in the optimization process. The main discoveries are threefold: 1) While in the organ-based model the selection of the objective function has an impact on the quality of the optimized plans, this is no longer an issue for the voxel-based model sin...

  11. A moment-based approach for DVH-guided radiotherapy treatment plan optimization

    Science.gov (United States)

    Zarepisheh, M.; Shakourifar, M.; Trigila, G.; Ghomi, P. S.; Couzens, S.; Abebe, A.; Noreña, L.; Shang, W.; Jiang, Steve B.; Zinchenko, Y.

    2013-03-01

    The dose-volume histogram (DVH) is a clinically relevant criterion to evaluate the quality of a treatment plan. It is hence desirable to incorporate DVH constraints into treatment plan optimization for intensity modulated radiation therapy. Yet, the direct inclusion of the DVH constraints into a treatment plan optimization model typically leads to great computational difficulties due to the non-convex nature of these constraints. To overcome this critical limitation, we propose a new convex-moment-based optimization approach. Our main idea is to replace the non-convex DVH constraints by a set of convex moment constraints. In turn, the proposed approach is able to generate a Pareto-optimal plan whose DVHs are close to, or if possible even outperform, the desired DVHs. In particular, our experiment on a prostate cancer patient case demonstrates the effectiveness of this approach by employing two and three moment formulations to approximate the desired DVHs.

  12. An epidemic model for cholera with optimal control treatment

    OpenAIRE

    Lemos-Paiao, Ana P.; Silva, Cristiana J.; Torres, Delfim F. M.

    2016-01-01

    We propose a mathematical model for cholera with treatment through quarantine. The model is shown to be both epidemiologically and mathematically well posed. In particular, we prove that all solutions of the model are positive and bounded; and that every solution with initial conditions in a certain meaningful set remains in that set for all time. The existence of unique disease-free and endemic equilibrium points is proved and the basic reproduction number is computed. Then, we study the loc...

  13. Three-Dimensional Dose Optimization for Noncoplanar Treatment Planning with Conformal Fields.

    Science.gov (United States)

    Ma, Ying-Chang L.

    1990-01-01

    Recent advances in imaging techniques, especially three dimensional reconstruction of CT images, have made precision tumor localization feasible. These imaging techniques along with developments in computer controlled radiation treatment machines have provided an important thrust in developing better techniques for cancer treatment. This often requires a complex noncoplanar beam arrangements and elaborate treatment planning, which, unfortunately, are time consuming, costly and dependent on operator expertise and experience. A reliable operator-independent dose optimization tool is therefore desirable, especially for 3D treatment planning. In this dissertation, several approaches (linear programming, quadratic programming, and direct search methods) of computer optimization using various criteria including least sire fitting on the 90% isodose to target periphery, dose uniformity, and integral dose are presented. All of these methods are subject to restrictions on the upper limit of the dose to critical organs. In the quadratic programming approach, Kuhn-Tucker theory was employed to convert the quadratic problem into one which permits application of the very powerful, revised simplex method. Several examples are used to analyze the effectiveness of these dose optimization approaches. The studies show that the quadratic programming approach with the criteria of least square fitting and critical organ constraints is superior in efficiency for dose optimization in 3D treatment planning, particularly for cases with a large number of beams. Use of least square fitting allows one to deduce optimized plans for irregularly shaped targets by employing a multi-isocentric technique. Our studies also illustrate the advantages of using irregular conformal fields, optimized beam energy, and noncoplanar beam arrangements in contrast to the conventional treatment which uses a symmetrical rectangular collimator, fixed beam energy, and coplanar beam arrangements. Optimized plans can

  14. Treatment of B-cells non-Hodgkin lymphomas with combined immunochemotherapy: ability to treatment optimization

    Directory of Open Access Journals (Sweden)

    N. V. Smirnova

    2015-01-01

    Full Text Available The results of two consecutive multicenter clinical trials enrolled 241 patient with childhood mature B-cells non-Hodgkin lymphomas/leukemia are presented. Patients received treatment according B-NHL 2004mab protocol (n = 83 and B-NHL 2010M (n = 158 with combined immunochemotherapy (ICT in Russian and Belarus pediatric clinics from 2004 to 2015 years. Primary patients with different mature B-NHL (Burkitt lymphoma/leukemia, diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma (DLBCL and PMBCL aged from 2 to 18 years are included in the studies.Protocol B-NHL 2004mab for treatment of children and adolescents with B-NHL/B-AL, stage III and IV, includes a combination of chemotherapy (PCT and rituximab – an antibody against the B-cells receptor CD20. PCT courses similar to those in the B-NHL BFM90 protocol (group III with the exception of methotrexate dose in induction courses, reduced to 1 g/m2 /24 h in order to reduce toxicity. Rituximab (Mabthera, 375 mg/m2 /h used for the first time in the treatment of children and adolescents with B-NHL. Of the 83 patients included, clinical remission was achieved in 77 (92.8 %. With a median follow time of 51.6 months, remission continued in 23 (85.2 % patients with B-AL, in 32 (88.9 % patients with LB and 19 (95.0 % patients – with DLBCL. With median follow time of 65.2 months, event-free and overall survival was 84 ± 6 and 82 ± 8 %, respectively.Based on previous experience in order to further optimize B-NHL treatment, new protocol B-NHL 2010M with effect-adapted therapy and improvement of stratification risk group criteria was proposed. Overall survival in patients of 1st and 2nd risk groups with full implementation of diagnosis and treatment is approaching 100 %. In interim analysis of 3rd risk group patients, pOS was 88 ± 3 %. The incidence of induction death (infections, metabolic complications remains within 2.7 % (n = 4; refractory cases (n = 2; 1.3 % and relapses (n = 4; 2

  15. How to study optimal timing of PET/CT for monitoring of cancer treatment

    DEFF Research Database (Denmark)

    Vach, Werner; Høilund-Carlsen, Poul Flemming; Fischer, Barbara Malene Bjerregaard

    2011-01-01

    Purpose: The use of PET/CT for monitoring treatment response in cancer patients after chemo- or radiotherapy is a very promising approach to optimize cancer treatment. However, the timing of the PET/CT-based evaluation of reduction in viable tumor tissue is a crucial question. We investigated how...

  16. How to study optimal timing of PET/CT for monitoring of cancer treatment

    DEFF Research Database (Denmark)

    Vach, Werner; Høilund-Carlsen, Poul Flemming; Fischer, Barbara Malene Bjerregaard;

    2011-01-01

    Purpose: The use of PET/CT for monitoring treatment response in cancer patients after chemo- or radiotherapy is a very promising approach to optimize cancer treatment. However, the timing of the PET/CT-based evaluation of reduction in viable tumor tissue is a crucial question. We investigated how...

  17. Fluorescence Guided PDT for Optimization of Skin Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Kate Cristina Blanco

    2015-04-01

    Full Text Available The photodynamic therapy (PDT is an alternative technique that can be indicated for superficial basal cell carcinoma (sBCC, Bowen’s disease and actinic keratosis with high efficiency. The objective of this study is to present the importance of fluorescence imaging for PDT guidance and monitoring in real time. Confirming that the lesion is well prepared and the photosensitizer shows a homogenous distribution, the outcome after few PDT sessions will be positive and the recurrence should be lower. Our proposition in this study is use the widefield fluorescence imaging to evaluate the PDT protocol in situ and in real time for each lesion. This evaluation procedure is performed in two steps: first with the monitoring of the production of protoporphyrin IX (PpIX induced by methyl aminolevulinate (MAL, an derivative of 5-aminolevulinic acid (ALA and second with the detection of PpIX photobleaching after illumination. The fluorescence images provide information correlated with distinct clinical features and with the treatment outcome. Eight BCC lesions are presented and discussed in this study. Different fluorescence patterns of PpIX production and photobleaching could be correlated with the treatment response. The presented results show the potential of using widefield fluorescence imaging as a guidance tool to customized PDT.

  18. Effects of disintegration-promoting agent, lubricants and moisture treatment on optimized fast disintegrating tablets.

    Science.gov (United States)

    Late, Sameer G; Yu, Yi-Ying; Banga, Ajay K

    2009-01-05

    Effects of calcium silicate (disintegration-promoting agent) and various lubricants on an optimized beta-cyclodextrin-based fast-disintegrating tablet formulation were investigated. Effects of moisture treatment were also evaluated at 75, 85 and 95% relative humidities. A two factor, three levels (3(2)) full factorial design was used to optimize concentrations of calcium silicate and lubricant. Magnesium stearate, being commonly used lubricant, was used to optimize lubricant concentration in optimization study. Other lubricants were evaluated at an obtained optimum concentration. Desiccator with saturated salt solutions was used to analyze effects of moisture treatments. Results of multiple linear regression analysis revealed that concentration of calcium silicate had no effect; however concentration of lubricant was found to be important for tablet disintegration and hardness. An optimized value of 1.5% of magnesium stearate gave disintegration time of 23.4 s and hardness of 1.42 kg. At an optimized concentration, glycerol dibehenate and L-leucine significantly affected disintegration time, while talc and stearic acid had no significant effect. Tablet hardness was significantly affected with L-leucine, while other lubricants had no significant effect. Hardness was not affected at 75% moisture treatment. Moisture treatment at 85 and 95% increased hardness of the tablets; however at the same time it negatively affected the disintegration time.

  19. Dosimetric Comparison of Two Craniospinal Radiotherapy Techniques for Treatment Optimization

    Directory of Open Access Journals (Sweden)

    Hamidreza Baghani

    2010-06-01

    Full Text Available Introduction: Orthogonal radial fields are those in which the central axes are perpendicular to each other. An example of these orthogonal fields is the set of craniospinal orthogonal fields that are used for radiotherapy of medulloblastoma. Craniospinal radial fields consist of two parallel-opposed fields for brain exposure and one or two posterior spinal fields for spinal cord exposure. The main problem in using these combinative fields is the overlap of radial fields, where they adjoin. Therefore, adjusting radial fields in craniospinal radiotherapy is of remarkable significance and can outstandingly affect the reduction of the side effects due to radiotherapy. In doing so, two different setups were used for craniospinal radiotherapy, and by using dosimetry in each adjustment in the junction region between brain and upper spine fields and in organs at risk, the results of the two adjustments were compared. Materials and Methods: Each one of these two setups was separately performed on a Rando phantom. In the first setup, the arrangement of radial fields was performed without the rotation of the treatment bed and the collimators of the brain fields. In the second setup, the arrangement of radial fields was performed using the rotation of the treatment bed and the collimators of brain fields. For dosimetry, GR-200 TLDs were used. For radiotherapy, a varian linac (2100 C/D Model was used. Results: The results of dosimetry in the brain CTV, junction of brain and upper spine fields, thyroid and heart in the first setup were equal to 105, 168, 46 and 44 cGy, respectively, and in second setup, 106, 140, 48 and 44 cGy, respectively. Absorbed dose to the testes in both setups was negligible.  Discussion and Conclusion: The results of dosimetry in both setups showed that angling the bed and the collimators for the brain fields prevents the overlap of radial fields and reduces the side effects due to radiotherapy.

  20. Optimization of Soybean Press Cake Treatments and Processing

    Directory of Open Access Journals (Sweden)

    Dumitru Tucu

    2007-09-01

    Full Text Available This paper presents some results given by a systemic study of methods used in soybeans press cake treatment and processing. The influence of raw materials on soybean pressing system and the parameters of extrusion process are analyzed. Principally, the experiments confirm the influences of heat process parameters in case of soybean press cakes production using classic solutions and microwave energy. These experiments start up by manufacturing soybean press cake in industrial conditions at “S.C. International romoster srl” –Dudestii Vechi, Timis County. For ensuring the best conditions, the experimental stand included an extruder, a system for toasting the soybeans press cake, a system for parameters’ control and the system for ensuring the processing of water. The following possibilities were analyzed: (1 Soybeans press cake obtained by the classical method without toasting at pressure of extrusion p1 = 75 kgf cm-2 and flow Q1 = 800 kg h-1; (2 Soybeans press cake obtained at pressure of extrusion head p2 = 85 kgf cm-2 and flow Q2 = 600 kg h-1; (3 Soybeans press cake obtained at pressure of extrusion head p3 = 95 kgf cm-2 and fl ow Q3 = 300 kg h-1; Using this application we tested a new method for treatment and studied the special systems which can be applied in industrial practice at “S.C. International romoster srl” – Dudestii Vechi, Timis County. During the testings and researches the variation of electrical permeability was observed. Differences between theoretical equation and practical results in calculus and energy measurement in the workspace were noticed.

  1. Can Optimism, Pessimism, Hope, Treatment Credibility and Treatment Expectancy Be Distinguished in Patients Undergoing Total Hip and Total Knee Arthroplasty?

    Science.gov (United States)

    Haanstra, Tsjitske M; Tilbury, Claire; Kamper, Steven J; Tordoir, Rutger L; Vliet Vlieland, Thea P M; Nelissen, Rob G H H; Cuijpers, Pim; de Vet, Henrica C W; Dekker, Joost; Knol, Dirk L; Ostelo, Raymond W

    2015-01-01

    The constructs optimism, pessimism, hope, treatment credibility and treatment expectancy are associated with outcomes of medical treatment. While these constructs are grounded in different theoretical models, they nonetheless show some conceptual overlap. The purpose of this study was to examine whether currently available measurement instruments for these constructs capture the conceptual differences between these constructs within a treatment setting. Patients undergoing Total Hip and Total Knee Arthroplasty (THA and TKA) (Total N = 361; 182 THA; 179 TKA), completed the Life Orientation Test-Revised for optimism and pessimism, the Hope Scale, the Credibility Expectancy Questionnaire for treatment credibility and treatment expectancy. Confirmatory factor analysis was used to examine whether the instruments measure distinct constructs. Four theory-driven models with one, two, four and five latent factors were evaluated using multiple fit indices and Δχ2 tests, followed by some posthoc models. The results of the theory driven confirmatory factor analysis showed that a five factor model in which all constructs loaded on separate factors yielded the most optimal and satisfactory fit. Posthoc, a bifactor model in which (besides the 5 separate factors) a general factor is hypothesized accounting for the commonality of the items showed a significantly better fit than the five factor model. All specific factors, except for the hope factor, showed to explain a substantial amount of variance beyond the general factor. Based on our primary analyses we conclude that optimism, pessimism, hope, treatment credibility and treatment expectancy are distinguishable in THA and TKA patients. Postdoc, we determined that all constructs, except hope, showed substantial specific variance, while also sharing some general variance.

  2. IMRT treatment planning for prostate cancer using prioritized prescription optimization and mean-tail-dose functions

    OpenAIRE

    2008-01-01

    Treatment planning for intensity modulated radiation therapy (IMRT) is challenging due to both the size of the computational problems (thousands of variables and constraints) and the multi-objective, imprecise nature of the goals. We apply hierarchical programming to IMRT treatment planning. In this formulation, treatment planning goals/objectives are ordered in an absolute hierarchy, and the problem is solved from the top-down such that more important goals are optimized in turn. After each ...

  3. An integrated prediction and optimization model of biogas production system at a wastewater treatment facility.

    Science.gov (United States)

    Akbaş, Halil; Bilgen, Bilge; Turhan, Aykut Melih

    2015-11-01

    This study proposes an integrated prediction and optimization model by using multi-layer perceptron neural network and particle swarm optimization techniques. Three different objective functions are formulated. The first one is the maximization of methane percentage with single output. The second one is the maximization of biogas production with single output. The last one is the maximization of biogas quality and biogas production with two outputs. Methane percentage, carbon dioxide percentage, and other contents' percentage are used as the biogas quality criteria. Based on the formulated models and data from a wastewater treatment facility, optimal values of input variables and their corresponding maximum output values are found out for each model. It is expected that the application of the integrated prediction and optimization models increases the biogas production and biogas quality, and contributes to the quantity of electricity production at the wastewater treatment facility.

  4. Optimization of Treatment Policy for Acute Carbon Monoxide Poisoning

    Directory of Open Access Journals (Sweden)

    R. N. Akalayev

    2012-01-01

    Full Text Available Objective: to evaluate the efficiency of combination use of hyperbaric oxygenation, succinate-containing solutions, and anti-edematous agents in patients with acute carbon monoxide poisoning. Subjects and methods. The results of treatment were analyzed in 32 patients admitted in 2009—2011 for severe acute carbon monoxide poisoning and a Glasgow coma score of 6—8. The patients were divided into 2 groups: 1 patients whose combination therapy involved hyperbaric oxygenation, Succinasol infusions, and L-lysine-aescinate injections; 2 those who received traditional therapy. All the patients underwent complex clinical, laboratory, and neurophysiologic examinations. Results. Just 24 hours after the combination use of Succinasol and L-lysine-aescinate, Group I patients were observed to have substantially reduced lactate, the content of the latter approached the normal value following 48 hours, which was much below the values in the control group. The similar pattern was observed when endogenous intoxication parameters were examined. During the performed therapy, the level of consciousness and that of intellect according to the MMSE and FAB scales were restored more rapidly in the study group patients than in Group 2. Conclusion. The combination use of hyperbaric oxygenation, the succinate-containing solution Succinasol, and the anti-edematous agent L-lysine-aescinate considerably enhances the efficiency of intensive therapy for acute carbon monoxide poisoning. Key words: carbon monoxide, toxic hypoxic encephalopathy, combination therapy, hyperbaric oxygenation, succinic acid, L-lysine-aescinate.

  5. Speedup of lexicographic optimization by superiorization and its applications to cancer radiotherapy treatment

    Science.gov (United States)

    Bonacker, Esther; Gibali, Aviv; Küfer, Karl-Heinz; Süss, Philipp

    2017-04-01

    Multicriteria optimization problems occur in many real life applications, for example in cancer radiotherapy treatment and in particular in intensity modulated radiation therapy (IMRT). In this work we focus on optimization problems with multiple objectives that are ranked according to their importance. We solve these problems numerically by combining lexicographic optimization with our recently proposed level set scheme, which yields a sequence of auxiliary convex feasibility problems; solved here via projection methods. The projection enables us to combine the newly introduced superiorization methodology with multicriteria optimization methods to speed up computation while guaranteeing convergence of the optimization. We demonstrate our scheme with a simple 2D academic example (used in the literature) and also present results from calculations on four real head neck cases in IMRT (Radiation Oncology of the Ludwig-Maximilians University, Munich, Germany) for two different choices of superiorization parameter sets suited to yield fast convergence for each case individually or robust behavior for all four cases.

  6. Plasma drug activity assay for treatment optimization in tuberculosis patients.

    Science.gov (United States)

    Heysell, Scott K; Mtabho, Charles; Mpagama, Stellah; Mwaigwisya, Solomon; Pholwat, Suporn; Ndusilo, Norah; Gratz, Jean; Aarnoutse, Rob E; Kibiki, Gibson S; Houpt, Eric R

    2011-12-01

    Low antituberculosis (TB) drug levels are common, but their clinical significance remains unclear, and methods of measurement are resource intensive. Subjects initiating treatment for sputum smear-positive pulmonary TB were enrolled from Kibong'oto National TB Hospital, Tanzania, and levels of isoniazid, rifampin, ethambutol, and pyrazinamide were measured at the time of typical peak plasma concentration (C(2 h)). To evaluate the significance of the effect of observed drug levels on Mycobacterium tuberculosis growth, a plasma TB drug activity (TDA) assay was developed using the Bactec MGIT system. Time to detection of plasma-cocultured M. tuberculosis versus time to detection of control growth was defined as a TDA ratio. TDA assays were later performed using the subject's own M. tuberculosis isolate and C(2 h) plasma from the Tanzanian cohort and compared to drug levels and clinical outcomes. Sixteen subjects with a mean age of 37.8 years ± 10.7 were enrolled. Fourteen (88%) had C(2 h) rifampin levels and 11 (69%) had isoniazid levels below 90% of the lower limit of the expected range. Plasma spiked with various concentrations of antituberculosis medications found TDA assay results to be unaffected by ethambutol or pyrazinamide. Yet with a range of isoniazid and rifampin concentrations, TDA exhibited a statistically significant correlation with drug level and drug MIC, and a TDA of ~1.0 indicated the presence of multidrug-resistant TB. In Tanzania, low (≤ 2.0) TDA was significantly associated with both lower isoniazid and rifampin C(2 h) levels, and very low (≤ 1.5) TDA corresponded to a trend toward lack of cure. Study of TDA compared to additional clinical outcomes and as a therapeutic management tool is warranted.

  7. Pancreatic cancer: optimizing treatment options, new, and emerging targeted therapies.

    Science.gov (United States)

    Chiorean, Elena Gabriela; Coveler, Andrew L

    2015-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in the US and is expected to become the second leading cause of cancer-related deaths in the next decade. Despite 5-fluorouracil/leucovorin with irinotecan and oxaliplatin (FOLFIRINOX) and gemcitabine/nab-paclitaxel significantly improving outcomes for metastatic cancer, refractory disease still poses significant challenges. Difficulties with early detection and the inherent chemo- and radio-resistant nature of this malignancy led to attempts to define the sequential biology of pancreatic cancer in order to improve survival outcomes. Pancreatic adenocarcinoma is characterized by several germline or acquired genetic mutations, the most common being KRAS (90%), CDK2NA (90%), TP53 (75%-90%), DPC4/SMAD4 (50%). In addition, the tumor microenvironment, chemoresistant cancer stem cells, and the desmoplastic stroma have been the target of some promising clinical investigations. Among the core pathways reproducibly shown to lead the development and progression of this disease, DNA repair, apoptosis, G1/S cell cycle transition, KRAS, Wnt, Notch, Hedgehog, TGF-beta, and other cell invasion pathways, have been the target of "precision therapeutics". No single molecularly targeted therapeutic though has been uniformly successful, probably due to the tumor heterogeneity, but biomarker research is evolving and it hopes to select more patients likely to benefit. Recent reports note activity with immunotherapies such as CD40 agonists, CCR2 inhibitors, cancer vaccines, and novel combinations against the immunosuppressive tumor milieu are ongoing. While many obstacles still exist, clearly we are making progress in deciphering the heterogeneity within pancreatic cancers. Integrating conventional and immunological targeting will be the key to effective treatment of this deadly disease.

  8. Pancreatic cancer: optimizing treatment options, new, and emerging targeted therapies

    Directory of Open Access Journals (Sweden)

    Chiorean EG

    2015-07-01

    Full Text Available Elena Gabriela Chiorean, Andrew L Coveler Department of Medicine, Division of Oncology, University of Washington, Seattle, WA, USA Abstract: Pancreatic cancer is the fourth leading cause of cancer death in the US and is expected to become the second leading cause of cancer-related deaths in the next decade. Despite 5-fluorouracil/leucovorin with irinotecan and oxaliplatin (FOLFIRINOX and gemcitabine/nab-paclitaxel significantly improving outcomes for metastatic cancer, refractory disease still poses significant challenges. Difficulties with early detection and the inherent chemo- and radio-resistant nature of this malignancy led to attempts to define the sequential biology of pancreatic cancer in order to improve survival outcomes. Pancreatic adenocarcinoma is characterized by several germline or acquired genetic mutations, the most common being KRAS (90%, CDK2NA (90%, TP53 (75%–90%, DPC4/SMAD4 (50%. In addition, the tumor microenvironment, chemoresistant cancer stem cells, and the desmoplastic stroma have been the target of some promising clinical investigations. Among the core pathways reproducibly shown to lead the development and progression of this disease, DNA repair, apoptosis, G1/S cell cycle transition, KRAS, Wnt, Notch, Hedgehog, TGF-beta, and other cell invasion pathways, have been the target of “precision therapeutics”. No single molecularly targeted therapeutic though has been uniformly successful, probably due to the tumor heterogeneity, but biomarker research is evolving and it hopes to select more patients likely to benefit. Recent reports note activity with immunotherapies such as CD40 agonists, CCR2 inhibitors, cancer vaccines, and novel combinations against the immunosuppressive tumor milieu are ongoing. While many obstacles still exist, clearly we are making progress in deciphering the heterogeneity within pancreatic cancers. Integrating conventional and immunological targeting will be the key to effective treatment of

  9. Optimal strategy for controlling the spread of Plasmodium Knowlesi malaria: Treatment and culling

    Science.gov (United States)

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

    2015-05-01

    Plasmodium Knowlesi malaria is a parasitic mosquito-borne disease caused by a eukaryotic protist of genus Plasmodium Knowlesi transmitted by mosquito, Anopheles leucosphyrus to human and macaques. We developed and analyzed a deterministic Mathematical model for the transmission of Plasmodium Knowlesi malaria in human and macaques. The optimal control theory is applied to investigate optimal strategies for controlling the spread of Plasmodium Knowlesi malaria using treatment and culling as control strategies. The conditions for optimal control of the Plasmodium Knowlesi malaria are derived using Pontryagin's Maximum Principle. Finally, numerical simulations suggested that the combination of the control strategies is the best way to control the disease in any community.

  10. Optimizing rTMS treatment of a balance disorder with EEG neural synchrony and functional connectivity.

    Science.gov (United States)

    Guofa Shou; Han Yuan; Urbano, Diamond; Yoon-Hee Cha; Lei Ding

    2016-08-01

    Repetitive transcranial magnetic stimulation (rTMS) has been increasingly used for its potential treatment effects across diverse mental disorders. However, the treatment effect is elusive and the rate of positive responders is not high, which make it in great demand of optimizing rTMS protocols to improve the treatment effects and the rate. In this regard, neural activity guided optimization has indicated great potential in several neuroimaging studies. In this paper, we present our ongoing work on optimizing rTMS treatment of a balance disorder, i.e., Mal de Debarquement syndrome (MdDS), by investigating treatment-related EEG neural synchrony and functional connectivity changes. Motivated by our previous pilot study of rTMS on MdDS, we firstly applied a bilateral dorsolateral prefrontal cortex (DLPFC) rTMS protocol to evaluate its efficacy and the treatment-related neural responses via an independent component analysis (ICA)-based framework. Thereafter, guided by identified EEG neural synchrony and functional connectivity patterns, we proposed three potential stimulation targets covering posterior nodes of the default mode network (DMN), and implemented a new rTMS protocol by stimulating the target with the great symptoms relief. The preliminary clinical response data has indicated that the new rTMS protocol significantly increase the rate of positive responders and the degrees of the improvement. The present study demonstrates that it is promising to integrate EEG neural synchrony and functional connectivity into the optimization of rTMS protocols for different mental disorders.

  11. Topology Optimization for Minimizing the Resonant Response of Plates with Constrained Layer Damping Treatment

    Directory of Open Access Journals (Sweden)

    Zhanpeng Fang

    2015-01-01

    Full Text Available A topology optimization method is proposed to minimize the resonant response of plates with constrained layer damping (CLD treatment under specified broadband harmonic excitations. The topology optimization problem is formulated and the square of displacement resonant response in frequency domain at the specified point is considered as the objective function. Two sensitivity analysis methods are investigated and discussed. The derivative of modal damp ratio is not considered in the conventional sensitivity analysis method. An improved sensitivity analysis method considering the derivative of modal damp ratio is developed to improve the computational accuracy of the sensitivity. The evolutionary structural optimization (ESO method is used to search the optimal layout of CLD material on plates. Numerical examples and experimental results show that the optimal layout of CLD treatment on the plate from the proposed topology optimization using the conventional sensitivity analysis or the improved sensitivity analysis can reduce the displacement resonant response. However, the optimization method using the improved sensitivity analysis can produce a higher modal damping ratio than that using the conventional sensitivity analysis and develop a smaller displacement resonant response.

  12. Opioids for cancer pain: the challenge of optimizing treatment.

    Science.gov (United States)

    Plante, Gérard E; VanItallie, Theodore B

    2010-10-01

    During 2007, 11.7 million US men and women of all ages suffered from some form of invasive cancer. During their illness, at least 70% (8.2 million) will experience pain sufficiently severe to require chronic opioid treatment. Cancer-induced pain is usually described under 3 headings: acute pain, chronic pain, and breakthrough pain. Among patients with chronic, persistent cancer pain controlled by around-the-clock analgesics, there is a high prevalence of breakthrough pain-often precipitated by some form of physical activity. Breakthrough pain seems best treated by a powerful, fast-acting opioid such as intravenous morphine or transmucosal fentanyl. At present, opioids are virtually the only analgesics capable of controlling moderate and severe cancer pain. In recent years, a veritable arsenal of opioids with a wide range of pharmacologic properties has become available for use in different pain situations. The World Health Organization has developed a 3-step "analgesic ladder" to guide management of cancer pain, based on the pain's severity, estimated by means of a 1 to 10 numeric rating scale. As the severity of the pain escalates, more potent (World Health Organization Step III) opioids are used. When faced with a difficult case of cancer pain, the physician must choose-from an array of options-the safest and most effective opioid analgesic and the most appropriate delivery system. Such decisions require an adequate understanding of the available opioids and experience with their use. The pharmacodynamic response to a given opioid depends on the nature of the receptor to which the opioid binds and its affinity for the receptor. Morphine activates the μ-opioid receptors, resulting in not only analgesia and sedation, but also euphoria, respiratory depression, constipation, and pruritus. The existence of a number of opioid receptor subtypes, each with its own repertoire of responses, has given rise to the hope (as yet unrealized) that an opioid can be found (or

  13. Vaccination and treatment as control interventions in an infectious disease model with their cost optimization

    Science.gov (United States)

    Kumar, Anuj; Srivastava, Prashant K.

    2017-03-01

    In this work, an optimal control problem with vaccination and treatment as control policies is proposed and analysed for an SVIR model. We choose vaccination and treatment as control policies because both these interventions have their own practical advantage and ease in implementation. Also, they are widely applied to control or curtail a disease. The corresponding total cost incurred is considered as weighted combination of costs because of opportunity loss due to infected individuals and costs incurred in providing vaccination and treatment. The existence of optimal control paths for the problem is established and guaranteed. Further, these optimal paths are obtained analytically using Pontryagin's Maximum Principle. We analyse our results numerically to compare three important strategies of proposed controls, viz.: vaccination only; with both treatment and vaccination; and treatment only. We note that first strategy (vaccination only) is less effective as well as expensive. Though, for a highly effective vaccine, vaccination alone may also work well in comparison with treatment only strategy. Among all the strategies, we observe that implementation of both treatment and vaccination is most effective and less expensive. Moreover, in this case the infective population is found to be relatively very low. Thus, we conclude that the comprehensive effect of vaccination and treatment not only minimizes cost burden due to opportunity loss and applied control policies but also keeps a tab on infective population.

  14. Optimism

    Science.gov (United States)

    Carver, Charles S.; Scheier, Michael F.; Segerstrom, Suzanne C.

    2010-01-01

    Optimism is an individual difference variable that reflects the extent to which people hold generalized favorable expectancies for their future. Higher levels of optimism have been related prospectively to better subjective well-being in times of adversity or difficulty (i.e., controlling for previous well-being). Consistent with such findings, optimism has been linked to higher levels of engagement coping and lower levels of avoidance, or disengagement, coping. There is evidence that optimism is associated with taking proactive steps to protect one's health, whereas pessimism is associated with health-damaging behaviors. Consistent with such findings, optimism is also related to indicators of better physical health. The energetic, task-focused approach that optimists take to goals also relates to benefits in the socioeconomic world. Some evidence suggests that optimism relates to more persistence in educational efforts and to higher later income. Optimists also appear to fare better than pessimists in relationships. Although there are instances in which optimism fails to convey an advantage, and instances in which it may convey a disadvantage, those instances are relatively rare. In sum, the behavioral patterns of optimists appear to provide models of living for others to learn from. PMID:20170998

  15. Bone marrow mesenchymal stem cell therapy in ischemic stroke: mechanisms of action and treatment optimization strategies

    Directory of Open Access Journals (Sweden)

    Guihong Li

    2016-01-01

    Full Text Available Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research.

  16. Optimization

    CERN Document Server

    Pearce, Charles

    2009-01-01

    Focuses on mathematical structure, and on real-world applications. This book includes developments in several optimization-related topics such as decision theory, linear programming, turnpike theory, duality theory, convex analysis, and queuing theory.

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

    Science.gov (United States)

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

    2017-06-01

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

  18. Sufficient conditions for optimality for a mathematical model of drug treatment with pharmacodynamics

    Directory of Open Access Journals (Sweden)

    Maciej Leszczyński

    2017-01-01

    Full Text Available We consider an optimal control problem for a general mathematical model of drug treatment with a single agent. The control represents the concentration of the agent and its effect (pharmacodynamics is modelled by a Hill function (i.e., Michaelis-Menten type kinetics. The aim is to minimize a cost functional consisting of a weighted average related to the state of the system (both at the end and during a fixed therapy horizon and to the total amount of drugs given. The latter is an indirect measure for the side effects of treatment. It is shown that optimal controls are continuous functions of time that change between full or no dose segments with connecting pieces that take values in the interior of the control set. Sufficient conditions for the strong local optimality of an extremal controlled trajectory in terms of the existence of a solution to a piecewise defined Riccati differential equation are given.

  19. Reducing the public health risk of cryptosporidiosis by optimizing treatment processes at a military water system.

    Science.gov (United States)

    Clarke, Steven H

    2011-01-01

    Safe drinking water supplies are critical to public health and mission success. One of the primary goals of water treatment is to effectively reduce the acute health risks posed by pathogenic microorganisms present in our raw, untreated water supplies. As a result of recent drinking water regulations, a military water system identified significant levels of Cryptosporidium in their raw water supply requiring additional or improved treatment to remove. Cryptosporidium, the pathogenic microorganism that causes Cryptosporidiosis, has been indicated in numerous waterborne outbreaks worldwide, including the United States. The US Army Public Health Command conducted a year-long study evaluating the ability of the water system to provide improved treatment by optimizing the existing treatment processes. Study results show that optimizing existing treatment processes and switching to an alternative coagulant chemical will achieve the Cryptosporidium removal required to comply with drinking water regulations, with subsequent reduction in the risk of Cryptosporidiosis. These improvements will also ensure effective treatment in all raw water quality conditions and reduce overall chemical costs without increasing operational and maintenance burdens. The optimization evaluation and techniques used for this water system can be applied to all military-owned water systems to help ensure the protection of public health and mission success.

  20. Optimization-based methodology for wastewater treatment plant synthesis – a full scale retrofitting case study

    DEFF Research Database (Denmark)

    Bozkurt, Hande; Gernaey, Krist; Sin, Gürkan

    2015-01-01

    technologies. The superstructure optimization problem is formulated as a Mixed Integer (non)Linear Programming problem and solved for different scenarios - represented by different objective functions and constraint definitions. A full-scale domestic wastewater treatment plant (265,000 PE) is used as a case...

  1. Developing optimal search strategies for detecting clinically sound treatment studies in EMBASE*

    OpenAIRE

    Wong, Sharon S.-L.; Wilczynski, Nancy L; Haynes, R Brian

    2006-01-01

    Objective: The ability to accurately identify articles about therapy in large bibliographic databases such as EMBASE is important for researchers and clinicians. Our study aimed to develop optimal search strategies for detecting sound treatment studies in EMBASE in the year 2000.

  2. Fast thermal simulations and temperature optimization for hyperthermia treatment planning, including realistic 3D vessel networks.

    Science.gov (United States)

    Kok, H P; van den Berg, C A T; Bel, A; Crezee, J

    2013-10-01

    Accurate thermal simulations in hyperthermia treatment planning require discrete modeling of large blood vessels. The very long computation time of the finite difference based DIscrete VAsculature model (DIVA) developed for this purpose is impractical for clinical applications. In this work, a fast steady-state thermal solver was developed for simulations with realistic 3D vessel networks. Additionally, an efficient temperature-based optimization method including the thermal effect of discrete vasculature was developed. The steady-state energy balance for vasculature and tissue was described by a linear system, which was solved with an iterative method on the graphical processing unit. Temperature calculations during optimization were performed by superposition of several precomputed temperature distributions, calculated with the developed thermal solver. The thermal solver and optimization were applied to a human anatomy, with the prostate being the target region, heated with the eight waveguide 70 MHz AMC-8 system. Realistic 3D pelvic vasculature was obtained from angiography. Both the arterial and venous vessel networks consisted of 174 segments and 93 endpoints with a diameter of 1.2 mm. Calculation of the steady-state temperature distribution lasted about 3.3 h with the original DIVA model, while the newly developed method took only ≈ 1-1.5 min. Temperature-based optimization with and without taking the vasculature into account showed differences in optimized waveguide power of more than a factor 2 and optimized tumor T90 differed up to ≈ 0.5°C. This shows the necessity to take discrete vasculature into account during optimization. A very fast method was developed for thermal simulations with realistic 3D vessel networks. The short simulation time allows online calculations and makes temperature optimization with realistic vasculature feasible, which is an important step forward in hyperthermia treatment planning.

  3. Novel tools for stepping source brachytherapy treatment planning: Enhanced geometrical optimization and interactive inverse planning

    Energy Technology Data Exchange (ETDEWEB)

    Dinkla, Anna M., E-mail: a.m.dinkla@amc.uva.nl; Laarse, Rob van der; Koedooder, Kees; Petra Kok, H.; Wieringen, Niek van; Pieters, Bradley R.; Bel, Arjan [Department of Radiation Oncology, Academic Medical Center Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ (Netherlands)

    2015-01-15

    Purpose: Dose optimization for stepping source brachytherapy can nowadays be performed using automated inverse algorithms. Although much quicker than graphical optimization, an experienced treatment planner is required for both methods. With automated inverse algorithms, the procedure to achieve the desired dose distribution is often based on trial-and-error. Methods: A new approach for stepping source prostate brachytherapy treatment planning was developed as a quick and user-friendly alternative. This approach consists of the combined use of two novel tools: Enhanced geometrical optimization (EGO) and interactive inverse planning (IIP). EGO is an extended version of the common geometrical optimization method and is applied to create a dose distribution as homogeneous as possible. With the second tool, IIP, this dose distribution is tailored to a specific patient anatomy by interactively changing the highest and lowest dose on the contours. Results: The combined use of EGO–IIP was evaluated on 24 prostate cancer patients, by having an inexperienced user create treatment plans, compliant to clinical dose objectives. This user was able to create dose plans of 24 patients in an average time of 4.4 min/patient. An experienced treatment planner without extensive training in EGO–IIP also created 24 plans. The resulting dose-volume histogram parameters were comparable to the clinical plans and showed high conformance to clinical standards. Conclusions: Even for an inexperienced user, treatment planning with EGO–IIP for stepping source prostate brachytherapy is feasible as an alternative to current optimization algorithms, offering speed, simplicity for the user, and local control of the dose levels.

  4. Risk preferences: consequences for test and treatment thresholds and optimal cutoffs.

    Science.gov (United States)

    Felder, Stefan; Mayrhofer, Thomas

    2014-01-01

    Risk attitudes include risk aversion as well as higher-order risk preferences such as prudence and temperance. This article analyzes the effects of such preferences on medical test and treatment decisions, represented either by test and treatment thresholds or-when the test result is not given-by optimal cutoff values for diagnostic tests. For a risk-averse decision maker, effective treatment is a risk-reducing strategy since it prevents the low health outcome of forgoing treatment in the sick state. Compared with risk neutrality, risk aversion thus lowers both the test and the treatment threshold and decreases the optimal test cutoff value. Risk vulnerability, which combines risk aversion, prudence, and temperance, is relevant if there is a comorbidity risk: thresholds and optimal cutoff values decrease even more. Since common utility functions imply risk vulnerability, our findings suggest that diagnostics in low prevalence settings (e.g., screening) may be considered more beneficial when risk preferences are taken into account.

  5. Optimal Subdivision for Treatment and Management of Catastrophic Landslides in a Watershed Using Topographic Factors

    Science.gov (United States)

    Lin, Chao-Yuan; Fu, Kuei-Lin; Lin, Cheng-Yu

    2016-11-01

    Recent extreme rainfall events led to many landslides due to climate changes in Taiwan. How to effectively promote post-disaster treatment and/or management works in a watershed/drainage basin is a crucial issue. Regarding the processes of watershed treatment and/or management works, disaster hotspot scanning and treatment priority setup should be carried out in advance. A scanning method using landslide ratio to determine the appropriate outlet of an interested watershed, and an optimal subdivision system with better homogeneity and accuracy in landslide ratio estimation were developed to help efficient executions of treatment and/or management works. Topography is a key factor affecting watershed landslide ratio. Considering the complexity and uncertainty of the natural phenomenon, multivariate analysis was applied to understand the relationship between topographic factors and landslide ratio in the interested watershed. The concept of species-area curve, which is usually adopted at on-site vegetation investigation to determinate the suitable quadrate size, was used to derive the optimal threshold in subdivisions. Results show that three main component axes including factors of scale, network and shape extracted from Digital Terrain Model coupled with areas of landslide can effectively explain the characteristics of landslide ratio in the interested watershed, and a relation curve obtained from the accuracy of landslide ratio classification and number of subdivisions could be established to derive optimal subdivision of the watershed. The subdivision method promoted in this study could be further used for priority rank and benefit assessment of landslide treatment in a watershed.

  6. Optimization-based methodology for wastewater treatment plant synthesis – a full scale retrofitting case study

    DEFF Research Database (Denmark)

    Bozkurt, Hande; Gernaey, Krist; Sin, Gürkan

    2015-01-01

    technologies. The superstructure optimization problem is formulated as a Mixed Integer (non)Linear Programming problem and solved for different scenarios - represented by different objective functions and constraint definitions. A full-scale domestic wastewater treatment plant (265,000 PE) is used as a case...... framework to manage the multi-criteria WWTP design/retrofit problem for domestic wastewater treatment. The design space (i.e. alternative treatment technologies) is represented in a superstructure, which is coupled with a database containing data for both performance and economics of the novel alternative...

  7. Heat treatment process optimization for face gearsbased on deformation and residual stress control

    Institute of Scientific and Technical Information of China (English)

    WANG Yan-zhong; LAN Zhou‡; HOU Liang-wei; ZHAO Hong-pu; ZHONG Yang

    2015-01-01

    In this paper, based on the principle of heat transfer and thermal elastic-plastic theory, the heat treatment process optimization scheme for face gearsis proposed according to the structural characteristics oftheface gear and material properties of 12Cr2Ni4 steel.To simulate the effect of carburizing and quenching process on tooth deformation and residual stress distribution,aheat treatment analysis model of face gearsis established, and the microstructure, stress and deformation of face gear teeth changing with time are analyzed. The simulation results show that face gear tooth hardness increases, tooth surface residual compressive stress increases and tooth deformation decreases after heat treatment process optimization.It is beneficialto improvingthe fatigue strength and performance of face gears.

  8. Patient specific optimization-based treatment planning for catheter-based ultrasound hyperthermia and thermal ablation

    Science.gov (United States)

    Prakash, Punit; Chen, Xin; Wootton, Jeffery; Pouliot, Jean; Hsu, I.-Chow; Diederich, Chris J.

    2009-02-01

    A 3D optimization-based thermal treatment planning platform has been developed for the application of catheter-based ultrasound hyperthermia in conjunction with high dose rate (HDR) brachytherapy for treating advanced pelvic tumors. Optimal selection of applied power levels to each independently controlled transducer segment can be used to conform and maximize therapeutic heating and thermal dose coverage to the target region, providing significant advantages over current hyperthermia technology and improving treatment response. Critical anatomic structures, clinical target outlines, and implant/applicator geometries were acquired from sequential multi-slice 2D images obtained from HDR treatment planning and used to reconstruct patient specific 3D biothermal models. A constrained optimization algorithm was devised and integrated within a finite element thermal solver to determine a priori the optimal applied power levels and the resulting 3D temperature distributions such that therapeutic heating is maximized within the target, while placing constraints on maximum tissue temperature and thermal exposure of surrounding non-targeted tissue. This optimizationbased treatment planning and modeling system was applied on representative cases of clinical implants for HDR treatment of cervix and prostate to evaluate the utility of this planning approach. The planning provided significant improvement in achievable temperature distributions for all cases, with substantial increase in T90 and thermal dose (CEM43T90) coverage to the hyperthermia target volume while decreasing maximum treatment temperature and reducing thermal dose exposure to surrounding non-targeted tissues and thermally sensitive rectum and bladder. This optimization based treatment planning platform with catheter-based ultrasound applicators is a useful tool that has potential to significantly improve the delivery of hyperthermia in conjunction with HDR brachytherapy. The planning platform has been extended

  9. Multi-point optimization of recirculation flow type casing treatment in centrifugal compressors

    Science.gov (United States)

    Tun, Min Thaw; Sakaguchi, Daisaku

    2016-06-01

    High-pressure ratio and wide operating range are highly required for a turbocharger in diesel engines. A recirculation flow type casing treatment is effective for flow range enhancement of centrifugal compressors. Two ring grooves on a suction pipe and a shroud casing wall are connected by means of an annular passage and stable recirculation flow is formed at small flow rates from the downstream groove toward the upstream groove through the annular bypass. The shape of baseline recirculation flow type casing is modified and optimized by using a multi-point optimization code with a metamodel assisted evolutionary algorithm embedding a commercial CFD code CFX from ANSYS. The numerical optimization results give the optimized design of casing with improving adiabatic efficiency in wide operating flow rate range. Sensitivity analysis of design parameters as a function of efficiency has been performed. It is found that the optimized casing design provides optimized recirculation flow rate, in which an increment of entropy rise is minimized at grooves and passages of the rotating impeller.

  10. Functional Recovery in Major Depressive Disorder: Focus on Early Optimized Treatment.

    Science.gov (United States)

    Habert, Jeffrey; Katzman, Martin A; Oluboka, Oloruntoba J; McIntyre, Roger S; McIntosh, Diane; MacQueen, Glenda M; Khullar, Atul; Milev, Roumen V; Kjernisted, Kevin D; Chokka, Pratap R; Kennedy, Sidney H

    2016-09-01

    This article presents the case that a more rapid, individualized approach to treating major depressive disorder (MDD) may increase the likelihood of achieving full symptomatic and functional recovery for individual patients and that studies show it is possible to make earlier decisions about appropriateness of treatment in order to rapidly optimize that treatment. A PubMed search was conducted using terms including major depressive disorder, early improvement, predictor, duration of untreated illness, and function. English-language articles published before September 2015 were included. Additional studies were found within identified research articles and reviews. Thirty antidepressant studies reporting predictor criteria and outcome measures are included in this review. Studies were reviewed to extract definitions of predictors, outcome measures, and results of the predictor analysis. Results were summarized separately for studies reporting effects of early improvement, baseline characteristics, and duration of untreated depression. Shorter duration of the current depressive episode and duration of untreated depression are associated with better symptomatic and functional outcomes in MDD. Early improvement of depressive symptoms predicts positive symptomatic outcomes (response and remission), and early functional improvement predicts an increased likelihood of functional remission. The approach to treatment of depression that exhibits the greatest potential for achieving full symptomatic and functional recovery is early optimized treatment: early diagnosis followed by rapid individualized treatment. Monitoring symptoms and function early in treatment is crucial to ensuring that patients do not remain on ineffective or poorly tolerated treatment, which may delay recovery and heighten the risk of residual functional deficits.

  11. Determining a sustainable and economically optimal wastewater treatment and discharge strategy.

    Science.gov (United States)

    Hardisty, Paul E; Sivapalan, Mayuran; Humphries, Robert

    2013-01-15

    Options for treatment and discharge of wastewater in regional Western Australia (WA) are examined from the perspective of overall sustainability and social net benefit. Current practice in the state has typically involved a basic standard of treatment deemed to be protective of human health, followed by discharge to surface water bodies. Community and regulatory pressure to move to higher standards of treatment is based on the presumption that a higher standard of treatment is more protective of the environment and society, and thus is more sustainable. This analysis tests that hypothesis for Western Australian conditions. The merits of various wastewater treatment and discharge strategies are examined by quantifying financial costs (capital and operations), and by monetising the wider environmental and social costs and benefits of each option over an expanded planning horizon (30 years). Six technical treatment-disposal options were assessed at a test site, all of which met the fundamental criterion of protecting human health. From a financial perspective, the current business-as-usual option is preferred - it is the least cost solution. However, valuing externalities such as water, greenhouse gases, ecological impacts and community amenity, the status quo is revealed as sub-optimal. Advanced secondary treatment with stream disposal improves water quality and provides overall net benefit to society. All of the other options were net present value (NPV) negative. Sensitivity analysis shows that the favoured option outperforms all of the others under a wide range of financial and externality values and assumptions. Expanding the findings across the state reveals that moving from the identified socially optimal level of treatment to higher (tertiary) levels of treatment would result in a net loss to society equivalent to several hundred million dollars. In other words, everyone benefits from improving treatment to the optimum point. But society, the environment, and

  12. A comparison of inverse optimization algorithms for HDR/PDR prostate brachytherapy treatment planning.

    Science.gov (United States)

    Dinkla, Anna M; van der Laarse, Rob; Kaljouw, Emmie; Pieters, Bradley R; Koedooder, Kees; van Wieringen, Niek; Bel, Arjan

    2015-01-01

    Graphical optimization (GrO) is a common method for high-dose-rate/pulsed-dose-rate (PDR) prostate brachytherapy treatment planning. New methods performing inverse optimization of the dose distribution have been developed over the past years. The purpose is to compare GrO and two established inverse methods, inverse planning simulated annealing (IPSA) and hybrid inverse treatment planning and optimization (HIPO), and one new method, enhanced geometric optimization-interactive inverse planning (EGO-IIP), in terms of speed and dose-volume histogram (DVH) parameters. For 26 prostate cancer patients treated with a PDR brachytherapy boost, an experienced treatment planner optimized the dose distributions using four different methods: GrO, IPSA, HIPO, and EGO-IIP. Relevant DVH parameters (prostate-V100%, D90%, V150%; urethra-D(0.1cm3) and D(1.0cm3); rectum-D(0.1cm3) and D(2.0cm3); bladder-D(2.0cm3)) were evaluated and their compliance to the constraints. Treatment planning time was also recorded. All inverse methods resulted in shorter planning time (mean, 4-6.7 min), as compared with GrO (mean, 7.6 min). In terms of DVH parameters, none of the inverse methods outperformed the others. However, all inverse methods improved on compliance to the planning constraints as compared with GrO. On average, EGO-IIP and GrO resulted in highest D90%, and the IPSA plans resulted in lowest bladder D2.0cm3 and urethra D(1.0cm3). Inverse planning methods decrease planning time as compared with GrO for PDR/high-dose-rate prostate brachytherapy. DVH parameters are comparable for all methods. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  13. An exact approach to direct aperture optimization in IMRT treatment planning

    Energy Technology Data Exchange (ETDEWEB)

    Men Chunhua [Department of Industrial and Systems Engineering, University of Florida, Gainesville, Florida 32611-6595 (United States); Romeijn, H Edwin [Department of Industrial and Systems Engineering, University of Florida, Gainesville, Florida 32611-6595 (United States); Taskin, Z Caner [Department of Industrial and Systems Engineering, University of Florida, Gainesville, Florida 32611-6595 (United States); Dempsey, James F [Department of Radiation Oncology, University of Florida, Gainesville, Florida 32610-0385 (United States)

    2007-12-21

    We consider the problem of intensity-modulated radiation therapy (IMRT) treatment planning using direct aperture optimization. While this problem has been relatively well studied in recent years, most approaches employ a heuristic approach to the generation of apertures. In contrast, we use an exact approach that explicitly formulates the fluence map optimization (FMO) problem as a convex optimization problem in terms of all multileaf collimator (MLC) deliverable apertures and their associated intensities. However, the number of deliverable apertures, and therefore the number of decision variables and constraints in the new problem formulation, is typically enormous. To overcome this, we use an iterative approach that employs a subproblem whose optimal solution either provides a suitable aperture to add to a given pool of allowable apertures or concludes that the current solution is optimal. We are able to handle standard consecutiveness, interdigitation and connectedness constraints that may be imposed by the particular MLC system used, as well as jaws-only delivery. Our approach has the additional advantage that it can explicitly account for transmission of dose through the part of an aperture that is blocked by the MLC system, yielding a more precise assessment of the treatment plan than what is possible using a traditional beamlet-based FMO problem. Finally, we develop and test two stopping rules that can be used to identify treatment plans of high clinical quality that are deliverable very efficiently. Tests on clinical head-and-neck cancer cases showed the efficacy of our approach, yielding treatment plans comparable in quality to plans obtained by the traditional method with a reduction of more than 75% in the number of apertures and a reduction of more than 50% in beam-on time, with only a modest increase in computational effort. The results also show that delivery efficiency is very insensitive to the addition of traditional MLC constraints; however, jaws

  14. Treatment planning, optimization, and beam delivery technqiues for intensity modulated proton therapy

    Science.gov (United States)

    Sengbusch, Evan R.

    Physical properties of proton interactions in matter give them a theoretical advantage over photons in radiation therapy for cancer treatment, but they are seldom used relative to photons. The primary barriers to wider acceptance of proton therapy are the technical feasibility, size, and price of proton therapy systems. Several aspects of the proton therapy landscape are investigated, and new techniques for treatment planning, optimization, and beam delivery are presented. The results of these investigations suggest a means by which proton therapy can be delivered more efficiently, effectively, and to a much larger proportion of eligible patients. An analysis of the existing proton therapy market was performed. Personal interviews with over 30 radiation oncology leaders were conducted with regard to the current and future use of proton therapy. In addition, global proton therapy market projections are presented. The results of these investigations serve as motivation and guidance for the subsequent development of treatment system designs and treatment planning, optimization, and beam delivery methods. A major factor impacting the size and cost of proton treatment systems is the maximum energy of the accelerator. Historically, 250 MeV has been the accepted value, but there is minimal quantitative evidence in the literature that supports this standard. A retrospective study of 100 patients is presented that quantifies the maximum proton kinetic energy requirements for cancer treatment, and the impact of those results with regard to treatment system size, cost, and neutron production is discussed. This study is subsequently expanded to include 100 cranial stereotactic radiosurgery (SRS) patients, and the results are discussed in the context of a proposed dedicated proton SRS treatment system. Finally, novel proton therapy optimization and delivery techniques are presented. Algorithms are developed that optimize treatment plans over beam angle, spot size, spot spacing

  15. A treatment planning code for inverse planning and 3D optimization in hadrontherapy.

    Science.gov (United States)

    Bourhaleb, F; Marchetto, F; Attili, A; Pittà, G; Cirio, R; Donetti, M; Giordanengo, S; Givehchi, N; Iliescu, S; Krengli, M; La Rosa, A; Massai, D; Pecka, A; Pardo, J; Peroni, C

    2008-09-01

    The therapeutic use of protons and ions, especially carbon ions, is a new technique and a challenge to conform the dose to the target due to the energy deposition characteristics of hadron beams. An appropriate treatment planning system (TPS) is strictly necessary to take full advantage. We developed a TPS software, ANCOD++, for the evaluation of the optimal conformal dose. ANCOD++ is an analytical code using the voxel-scan technique as an active method to deliver the dose to the patient, and provides treatment plans with both proton and carbon ion beams. The iterative algorithm, coded in C++ and running on Unix/Linux platform, allows the determination of the best fluences of the individual beams to obtain an optimal physical dose distribution, delivering a maximum dose to the target volume and a minimum dose to critical structures. The TPS is supported by Monte Carlo simulations with the package GEANT3 to provide the necessary physical lookup tables and verify the optimized treatment plans. Dose verifications done by means of full Monte Carlo simulations show an overall good agreement with the treatment planning calculations. We stress the fact that the purpose of this work is the verification of the physical dose and a next work will be dedicated to the radiobiological evaluation of the equivalent biological dose.

  16. Dynamic analysis and optimal control for a model of hepatitis C with treatment

    Science.gov (United States)

    Zhang, Suxia; Xu, Xiaxia

    2017-05-01

    A model for hepatitis C is formulated to study the effects of treatment and public concern on HCV transmission dynamics. The stability of equilibria and persistence of the model are analyzed, and an optimal control measure is performed to prevent the spread of HCV with minimal infected individuals and cost. The dynamical analysis reveals that the disease-free equilibrium of the model is asymptotically stable if the basic reproductive number R0 is less than unity. On the other hand, if R0 > 1 , the disease is uniformly persistent. Numerical simulations are conducted to investigate the influence of different vital parameters on R0. For the corresponding optimality system, the optimal solution is discussed by Pontryagin Maximum Principle, and the comparisons of model-predicted consequences with control or not are presented.

  17. MO-B-BRB-01: Optimize Treatment Planning Process in Clinical Environment

    Energy Technology Data Exchange (ETDEWEB)

    Feng, W. [New York Presbyterian Hospital (United States)

    2015-06-15

    The radiotherapy treatment planning process has evolved over the years with innovations in treatment planning, treatment delivery and imaging systems. Treatment modality and simulation technologies are also rapidly improving and affecting the planning process. For example, Image-guided-radiation-therapy has been widely adopted for patient setup, leading to margin reduction and isocenter repositioning after simulation. Stereotactic Body radiation therapy (SBRT) and Radiosurgery (SRS) have gradually become the standard of care for many treatment sites, which demand a higher throughput for the treatment plans even if the number of treatments per day remains the same. Finally, simulation, planning and treatment are traditionally sequential events. However, with emerging adaptive radiotherapy, they are becoming more tightly intertwined, leading to iterative processes. Enhanced efficiency of planning is therefore becoming more critical and poses serious challenge to the treatment planning process; Lean Six Sigma approaches are being utilized increasingly to balance the competing needs for speed and quality. In this symposium we will discuss the treatment planning process and illustrate effective techniques for managing workflow. Topics will include: Planning techniques: (a) beam placement, (b) dose optimization, (c) plan evaluation (d) export to RVS. Planning workflow: (a) import images, (b) Image fusion, (c) contouring, (d) plan approval (e) plan check (f) chart check, (g) sequential and iterative process Influence of upstream and downstream operations: (a) simulation, (b) immobilization, (c) motion management, (d) QA, (e) IGRT, (f) Treatment delivery, (g) SBRT/SRS (h) adaptive planning Reduction of delay between planning steps with Lean systems due to (a) communication, (b) limited resource, (b) contour, (c) plan approval, (d) treatment. Optimizing planning processes: (a) contour validation (b) consistent planning protocol, (c) protocol/template sharing, (d) semi

  18. MO-B-BRB-03: Systems Engineering Tools for Treatment Planning Process Optimization in Radiation Medicine

    Energy Technology Data Exchange (ETDEWEB)

    Kapur, A. [Long Island Jewish Medical Center (United States)

    2015-06-15

    The radiotherapy treatment planning process has evolved over the years with innovations in treatment planning, treatment delivery and imaging systems. Treatment modality and simulation technologies are also rapidly improving and affecting the planning process. For example, Image-guided-radiation-therapy has been widely adopted for patient setup, leading to margin reduction and isocenter repositioning after simulation. Stereotactic Body radiation therapy (SBRT) and Radiosurgery (SRS) have gradually become the standard of care for many treatment sites, which demand a higher throughput for the treatment plans even if the number of treatments per day remains the same. Finally, simulation, planning and treatment are traditionally sequential events. However, with emerging adaptive radiotherapy, they are becoming more tightly intertwined, leading to iterative processes. Enhanced efficiency of planning is therefore becoming more critical and poses serious challenge to the treatment planning process; Lean Six Sigma approaches are being utilized increasingly to balance the competing needs for speed and quality. In this symposium we will discuss the treatment planning process and illustrate effective techniques for managing workflow. Topics will include: Planning techniques: (a) beam placement, (b) dose optimization, (c) plan evaluation (d) export to RVS. Planning workflow: (a) import images, (b) Image fusion, (c) contouring, (d) plan approval (e) plan check (f) chart check, (g) sequential and iterative process Influence of upstream and downstream operations: (a) simulation, (b) immobilization, (c) motion management, (d) QA, (e) IGRT, (f) Treatment delivery, (g) SBRT/SRS (h) adaptive planning Reduction of delay between planning steps with Lean systems due to (a) communication, (b) limited resource, (b) contour, (c) plan approval, (d) treatment. Optimizing planning processes: (a) contour validation (b) consistent planning protocol, (c) protocol/template sharing, (d) semi

  19. Optimizing treatment parameters for the vascular malformations using 1064-nm Nd:YAG laser

    Science.gov (United States)

    Gong, Wei; Lin, He; Xie, Shusen

    2010-02-01

    Near infrared Nd:YAG pulsed laser treatment had been proved to be an efficient method to treat large-sized vascular malformations like leg telangiectasia for deep penetrating depth into skin and uniform light distribution in vessel. However, optimal clinical outcome was achieved by various laser irradiation parameters and the key factor governing the treatment efficacy was still unclear. A mathematical model in combination with Monte Carlo algorithm and finite difference method was developed to estimate the light distribution, temperature profile and thermal damage in epidermis, dermis and vessel during and after 1064 nm pulsed Nd:YAG laser irradiation. Simulation results showed that epidermal protection could be achieved during 1064 nm Nd:YAG pulsed laser irradiation in conjunction with cryogen spray cooling. However, optimal vessel closure and blood coagulation depend on a compromise between laser spot size and pulse duration.

  20. Drug regimens identified and optimized by output-driven platform markedly reduce tuberculosis treatment time

    Science.gov (United States)

    Lee, Bai-Yu; Clemens, Daniel L.; Silva, Aleidy; Dillon, Barbara Jane; Masleša-Galić, Saša; Nava, Susana; Ding, Xianting; Ho, Chih-Ming; Horwitz, Marcus A.

    2017-01-01

    The current drug regimens for treating tuberculosis are lengthy and onerous, and hence complicated by poor adherence leading to drug resistance and disease relapse. Previously, using an output-driven optimization platform and an in vitro macrophage model of Mycobacterium tuberculosis infection, we identified several experimental drug regimens among billions of possible drug-dose combinations that outperform the current standard regimen. Here we use this platform to optimize the in vivo drug doses of two of these regimens in a mouse model of pulmonary tuberculosis. The experimental regimens kill M. tuberculosis much more rapidly than the standard regimen and reduce treatment time to relapse-free cure by 75%. Thus, these regimens have the potential to provide a markedly shorter course of treatment for tuberculosis in humans. As these regimens omit isoniazid, rifampicin, fluoroquinolones and injectable aminoglycosides, they would be suitable for treating many cases of multidrug and extensively drug-resistant tuberculosis. PMID:28117835

  1. Optimization of prostate cancer treatment plans using the adjoint transport method and discrete ordinates codes

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, S.; Henderson, D.L. [Dept. of Medical Physics, Madison, WI (United States); Thomadsen, B.R. [Dept. of Medical Physics and Dept. of Human Oncology, Madison (United States)

    2001-07-01

    Interstitial brachytherapy is a type of radiation in which radioactive sources are implanted directly into cancerous tissue. Determination of dose delivered to tissue by photons emitted from implanted seeds is an important step in the treatment plan process. In this paper we will investigate the use of the discrete ordinates method and the adjoint method to calculate absorbed dose in the regions of interest. MIP (mixed-integer programming) is used to determine the optimal seed distribution that conforms the prescribed dose to the tumor and delivers minimal dose to the sensitive structures. The patient treatment procedure consists of three steps: (1) image acquisition with the transrectal ultrasound (TRUS) and assessing the region of interest, (2) adjoint flux computation with discrete ordinate code for inverse dose calculation, and (3) optimization with the MIP branch-and-bound method.

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

    Science.gov (United States)

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

    2016-05-01

    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 enabling 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. 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.

  3. Optimized Protocol of Methanol Treatment for Immunofluorescent Staining in Fixed Brain Slices

    Science.gov (United States)

    Yuan, Feng; Cohen, Noam A.; Cohen, Akiva S.

    2017-01-01

    We optimized methanol treatment in paraformaldehyde-fixed slices for immunofluorescent staining of ependymal basal bodies in brain ventricles. As 100% methanol induced severe deformations to the slices (including rolling and folding over), we tried to decrease methanol concentration. We found that 33.3% to 75% methanol could result in ideal immunostaining of basal bodies without inducing obvious deformations. Instead of treating slices at −20°C (without proper cryoprotection measurements) as suggested in previous studies, we carried out methanol treatment at room temperature. Our modified protocol can not only raise immunostaining efficiency in tissue slices, it may also prevent potential freezing damages to the samples. PMID:26509907

  4. The optimization of treatment and management of schizophrenia in Europe (OPTiMiSE) trial

    DEFF Research Database (Denmark)

    Leucht, Stefan; Winter-van Rossum, Inge; Heres, Stephan;

    2015-01-01

    gap leaves important questions unanswered. For example, when a first antipsychotic failed, is switching to another drug effective? And when should we use clozapine? The aim of this article is to review the efficacy of switching antipsychotics in case of nonresponse. We also present the European...... Commission sponsored "Optimization of Treatment and Management of Schizophrenia in Europe" (OPTiMiSE) trial which aims to provide a treatment algorithm for patients with a first episode of schizophrenia. METHODS: We searched Pubmed (October 29, 2014) for randomized controlled trials (RCTs) that examined...

  5. Optimizing drugs to reach treatment targets for children and adolescents living with HIV

    Directory of Open Access Journals (Sweden)

    Martina Penazzato

    2015-12-01

    Full Text Available Introduction: As the global community makes progress towards the 90-90-90 targets by 2020, a key challenge is ensuring that antiretroviral drugs for children and adolescents are suitable to the context of resource-limited settings. Drug optimization aims to support the expanded use of more simplified, less toxic drug regimens with high barriers to drug resistance that require minimal clinical monitoring while maintaining therapeutic efficacy. This manuscript summarizes the progress made and outlines further critical steps required to ensure that the right drugs are available to start children and adolescents on treatment and to keep them virologically suppressed. Discussion: Building upon previous work in drug optimization, several important steps were taken in 2014 to ensure alignment between WHO dosing recommendations and the requirements of regulatory bodies, to accelerate drug development, to reduce intellectual property barriers to generic production of combined formulations and rationalize drug selection in countries. The priority for the future is to improve access to antiretroviral therapy (ART at the two ends of the paediatric age spectrum – infants and adolescents – where the treatment gap is greatest, and optimize drug sequencing with better use of available medicines for second- and third-line ART. Future efforts in this area will require continuous collaboration and coordination, and the promotion of innovative approaches to accelerate access to new drugs and formulations. Conclusions: While significant progress has been made, additional efforts are needed to ensure that treatment targets are reached by 2020.

  6. Dependence of patients' life quality on severity of oral pathology: optimization of treatment approaches

    Directory of Open Access Journals (Sweden)

    Ivanova S.V.

    2011-03-01

    Full Text Available The research goals include: 1 assessment the quality of life of those patients who have defects of tooth rows not replaced by orthopedic appliances on the basis of the complex analysis; 2 choice of more reasonable method of treatment. The use of dental questionnaires such as Oral Health Impact Profile-14 (OHIP-14 while treating oral pathology allows both optimizing an approach to choosing an appropriate treatment method and making more successful prognosis as to the efficiency of treatment being performed. The quality of life of those patients who have tooth rows defects not replaced by orthopedic appliances depends on sex, age, family status, employment and extent of tooth rows defects. Patients with tooth rows defects not replaced by orthopedic appliances accompanied by diseases of peri-odontium are characterized by worse quality of life. This fact must be taken into consideration while planning patients' treatment

  7. Investigations into the Optimization of Multi-Source Strength Brachytherapy Treatment Procedures

    CERN Document Server

    Henderson, D L; Yoo, S

    2002-01-01

    The goal of this project is to investigate the use of multi-strength and multi-specie radioactive sources in permanent prostate implant brachytherapy. In order to fulfill the requirement for an optimal dose distribution, the prescribed dose should be delivered to the target in a nearly uniform dose distribution while simultaneously sparing sensitive structures. The treatment plan should use a small number of needles and sources while satisfying the treatment requirements. The hypothesis for the use of multi-strength and/or multi-specie sources is that a better treatment plan using fewer sources and needles could be obtained than by treatment plans using single-strength sources could reduce the overall number of sources used for treatment. We employ a recently developed greedy algorithm based on the adjoint concept as the optimization search engine. The algorithm utilizes and ''adjoint ratio'', which provides a means of ranking source positions, as the pseudo-objective function. It ha s been shown that the gre...

  8. Optimization of antitumor treatment conditions for transcutaneous CO2 application: An in vivo study.

    Science.gov (United States)

    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.

  9. Radiobiological effect based treatment plan optimization with the linear quadratic model

    Energy Technology Data Exchange (ETDEWEB)

    Schell, Stefan; Wilkens, Jan J.; Oelfke, Uwe [German Cancer Research Center, Heidelberg (Germany). Dept. of Medical Physics in Radiation Oncology

    2010-07-01

    As an approach towards more biology-oriented treatment planning for external beam radiation therapy, we present the incorporation of local radiation damage models into three dimensional treatment planning. This allows effect based instead of dose based plan optimization which could potentially better match the biologically relevant tradeoff between target and normal tissues. In particular, our approach facilitates an effective comparison of different fractionation schemes. It is based on the linear quadratic model to describe the biological radiation effect. Effect based optimization was integrated into our inverse treatment planning software KonRad, and we demonstrate the resulting differences between conventional and biological treatment planning. Radiation damage can be analyzed both qualitatively and quantitatively in dependence of the fractionation scheme and tissue specific parameters in a three dimensional voxel based system. As an example the potential advantages as well as the associated risks of hypofractionation for prostate cancer are analyzed and visualized with the help of effective dose volume histograms. Our results suggest a very conservative view regarding alternative fractionation schemes since uncertainties in biological parameters are still too big to make reliable clinical predictions. (orig.)

  10. Photo-Electrochemical Treatment of Reactive Dyes in Wastewater and Reuse of the Effluent: Method Optimization

    Directory of Open Access Journals (Sweden)

    Mireia Sala

    2014-11-01

    Full Text Available In this work, the efficiency of a photo-electrochemical method to remove color in textile dyeing effluents is discussed. The decolorization of a synthetic effluent containing a bi-functional reactive dye was carried out by applying an electrochemical treatment at different intensities (2 A, 5 A and 10 A, followed by ultraviolet irradiation. The combination of both treatments was optimized. The final percentage of effluent decolorization, the reduction of halogenated organic volatile compound and the total organic carbon removal were the determinant factors in the selection of the best treatment conditions. The optimized method was applied to the treatment of nine simulated dyeing effluents prepared with different reactive dyes in order to compare the behavior of mono, bi, and tri-reactive dyes. Finally, the nine treated effluents were reused in new dyeing processes and the color differences (DECMC (2:1 with respect to a reference were evaluated. The influence of the effluent organic matter removal on the color differences was also studied. The reuse of the treated effluents provides satisfactory dyeing results, and an important reduction in water consumption and salt discharge is achieved.

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

    Science.gov (United States)

    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.

  12. Optimization of a general-purpose, actively scanned proton beamline for ocular treatments: Geant4 simulations.

    Science.gov (United States)

    Piersimoni, Pierluigi; Rimoldi, Adele; Riccardi, Cristina; Pirola, Michele; Molinelli, Silvia; Ciocca, Mario

    2015-03-08

    The Italian National Center for Hadrontherapy (CNAO, Centro Nazionale di Adroterapia Oncologica), a synchrotron-based hospital facility, started the treatment of patients within selected clinical trials in late 2011 and 2012 with actively scanned proton and carbon ion beams, respectively. The activation of a new clinical protocol for the irradiation of uveal melanoma using the existing general-purpose proton beamline is foreseen for late 2014. Beam characteristics and patient treatment setup need to be tuned to meet the specific requirements for such a type of treatment technique. The aim of this study is to optimize the CNAO transport beamline by adding passive components and minimizing air gap to achieve the optimal conditions for ocular tumor irradiation. The CNAO setup with the active and passive components along the transport beamline, as well as a human eye-modeled detector also including a realistic target volume, were simulated using the Monte Carlo Geant4 toolkit. The strong reduction of the air gap between the nozzle and patient skin, as well as the insertion of a range shifter plus a patient-specific brass collimator at a short distance from the eye, were found to be effective tools to be implemented. In perspective, this simulation toolkit could also be used as a benchmark for future developments and testing purposes on commercial treatment planning systems.

  13. Strategies to optimize treatment adherence in adolescent patients with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Bishay LC

    2016-10-01

    Full Text Available Lara C Bishay, Gregory S Sawicki Division of Respiratory Diseases, Boston Children’s Hospital, Boston, MA, USA Abstract: While development of new treatments for cystic fibrosis (CF has led to a significant improvement in survival age, routine daily treatment for CF is complex, burdensome, and time intensive. Adolescence is a period of decline in pulmonary function in CF, and is also a time when adherence to prescribed treatment plans for CF tends to decrease. Challenges to adherence in adolescents with CF include decreased parental involvement, time management and significant treatment burden, and adolescent perceptions of the necessity and value of the treatments prescribed. Studies of interventions to improve adherence are limited and focus on education, without significant evidence of success. Smaller studies on behavioral techniques do not focus on adolescents. Other challenges for improving adherence in adolescents with CF include infection control practices limiting in-person interactions. This review focuses on the existing evidence base on adherence intervention in adolescents with CF. Future directions for efforts to optimize treatment adherence in adolescents with CF include reducing treatment burden, developing patient-driven technology to improve tracking, communication, and online support, and rethinking the CF health services model to include assessment of individualized adherence barriers. Keywords: compliance, adolescence, medication, self management, intervention

  14. Optimal management of pulmonary arterial hypertension: prognostic indicators to determine treatment course

    Science.gov (United States)

    Baldi, Fabiana; Fuso, Leonello; Arrighi, Eugenio; Valente, Salvatore

    2014-01-01

    Pulmonary arterial hypertension (PAH) is a rapidly progressive pulmonary vascular disease with a multifactorial etiopathogenesis that can result in right-sided heart failure and death. A number of studies indicate that an early therapeutic intervention yields better results on disease progression as compared to delayed treatment. In this review, we will analyze treatment strategies that may be used for monitoring disease progression and for guiding treatment decisions. Several factors (ie, symptoms, functional class, exercise capacity as assessed by a walking test and cardiopulmonary stress testing, hemodynamic parameters, cardiac magnetic resonance imaging, and plasma levels of biochemical markers) have been prognostic of survival. These indicators may be used both at the time of diagnosis and during treatment follow-up. No resolutive therapy is currently available for PAH; however, in the last decade, the advent of specific pharmacological treatments has given new hope to patients suffering from this debilitating disease with a poor prognosis. Combination drug therapies offer increased benefits over monotherapy, and current guidelines recommend a sequential “add on” design approach for patients in functional class II–IV. The goal-oriented “treat to target” therapy sets the timing for treatment escalation in case of inadequate response to currently known prognostic indicators. To date, further longitudinal studies should be urgently conducted to identify new goals that may improve therapeutic strategies in order to optimize personalized treatment in PAH patients. PMID:25328398

  15. Strategies to optimize treatment adherence in adolescent patients with cystic fibrosis

    Science.gov (United States)

    Bishay, Lara C; Sawicki, Gregory S

    2016-01-01

    While development of new treatments for cystic fibrosis (CF) has led to a significant improvement in survival age, routine daily treatment for CF is complex, burdensome, and time intensive. Adolescence is a period of decline in pulmonary function in CF, and is also a time when adherence to prescribed treatment plans for CF tends to decrease. Challenges to adherence in adolescents with CF include decreased parental involvement, time management and significant treatment burden, and adolescent perceptions of the necessity and value of the treatments prescribed. Studies of interventions to improve adherence are limited and focus on education, without significant evidence of success. Smaller studies on behavioral techniques do not focus on adolescents. Other challenges for improving adherence in adolescents with CF include infection control practices limiting in-person interactions. This review focuses on the existing evidence base on adherence intervention in adolescents with CF. Future directions for efforts to optimize treatment adherence in adolescents with CF include reducing treatment burden, developing patient-driven technology to improve tracking, communication, and online support, and rethinking the CF health services model to include assessment of individualized adherence barriers. PMID:27799838

  16. Comparisons of treatment optimization directly incorporating random patient setup uncertainty with a margin-based approach.

    Science.gov (United States)

    Moore, Joseph A; Gordon, John J; Anscher, Mitchell S; Siebers, Jeffrey V

    2009-09-01

    The purpose of this study is to incorporate the dosimetric effect of random patient positioning uncertainties directly into a commercial treatment planning system's IMRT plan optimization algorithm through probabilistic treatment planning (PTP) and compare coverage of this method with margin-based planning. In this work, PTP eliminates explicit margins and optimizes directly on the estimated integral treatment dose to determine optimal patient dose in the presence of setup uncertainties. Twenty-eight prostate patient plans adhering to the RTOG-0126 criteria are optimized using both margin-based and PTP methods. Only random errors are considered. For margin-based plans, the planning target volume is created by expanding the clinical target volume (CTV) by 2.1 mm to accommodate the simulated 3 mm random setup uncertainty. Random setup uncertainties are incorporated into IMRT dose evaluation by convolving each beam's incident fluence with a sigma = 3 mm Gaussian prior to dose calculation. PTP optimization uses the convolved fluence to estimate dose to ensure CTV coverage during plan optimization. PTP-based plans are compared to margin-based plans with equal CTV coverage in the presence of setup errors based on dose-volume metrics. The sensitivity of the optimized plans to patient-specific setup uncertainty variations is assessed by evaluating dose metrics for dose distributions corresponding to halving and doubling of the random setup uncertainty used in the optimization. Margin-based and PTP-based plans show similar target coverage. A physician review shows that PTP is preferred for 21 patients, margin-based plans are preferred in 2 patients, no preference is expressed for 1 patient, and both autogenerated plans are rejected for 4 patients. For the PTP-based plans, the average CTV receiving the prescription dose decreases by 0.5%, while the mean dose to the CTV increases by 0.7%. The CTV tumor control probability (TCP) is the same for both methods with the exception

  17. Pareto Optimization Identifies Diverse Set of Phosphorylation Signatures Predicting Response to Treatment with Dasatinib.

    Science.gov (United States)

    Klammer, Martin; Dybowski, J Nikolaj; Hoffmann, Daniel; Schaab, Christoph

    2015-01-01

    Multivariate biomarkers that can predict the effectiveness of targeted therapy in individual patients are highly desired. Previous biomarker discovery studies have largely focused on the identification of single biomarker signatures, aimed at maximizing prediction accuracy. Here, we present a different approach that identifies multiple biomarkers by simultaneously optimizing their predictive power, number of features, and proximity to the drug target in a protein-protein interaction network. To this end, we incorporated NSGA-II, a fast and elitist multi-objective optimization algorithm that is based on the principle of Pareto optimality, into the biomarker discovery workflow. The method was applied to quantitative phosphoproteome data of 19 non-small cell lung cancer (NSCLC) cell lines from a previous biomarker study. The algorithm successfully identified a total of 77 candidate biomarker signatures predicting response to treatment with dasatinib. Through filtering and similarity clustering, this set was trimmed to four final biomarker signatures, which then were validated on an independent set of breast cancer cell lines. All four candidates reached the same good prediction accuracy (83%) as the originally published biomarker. Although the newly discovered signatures were diverse in their composition and in their size, the central protein of the originally published signature - integrin β4 (ITGB4) - was also present in all four Pareto signatures, confirming its pivotal role in predicting dasatinib response in NSCLC cell lines. In summary, the method presented here allows for a robust and simultaneous identification of multiple multivariate biomarkers that are optimized for prediction performance, size, and relevance.

  18. Optimization of Electrochemical Treatment Process Conditions for Distillery Effluent Using Response Surface Methodology.

    Science.gov (United States)

    Arulmathi, P; Elangovan, G; Begum, A Farjana

    2015-01-01

    Distillery industry is recognized as one of the most polluting industries in India with a large amount of annual effluent production. In this present study, the optimization of electrochemical treatment process variables was reported to treat the color and COD of distillery spent wash using Ti/Pt as an anode in a batch mode. Process variables such as pH, current density, electrolysis time, and electrolyte dose were selected as operation variables and chemical oxygen demand (COD) and color removal efficiency were considered as response variable for optimization using response surface methodology. Indirect electrochemical-oxidation process variables were optimized using Box-Behnken response surface design (BBD). The results showed that electrochemical treatment process effectively removed the COD (89.5%) and color (95.1%) of the distillery industry spent wash under the optimum conditions: pH of 4.12, current density of 25.02 mA/cm(2), electrolysis time of 103.27 min, and electrolyte (NaCl) concentration of 1.67 g/L, respectively.

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

    Science.gov (United States)

    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.

  20. Fabrication and Optimal Design of Biodegradable Polymeric Stents for Aneurysms Treatments.

    Science.gov (United States)

    Han, Xue; Wu, Xia; Kelly, Michael; Chen, Xiongbiao

    2017-02-28

    An aneurysm is a balloon-like bulge in the wall of blood vessels, occurring in major arteries of the heart and brain. Biodegradable polymeric stent-assisted coiling is expected to be the ideal treatment of wide-neck complex aneurysms. This paper presents the development of methods to fabricate and optimally design biodegradable polymeric stents for aneurysms treatment. Firstly, a dispensing-based rapid prototyping (DBRP) system was developed to fabricate coil and zigzag structures of biodegradable polymeric stents. Then, compression testing was carried out to characterize the radial deformation of the stents fabricated with the coil or zigzag structure. The results illustrated the stent with a zigzag structure has a stronger radial stiffness than the one with a coil structure. On this basis, the stent with a zigzag structure was chosen for the development of a finite element model for simulating the real compression tests. The result showed the finite element model of biodegradable polymeric stents is acceptable within a range of radial deformation around 20%. Furthermore, the optimization of the zigzag structure was performed with ANSYS DesignXplorer, and the results indicated that the total deformation could be decreased by 35.7% by optimizing the structure parameters, which would represent a significant advance of the radial stiffness of biodegradable polymeric stents.

  1. Optimization of the preparation conditions of ceramic products using drinking water treatment sludges.

    Science.gov (United States)

    Zamora, R M Ramirez; Ayala, F Espesel; Garcia, L Chavez; Moreno, A Duran; Schouwenaars, R

    2008-11-01

    The aim of this work is to optimize, via Response Surface Methodology, the values of the main process parameters for the production of ceramic products using sludges obtained from drinking water treatment in order to valorise them. In the first experimental stage, sludges were collected from a drinking water treatment plant for characterization. In the second stage, trials were carried out to elaborate thin cross-section specimens and fired bricks following an orthogonal central composite design of experiments with three factors (sludge composition, grain size and firing temperature) and five levels. The optimization parameters (Y(1)=shrinking by firing (%), Y(2)=water absorption (%), Y(3)=density (g/cm(3)) and Y(4)=compressive strength (kg/cm(2))) were determined according to standardized analytical methods. Two distinct physicochemical processes were active during firing at different conditions in the experimental design, preventing the determination of a full response surface, which would allow direct optimization of production parameters. Nevertheless, the temperature range for the production of classical red brick was closely delimitated by the results; above this temperature, a lightweight ceramic with surprisingly high strength was produced, opening possibilities for the valorisation of a product with considerably higher added value than what was originally envisioned.

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

    Science.gov (United States)

    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.

  3. Fish canning wastewater treatment by activated sludge: Application of factorial design optimization

    Directory of Open Access Journals (Sweden)

    Raquel O. Cristóvão

    2015-06-01

    Full Text Available The optimization of hydraulic retention time (HRT and initial organic matter concentration for dissolved organic carbon (DOC abatement of wastewater from a fish canning industry of northern Portugal by activated sludge was investigated using response surface methodology (RSM. The two parameters were chosen since it was found that the treatment efficiency is mainly influenced by them. The experimental data on DOC removal were fitted into a quadratic polynomial model using factorial design and RSM. The optimum process conditions were determined by analyzing the response surface of a three-dimensional plot and by solving the regression model equation. The obtained results showed a HRT of 6.4 h and an initial DOC of 406.2 mg/L as the best treatment conditions. Under these conditions, the maximum predicted DOC removal was 88.0%, confirming the feasibility and the reliability of fish canning wastewater treatment by activated sludge for organic content removal.

  4. Optimizing the heat treatment of Ni-based superalloy turbine discs

    Science.gov (United States)

    Furrer, D. U.; Shankar, R.; White, C.

    2003-03-01

    The heat-treatment processes for nickel-based superalloys continue to change due to the development of new alloys, new requirements, and subsequent new manufacturing facilities. Nickel-based superalloys are continuing to evolve to meet emerging applications, while new alloys are also being introduced for advanced applications. These new materials are also being optimized for numerous mechanical and physical properties, making the selection of heat-treatment parameters increasingly challenging. New processing facilities and methods are also being implemented to allow tailoring of heat-treating parameters to meet these new challenges. For example, the Ladish SuperCooler technology allows engineering and control of all aspects of the heat-treatment process for nickel-based components, resulting in never-before possible disc properties.

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

    Science.gov (United States)

    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 (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.

  6. Q- and A-learning Methods for Estimating Optimal Dynamic Treatment Regimes

    CERN Document Server

    Schulte, Phillip J; Laber, Eric B; Davidian, Marie

    2012-01-01

    In clinical practice, physicians make a series of treatment decisions over the course of a patient's disease based on his/her baseline and evolving characteristics. A dynamic treatment regime is a set of sequential decision rules that operationalizes this process. Each rule corresponds to a key decision point and dictates the next treatment action among the options available as a function of accrued information on the patient. Using data from a clinical trial or observational study, a key goal is estimating the optimal regime, that, if followed by the patient population, would yield the most favorable outcome on average. Q-learning and advantage (A-)learning are two main approaches for this purpose. We provide a detailed account of Q- and A-learning and study systematically the performance of these methods. The methods are illustrated using data from a study of depression.

  7. Ultra-fast treatment plan optimization for volumetric modulated arc therapy (VMAT)

    CERN Document Server

    Men, Chunhua; Jia, Xun; Jiang, Steve B

    2010-01-01

    Purpose: To develop a novel aperture-based algorithm for volumetric modulated arc therapy (VMAT) treatment plan optimization with high quality and high efficiency. Methods: The VMAT optimization problem is formulated as a large-scale convex programming problem solved by a column generation approach. We consider a cost function consisting two terms, the first which enforces a desired dose distribution while the second guarantees a smooth dose rate variation between successive gantry angles. At each iteration of the column generation method, a subproblem is first solved to generate one more deliverable MLC aperture which potentially decreases the cost function most effectively. A subsequent master problem is then solved to determine the dose rate at all currently generated apertures by minimizing the cost function. The iteration of such an algorithm yields a set of deliverable apertures, as well as dose rates, at all gantry angles. Results: The algorithm was preliminarily tested on five prostate and five head-a...

  8. Optimized treatment parameters to account for interfractional variability in scanned ion beam therapy of lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Brevet, Romain

    2015-02-04

    Scanned ion beam therapy of lung tumors is severely limited in its clinical applicability by intrafractional organ motion, interference effects between beam and tumor motion (interplay) as well as interfractional anatomic changes. To compensate for dose deterioration by intrafractional motion, motion mitigation techniques, such as gating have been developed. The latter confines the irradiation to a predetermined breathing state, usually the stable end-exhale phase. However, optimization of the treatment parameters is needed to further improve target dose coverage and normal tissue sparing. The aim of the study presented in this dissertation was to determine treatment planning parameters that permit to recover good target coverage and homogeneity during a full course of lung tumor treatments. For 9 lung tumor patients from MD Anderson Cancer Center (MDACC), a total of 70 weekly time-resolved computed tomography (4DCT) datasets were available, which depict the evolution of the patient anatomy over the several fractions of the treatment. Using the GSI in-house treatment planning system (TPS) TRiP4D, 4D simulations were performed on each weekly 4DCT for each patient using gating and optimization of a single treatment plan based on a planning CT acquired prior to treatment. It was found that using a large beam spot size, a short gating window (GW), additional margins and multiple fields permitted to obtain the best results, yielding an average target coverage (V95) of 96.5%. Two motion mitigation techniques, one approximating the rescanning process (multiple irradiations of the target with a fraction of the planned dose) and one combining the latter and gating, were then compared to gating. Both did neither show an improvement in target dose coverage nor in normal tissue sparing. Finally, the total dose delivered to each patient in a simulation of a fractioned treatment was calculated and clinical requirements in terms of target coverage and normal tissue sparing were

  9. "One-size-fits-all"? Optimizing treatment duration for bacterial infections.

    Directory of Open Access Journals (Sweden)

    Patricia Geli

    Full Text Available Historically, antibiotic treatment guidelines have aimed to maximize treatment efficacy and minimize toxicity, but have not considered the evolution of antibiotic resistance. Optimizing the duration and dosing of treatment to minimize the duration of symptomatic infection and selection pressure for resistance simultaneously has the potential to extend the useful therapeutic life of these valuable life-saving drugs without compromising the interests of individual patients.Here, using mathematical models, we explore the theoretical basis for shorter durations of treatment courses, including a range of ecological dynamics of bacteria that cause infections or colonize hosts as commensals. We find that immunity is an important mediating factor in determining the need for long duration of treatment. When immunity to infection is expected, shorter durations that reduce the selection for resistance without interfering with successful clinical outcome are likely to be supported. Adjusting drug treatment strategies to account for the impact of the differences in the ecological niche occupied by commensal flora relative to invasive bacteria could be effective in delaying the spread of bacterial resistance.

  10. “One-Size-Fits-All”? Optimizing Treatment Duration for Bacterial Infections

    Science.gov (United States)

    Geli, Patricia; Laxminarayan, Ramanan; Dunne, Michael; Smith, David L.

    2012-01-01

    Historically, antibiotic treatment guidelines have aimed to maximize treatment efficacy and minimize toxicity, but have not considered the evolution of antibiotic resistance. Optimizing the duration and dosing of treatment to minimize the duration of symptomatic infection and selection pressure for resistance simultaneously has the potential to extend the useful therapeutic life of these valuable life-saving drugs without compromising the interests of individual patients. Here, using mathematical models, we explore the theoretical basis for shorter durations of treatment courses, including a range of ecological dynamics of bacteria that cause infections or colonize hosts as commensals. We find that immunity is an important mediating factor in determining the need for long duration of treatment. When immunity to infection is expected, shorter durations that reduce the selection for resistance without interfering with successful clinical outcome are likely to be supported. Adjusting drug treatment strategies to account for the impact of the differences in the ecological niche occupied by commensal flora relative to invasive bacteria could be effective in delaying the spread of bacterial resistance. PMID:22253798

  11. Resource Communication. Temporal optimization of fuel treatment design in blue gum (Eucalyptus globulus plantations

    Directory of Open Access Journals (Sweden)

    Ana Martin

    2016-07-01

    Material and methods: At each of four temporal stages (2015-2018-2021-2024 we simulated: (1 surface and canopy fuels, timber volume (m3 ha-1 and carbon storage (Mg ha-1; (2 fire behaviour characteristics, i.e. rate of spread (m min-1, and flame length (m, with FlamMap fire modelling software; (3 optimal treatment locations as determined by the Landscape Treatment Designer (LTD. Main results: The higher pressure of fire behaviour in the earlier stages of the study period triggered most of the spatial fuel treatments within eucalypt plantations in a juvenile stage. At later stages fuel treatments also included shrublands areas. The results were consistent with observations and simulation results that show high fire hazard in juvenile eucalypt stands. Research highlights: Forest management planning in commercial eucalypt plantations can potentially accomplish multiple objectives such as augmenting profits and sustaining ecological assets while reducing wildfire risk at landscape scale. However, limitations of simulation models including FlamMap and LTD are important to recognise in studies of long term wildfire management strategies. Keywords: Eucalypt plantations; Fire hazard; FlamMap; fuel treatment optimisation; Landscape Treatment Designer; wildfire risk management.

  12. Model-Based Individualized Treatment of Chemotherapeutics: Bayesian Population Modeling and Dose Optimization.

    Directory of Open Access Journals (Sweden)

    Devaraj Jayachandran

    Full Text Available 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.

  13. Model-Based Individualized Treatment of Chemotherapeutics: Bayesian Population Modeling and Dose Optimization.

    Science.gov (United States)

    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.

  14. Comment on genetic and global algorithms for optimization of three-dimensional conformal radiotherapy treatment planning

    Energy Technology Data Exchange (ETDEWEB)

    Vaarkamp, Jaap [Joint Department of Physics, Royal Marsden NHS Trust, Sutton, Surrey (United Kingdom). E-mail: jaap@icr.ac.uk

    2001-06-01

    Full text: I would like to make four comments on three papers by two authors (Wu and Zhu 2000, 2001, Wu et al 2000) on one topic: optimization of 3D conformal radiotherapy treatment planning. In the papers, genetic and global algorithms are proposed for this optimization, and the authors claim to be able to generate better treatment plans than those produced manually and used for patient treatment (Wu and Zhu 2000). However, the data in the papers do not warrant such a conclusion and the work contains such serious methodological flaws that only the opposite can have been true. First, in the papers a few treatment plans for patients with different brain tumours are discussed. Dose volume histograms (DVHs) are presented for the target, sometimes the planning target volume, sometimes the clinical target volume, and the organs at risk (OARs): left and right eye, and thyroid or spinal cord. However, other OARs limit dose more in clinical treatment planning, and it is those OARs to which the planner must direct all effort when optimizing the treatment plan. One such important OAR when treating children is the temporal lobes because the dose to the temporal lobes has been associated with a reduction in IQ points (Fuss et al 2000). Also particularly important when treating children are the hypothalamus and pituitary, because they influence growth and the further hormonal development (Schmiegelow et al 1999, 2000). Furthermore, rather than the eyes themselves, the optic chiasm usually gets more serious attention (Fuss et al 1999) and is considered so important that it is often blocked from the treatment fields during the final fractions, thus compromising dose homogeneity in the target. Finally, irradiating the auditory apparatus can lead to a loss of hearing (Lin et al 2000), and, in particular when one side receives a high dose, every effort is made to at least spare the other side. Hence, it is not surprising to find a treatment plan that is superior in some of the

  15. Optimization of Heart Block in the Left-sided Whole Breast Radiation Treatments

    Directory of Open Access Journals (Sweden)

    Ning Jeff Yue

    2014-12-01

    Full Text Available Purpose: Blocks have been used to protect heart from potential radiation damage in left-sided breast treatments. Since cardiac motion pattern may not be fully captured on conventional 3DCT or 4DCT simulation scans, this study was intended to investigate the optimization of the heart block design taking the cardiac motion into consideration.Materials and Methods: Whole breast treatment plans using two opposed tangential fields were designed based on 4DCT simulation images for 10 left-sided breast cancer patients. Using an OBI system equipped to a Varian Linac, beam-eye viewed fluoroscopy images were acquired for each of the treatment beams after patient treatment setup, and the MLC heart blocks were overlaid onto the fluoroscopy images with an in-house software package. A non-rigid image registration and tracking algorithm was utilized to track the cardiac motion on the fluoroscopy images with minimal manual delineation for initialization, and the tracked cardiac motion information was used to optimize the heart block design to minimize the radiation damage to heart while avoiding the over-shielding that may lead to underdosing certain breast tissues. Results: Twenty-three sets of fluoroscopy images were acquired on 23 different days of treatment for the 10 patients. As expected, heart moved under the influences of both respiratory and cardiac motion. It was observed that for 16 out of the 23 treatments heart moved beyond the planed heart block into treatment fields and MLC had to be adjusted to fully block heart. The adjustment was made for all but one patient. The number of the adjusted MLC leaves ranged from 1 to 16 (mean = 10, and the MLC leaf position adjustment ranged from 2 mm to 10 mm (mean = 6 mm. The added heart block areas ranged from 3 mm2 to 1230 mm2 (mean = 331 mm2. Conclusion: In left-sided whole breast radiation treatments, simulation CT (and 4DCT based heart block design may not provide adequate heart protection for all the

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

    Energy Technology Data Exchange (ETDEWEB)

    Yan Di; Liang Jian [Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan 48073 (United States)

    2013-02-15

    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 to 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

  17. Optimization of metal working fluids treatment using calcium chloride by response surface methodology

    Directory of Open Access Journals (Sweden)

    HA. Jamali

    2016-11-01

    Full Text Available Background: Extensive use of metal working fluids degrades their chemical composition. They should be treated using a safe method. Chemical coagulation-flocculation process is one the treatment methods. Objective: The aim of this study was to optimize the coagulation-flocculation process using calcium chloride in metal working fluids treatment. Methods: This laboratory based study was performed in School of Health affiliated to Qazvin University of Medical Sciences in 2014. Using calcium chloride and a six-compartment jar, the efficiency of coagulation-flocculation process was assessed for removal of chemical oxygen demand (COD and turbidity and amount of released oil. Central composite design (CCD and response surface methodology (RSM were applied to optimize the treatment operation parameters (pH and dosage of coagulant. Quadratic models were developed for calculation of the three responses (COD, turbidity, and released oil. Findings: The optimum condition for coagulation-flocculation process was seen after treatment with 4.2 g/L calcium chloride at pH 3.71 in which COD and turbidity removal efficiency were 93% and 96.9%, respectively and the amount of released oil was 31.8 ml. The level of desirability was 91.2%. The values of laboratory study were in good agreement with the values predicted by the model. Conclusion: Metal working fluids treatment with calcium chloride was efficient in the removal of pollution parameters. Dosage of calcium chloride was similar to the conventional coagulants such as Alum, but its efficiency was higher.

  18. Identifying the microbial communities and operational conditions for optimized wastewater treatment in microbial fuel cells.

    Science.gov (United States)

    Ishii, Shun'ichi; Suzuki, Shino; Norden-Krichmar, Trina M; Wu, Angela; Yamanaka, Yuko; Nealson, Kenneth H; Bretschger, Orianna

    2013-12-01

    Microbial fuel cells (MFCs) are devices that exploit microorganisms as "biocatalysts" to recover energy from organic matter in the form of electricity. MFCs have been explored as possible energy neutral wastewater treatment systems; however, fundamental knowledge is still required about how MFC-associated microbial communities are affected by different operational conditions and can be optimized for accelerated wastewater treatment rates. In this study, we explored how electricity-generating microbial biofilms were established at MFC anodes and responded to three different operational conditions during wastewater treatment: 1) MFC operation using a 750 Ω external resistor (0.3 mA current production); 2) set-potential (SP) operation with the anode electrode potentiostatically controlled to +100 mV vs SHE (4.0 mA current production); and 3) open circuit (OC) operation (zero current generation). For all reactors, primary clarifier effluent collected from a municipal wastewater plant was used as the sole carbon and microbial source. Batch operation demonstrated nearly complete organic matter consumption after a residence time of 8-12 days for the MFC condition, 4-6 days for the SP condition, and 15-20 days for the OC condition. These results indicate that higher current generation accelerates organic matter degradation during MFC wastewater treatment. The microbial community analysis was conducted for the three reactors using 16S rRNA gene sequencing. Although the inoculated wastewater was dominated by members of Epsilonproteobacteria, Gammaproteobacteria, and Bacteroidetes species, the electricity-generating biofilms in MFC and SP reactors were dominated by Deltaproteobacteria and Bacteroidetes. Within Deltaproteobacteria, phylotypes classified to family Desulfobulbaceae and Geobacteraceae increased significantly under the SP condition with higher current generation; however those phylotypes were not found in the OC reactor. These analyses suggest that species

  19. Developing and optimizing bacteriophage treatment to control enterohemorrhagic Escherichia coli on fresh produce.

    Science.gov (United States)

    Snyder, Abigail B; Perry, Jennifer J; Yousef, Ahmed E

    2016-11-07

    Bacteriophages are potentially useful in controlling foodborne pathogens on minimally processed products since phage application is a non-destructive treatment. The purpose of this study was to evaluate the efficacy of a newly isolated environmental bacteriophage against enterohemorrhagic Escherichia coli on fresh produce, and optimize the treatment with consideration for potential application. Seven anti E. coli O157:H7 EDL933 bacteriophages were isolated from various sources; the most promising was isolated from municipal wastewater. This isolate (designated as E. coli phage OSY-SP) was propagated with the host, in a growth medium, to a titer of 10(8) PFU/ml. Before inoculation into fresh produce, E. coli phage OSY-SP was incubated with the host bacterium, spent medium was filter-sterilized, and the resulting crude lysate was used as a source of phage inocula for preliminary experiments. For optimized testing, phage in the crude lysate was purified by ultra-centrifugation and resuspension in phosphate-buffered saline. Efficacy of phage treatments was determined as a function of fresh produce type (cut green pepper or spinach leaves), treatment time (2 or 5min rinsing), and temperature of holding treated produce (4°C, 25°, or a combination of both temperatures). Cut green pepper was treated with UV light, to eliminate background microbiota, then spot-inoculated with E. coli O157:H7 EDL933 on cut edges, and the inoculum was allowed to dry. Because of its susceptibility to damage, baby spinach leaves were not subjected to a decontamination treatment. These leaves were inoculated with the green fluorescent protein-labeled E. coli O157:H7 B6-914 to facilitate inoculum enumeration in the presence of background microbiota. Phage suspension was applied to the inoculated fresh produce that was subsequently held for three days under variable storage conditions. The optimized phage treatment decreased the populations of pathogenic E. coli by 2.4-3.0logCFU/g on cut green

  20. Team management of the female athlete triad part 2: optimal treatment and prevention tactics.

    Science.gov (United States)

    Joy, E; Clark, N; Ireland, M L; Martire, J; Nattiv, A; Varechok, S

    1997-04-01

    Multidisciplinary management of the female athlete triad (disordered eating, amenorrhea, and osteoporosis) is optimal, but what exactly does it entail? With the primary care physician as the point person, the healthcare team addresses the underlying causes of disordered eating through such measures as drawing up a contract for returning to play, resolving nutrition issues, exploring psychotherapy options, and, sometimes, prescribing antidepressants. Hormone replacement therapy and conservative or orthopedic intervention for stress fractures may also be required. Communication among the members of the treatment team is crucial, and athletic trainers especially can provide valuable input. Prevention strategies need to involve education of coaches, teachers, trainers, parents, and others who work closely with female athletes.

  1. Optimized Treatment of Fibromyalgia Using System Identification and Hybrid Model Predictive Control.

    Science.gov (United States)

    Deshpande, Sunil; Nandola, Naresh N; Rivera, Daniel E; Younger, Jarred W

    2014-12-01

    The term adaptive intervention is used in behavioral health to describe individually-tailored strategies for preventing and treating chronic, relapsing disorders. This paper describes a system identification approach for developing dynamical models from clinical data, and subsequently, a hybrid model predictive control scheme for assigning dosages of naltrexone as treatment for fibromyalgia, a chronic pain condition. A simulation study that includes conditions of significant plant-model mismatch demonstrates the benefits of hybrid predictive control as a decision framework for optimized adaptive interventions. This work provides insights on the design of novel personalized interventions for chronic pain and related conditions in behavioral health.

  2. Cherenkov imaging method for rapid optimization of clinical treatment geometry in total skin electron beam therapy

    Energy Technology Data Exchange (ETDEWEB)

    Andreozzi, Jacqueline M., E-mail: Jacqueline.M.Andreozzi.th@dartmouth.edu, E-mail: Lesley.A.Jarvis@hitchcock.org; Glaser, Adam K. [Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755 (United States); Zhang, Rongxiao [Department of Physics and Astronomy, Dartmouth College, Hanover, New Hampshire 03755 (United States); Gladstone, David J.; Williams, Benjamin B.; Jarvis, Lesley A., E-mail: Jacqueline.M.Andreozzi.th@dartmouth.edu, E-mail: Lesley.A.Jarvis@hitchcock.org [Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03766 (United States); Pogue, Brian W. [Thayer School of Engineering and Department of Physics and Astronomy, Dartmouth College, Hanover, New Hampshire 03755 (United States)

    2016-02-15

    Purpose: A method was developed utilizing Cherenkov imaging for rapid and thorough determination of the two gantry angles that produce the most uniform treatment plane during dual-field total skin electron beam therapy (TSET). Methods: Cherenkov imaging was implemented to gather 2D measurements of relative surface dose from 6 MeV electron beams on a white polyethylene sheet. An intensified charge-coupled device camera time-gated to the Linac was used for Cherenkov emission imaging at sixty-two different gantry angles (1° increments, from 239.5° to 300.5°). Following a modified Stanford TSET technique, which uses two fields per patient position for full body coverage, composite images were created as the sum of two beam images on the sheet; each angle pair was evaluated for minimum variation across the patient region of interest. Cherenkov versus dose correlation was verified with ionization chamber measurements. The process was repeated at source to surface distance (SSD) = 441, 370.5, and 300 cm to determine optimal angle spread for varying room geometries. In addition, three patients receiving TSET using a modified Stanford six-dual field technique with 6 MeV electron beams at SSD = 441 cm were imaged during treatment. Results: As in previous studies, Cherenkov intensity was shown to directly correlate with dose for homogenous flat phantoms (R{sup 2} = 0.93), making Cherenkov imaging an appropriate candidate to assess and optimize TSET setup geometry. This method provided dense 2D images allowing 1891 possible treatment geometries to be comprehensively analyzed from one data set of 62 single images. Gantry angles historically used for TSET at their institution were 255.5° and 284.5° at SSD = 441 cm; however, the angles optimized for maximum homogeneity were found to be 252.5° and 287.5° (+6° increase in angle spread). Ionization chamber measurements confirmed improvement in dose homogeneity across the treatment field from a range of 24.4% at the initial

  3. Optimization of Pre-treatment Process of Cocoa Pod Husk Using Various Chemical Solvents

    Directory of Open Access Journals (Sweden)

    Novizar Nazir

    2016-06-01

    Full Text Available The purpose of research is to see the effect of type of reagent (NaOH, H2O2 and H2SO4 and the condition of  pre-treatment  of cocoa pod husk towards lignin content after pre-treatment and hydrolysis,  reducing sugar and total sugar content.  Response Surface Method (RSM was used to optimize process conditions of pre-treatment (delignification.  Hydrolysis for all pre-treated sample were carried out using 3% H2SO4 with a ratio of cocoa pod husk to solvent (1:10  for 2 hours at a temperature of 110 oC using an autoclave.  The chemical  pre-treatment with NaOH was optimized by varying the  concentrations of NaOH (4-8% (w/v, centre point: 6%,  reaction time (60-100 minutes, centre point: 80 minutes and ratio of biomass to solvent (1:15-1:25, centre point 1:20 w/v.  The optimum conditions in this study was at the concentration of NaOH (X1 of 4% w/v, reaction time  (X2 of 100 minutes; ratio of biomass/solvent  (X3 of 1:25 (w/v.   The lignin content after pre-treatment was  15.03% lignin, lignin content after hydrolysis was  19.57%,  11.75% of reducing sugar, and 12.78% of total sugar. The chemical  pre-treatment with alkaline peroxide  (H2O2  was optimized by varying the  concentrations of H2O2  (4-7% w/v, centre point 5.5% (w/v,  reaction time (40-90 minutes, centre point: 65 minutes, and ratio of biomass/solvent (4-7% w/v.   The optimum conditions in this study was at the concentration of H2O2 concentration (X1 of 5.52% w/v, reaction time (X2 of 61.97 minutes, biomass loading in solvent (X3 7% w/v.  The lignin content after pre-treatment was  8.759, lignin content after  hydrolysis was 25.029%,  8.169%  of reducing sugar, and 10.371% of total sugar.  The chemical pre-treatment with H2SO4  was optimized by varying the  concentrations of H2SO4  (0.5-1.5% w/v,  reaction time (60-120 minutes, centre point: 90 minutes, and ratio of biomass to solvent (1:4-1:6 w/v, centre point 1:5 w/v. The

  4. Optimal policies for activated sludge treatment systems with multi effluent stream generation

    Directory of Open Access Journals (Sweden)

    Gouveia R.

    2000-01-01

    Full Text Available Most industrial processes generate liquid waste, which requires treatment prior to disposal. These processes are divided into sectors that generate effluents with time dependent characteristics. Each sector sends the effluent to wastewater treatment plants through pumping-stations. In general, activated sludge is the most suitable treatment and consists of equalization, aeration and settling tanks. During the treatment, there is an increase in the mass of microorganisms, which needs to be removed. Sludge removal represents the major operating costs for wastewater treatment plants. The objective of this work is to propose an optimization model to minimize sludge generation using a superstructure in which the streams from pumping-stations can be sent to the equalization tank. In addition, the aeration tank is divided into cells that can be fed in series and parallel. The model relies on mass balances, kinetic equations, and the resulting Nonlinear Programming problem generates the best operational strategy for the system feed streams with a high substrate removal. Reductions of up to 30 % can be achieved with the proposed strategy maintened BOD efficiency removal upper than 98 %.

  5. Optimization of the geometry and composition of a neutron system for treatment by Boron Neutron Capture Therapy

    OpenAIRE

    2015-01-01

    Background: In the field of the treatment by Boron Neutron Capture Therapy (BNCT), an optimized neutron system was proposed. This study (simulation) was conducted to optimize the geometry and composition of neutron system and increase the epithermal neutron flux for the treatment of deep tumors is performed. Materials and Methods: A neutron system for BNCT was proposed. The system included 252Cf neutron source, neutron moderator/reflector arrangement, filter and concrete. To capture fast ...

  6. [Impact of optimization algorithms on the intensity map in IMRT treatment planning.].

    Science.gov (United States)

    Shimada, Mari; Nakamura, Mitsuhiro; Miyabe, Yuki; Yamamoto, Tokihiro; Teshima, Teruki; Narita, Yuichiro; Mizowaki, Takashi; Nagata, Yasushi; Hiraoka, Masahiro

    2006-01-01

    In inverse planning of IMRT, optimum intensity maps are generated using an optimization algorithm. In this paper, impacts of two different optimization algorithms on the intensity map in IMRT treatment planning were evaluated. These were from the steepest descent (SD) and simulated annealing (SA) methods. The following five patterns were compared: [1] SD with calculation time of 5 min; [2] SD with the terminal criterion based on cost function; [3] SA with calculation time of 5 min; [4] SA with the terminal criterion; and [5] SA with the terminal criterion using a smoothing filter. Differences of D(95%) for the planning target volume, V(70Gy) for the rectum wall and the bladder wall were up to 0.5, 1.8 and 3.2 %, respectively in all patterns. The dosimetric impact was negligible. In contrast, generated intensity maps were sensitive to the algorithms. Intensity maps generated by SA tended to have much fluctuation due to numerical artifacts compared to those generated by SD. The difference in the profile was over 7 % between the algorithms. The smoothing filter decreased the fluctuation in intensity maps of SA. In conclusion, it is important to understand impacts of optimization algorithms on the intensity map and the dose distribution.

  7. Optimized Reduction of Unsteady Radial Forces in a Singlechannel Pump for Wastewater Treatment

    Science.gov (United States)

    Kim, Jin-Hyuk; Cho, Bo-Min; Choi, Young-Seok; Lee, Kyoung-Yong; Peck, Jong-Hyeon; Kim, Seon-Chang

    2016-11-01

    A single-channel pump for wastewater treatment was optimized to reduce unsteady radial force sources caused by impeller-volute interactions. The steady and unsteady Reynolds- averaged Navier-Stokes equations using the shear-stress transport turbulence model were discretized by finite volume approximations and solved on tetrahedral grids to analyze the flow in the single-channel pump. The sweep area of radial force during one revolution and the distance of the sweep-area center of mass from the origin were selected as the objective functions; the two design variables were related to the internal flow cross-sectional area of the volute. These objective functions were integrated into one objective function by applying the weighting factor for optimization. Latin hypercube sampling was employed to generate twelve design points within the design space. A response-surface approximation model was constructed as a surrogate model for the objectives, based on the objective function values at the generated design points. The optimized results showed considerable reduction in the unsteady radial force sources in the optimum design, relative to those of the reference design.

  8. Heat Treatment Optimization Studies on PIT Nb$_3$Sn Strand for the NED Project

    CERN Document Server

    Boutboul, T; den Ouden, A; Pedrini, D; Seeber, B; Volpini, G

    2009-01-01

    For the Next European Dipole (NED) program, a Powder-In-Tube (PIT) strand was successfully developed by SMI. This high-performance Nb3Sn strand presents a non-copper critical current density of ~ 2500 A/mm2 at 12 T applied field and 4.2 K and a filament diameter around 50 µm. Extensive heat treatment optimization studies were performed in order to maximize both critical current and RRR, with a plateau temperature down to 625 oC and duration up to 400 hours. It appears that a critical current enhancement of ~ 10 % can be achieved for a reaction schedule of 320 hours at 625 oC with non-copper critical current density respectively exceeding 2700 and 1500 A/mm2 at 12 and 15 T (4.2 K). Thanks to this modified heat treatment, this strand completely fulfils the NED stringent specification.

  9. Particle sedimentation in curved tubes: A 3D simulation and optimization for treatment of vestibular vertigo

    Science.gov (United States)

    White, Brian; Squires, Todd M.; Hain, Timothy C.; Stone, Howard A.

    2003-11-01

    Benign paroxysmal positional vertigo (BPPV) is a mechanical disorder of the vestibular system where micron-size crystals abnormally drift into the semicircular canals of the inner ear that sense angular motion of the head. Sedimentation of these crystals causes sensation of motion after true head motion has stopped: vertigo results. The usual clinical treatment is through a series of head maneuvers designed to move the particles into a less sensitive region of the canal system. We present a three-dimensional model to simulate treatment of BPPV by determining the complete hydrodynamic motion of the particles through the course of a therapeutic maneuver while using a realistic representation of the actual geometry. Analyses of clinical maneuvers show the parameter range for which they are effective, and indicate inefficiencies in current practice. In addition, an optimization process determines the most effective head maneuver, which significantly differs from those currently in practice.

  10. A discussion of the optimal treatment of intracranial aneurysm rupture in elderly patients.

    Science.gov (United States)

    Liu, C

    2014-08-25

    This study aimed to find an optimal treatment for intracranial aneurysm rupture in elderly patients. We adopted endovascular embolization and combined it with mini-invasive aspiration, vascular stenosis stenting, and rehabilitation training to treat 13 elderly patients with intracranial aneurysm rupture. When the 13 patients were discharged and evaluated by the Glasgow Outcome Score (GOS), 7 patients were grade 5, 4 patients were grade 4, and 2 patients were grade 2. We found that a combination of endovascular embolization with mini-invasive aspiration and vascular stenosis stenting allowed us to adapt this treatment to various types of aneurysms. Our approach is especially suitable for elderly patients, because it reduces the occurrence of complications, improves patient prognoses, shortens the duration of hospitalization, and improves the quality of life.

  11. Optimizing proton pump inhibitor therapy for treatment of nonvariceal upper gastrointestinal bleeding.

    Science.gov (United States)

    Worden, Jarett C; Hanna, Kirollos S

    2017-02-01

    The pharmacology, rationale, and dosing optimization strategies of proton pump inhibitors (PPIs) for the treatment of upper gastrointestinal bleeding (UGIB) are discussed. In combination with endoscopic therapy, PPIs are the treatment of choice for UGIB. While the advent of PPIs has improved patient outcomes, controversy still exists over optimal PPI therapy for UGIB. Pharmacologic treatment in combination with endoscopic therapy has demonstrated improved outcomes in patients with nonvariceal UGIB. PPIs are the treatment of choice for suppressing gastric acid and preventing rebleeding, though a mortality benefit from these agents has not been strongly established. Although the current guidelines recommend an i.v. bolus injection followed by continuous infusion of a high-dose PPI, intermittent PPI therapy has been found to be safe and effective while significantly reducing cost, even in patients with high-risk stigmata after endoscopy. Oral PPIs may be effective in patients who can tolerate oral therapy but require further evaluation in patients with higher-risk stigmata. Regardless of stigmata, after 72 hours of i.v. therapy, patients with UGIB may be safely transitioned to oral PPIs if hemodynamically stable and able to tolerate oral medication. As the risk of rebleeding significantly decreases after the first three days, continuation of high-dose therapy beyond 72 hours is not necessary in hemodynamically stable patients. Current guidelines recommend that PPIs be given as an i.v. bolus injection followed by a continuous infusion, but intermittent i.v. dosing and oral PPI therapy have been found to be effective in treating patients with UGIB and associated with reductions in cost. Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  12. Pregnancy Research on Osteopathic Manipulation Optimizing Treatment Effects: the PROMOTE study.

    Science.gov (United States)

    Hensel, Kendi L; Buchanan, Steve; Brown, Sarah K; Rodriguez, Mayra; Cruser, des Anges

    2015-01-01

    The purpose of this study was to evaluate the efficacy of osteopathic manipulative treatment (OMT) to reduce low back pain and improve functioning during the third trimester in pregnancy and to improve selected outcomes of labor and delivery. Pregnancy research on osteopathic manipulation optimizing treatment effects was a randomized, placebo-controlled trial of 400 women in their third trimester. Women were assigned randomly to usual care only (UCO), usual care plus OMT (OMT), or usual care plus placebo ultrasound treatment (PUT). The study included 7 treatments over 9 weeks. The OMT protocol included specific techniques that were administered by board-certified OMT specialists. Outcomes were assessed with the use of self-report measures for pain and back-related functioning and medical records for delivery outcomes. There were 136 women in the OMT group: 131 women in the PUT group and 133 women in the UCO group. Characteristics at baseline were similar across groups. Findings indicate significant treatment effects for pain and back-related functioning (P OMT group similar to that of the PUT group; however, both groups were significantly improved compared with the UCO group. For secondary outcome of meconium-stained amniotic fluid, there were no differences among the groups. OMT was effective for mitigating pain and functional deterioration compared with UCO; however, OMT did not differ significantly from PUT. This may be attributed to PUT being a more active treatment than intended. There was no higher likelihood of conversion to high-risk status based on treatment group. Therefore, OMT is a safe, effective adjunctive modality to improve pain and functioning during the third trimester. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. From current status to optimization of HCV treatment: Recommendations from an expert panel.

    Science.gov (United States)

    Craxì, Antonio; Perno, Carlo Federico; Viganò, Mauro; Ceccherini-Silberstein, Francesca; Petta, Salvatore

    2016-09-01

    Chronic hepatitis C virus (HCV) infection is a major public health problem at a global level, causing an enormous burden of hepatic and extra-hepatic morbidity and mortality. Treatment of chronic HCV (CHC) has been revolutionized in the last few years by the introduction of highly effective and well tolerated direct acting antiviral agents (DAAs) able to achieve >90% rates of sustained virological response (SVR) in many groups of patients, including those previously excluded from interferon-based regimens. For such reason interferon-free regimens are now the treatments of choice for all patients. Successful anti-HCV treatment can stop liver disease progression and can solve the HCV-related extra hepatic manifestations, eventually reducing both liver-related and overall mortality. Together with the rapidly accumulating data about the evolution of treatment landscape, different guidelines from national and international Liver Scientific Societies have been published until today. However, these recommendations may not be applied worldwide as, due to high treatment costs, most of them identify as priority groups only patients with advanced liver disease. Moreover some types of patients pose clinical management problems for which even the guidelines do not always provide useful answers. With the aim of treatment optimization by filling some of the gaps of the current guidelines and addressing the remaining unmet needs in practice, a group of Italian experts, experienced on treatment of HCV infection, met in Stresa in February 2016. The summary of all the considerations arising from this two-day meeting and the final statements are reported in this position paper.

  14. Simulation and optimization of a coking wastewater biological treatment process by activated sludge models (ASM).

    Science.gov (United States)

    Wu, Xiaohui; Yang, Yang; Wu, Gaoming; Mao, Juan; Zhou, Tao

    2016-01-01

    Applications of activated sludge models (ASM) in simulating industrial biological wastewater treatment plants (WWTPs) are still difficult due to refractory and complex components in influents as well as diversity in activated sludges. In this study, an ASM3 modeling study was conducted to simulate and optimize a practical coking wastewater treatment plant (CWTP). First, respirometric characterizations of the coking wastewater and CWTP biomasses were conducted to determine the specific kinetic and stoichiometric model parameters for the consecutive aeration-anoxic-aeration (O-A/O) biological process. All ASM3 parameters have been further estimated and calibrated, through cross validation by the model dynamic simulation procedure. Consequently, an ASM3 model was successfully established to accurately simulate the CWTP performances in removing COD and NH4-N. An optimized CWTP operation condition could be proposed reducing the operation cost from 6.2 to 5.5 €/m(3) wastewater. This study is expected to provide a useful reference for mathematic simulations of practical industrial WWTPs.

  15. Optimization and kinetic studies on treatment of textile dye wastewater using Pleurotus floridanus

    Science.gov (United States)

    Sathian, S.; Radha, G.; Shanmugapriya, V.; Rajasimman, M.; Karthikeyan, C.

    2013-03-01

    Treatment of textile dye wastewater was carried using Pleurotus floridanus in a batch reactor. Response surface methodology (RSM) was used to optimize the process parameters like pH, temperature, agitation speed and dye wastewater concentration for the decolorization of textile dye wastewater. The optimum conditions for the maximum decolorization was: pH 6.6, temperature 28.8 °C, agitation speed 183 rpm and dye wastewater concentration 1:2. From the results it was found that, the linear effect of agitation speed and initial textile dye wastewater concentration were more significant than other factors for the textile dye wastewater treatment. At these optimized conditions, the maximum decolorization and COD reduction was found to be 71.2 and 80.5 %, respectively. Kinetics of textile dye degradation process was studied by various models like first order, diffusional and Singh model. From the results it was found that the degradation follows first order model with R 2 value of 0.9550.

  16. Performance of SBR for the treatment of textile dye wastewater: Optimization and kinetic studies

    Directory of Open Access Journals (Sweden)

    S. Sathian

    2014-06-01

    Full Text Available In this work, sequential batch reactor (SBR was employed for the treatment of textile dye wastewater. The performance of four white rot fungi (WRF viz. Coriolus versicolor, Pleurotus floridanus, Ganoderma lucidum and Trametes pubescens was evaluated in pure and mixed combinations in terms of decolorization. From the results it was found that the combination of Pleurotus floridanus, Ganoderma lucidum and Trametes pubescens was best and they were used in the SBR. The process parameters like air flow rate, sludge retention time (SRT and cycle period were optimized using response surface methodology (RSM. At these optimized conditions, treatment of textile dye wastewater was carried out at various initial dye wastewater concentration and hydraulic retention time. The performance of SBR was analyzed in terms of decolorization, COD reduction and sludge volume index (SVI. From the results it was found that a maximum decolorization and COD reduction of 71.3% and 79.4%, respectively, was achieved in the SBR at an organic loading rate of 0.165 KgCOD/m3 d. The sludge volume index (SVI was found to be low in the range of 90–103 mL/g. The kinetic study was carried out using a first order based model and the degradation follows the first order system.

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

    CERN Document Server

    Yarmand, Hamed

    2013-01-01

    Stereotactic body radiotherapy (SBRT) is characterized by delivering a high amount of dose in a short period of time. In SBRT the dose is delivered using open fields (e.g., beam's-eye-view) known as "apertures". Mathematical methods can be used for optimizing treatment planning for delivery of sufficient dose to the cancerous cells while keeping the dose to surrounding organs at risk (OARs) minimal. Two important elements of a treatment plan are quality and delivery time. Quality of a plan is measured based on the target coverage and dose to OARs. Delivery time heavily depends on the number of beams used in the plan since the setup times for different beam directions constitute a large portion of the delivery time. Therefore the ideal plan, in which all potential beams can be used simultaneously, will be associated with a long impractical delivery time. We use the dose to OARs in the ideal plan to find the plan with the minimum number of beams which is guaranteed to be epsilon-optimal (i.e., a predetermined m...

  18. Optimal Control Problem of Treatment for Obesity in a Closed Population

    Directory of Open Access Journals (Sweden)

    D. Aldila

    2014-01-01

    Full Text Available Variety of intervention programs for controlling the obesity epidemic has been done worldwide. However, it is still not yet available a scientific tool to measure the effectiveness of those programs. This is due to the difficulty in parameterizing the human interaction and transition process of obesity. A dynamical model for simulating the interaction between healthy people, overweight people, and obese people in a randomly mixed population is discussed in here. Two scenarios of intervention programs were implemented in the model, dietary program for overweight people with healthy life campaign and treatment program for obese people. Assuming all control rates are constant, disease free equilibrium point, endemic equilibrium point, and basic reproductive ratio (ℛ0 as the epidemic indicator were shown analytically. We find that the disease free equilibrium point is locally asymptotical stable if and only if ℛ0<1. From sensitivity analysis of ℛ0, we obtain that larger rate of dietary program and treatment program will reduce ℛ0 significantly. With control rates are continuous in time, an optimal control approach was applied into the model to find the best way to minimize the number of overweight and obese people. Some numerical analysis and simulations for optimal control of the intervention were shown to support the analytical results.

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

    Science.gov (United States)

    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.

  20. Agent-based model of laser hair removal: A treatment optimization and patient education tool

    Directory of Open Access Journals (Sweden)

    Eapen Bell

    2009-01-01

    Full Text Available Background: Tracking of various parameters associated with laser hair removal is tedious and time consuming. The currently available mathematical models are not simple enough for physicians to be used as a treatment optimization and patient education tool. Aim: The aim of the study was to develop a mathematical model for laser hair removal using agent-based modeling and to make a user-friendly simulation environment. Methods: The model was created using NetLogo. The hairs were modeled as agents oscillating between anagen and telogen. The variables were assigned based on published data whenever possible and the various paths the agent could take were coded as conditional statements. The improvement was assessed using an arbitrary index which takes into account the mean diameter and pigmentation along with the number and length of hairs visible above the surface. Few of the commonly encountered scenarios were simulated using the model. Results: The model is made freely available online (http://www.gulfdoctor.net/model/lhr.htm. Limited number of simulations performed indicated that an eight-week gap between laser sessions may be more effective than a four-week gap. Conclusions: The simulation provides a reliable tool for treatment optimization and patient education as obtaining relevant clinical data is slow and labor-intensive. Its visual interface and online availability makes it useful for everyday use.

  1. Optimization of the anaerobic treatment of a waste stream from an enhanced oil recovery process.

    Science.gov (United States)

    Alimahmoodi, Mahmood; Mulligan, Catherine N

    2011-01-01

    The aim of this work was to optimize the anaerobic treatment of a waste stream from an enhanced oil recovery (EOR) process. The treatment of a simulated waste water containing about 150 mg chemical oxygen demand (COD)/L of total petroleum hydrocarbons (TPH) and the saturation level of CO2 was evaluated. A two-step anaerobic system was undertaken in the mesophilic temperature range (30-40°C). The method of evolutionary operation EVOP factorial design was used to optimize pH, temperature and organic loading rate with the target parameters of CO2 reduction and CH4 production in the first reactor and TPH removal in the second reactor. The results showed 98% methanogenic removal of CO2 and CH4 yield of 0.38 L/gCOD in the first reactor and 83% TPH removal in the second reactor. In addition to enhancing CO2 and TPH removal and CH4 production, application of this method showed the degree of importance of the operational variables and their interactive effects for the two reactors in series. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. Optimal Control of Hepatitis C Antiviral Treatment Programme Delivery for Prevention amongst a Population of Injecting Drug Users

    OpenAIRE

    Martin, Natasha K.; Pitcher, Ashley B.; Vickerman, Peter; Vassall, Anna; Hickman, Matthew

    2011-01-01

    In most developed countries, HCV is primarily transmitted by injecting drug users (IDUs). HCV antiviral treatment is effective, and deemed cost-effective for those with no re-infection risk. However, few active IDUs are currently treated. Previous modelling studies have shown antiviral treatment for active IDUs could reduce HCV prevalence, and there is emerging interest in developing targeted IDU treatment programmes. However, the optimal timing and scale-up of treatment is unknown, given the...

  3. Optimal Control of Hepatitis C Antiviral Treatment Programme Delivery for Prevention amongst a Population of Injecting Drug Users

    OpenAIRE

    Martin, NK; Pitcher, AB; Vickerman, P.; Vassall, A; Hickman, M

    2011-01-01

    : In most developed countries, HCV is primarily transmitted by injecting drug users (IDUs). HCV antiviral treatment is effective, and deemed cost-effective for those with no re-infection risk. However, few active IDUs are currently treated. Previous modelling studies have shown antiviral treatment for active IDUs could reduce HCV prevalence, and there is emerging interest in developing targeted IDU treatment programmes. However, the optimal timing and scale-up of treatment is unknown, given t...

  4. Nanoethosomal transdermal delivery of vardenafil for treatment of erectile dysfunction: optimization, characterization, and in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Fahmy UA

    2015-11-01

    Full Text Available Usama A Fahmy Department of Pharmaceutics & Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: Vesicular drug delivery systems have recently gained attention as a way of improving dosing accuracy for drugs with poor transdermal permeation. The current study focuses on utilization of the natural biocompatible vesicles to formulate vardenafil nanoethosomes (VRD-NE, for the enhancement of their transdermal permeation and bioavailability. Fifteen formulations were prepared by thin-layer evaporation technique according to Box–Behnken design to optimize formulation variables. The effects of lipid composition, sonication time, and ethanol concentration on particle size and encapsulation efficiency were studied. The diffusion of vardenafil (VRD from the prepared nanoethosomes specified by the design was carried out using automated Franz diffusion cell apparatus. The optimized formula was investigated for in vivo pharmacokinetic parameters compared with oral VRD suspension. Confocal laser scanning microscopy images were used to confirm enhanced diffusion release of VRD in rat skin. The results showed that the optimized formula produced nanoethosomes with an average size of 128 nm and an entrapment efficiency of 76.23%. VRD-NE provided a significant improvement in permeation with an enhancement ratio of 3.05-fold for a film made with optimally formulated VRD-NE compared with a film made with VRD powder. The transdermal bioavailability of VRD from the nanoethosome film was approximately twofold higher than the oral bioavailability from an aqueous suspension. VRD-NE thus provide a promising transdermal drug delivery system. As a result, management of impotence for a longer duration could be achieved with a reduced dosage rate that improves patient tolerability and compliance for the treatment of erectile dysfunction.Keywords: Box–Behnken design, impotence, vesicles, nanoparticles

  5. Pareto Optimization Identifies Diverse Set of Phosphorylation Signatures Predicting Response to Treatment with Dasatinib.

    Directory of Open Access Journals (Sweden)

    Martin Klammer

    Full Text Available Multivariate biomarkers that can predict the effectiveness of targeted therapy in individual patients are highly desired. Previous biomarker discovery studies have largely focused on the identification of single biomarker signatures, aimed at maximizing prediction accuracy. Here, we present a different approach that identifies multiple biomarkers by simultaneously optimizing their predictive power, number of features, and proximity to the drug target in a protein-protein interaction network. To this end, we incorporated NSGA-II, a fast and elitist multi-objective optimization algorithm that is based on the principle of Pareto optimality, into the biomarker discovery workflow. The method was applied to quantitative phosphoproteome data of 19 non-small cell lung cancer (NSCLC cell lines from a previous biomarker study. The algorithm successfully identified a total of 77 candidate biomarker signatures predicting response to treatment with dasatinib. Through filtering and similarity clustering, this set was trimmed to four final biomarker signatures, which then were validated on an independent set of breast cancer cell lines. All four candidates reached the same good prediction accuracy (83% as the originally published biomarker. Although the newly discovered signatures were diverse in their composition and in their size, the central protein of the originally published signature - integrin β4 (ITGB4 - was also present in all four Pareto signatures, confirming its pivotal role in predicting dasatinib response in NSCLC cell lines. In summary, the method presented here allows for a robust and simultaneous identification of multiple multivariate biomarkers that are optimized for prediction performance, size, and relevance.

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

    Science.gov (United States)

    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

  7. Treatment optimization with concurrent SBRT and intracavitary brachytherapy for locally advanced cervical cancer.

    Science.gov (United States)

    Wan, Bin; Lang, Jinyi; Wang, Pei; Ma, C-M

    2016-01-01

    This work is aimed at investigating treatment planning strategies to optimally combine stereotactic body radiation therapy (SBRT) with intracavitary brachytherapy (ICBT) for the treatment of locally advanced cervical cancer. Forty patients (stage IIB - IIIB) previously treated with combined SBRT and ICBT were randomly selected for this retrospective study. All patients were CT- and MR-scanned with a ring applicator in situ. HR-CTV and OARs were contoured according to fused CT and MR images. Several ICBT plans were generated for each patient based on different dose prescription points, and then a matching SBRT plan was generated for each ICBT plan. The dose distribution of each composite plan was analyzed with a focus on the doses received by 90% and 100% of the target volume (D90 and D100), the target volume receiving 100% of the prescription dose (V100%), and the doses received by 2 cc and 40% of the OARs (D2cc and D40). As the distance, d, between the prescription point and the tandem varied within 1.0 and 1.9 cm, the D90, D100 and V100% for the target, as well as D2cc and D40 for the bladder and rectum approached their optimal values for d value between 1.0 and 1.4 cm. When designing a combined ICBT+SBRT plan, one should measure the size of the cervix and set the prescription isodose line 1.0 to 1.4 cm away from the tandem for the ICBT plan first and then optimize the SBRT plan based on the ICBT dose distribution to achieve the best target coverage and critical structures sparing. PACS number: 87.53.jw; 87.55.D. © 2016 The Authors.

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

    Science.gov (United States)

    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.

  9. Investigations into the Optimization of Multi-Source Strength Brachytherapy Treatment Procedures

    Energy Technology Data Exchange (ETDEWEB)

    D. L. Henderson; S. Yoo; B.R. Thomadsen

    2002-09-30

    The goal of this project is to investigate the use of multi-strength and multi-specie radioactive sources in permanent prostate implant brachytherapy. In order to fulfill the requirement for an optimal dose distribution, the prescribed dose should be delivered to the target in a nearly uniform dose distribution while simultaneously sparing sensitive structures. The treatment plan should use a small number of needles and sources while satisfying the treatment requirements. The hypothesis for the use of multi-strength and/or multi-specie sources is that a better treatment plan using fewer sources and needles could be obtained than by treatment plans using single-strength sources could reduce the overall number of sources used for treatment. We employ a recently developed greedy algorithm based on the adjoint concept as the optimization search engine. The algorithm utilizes and ''adjoint ratio'', which provides a means of ranking source positions, as the pseudo-objective function. It ha s been shown that the greedy algorithm can solve the optimization problem efficiently and arrives at a clinically acceptable solution in less than 10 seconds. Our study was inclusive, that is there was no combination of sources that clearly stood out from the others and could therefore be considered the preferred set of sources for treatment planning. Source strengths of 0.2 mCi (low), 0.4 mCi (medium), and 0.6 mCi (high) of {sup 125}I in four different combinations were used for the multi-strength source study. The combination of high- and medium-strength sources achieved a more uniform target dose distribution due to few source implants whereas the combination of low-and medium-strength sources achieved better sparing of sensitive tissues including that of the single-strength 0.4 mCi base case. {sup 125}I at 0.4 mCi and {sup 192}Ir at 0.12 mCi and 0.25 mCi source strengths were used for the multi-specie source study. This study also proved inconclusive , Treatment

  10. Optimization of Conversion Treatment on Austenitic Stainless Steel Using Experimental Designs

    Directory of Open Access Journals (Sweden)

    S. El Hajjaji

    2013-01-01

    Full Text Available Conversion coating is commonly used as treatment to improve the adherence of ceramics films. The conversion coating properties depend on the structure of alloy as well as on the treatment parameters. These conversion coatings must be characterized by strong interfacial adhesion, high roughness, and high real surface area, which were measured by an electrochemical method. The influence of all the elaboration factors (temperature, time, and bath composition: sulphuric acid, thiosulphate as accelerator, propargyl alcohol as inhibitor, and surface state and also the interactions between these factors were evaluated, using statistical experimental design. The specific surface area and optical factor (α correspond to the quantitative responses. The evaluation showed, by using a designed experimental procedure, that the most important factor was “surface state.” Sanded surface allows the formation of conversion coating with high real surface area. A further aim was to optimise two parameters: treatment time and temperature using Doehlert shell design and simplex method. The growth of the conversion coating is also influenced by treatment time and temperature. With such optimized conditions, the real surface area of conversion coating obtained was about 235 m2/m2.

  11. Orthogonal experiment on reclaimed water treatment and economic optimization model in green building

    Institute of Scientific and Technical Information of China (English)

    何强; 张成; 柴宏祥; 樊明玉

    2009-01-01

    The efficacy of superior drainage in green building treated by combinational technique of coagulation sedimentation and constructed wetland was launched. The results show that the regression equation relating to effluent BOD5,cubage load (Nv),temperature (t) and addition dosage (ρ) is BOD5=2.05Nv-0.41t-0.82ρ+38.9. The orthogonal experiment results of constructed wetland post-treatment show that the regression equation relating to effluent BOD5,cubage load (NA),and temperature (t) is BOD5=1 190NA-0.32t+12.2. Based on the two orthogonal regression equations,combined of green building municipal gray reclaimed water quantity requirements in different seasons,a technology investment on economic optimization model of combinational technique was established. The results offer technological support for reclaimed water treatment,which regards superior drainage as the source and is purified by combinational technique of coagulation sedimentation and constructed wetland. According to the model,the reasonable scale of reclaimed water treatment systems can be determined,the treatment efficacy can be well predicted,and both the design and operating can be effectively guided.

  12. Optimal Control of a Spatio-Temporal Model for Malaria: Synergy Treatment and Prevention

    Directory of Open Access Journals (Sweden)

    Malicki Zorom

    2012-01-01

    Full Text Available We propose a metapopulation model for malaria with two control variables, treatment and prevention, distributed between different patches (localities. Malaria spreads between these localities through human travel. We used the theory of optimal control and applied a mathematical model for three connected patches. From previous studies with the same data, two patches were identified as reservoirs of malaria infection, namely, the patches that sustain malaria epidemic in the other patches. We argue that to reduce the number of infections and semi-immunes (i.e., asymptomatic carriers of parasites in overall population, two considerations are needed, (a For the reservoir patches, we need to apply both treatment and prevention to reduce the number of infections and to reduce the number of semi-immunes; neither the treatment nor prevention were specified at the beginning of the control application, except prevention that seems to be effective at the end. (b For unreservoir patches, we should apply the treatment to reduce the number of infections, and the same strategy should be applied to semi-immune as in (a.

  13. Optimizing treatment of the partially platinum-sensitive ovarian cancer patient.

    Science.gov (United States)

    Colombo, Nicoletta

    2013-12-01

    Ovarian cancer is the leading cause of gynecological cancer deaths worldwide. Despite primary treatment with platinum-containing regimens, the majority of women will experience recurrent disease and subsequent death. Recurrent ovarian cancer remains a challenge for successful management, and the choice of second-line chemotherapy is complex due to the range of different factors that need to be considered. One of the main considerations is the platinum-free interval and, specifically, the optimal treatment for patients who are partially platinum-sensitive (platinum-free interval: 6-12 months). Data from the large, multicenter, randomized OVA-301 study have shown that combined trabectedin-pegylated liposomal doxorubicin (PLD) significantly prolonged median overall survival compared with PLD alone (p = 0.0027) in 214 patients with partially platinum-sensitive advanced relapsed ovarian cancer. Furthermore, in OVA-301 patients with partially platinum-sensitive disease who received platinum therapy immediately after disease progression (n = 94), final median overall survival was improved by 9 months (p = 0.0153) in trabectedin-PLD patients compared with PLD alone. In addition to demonstrating a survival advantage, trabectedin-PLD may also allow the treatment of patients having not yet recovered from previous platinum toxicity. In summary, the data suggest the use of combined trabectedin-PLD as a second-line treatment option in patients with partially platinum-sensitive recurrent ovarian cancer, followed by a third-line platinum-containing regimen.

  14. Organ sample generator for expected treatment dose construction and adaptive inverse planning optimization

    Energy Technology Data Exchange (ETDEWEB)

    Nie Xiaobo; Liang Jian; Yan Di [Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan 48073 (United States)

    2012-12-15

    Purpose: To create an organ sample generator (OSG) for expected treatment dose construction and adaptive inverse planning optimization. The OSG generates random samples of organs of interest from a distribution obeying the patient specific organ variation probability density function (PDF) during the course of adaptive radiotherapy. Methods: Principle component analysis (PCA) and a time-varying least-squares regression (LSR) method were used on patient specific geometric variations of organs of interest manifested on multiple daily volumetric images obtained during the treatment course. The construction of the OSG includes the determination of eigenvectors of the organ variation using PCA, and the determination of the corresponding coefficients using time-varying LSR. The coefficients can be either random variables or random functions of the elapsed treatment days depending on the characteristics of organ variation as a stationary or a nonstationary random process. The LSR method with time-varying weighting parameters was applied to the precollected daily volumetric images to determine the function form of the coefficients. Eleven h and n cancer patients with 30 daily cone beam CT images each were included in the evaluation of the OSG. The evaluation was performed using a total of 18 organs of interest, including 15 organs at risk and 3 targets. Results: Geometric variations of organs of interest during h and n cancer radiotherapy can be represented using the first 3 {approx} 4 eigenvectors. These eigenvectors were variable during treatment, and need to be updated using new daily images obtained during the treatment course. The OSG generates random samples of organs of interest from the estimated organ variation PDF of the individual. The accuracy of the estimated PDF can be improved recursively using extra daily image feedback during the treatment course. The average deviations in the estimation of the mean and standard deviation of the organ variation PDF for h

  15. Resource Communication. Temporal optimization of fuel treatment design in blue gum (Eucalyptus globulus) plantations

    Energy Technology Data Exchange (ETDEWEB)

    Martin, A.; Botequim, B.; Oliveira, T.M.; Ager, A.; Pirotti, F.

    2016-07-01

    Aim of the study: This study was conducted to support fire and forest management planning in eucalypt plantations based on economic, ecological and fire prevention criteria, with a focus on strategic prioritisation of fuel treatments over time. The central objective was to strategically locate fuel treatments to minimise losses from wildfire while meeting budget constraints and demands for wood supply for the pulp industry and conserving carbon. Area of study: The study area was located in Serra do Socorro (Torres Vedras, Portugal, covering ~1449 ha) of predominantly Eucalyptus globulus Labill forests managedcultivated for pulpwood by The Navigator Company. Material and methods: At each of four temporal stages (2015-2018-2021-2024) we simulated: (1) surface and canopy fuels, timber volume (m3 ha-1) and carbon storage (Mg ha-1); (2) fire behaviour characteristics, i.e. rate of spread (m min-1), and flame length (m), with FlamMap fire modelling software; (3) optimal treatment locations as determined by the Landscape Treatment Designer (LTD). Main results: The higher pressure of fire behaviour in the earlier stages of the study period triggered most of the spatial fuel treatments within eucalypt plantations in a juvenile stage. At later stages fuel treatments also included shrublands areas. The results were consistent with observations and simulation results that show high fire hazard in juvenile eucalypt stands. Research highlights: Forest management planning in commercial eucalypt plantations can potentially accomplish multiple objectives such as augmenting profits and sustaining ecological assets while reducing wildfire risk at landscape scale. However, limitations of simulation models including FlamMap and LTD are important to recognise in studies of long term wildfire management strategies. (Author)

  16. Optimizing the treatment of landfill leachate by conventional Fenton and photo-Fenton processes

    Energy Technology Data Exchange (ETDEWEB)

    Hermosilla, Daphne, E-mail: dhermosilla@quim.ucm.es [Departamento de Ingenieria Quimica, Facultad de Ciencias Quimicas, Universidad Complutense de Madrid, Ciudad Universitaria s/n, 28040 Madrid (Spain); Cortijo, Manuel [U.D. Operaciones Basicas, Departamento de Ingenieria Forestal, E.T.S.I. Montes, Universidad Politecnica de Madrid, Avda. Ramiro de Maeztu s/n, 28040 Madrid (Spain); Huang, Chin Pao [Department of Civil and Environmental Engineering, 352C DuPont Hall, University of Delaware, Newark, DE 19716 (United States)

    2009-05-15

    Landfill, a matured and economically appealing technology, is the ultimate approach for the management of municipal solid wastes. However, the inevitable generation of leachate from landfill requires further treatment. Among the various leachate treatment technologies available, advanced oxidation processes (AOPs) are among powerful methods to deal with the refractory organic constituents, and the Fenton reagent has evolved as one promising AOPs for the treatment of leachates. Particularly, the combination of UV-radiation with Fenton's reagent has been reported to be a method that allows both the photo-regeneration of Fe{sup 2+} and photo-decarboxylation of ferric carboxylates. In this study, Fenton and photo-Fenton processes were fine tuned for the treatment of leachates from the Colmenar Viejo (Madrid, Spain) Landfill. Results showed that it is possible to define a set of conditions under which the same COD and TOC removals (approx 70%) could be achieved with both the conventional and photo-Fenton processes. But Fenton process generated an important quantity of iron sludge, which will require further disposal, when performed under optimal COD removal conditions. Furthermore conventional Fenton process was able to achieve slightly over an 80% COD removal from a 'young' leachate, while for 'old' and 'mixed' leachates was close to a 70%. The main advantage showed by the photo-assisted Fenton treatment of landfill leachate was that it consumed 32 times less iron and produced 25 times less sludge volume yielding the same COD removal results than a conventional Fenton treatment.

  17. The Adjoint Method for The Optimization of Brachytherapy and Radiotherapy Patient Treatment Planning Procedures Using Monte Carlo Calculations

    Energy Technology Data Exchange (ETDEWEB)

    D.L. Henderson; S. Yoo; M. Kowalok; T.R. Mackie; B.R. Thomadsen

    2001-10-30

    The goal of this project is to investigate the use of the adjoint method, commonly used in the reactor physics community, for the optimization of radiation therapy patient treatment plans. Two different types of radiation therapy are being examined, interstitial brachytherapy and radiotherapy. In brachytherapy radioactive sources are surgically implanted within the diseased organ such as the prostate to treat the cancerous tissue. With radiotherapy, the x-ray source is usually located at a distance of about 1-metere from the patient and focused on the treatment area. For brachytherapy the optimization phase of the treatment plan consists of determining the optimal placement of the radioactive sources, which delivers the prescribed dose to the disease tissue while simultaneously sparing (reducing) the dose to sensitive tissue and organs. For external beam radiation therapy the optimization phase of the treatment plan consists of determining the optimal direction and intensity of beam, which provides complete coverage of the tumor region with the prescribed dose while simultaneously avoiding sensitive tissue areas. For both therapy methods, the optimal treatment plan is one in which the diseased tissue has been treated with the prescribed dose and dose to the sensitive tissue and organs has been kept to a minimum.

  18. Where does treatment optimism fit in? Examining factors associated with consistent condom use among people receiving antiretroviral treatment in Rio de Janeiro, Brazil.

    Science.gov (United States)

    Hanif, Homaira; Bastos, Francisco I; Malta, Monica; Bertoni, Neilane; Winch, Peter J; Kerrigan, Deanna

    2014-10-01

    In the era of highly active antiretrovirals, people living with HIV (PLWH) have resumed sexual activity in the context of longer and healthier lives, and thus the chances of transmitting the HIV virus, as well as the potential to be re-infected also increase. HIV treatment optimism has been found to be associated with sexual risk behaviors among PLWH in different settings. A cross sectional survey was conducted to examine the relationship between treatment optimism, safer sex burnout and consistent condom use as well as variables associated with treatment optimism in a sample of PLWH on antiretrovirals (ARVs) in Rio de Janeiro, Brazil (n = 604). Seventy-two percent of participants always used a condom in the last 6 months. Homosexual, bisexual, transexual persons were less likely to use condoms consistently than heterosexuals (AOR .58 CI .42-.78). Those who were treatment optimistic (AOR .46 CI .25-.88) were more likely not use a condom consistently in the past 6 months, as were participants who reported safer sex burnout (AOR .58 CI .36-.90). Sexual orientation, safer sex burnout, and lower education levels were significantly associated with higher treatment optimism in multivariate analysis. Study findings highlight the need to address psychosocial factors such as treatment optimism and safer sex burnout associated with lower consistent condom use among PLWH in Rio de Janeiro, Brazil.

  19. Optimization of low energy sonication treatment for granular activated carbon colonizing biomass assessment.

    Science.gov (United States)

    Saccani, G; Bernasconi, M; Antonelli, M

    2014-01-01

    This study is aimed at optimizing a low energy sonication (LES) treatment for granular activated carbon (GAC)-colonizing biomass detachment and determination, evaluating detachment efficiency and the effects of ultrasound exposure on bacterial cell viability. GAC samples were collected from two filters fed with groundwater. Conventional heterotrophic plate count (HPC) and fluorescence microscopy with a double staining method were used to evaluate cell viability, comparing two LES procedures, without and with periodical bulk substitution. A 20 min LES treatment, with bulk substitution after cycles of 5 min as maximum treatment time, allowed to recover 87%/100% of attached biomass, protecting detached bacteria from ultrasound damaging effects. Observed viable cell inactivation rate was 6.5/7.9% cell/min, with membrane-compromised cell damage appearing to be even higher (11.5%/13.1% cell/min). Assessing bacterial detachment and damaging ultrasound effects, fluorescence microscopy turned out to be more sensitive compared to conventional HPC. The optimized method revealed a GAC-colonizing biomass of 9.9 x 10(7) cell/gGAC for plant 1 and 8.8 x 10(7) cell/gGAC for plant 2, 2 log lower than reported in literature. The difference between the two GAC-colonizing biomasses is higher in terms of viable cells (46.3% of total cells in plant 1 GAC-colonizing biomass compared to the 33.3% in plant 2). Studying influent water contamination through multivariate statistical analyses, apossible combined toxic and genotoxic effect of chromium VI and trichloroethylene was suggested as a reason for the lower viable cell fraction observed in plant 2 GAC-colonizing population.

  20. Optimization of Residual Stress of High Temperature Treatment Using Genetic Algorithm and Neural Network

    Directory of Open Access Journals (Sweden)

    M. Susmikanti

    2015-12-01

    Full Text Available In a nuclear industry area, high temperature treatment of materials is a factor which requires special attention. Assessment needs to be conducted on the properties of the materials used, including the strength of the materials. The measurement of material properties under thermal processes may reflect residual stresses. The use of Genetic Algorithm (GA to determine the optimal residual stress is one way to determine the strength of a material. In residual stress modeling with several parameters, it is sometimes difficult to solve for the optimal value through analytical or numerical calculations. Here, GA is an efficient algorithm which can generate the optimal values, both minima and maxima. The purposes of this research are to obtain the optimization of variable in residual stress models using GA and to predict the center of residual stress distribution, using fuzzy neural network (FNN while the artificial neural network (ANN used for modeling. In this work a single-material 316/316L stainless steel bar is modeled. The minimal residual stresses of the material at high temperatures were obtained with GA and analytical calculations. At a temperature of 6500C, the GA optimal residual stress estimation converged at –711.3689 MPa at adistance of 0.002934 mm from center point, whereas the analytical calculation result at that temperature and position is -975.556 MPa . At a temperature of 8500C, the GA result was -969.868 MPa at 0.002757 mm from the center point, while with analytical result was -1061.13 MPa. The difference in residual stress between GA and analytical results at a temperatureof6500C is about 27 %, while at 8500C it is 8.67 %. The distribution of residual stress showed a grouping concentrated around a coordinate of (-76; 76 MPa. The residuals stress model is a degree-two polynomial with coefficients of 50.33, -76.54, and -55.2, respectively, with a standard deviation of 7.874.

  1. An integrated knowledge-based and optimization tool for the sustainable selection of wastewater treatment process concepts

    DEFF Research Database (Denmark)

    Castillo, A.; Cheali, Peam; Gómez, V.

    2016-01-01

    The increasing demand on wastewater treatment plants (WWTPs) has involved an interest in improving the alternative treatment selection process. In this study, an integrated framework including an intelligent knowledge-based system and superstructure-based optimization has been developed and appli...

  2. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment.

    Science.gov (United States)

    Wiegman, Albert; Gidding, Samuel S; Watts, Gerald F; Chapman, M John; Ginsberg, Henry N; Cuchel, Marina; Ose, Leiv; Averna, Maurizio; Boileau, Catherine; Borén, Jan; Bruckert, Eric; Catapano, Alberico L; Defesche, Joep C; Descamps, Olivier S; Hegele, Robert A; Hovingh, G Kees; Humphries, Steve E; Kovanen, Petri T; Kuivenhoven, Jan Albert; Masana, Luis; Nordestgaard, Børge G; Pajukanta, Päivi; Parhofer, Klaus G; Raal, Frederick J; Ray, Kausik K; Santos, Raul D; Stalenhoef, Anton F H; Steinhagen-Thiessen, Elisabeth; Stroes, Erik S; Taskinen, Marja-Riitta; Tybjærg-Hansen, Anne; Wiklund, Olov

    2015-09-21

    Familial hypercholesterolaemia (FH) is a common genetic cause of premature coronary heart disease (CHD). Globally, one baby is born with FH every minute. If diagnosed and treated early in childhood, individuals with FH can have normal life expectancy. This consensus paper aims to improve awareness of the need for early detection and management of FH children. Familial hypercholesterolaemia is diagnosed either on phenotypic criteria, i.e. an elevated low-density lipoprotein cholesterol (LDL-C) level plus a family history of elevated LDL-C, premature coronary artery disease and/or genetic diagnosis, or positive genetic testing. Childhood is the optimal period for discrimination between FH and non-FH using LDL-C screening. An LDL-C ≥5 mmol/L (190 mg/dL), or an LDL-C ≥4 mmol/L (160 mg/dL) with family history of premature CHD and/or high baseline cholesterol in one parent, make the phenotypic diagnosis. If a parent has a genetic defect, the LDL-C cut-off for the child is ≥3.5 mmol/L (130 mg/dL). We recommend cascade screening of families using a combined phenotypic and genotypic strategy. In children, testing is recommended from age 5 years, or earlier if homozygous FH is suspected. A healthy lifestyle and statin treatment (from age 8 to 10 years) are the cornerstones of management of heterozygous FH. Target LDL-C is 10 years, or ideally 50% reduction from baseline if 8-10 years, especially with very high LDL-C, elevated lipoprotein(a), a family history of premature CHD or other cardiovascular risk factors, balanced against the long-term risk of treatment side effects. Identifying FH early and optimally lowering LDL-C over the lifespan reduces cumulative LDL-C burden and offers health and socioeconomic benefits. To drive policy change for timely detection and management, we call for further studies in the young. Increased awareness, early identification, and optimal treatment from childhood are critical to adding decades of healthy life for children and

  3. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment

    Science.gov (United States)

    Wiegman, Albert; Gidding, Samuel S.; Watts, Gerald F.; Chapman, M. John; Ginsberg, Henry N.; Cuchel, Marina; Ose, Leiv; Averna, Maurizio; Boileau, Catherine; Borén, Jan; Bruckert, Eric; Catapano, Alberico L.; Defesche, Joep C.; Descamps, Olivier S.; Hegele, Robert A.; Hovingh, G. Kees; Humphries, Steve E.; Kovanen, Petri T.; Kuivenhoven, Jan Albert; Masana, Luis; Nordestgaard, Børge G.; Pajukanta, Päivi; Parhofer, Klaus G.; Raal, Frederick J.; Ray, Kausik K.; Santos, Raul D.; Stalenhoef, Anton F.H.; Steinhagen- Thiessen, Elisabeth; Stroes, Erik S.; Taskinen, Marja-Riitta; Tybjærg-Hansen, Anne; Wiklund, Olov

    2015-01-01

    Familial hypercholesterolaemia (FH) is a common genetic cause of premature coronary heart disease (CHD). Globally, one baby is born with FH every minute. If diagnosed and treated early in childhood, individuals with FH can have normal life expectancy. This consensus paper aims to improve awareness of the need for early detection and management of FH children. Familial hypercholesterolaemia is diagnosed either on phenotypic criteria, i.e. an elevated low-density lipoprotein cholesterol (LDL-C) level plus a family history of elevated LDL-C, premature coronary artery disease and/or genetic diagnosis, or positive genetic testing. Childhood is the optimal period for discrimination between FH and non-FH using LDL-C screening. An LDL-C ≥5 mmol/L (190 mg/dL), or an LDL-C ≥4 mmol/L (160 mg/dL) with family history of premature CHD and/or high baseline cholesterol in one parent, make the phenotypic diagnosis. If a parent has a genetic defect, the LDL-C cut-off for the child is ≥3.5 mmol/L (130 mg/dL). We recommend cascade screening of families using a combined phenotypic and genotypic strategy. In children, testing is recommended from age 5 years, or earlier if homozygous FH is suspected. A healthy lifestyle and statin treatment (from age 8 to 10 years) are the cornerstones of management of heterozygous FH. Target LDL-C is 10 years, or ideally 50% reduction from baseline if 8–10 years, especially with very high LDL-C, elevated lipoprotein(a), a family history of premature CHD or other cardiovascular risk factors, balanced against the long-term risk of treatment side effects. Identifying FH early and optimally lowering LDL-C over the lifespan reduces cumulative LDL-C burden and offers health and socioeconomic benefits. To drive policy change for timely detection and management, we call for further studies in the young. Increased awareness, early identification, and optimal treatment from childhood are critical to adding decades of healthy life for children and

  4. Optimizing the productivity of acid-fracture treatments in horizontal wells

    Energy Technology Data Exchange (ETDEWEB)

    Allen, E.

    1995-12-31

    Existing prediction methods are inadequate for unstable radial displacement, with prediction errors of up to 500%. This work provides a new theoretical basis for understanding unstable displacements in both Newtonian and non-Newtonian fluids, based on a detailed analysis of the fingering morphology and a new derivation using fractional flow theory for radial flow. Design guidelines are given to assist in optimizing the design of fingered acid-fracture treatments for horizontal wells in carbonate formations. Unstable radial displacement creates power-law (fractal) displacement patterns, for a wide range of mobility ratios, and the displacement efficiency can be expressed as a function of the mobility ratio M. The finger wavelength is a function of the Peclet number and the fracture aperture, and the detailed morphology can be understood in terms of the fluid theology. The size of the fingering zone can be predicted from the mobility ratio and Peclet number. A productivity index factor PIF can be used to compare different treatment scenarios, and thus optimise the productivity of acid-fracture treatments.

  5. Hydraulic design to optimize the treatment capacity of Multi-Stage Filtration units

    Science.gov (United States)

    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.

  6. [Optimization of liquid ammonia treatment for enzymatic hydrolysis of Saccharum arundinaceum to fermentable sugars].

    Science.gov (United States)

    Liu, Jianjun; Peng, Hehuan; Zhao, Xiangjun; Cheng, Cheng; Chen, Feng; Shao, Qianjun

    2013-03-01

    China has abundant available marginal land that can be used for cultivation of lignocellulosic energy plants. Saccharum arundinaceum Retz. is a potential energy crop with both high biomass yield and low soil fertility requirements. It can be planted widely as cellulosic ethanol feedstock in southern China. In the present work Saccharum arundinaceum was pretreated by liquid ammonia treatment (LAT) to overcome biomass recalcitrance, followed by enzymatic hydrolysis. The monosaccharide contents (glucose, xylose, and arabinose) of the enzymatic hydrolysate were determined by high performance liquid chromatography. Experimental results show that the optimal LAT pretreatment conditions were 130 0C, 2:1 (W/W) ammonia to biomass ratio, 80% moisture content (dry weight basis) and 5 min residence time. Approximately 69.34% glucan and 82.60% xylan were converted after 72 h enzymatic hydrolysis at 1% glucan loading using 15 FPU/(g of glucan) of cellulase. The yields of glucose and xylose were 573% and 1 056% higher than those of the untreated biomass, and the LAT-pretreated substrates obtained an 8-fold higher of total monosaccharide yield than untreated substrates. LAT pretreatment was an effective to increase the enzymatic digestibility of Saccharum arundinaceum compared to acid impregnated steam explosion and similar to that of acid treatment and ammonia fiber expansion treatment.

  7. Maximizing dosimetric benefits of IMRT in the treatment of localized prostate cancer through multicriteria optimization planning

    Energy Technology Data Exchange (ETDEWEB)

    Wala, Jeremiah; Craft, David [Harvard Medical School, Boston, MA (United States); Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Paly, Jon [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Zietman, Anthony [Harvard Medical School, Boston, MA (United States); Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Efstathiou, Jason, E-mail: jefstathiou@partners.org [Harvard Medical School, Boston, MA (United States); Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States)

    2013-10-01

    We examine the quality of plans created using multicriteria optimization (MCO) treatment planning in intensity-modulated radiation therapy (IMRT) in treatment of localized prostate cancer. Nine random cases of patients receiving IMRT to the prostate were selected. Each case was associated with a clinically approved plan created using Corvus. The cases were replanned using MCO-based planning in RayStation. Dose-volume histogram data from both planning systems were presented to 2 radiation oncologists in a blinded evaluation, and were compared at a number of dose-volume points. Both physicians rated all 9 MCO plans as superior to the clinically approved plans (p<10{sup −5}). Target coverage was equivalent (p = 0.81). Maximum doses to the prostate and bladder and the V50 and V70 to the anterior rectum were reduced in all MCO plans (p<0.05). Treatment planning time with MCO took approximately 60 minutes per case. MCO-based planning for prostate IMRT is efficient and produces high-quality plans with good target homogeneity and sparing of the anterior rectum, bladder, and femoral heads, without sacrificing target coverage.

  8. Heat Treatment Optimization of Rutherford Cable for a 15 T Nb3Sn Dipole Demonstrator

    Energy Technology Data Exchange (ETDEWEB)

    Barzi, Emanuela [barzi@fnal.gov

    2016-12-22

    FNAL has been developing a 15 T Nb3Sn dipole demonstrator for a future Very High Energy pp Collider based on an optimized 60-mm aperture 4-layer “cos-theta” coil. To increase magnet efficiency, the coil was graded by using two cables with same 15 mm width and different thicknesses made of two different Restacked Rod Process (RRP®) wires. Due to the non-uniform field distribution in dipole coils the maximum field in the inner coil will reach 15-16 T, whereas the maximum field in the outer coil is 12-13 T. In preparation for the 15 T dipole coil reaction, heat treatment studies were performed on strands extracted from these cables with the goal of achieving the best coil performance in the corresponding magnetic fields. In particular, the effect of maximum temperature and time on the cable critical current was studied to take into account actual variations of these parameters during coil reaction. In parallel and in collaboration with OST, development was performed on optimizing Nb3Sn RRP® wire design and layout. Index Terms— Accelerator magnet, critical current density, Nb3Sn strand, Rutherford cable.

  9. Optimization of double chamber microbial fuel cell for domestic wastewater treatment and electricity production

    Institute of Scientific and Technical Information of China (English)

    Amr El-Hag Ali; Ola M Gomaa; Reham Fathey; Hussein Abd El Kareem; Mohamed Abou Zaid

    2015-01-01

    Microbial fuel cells ( MFCs) represent a new approach for treating waste water along with electricity production. The present study addressed electricity production from domestic wastewater using a mediator-less double chamber MFC. The electricity production was monitored under different operational conditions for both summer and winter samples. Optimization of the anodic and cathodic chambers resulted in a maximal current of 0. 784 and 0. 645 mA with the maximal power intensity of 209 and 117 mW/m2 in power duration of 24 h for the summer and winter samples, respectively. Scanning electron microscopy showed that the bacterial biofilm formation on the anode was denser for the summer sample than that when the winter sample was used, so was the total bacterial count. Therefore, samples taken during summer were considered better in electricity production and waste water treatment than those taken during winter basically because of the high microbial load during the hot season. In parallel, there was a decrease in both biological oxygen demand ( BOD5 ) and chemical oxygen demand ( COD) values which reached 71. 8% and 72. 85%, respectively at the end of the operation process for the summer sample, while there was no evident decrease for the winter sample. Optimizing the operating conditions not only increased the potential of using domestic waste water in microbial fuel cells to produce electricity, but also improved the quality of the domestic waste water.

  10. Optimization of Multicomponent Behavioral and Biobehavioral Interventions for the Prevention and Treatment of HIV/AIDS.

    Science.gov (United States)

    Collins, Linda M; Kugler, Kari C; Gwadz, Marya Viorst

    2016-01-01

    To move society toward an AIDS-free generation, behavioral interventions for prevention and treatment of HIV/AIDS must be not only effective, but also cost-effective, efficient, and readily scalable. The purpose of this article is to introduce to the HIV/AIDS research community the multiphase optimization strategy (MOST), a new methodological framework inspired by engineering principles and designed to develop behavioral interventions that have these important characteristics. Many behavioral interventions comprise multiple components. In MOST, randomized experimentation is conducted to assess the individual performance of each intervention component, and whether its presence/absence/setting has an impact on the performance of other components. This information is used to engineer an intervention that meets a specific optimization criterion, defined a priori in terms of effectiveness, cost, cost-effectiveness, and/or scalability. MOST will enable intervention science to develop a coherent knowledge base about what works and does not work. Ultimately this will improve behavioral interventions systematically and incrementally.

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

    CERN Document Server

    Engberg, Lovisa; Forsgren, Anders; Hårdemark, Björn

    2016-01-01

    Given the widespread agreement that doses-at-volume play important roles in quality assessment of radiation therapy treatment plans, planning objectives that correlate well with explicit dose-at-volume optimization are likely to correlate well with plan quality. In this study, planning objectives are formulated to explicitly either minimize or maximize convex approximations of dose-at-volume, namely, mean-tail-doses. This is in contrast to the conventionally used planning objectives, which are used to maximize clinical goal fulfilment by relating to deviations from dose-at-volume thresholds. Advantages of the proposed planning objectives are investigated through juxtaposition with conventional objectives in a computational study of two patient cases, each with three doses-at-volume to be minimized subject to PTV coverage. With proposed planning objectives, this is translated into minimizing three mean-tail-doses. Comparison with conventional objectives is carried out in the dose-at-volume domain and in the no...

  12. [Triazole antifungal agents: practice guidelines of therapeutic drug monitoring and perspectives in treatment optimization].

    Science.gov (United States)

    Scodavolpe, Simon; Quaranta, Sylvie; Lacarelle, Bruno; Solas, Caroline

    2014-01-01

    Antifungal triazole agents (fluconazole, voriconazole, itraconazole and posaconazole) are widely used for the management of invasive fungal infections (IFI). These drugs are indicated both for the prophylaxis and treatment of IFI, particularly in candidiasis and aspergillosis, major cause of mortality in immunocompromised patients. Due to a large interindividual pharmacokinetic variability leading to sub-therapeutic or toxic concentrations and to concentration-efficacy and/or -toxicity relationships, therapeutic drug monitoring (TDM) of antifungal triazole is fully justified. This review provides an overview of literature based data that confirm the usefulness of such TDM and its level of evidence as well as the practical guidelines for its implementation. In addition, we discuss the interest of new tools to improve the clinical management of IFI, such as genotyping tests optimizing initial voriconazole dosing regimen or the development of a new solid oral tablet of posaconazole improving its bioavailability and limiting absorption disorders.

  13. Palliative treatment of metastatic colorectal cancer: what is the optimal approach?

    Science.gov (United States)

    Strickler, John H; Hurwitz, Herbert I

    2014-01-01

    Worldwide, colorectal cancer (CRC) is responsible for over 600,000 deaths annually and remains a significant public health concern. Because of therapeutic advancements over the past two decades, patients with metastatic CRC are living longer with an improved quality of life. This review will highlight recent trial evidence that improves outcomes for patients with metastatic disease. Topics will include the optimal use of first-line combination chemotherapy, bevacizumab in patients with advanced age or comorbidities, maintenance chemotherapy, first-line use of anti-EGFR therapies, first-line cetuximab versus bevacizumab, anti-angiogenic therapies past progression, and management of treatment-refractory disease. Clinical trial evidence will be presented, along with guidance on how to integrate recent evidence into clinical practice. Finally, this review will examine innovative drug development strategies, and will discuss potentially actionable targets identified by molecular testing.

  14. Optimization Model for Land Treatment Planning, Design and Operation. Part 3. Model Description and User’s Guide.

    Science.gov (United States)

    1983-04-01

    land treatment equations is necessary to develop the user -supplied PARAM and INPUT files and to interpret the model results. A schematic of the system...land treatment equations and is supplied and named by the user . A total of 160 parameter values must be specified. The file must consist of 26 lines...7 AD-A134 461 OPTIMIZATION MODEL FOR LAND TREATMENT PLANNING DESIN 1/AND OPERATION PART 3..U) COLD REGIONS RESEARCH ANDENGINEERING LAB HANOVER NH J A

  15. Which strategies reduce breast cancer mortality most? Collaborative modeling of optimal screening, treatment, and obesity prevention.

    Science.gov (United States)

    Mandelblatt, Jeanne; van Ravesteyn, Nicolien; Schechter, Clyde; Chang, Yaojen; Huang, An-Tsun; Near, Aimee M; de Koning, Harry; Jemal, Ahmedin

    2013-07-15

    US breast cancer mortality is declining, but thousands of women still die each year. Two established simulation models examine 6 strategies that include increased screening and/or treatment or elimination of obesity versus continuation of current patterns. The models use common national data on incidence and obesity prevalence, competing causes of death, mammography characteristics, treatment effects, and survival/cure. Parameters are modified based on obesity (defined as BMI  ≥  30 kg/m(2) ). Outcomes are presented for the year 2025 among women aged 25+ and include numbers of cases, deaths, mammograms and false-positives; age-adjusted incidence and mortality; breast cancer mortality reduction and deaths averted; and probability of dying of breast cancer. If current patterns continue, the models project that there would be about 50,100-57,400 (range across models) annual breast cancer deaths in 2025. If 90% of women were screened annually from ages 40 to 54 and biennially from ages 55 to 99 (or death), then 5100-6100 fewer deaths would occur versus current patterns, but incidence, mammograms, and false-positives would increase. If all women received the indicated systemic treatment (with no screening change), then 11,400-14,500 more deaths would be averted versus current patterns, but increased toxicity could occur. If 100% received screening plus indicated therapy, there would be 18,100-20,400 fewer deaths. Eliminating obesity yields 3300-5700 fewer breast cancer deaths versus continuation of current obesity levels. Maximal reductions in breast cancer deaths could be achieved through optimizing treatment use, followed by increasing screening use and obesity prevention. © 2013 American Cancer Society.

  16. Optimal treatment of social phobia: systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Scott KM

    2012-05-01

    Full Text Available John Canton, Kate M Scott, Paul GlueDepartment of Psychological Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New ZealandAbstract: This article proposes a number of recommendations for the treatment of generalized social phobia, based on a systematic literature review and meta-analysis. An optimal treatment regimen would include a combination of medication and psychotherapy, along with an assertive clinical management program. For medications, selective serotonin reuptake inhibitors and dual serotonin-norepinephrine reuptake inhibitors are first-line choices based on their efficacy and tolerability profiles. The nonselective monoamine oxidase inhibitor, phenelzine, may be more potent than these two drug classes, but because of its food and drug interaction liabilities, its use should be restricted to patients not responding to selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors. There are other medication classes with demonstrated efficacy in social phobia (benzodiazepines, antipsychotics, alpha-2-delta ligands, but due to limited published clinical trial data and the potential for dependence and withdrawal issues with benzodiazepines, it is unclear how best to incorporate these drugs into treatment regimens. There are very few clinical trials on the use of combined medications. Cognitive behavior therapy appears to be more effective than other evidence-based psychological techniques, and its effects appear to be more enduring than those of pharmacotherapy. There is some evidence, albeit limited to certain drug classes, that the combination of medication and cognitive behavior therapy may be more effective than either strategy used alone. Generalized social phobia is a chronic disorder, and many patients will require long-term support and treatment.Keywords: social phobia, social anxiety disorder, psychotherapy, cognitive behavior therapy, antidepressant

  17. GIS based location optimization for mobile produced water treatment facilities in shale gas operations

    Science.gov (United States)

    Kitwadkar, Amol Hanmant

    Over 60% of the nation's total energy is supplied by oil and natural gas together and this demand for energy will continue to grow in the future (Radler et al. 2012). The growing demand is pushing the exploration and exploitation of onshore oil and natural gas reservoirs. Hydraulic fracturing has proven to not only create jobs and achieve economic growth, but also has proven to exert a lot of stress on natural resources---such as water. As water is one of the most important factors in the world of hydraulic fracturing, proper fluids management during the development of a field of operation is perhaps the key element to address a lot of these issues. Almost 30% of the water used during hydraulic fracturing comes out of the well in the form of flowback water during the first month after the well is fractured (Bai et. al. 2012). Handling this large amount of water coming out of the newly fractured wells is one of the major issues as the volume of the water after this period drops off and remains constant for a long time (Bai et. al. 2012) and permanent facilities can be constructed to take care of the water over a longer period. This paper illustrates development of a GIS based tool for optimizing the location of a mobile produced water treatment facility while development is still occurring. A methodology was developed based on a multi criteria decision analysis (MCDA) to optimize the location of the mobile treatment facilities. The criteria for MCDA include well density, ease of access (from roads considering truck hauls) and piping minimization if piping is used and water volume produced. The area of study is 72 square miles east of Greeley, CO in the Wattenberg Field in northeastern Colorado that will be developed for oil and gas production starting in the year 2014. A quarterly analysis is done so that we can observe the effect of future development plans and current circumstances on the location as we move from quarter to quarter. This will help the operators to

  18. Optimization of the route of platinum drugs administration to optimize the concomitant treatment with radiotherapy for glioblastoma implanted in the Fischer rat brain

    OpenAIRE

    Charest, Gabriel; Sanche, Léon; Fortin, David; Mathieu, David; Paquette, Benoit

    2013-01-01

    Treatment of glioblastoma with platinum compounds modestly improves progression-free survival and may cause toxic effects which prevent use at higher dose that would otherwise improve the antineoplastic effect. To reduce toxicity, we propose to encapsulate the platinum drug in a liposome. We have also tested three methods of drug administration (intra-venous, intra-arterial and intra-arterial combined with blood brain barrier disruption) to determine which one optimizes the tumor cell uptake,...

  19. Economic comparison of common treatment protocols and J5 vaccination for clinical mastitis in dairy herds using optimized culling decisions.

    Science.gov (United States)

    Kessels, J A; Cha, E; Johnson, S K; Welcome, F L; Kristensen, A R; Gröhn, Y T

    2016-05-01

    This study used an existing dynamic optimization model to compare costs of common treatment protocols and J5 vaccination for clinical mastitis in US dairy herds. Clinical mastitis is an infection of the mammary gland causing major economic losses in dairy herds due to reduced milk production, reduced conception, and increased risk of mortality and culling for infected cows. Treatment protocols were developed to reflect common practices in dairy herds. These included targeted therapy following pathogen identification, and therapy without pathogen identification using a broad-spectrum antimicrobial or treating with the cheapest treatment option. The cost-benefit of J5 vaccination was also estimated. Effects of treatment were accounted for as changes in treatment costs, milk loss due to mastitis, milk discarded due to treatment, and mortality. Following ineffective treatments, secondary decisions included extending the current treatment, alternative treatment, discontinuing treatment, and pathogen identification followed by recommended treatment. Average net returns for treatment protocols and vaccination were generated using an existing dynamic programming model. This model incorporates cow and pathogen characteristics to optimize management decisions to treat, inseminate, or cull cows. Of the treatment protocols where 100% of cows received recommended treatment, pathogen-specific identification followed by recommended therapy yielded the highest average net returns per cow per year. Out of all treatment scenarios, the highest net returns were achieved with selecting the cheapest treatment option and discontinuing treatment, or alternate treatment with a similar spectrum therapy; however, this may not account for the full consequences of giving nonrecommended therapies to cows with clinical mastitis. Vaccination increased average net returns in all scenarios. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  20. Treatment planning considerations in contrast-enhanced radiotherapy: energy and beam aperture optimization

    Energy Technology Data Exchange (ETDEWEB)

    Garnica-Garza, H M, E-mail: hgarnica@cinvestav.mx [Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional Unidad Monterrey, Via del Conocimiento 201 Parque de Investigacion e Innovacion Tecnologica, Apodaca NL CP 66600 (Mexico)

    2011-01-21

    It has been shown that the use of kilovoltage x-rays in conjunction with a contrast agent incorporated into the tumor can lead to acceptable treatment plans with regard to the absorbed dose distribution produced in the target as well as in the tissue and organs at risk surrounding it. In this work, several key aspects related to the technology and irradiation techniques necessary to clinically implement this treatment modality are addressed by means of Monte Carlo simulation. The Zubal phantom was used to model a prostate radiotherapy treatment, a challenging site due to the depth of the prostate and the presence of bony structures that must be traversed by the x-ray beam on its way to the target. It is assumed that the concentration levels of the enhancing agent present in the tumor are at or below 10 mg per 1 g of tissue. The Monte Carlo code PENELOPE was used to model a commercial x-ray tube having a tungsten target. X-ray energy spectra for several combinations of peak electron energy and added filtration were obtained. For each energy spectrum, a treatment plan was calculated, with the PENELOPE Monte Carlo code, by modeling the irradiation of the patient as 72 independent conformal beams distributed at intervals of 5{sup 0} around the phantom in order to model a full x-ray source rotation. The Cimmino optimization algorithm was then used to find the optimum beam weight and energy for different treatment strategies. It is shown that for a target dose prescription of 72 Gy covering the whole tumor, the maximum rectal wall and bladder doses are kept below 52 Gy for the largest concentration of contrast agent of 10 mg per 1 g of tissue. It is also shown that concentrations of as little as 5 mg per 1 g of tissue also render dose distributions with excellent sparing of the organs at risk. A treatment strategy to address the presence of non-uniform distributions of the contrast agent in the target is also modeled and discussed.

  1. Optimal Tests of Treatment Effects for the Overall Population and Two Subpopulations in Randomized Trials, using Sparse Linear Programming.

    Science.gov (United States)

    Rosenblum, Michael; Liu, Han; Yen, En-Hsu

    2014-01-01

    We propose new, optimal methods for analyzing randomized trials, when it is suspected that treatment effects may differ in two predefined subpopulations. Such subpopulations could be defined by a biomarker or risk factor measured at baseline. The goal is to simultaneously learn which subpopulations benefit from an experimental treatment, while providing strong control of the familywise Type I error rate. We formalize this as a multiple testing problem and show it is computationally infeasible to solve using existing techniques. Our solution involves a novel approach, in which we first transform the original multiple testing problem into a large, sparse linear program. We then solve this problem using advanced optimization techniques. This general method can solve a variety of multiple testing problems and decision theory problems related to optimal trial design, for which no solution was previously available. In particular, we construct new multiple testing procedures that satisfy minimax and Bayes optimality criteria. For a given optimality criterion, our new approach yields the optimal tradeoff between power to detect an effect in the overall population versus power to detect effects in subpopulations. We demonstrate our approach in examples motivated by two randomized trials of new treatments for HIV.

  2. Percutaneous vertebroplasty: optimizing the procedure after treatment of 250 vertebral levels under fluoroscopic guidance.

    Science.gov (United States)

    Pedicelli, A; Rollo, M; Piano, M; Grattacaso, G; Colosimo, C; Bonomo, L

    2009-10-01

    Percutaneous vertebroplasty (PVP) is a minimally invasive treatment for symptomatic vertebral compression fractures (VCFs). The aim of this study was to assess the effectiveness, complications and progress of results of PVP optimized in terms of technique, costs, time and strategic protocol after 3 years of procedures performed under fluoroscopic guidance alone. We treated 250 VCFs in 120 consecutive patients after assessing clinical and radiological indications. The effectiveness of the procedure was determined by statistical analysis of numerical scores for pain, mobility and drug consumption before and after treatment. No major complications and only three minor complications occurred. Clinically relevant improved mobility and reduction of pain and analgesics were observed, with overall significant results (p<0.0001) in all patients at 24 h after PVP and in 83 available patients at 6 months. A total of five asymptomatic refractures of cemented vertebrae and 14 new symptomatic vertebral fractures at different levels were observed between 1 and 10 months after the procedure. PVP is a safe, rapid, effective and costeffective therapy for VCFs, requiring only brief hospital admission and with long-lasting clinical results, when performed under good-quality radiological guidance, when correct indications are respected and when it is associated with rehabilitation therapy in the follow-up. It is a valid alternative to conservative therapy, which is burdened by high healthcare costs and often requires long-term immobilisation of frail and elderly patients at risk of clinical complications.

  3. Optimized treatment conditions for textile wastewater reuse using photocatalytic processes under UV and visible light sources.

    Science.gov (United States)

    Starling, Maria Clara V M; Castro, Luiz Augusto S; Marcelino, Rafaela B P; Leão, Mônica M D; Amorim, Camila C

    2017-03-01

    In this study, photo-Fenton systems using visible light sources with iron and ferrioxalate were tested for the DOC degradation and decolorization of textile wastewater. Textile wastewaters originated after the dyeing stage of dark-colored tissue in the textile industry, and the optimization of treatment processes was studied to produce water suitable for reuse. Dissolved organic carbon, absorbance, turbidity, anionic concentrations, carboxylic acids, and preliminary cost analysis were performed for the proposed treatments. Conventional photo-Fenton process achieved near 99 % DOC degradation rates and complete absorbance removal, and no carboxylic acids were found as products of degradation. Ferrioxalate photo-Fenton system achieved 82 % of DOC degradation and showed complete absorbance removal, and oxalic acid has been detected through HPLC analysis in the treated sample. In contrast, photo-peroxidation with UV light was proved effective only for absorbance removal, with DOC degradation efficiency near 50 %. Treated wastewater was compared with reclaimed water and had a similar quality, indicating that these processes can be effectively applied for textile wastewater reuse. The results of the preliminary cost analysis indicated costs of 0.91 to 1.07 US$ m(-3) for the conventional and ferrioxalate photo-Fenton systems, respectively. Graphical Abstract ᅟ.

  4. Heat Transfer Simulation for Optimization and Treatment Planning of Magnetic Hyperthermia Using Magnetic Particle Imaging

    CERN Document Server

    Banura, Natsuo; Nishimoto, Kohei; Murase, Kenya

    2016-01-01

    This study was undertaken to develop a system for heat transfer simulation for optimization and treatment planning of magnetic hyperthermia treatment (MHT) using magnetic particle imaging (MPI). First, we performed phantom experiments to obtain the regression equation between the MPI pixel value and the specific absorption rate (SAR) of magnetic nanoparticles (MNPs), from which the MPI pixel value was converted to the SAR value in the simulation. Second, we generated the geometries for use in the simulation by processing X-ray computed tomography (CT) and MPI images of tumor-bearing mice injected intratumorally with MNPs (Resovist). The geometries and MPI images were then imported into software based on a finite element method (COMSOL Multiphysics) to compute the time-dependent temperature distribution for 20 min after the start of MHT. There was an excellent correlation between the MPI pixel value and the SAR value (r = 0.956). There was good agreement between the time course of the temperature rise in the t...

  5. Optimization of continuous hydrothermal treatment for improving the dehulling of black gram (Vigna mungo L).

    Science.gov (United States)

    Jerish Joyner, J; Yadav, B K

    2015-12-01

    Black gram kernels with three initial moisture contents (10, 14 & 18 % w.b.) were steam treated in a continuous steaming unit at three inlet steam pressures (2, 3 & 4 kg/cm(2)) for three grain residence times (2, 4 & 6 min) in order to determine best treatment condition for maximizing the dhal yield while limiting the colour change in acceptable range. The dhal yield, dehulling loss and the colour difference (Delta E*) of the dehulled dhal were found to vary respectively, from 56.4 to 78.8 %, 30.8 to 8.6 % and 2.1 to 9.5 with increased severity of treatment. Optimization was done in order to obtain higher dhal yield while limiting the colour difference (Delta E*) within acceptable range i.e. 2.0 to 3.5 using response surface methodology. The best condition was obtained with the samples having 13.1 % initial moisture treated with 4 kg/cm(2) for about 6 min to achieve a dhal yield of 71.2 % and dehulling loss of 15.5 %.

  6. Treatment of biodiesel wastewater by adsorption with commercial chitosan flakes: parameter optimization and process kinetics.

    Science.gov (United States)

    Pitakpoolsil, Wipawan; Hunsom, Mali

    2014-01-15

    The possibility of using commercial chitosan flakes as an adsorbent for the removal of pollutants from biodiesel wastewater was evaluated. The effect of varying the adsorption time (0.5-5 h), initial wastewater pH (2-8), adsorbent dose (0.5-5.5 g/L) and mixing rate (120-350 rpm) on the efficiency of pollutant removal was explored by univariate analysis. Under the derived optimal conditions, greater than 59.3%, 87.9% and 66.2% of the biological oxygen demand (BOD), chemical oxygen demand (COD) and oil & grease, respectively, was removed by a single adsorption. Nevertheless, the remaining BOD, COD and oil & grease were still higher than the acceptable Thai government limits for discharge into the environment. When the treatment was repeated, a greater than 93.6%, 97.6% and 95.8% removal of the BOD, COD and oil & grease, respectively, was obtained. The reusability of commercial chitosan following NaOH washing (0.05-0.2 M) was not suitable, with less than 40% efficiency after just one recycling and declining rapidly thereafter. The adsorption kinetics of all pollutant types by the commercial chitosan flakes was controlled by a mixed process of diffusion and adsorption of the pollutants during the early treatment period (0-1.5 h) and then solely controlled by adsorption after 2 h. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Process optimization via response surface methodology in the treatment of metal working industry wastewater with electrocoagulation.

    Science.gov (United States)

    Guvenc, Senem Yazici; Okut, Yusuf; Ozak, Mert; Haktanir, Birsu; Bilgili, Mehmet Sinan

    2017-02-01

    In this study, process parameters in chemical oxygen demand (COD) and turbidity removal from metal working industry (MWI) wastewater were optimized by electrocoagulation (EC) using aluminum, iron and steel electrodes. The effects of process variables on COD and turbidity were investigated by developing a mathematical model using central composite design method, which is one of the response surface methodologies. Variance analysis was conducted to identify the interaction between process variables and model responses and the optimum conditions for the COD and turbidity removal. Second-order regression models were developed via the Statgraphics Centurion XVI.I software program to predict COD and turbidity removal efficiencies. Under the optimum conditions, removal efficiencies obtained from aluminum electrodes were found to be 76.72% for COD and 99.97% for turbidity, while the removal efficiencies obtained from iron electrodes were found to be 76.55% for COD and 99.9% for turbidity and the removal efficiencies obtained from steel electrodes were found to be 65.75% for COD and 99.25% for turbidity. Operational costs at optimum conditions were found to be 4.83, 1.91 and 2.91 €/m(3) for aluminum, iron and steel electrodes, respectively. Iron electrode was found to be more suitable for MWI wastewater treatment in terms of operational cost and treatment efficiency.

  8. Optimizing electrocoagulation process for the treatment of biodiesel wastewater using response surface methodology

    Institute of Scientific and Technical Information of China (English)

    Orathai Chavalparit; Maneerat Ongwandee

    2009-01-01

    The production of biodiesel through a transesterification method produces a large amount of wastewater that contains high levels of chemical oxygen demand (COD) and oil and grease (O&G).Currently,flotation is the conventional primary treatment for O&G removal prior to biological treatments.In this study,electrocoagulation (EC) was adopted to treat the biodiesel wastewater.The effects of initial pH,applied voltage,and reaction time on the EC process for the removal of COD,O&G,and suspended solids (SS) were investigated using one factor at a time experiments.Furthermore,the Box-Behnken design,an experimental design for response surface methodology (RSM),was used to create a set of 15 experimental runs needed for optimization of the operating conditions.Quadratic regression models with estimated coefficients were developed to describe the pollutant removals.The experimental results show that EC was effective at reducing COD,O&G,and SS by 55.43%,98.42%,and 96.59%,respectively,at the optimum conditions of pH 6.06,applied voltage 18.2 V,and reaction time 23.5 min.The experimental observations were in reasonable agreement with the modeled values.

  9. Post-treatment of molasses wastewater by electrocoagulation and process optimization through response surface analysis.

    Science.gov (United States)

    Tsioptsias, C; Petridis, D; Athanasakis, N; Lemonidis, I; Deligiannis, A; Samaras, P

    2015-12-01

    Molasses wastewater is a high strength effluent of food industry such as distilleries, sugar and yeast production plants etc. It is characterized by a dark brown color and exhibits a high content in substances of recalcitrant nature such as melanoidins. In this study, electrocoagulation (EC) was studied as a post treatment step for biologically treated molasses wastewater with high nitrogen content obtained from a baker's yeast industry. Iron and copper electrodes were used in various forms; the influence and interaction of current density, molasses wastewater dilution, and reaction time, on COD, color, ammonium and nitrate removal rates and operating cost were studied and optimized through Box Behnken's response surface analysis. Reaction time varied from 0.5 to 4 h, current density varied from 5 to 40 mA/cm(2) and dilution from 0 to 90% (v/v expressed as water concentration). pH, conductivity and temperature measurements were also carried out during each experiment. From preliminary experiments, it was concluded that the application of aeration and sample dilution, considerably influenced the kinetics of the process. The obtained results showed that COD removal varied between 10 and 54%, corresponding to an operation cost ranging from 0.2 to 33 euro/kg COD removed. Significant removal rates were obtained for nitrogen as nitrate and ammonium (i.e. 70% ammonium removal). A linear relation of COD and ammonium to the design parameters was observed, while operation cost and nitrate removal responded in a curvilinear function. A low ratio of electrode surface to treated volume was used, associated to a low investment cost; in addition, iron wastes could be utilized as low cost electrodes i.e. iron fillings from lathes, aiming to a low operation cost due to electrodes replacement. In general, electrocoagulation proved to be an effective and low cost process for biologically treated molasses-wastewater treatment for additional removal of COD and nitrogen content and

  10. On the selection of optimization parameters for an inverse treatment planning replacement of a forward planning technique for prostate cancer.

    Science.gov (United States)

    Hristov, Dimitre H; Moftah, Belal A; Charrois, Colette; Parker, William; Souhami, Luis; Podgorsak, Ervin B

    2002-01-01

    The influence of organ volume sampling, lateral scatter inclusion, and the selection of objectives and constraints on the inverse treatment planning process with a commercial treatment planning system is investigated and suitable parameters are identified for an inverse treatment planning replacement of a clinical forward planning technique for prostate cancer. For the beam geometries of the forward technique, a variable set of parameters is used for the calculation of dose from pencil beams. An optimal set is identified after the evaluation of optimized plans that correspond to different sets of pencil-beam parameters. This set along with a single, optimized set of objectives and constraints is used to perform inverse planning on ten randomly selected patients. The acceptability of the resulting plans is verified by comparisons to the clinical ones calculated with the forward techniques. For the particular commercial treatment planning system, the default values of the pencil beam parameters are found adequate for inverse treatment planning. For all ten patients, the optimized, single set of objectives and constraints results in plans with target coverage comparable to that of the forward plans. Furthermore inverse treatment planning reduces the overall mean rectal and bladder doses by 4.8% and 5.8% of the prescription dose respectively. The study indicates that (i) inverse treatment planning results depend implicitly on the sampling of the dose distribution, (ii) inverse treatment planning results depend on the method used by the dose calculation model to account for scatter, and (iii) for certain sites, a single set of optimization parameters can be used for all patient plans.

  11. Prevalence of optimal treatment regimens in patients with apparent treatment-resistant hypertension based on office blood pressure in a community-based practice network.

    Science.gov (United States)

    Egan, Brent M; Zhao, Yumin; Li, Jiexiang; Brzezinski, W Adam; Todoran, Thomas M; Brook, Robert D; Calhoun, David A

    2013-10-01

    Hypertensive patients with clinical blood pressure (BP) uncontrolled on ≥3 antihypertensive medications (ie, apparent treatment-resistant hypertension [aTRH]) comprise ≈28% to 30% of all uncontrolled patients in the United States. However, the proportion receiving these medications in optimal doses is unknown; aTRH is used because treatment adherence and measurement artifacts were not available in electronic record data from our >200 community-based clinics Outpatient Quality Improvement Network. This study sought to define the proportion of uncontrolled hypertensives with aTRH on optimal regimens and clinical factors associated with optimal therapy. During 2007-2010, 468 877 hypertensive patients met inclusion criteria. BP hypertension doses). Among 468 877 hypertensives, 147 635 (31.5%) were uncontrolled; among uncontrolled hypertensives, 44 684 were prescribed ≥3 BP medications (30.3%), of whom 22 189 (15.0%) were prescribed optimal therapy. Clinical factors independently associated with optimal BP therapy included black race (odds ratio, 1.40 [95% confidence interval, 1.32-1.49]), chronic kidney disease (1.31 [1.25-1.38]), diabetes mellitus (1.30 [1.24-1.37]), and coronary heart disease risk equivalent status (1.29 [1.14-1.46]). Clinicians more often prescribe optimal therapy for aTRH when cardiovascular risk is greater and treatment goals lower. Approximately 1 in 7 of all uncontrolled hypertensives and 1 in 2 with uncontrolled aTRH are prescribed ≥3 BP medications in optimal regimens. Prescribing more optimal pharmacotherapy for uncontrolled hypertensives including aTRH, confirmed with out-of-office BP, could improve hypertension control.

  12. Pharmacokinetic/pharmacodynamic-based optimization of levofloxacin administration in the treatment of MDR-TB.

    Science.gov (United States)

    Ghimire, Samiksha; Van't Boveneind-Vrubleuskaya, Natasha; Akkerman, Onno W; de Lange, Wiel C M; van Soolingen, Dick; Kosterink, Jos G W; van der Werf, Tjip S; Wilffert, Bob; Touw, Daniel J; Alffenaar, Jan-Willem C

    2016-10-01

    The emergence of MDR-TB and XDR-TB has complicated TB treatment success. Among many factors that contribute to the development of resistance, low drug exposure is not the least important. This review summarizes the available information on pharmacokinetic properties of levofloxacin in relation to microbial susceptibilities, in order to optimize the dose and make general treatment recommendations. A total of 37 studies on adult (32 studies) and paediatric (5 studies) MDR-TB patients were included. Among the 32 adult studies, 19 were on susceptibility of Mycobacterium tuberculosis isolates to levofloxacin by MIC, 1 was on susceptibility of M. tuberculosis isolates to levofloxacin by MBC, 1 was on susceptibility of M. tuberculosis isolates to levofloxacin by mutant prevention concentration and 4 were on pharmacokinetics of levofloxacin, and 7 others were included. Likewise, out of five studies on children, two dealt with levofloxacin pharmacokinetic parameters, one reviewed CSF concentrations and two dealt with background information. In adult MDR-TB patients, standard dosing of once-daily 1000 mg levofloxacin in TB treatment did not consistently attain the target concentration (i.e. fAUC/MIC >100 and fAUC/MBC >100) in 80% of the patients with MIC and MBC of 1 mg/L, leaving them at risk of developing drug resistance. However, with an MIC of 0.5 mg/L, 100% of the patients achieved the target concentration. Similarly, paediatric patients failed consistently in achieving given pharmacokinetic/pharmacodynamic targets due to age-related differences, demanding a shift towards once daily dosing of 15-20 mg/kg. Therefore, we recommend therapeutic drug monitoring for patients with strains having MICs of ≥0.5 mg/L and suggest revising the cut-off value from 2 to 1 mg/L.

  13. Bone marrow mesenchymal stem cell therapy in ischemic stroke:mechanisms of action and treatment optimization strategies

    Institute of Scientific and Technical Information of China (English)

    Guihong Li; Fengbo Yu; Ting Lei; Haijun Gao; Peiwen Li; Yuxue Sun; Haiyan Huang; Qingchun Mu

    2016-01-01

    Animal and clinical studies have conifrmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research.

  14. Treatment outcome of thymic epithelial tumor: prognostic factors and optimal postoperative radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Dong Ryul; Ahn, Yong Chan; Kim, Kwan Min; Kim, Jhin Gook; Shim, Young Mog; Han, Jung Ho [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2005-06-15

    This study was conducted to analyze treatment outcome and prognostic significance of World Health Organization (WHO)-defined thymic epithelial tumor (TET) subtype and to assess optimal radiation target volume in patients receiving surgery and adjuvant radiation therapy with TET. The record of 160 patients with TET, who received surgical resection at the Samsung medical Center, from December 1994 to June 2004, were reviewed. 99 patients were treated with postoperative radiation therapy (PORT). PORT was recommended when patients had more than one findings among suspicious incomplete resection or positive resection margin or Masaoka stage II {approx} IV or WHO tumor type B2 {approx} C. PORT performed to primary tumor bed only with a mean dose of 54 Gy. The prognostic factor and pattern of failure were analyzed retrospectively. The overall survival rate at 5 years was 87.3%. Age (more than 60 years 77.8%, less than 60 years 91.1%; {rho} = 0.03), Masaoka stage (I 92.2%, II 95.4%, III 82.1%, IV 67.5%; {rho} = 0.001), WHO tumor type (A-B1 96.0%, B2-C 82.3%; {rho} = 0.001), Extent of resection (R0 resection 92.3%, R1 or 2 resection 72.6%; {rho} = 0.001) were the prognostic factors according to univariate analysis. But WHO tumor type was the only significant prognostic factor according to multivariate analysis. Recurrence was observed in 5 patients of 71 Masoka stage I-III patients who received grossly complete tumor removal (R0, R1 resection ) and PORT to primary tumor bed. Mediastinal recurrence was observed in only one patients. There were no recurrence within irradiation field. WHO tumor type was the important prognostic factor to predict survival of patients with TET. This study suggest that PORT to only primary tumor bed was optimal. To avoid pleura-or pericardium-based recurrence, further study of effective chemotherapy should be investigated.

  15. Optimal control strategies for tuberculosis treatment: a case study in Angola

    CERN Document Server

    Silva, Cristiana J

    2012-01-01

    We apply optimal control theory to a tuberculosis model given by a system of ordinary differential equations. Optimal control strategies are proposed to minimize the cost of interventions. Numerical simulations are given using data from Angola.

  16. Optimal Finite Cancer Treatment Duration by Using Mixed Vaccine Therapy and Chemotherapy: State Dependent Riccati Equation Control

    Directory of Open Access Journals (Sweden)

    Ali Ghaffari

    2014-01-01

    Full Text Available The main objective of this paper is to propose an optimal finite duration treatment method for cancer. A mathematical model is proposed to show the interactions between healthy and cancerous cells in the human body. To extend the existing models, the effect of vaccine therapy and chemotherapy are also added to the model. The equilibrium points and the related local stability are derived and discussed. It is shown that the dynamics of the cancer model must be changed and modified for finite treatment duration. Therefore, the vaccine therapy is used to change the parameters of the system and the chemotherapy is applied for pushing the system to the domain of attraction of the healthy state. For optimal chemotherapy, an optimal control is used based on state dependent Riccati equation (SDRE. It is shown that, in spite of eliminating the treatment, the system approaches the healthy state conditions. The results show that the development of optimal vaccine-chemotherapy protocols for removing tumor cells would be an appropriate strategy in cancer treatment. Also, the present study states that a proper treatment method not only reduces the population of the cancer cells but also changes the dynamics of the cancer.

  17. CHALLENGES AND OPPORTUNITIES--INTEGRATED LIFE-CYCLE OPTIMIZATION INITIATIVES FOR THE HANFORD RIVER PROTECTION PROJECT--WASTE TREATMENT PLANT

    Energy Technology Data Exchange (ETDEWEB)

    Auclair, K. D.

    2002-02-25

    This paper describes the ongoing integrated life-cycle optimization efforts to achieve both design flexibility and design stability for activities associated with the Waste Treatment Plant at Hanford. Design flexibility is required to support the Department of Energy Office of River Protection Balance of Mission objectives, and design stability to meet the Waste Treatment Plant construction and commissioning requirements in order to produce first glass in 2007. The Waste Treatment Plant is a large complex project that is driven by both technology and contractual requirements. It is also part of a larger overall mission, as a component of the River Protection Project, which is driven by programmatic requirements and regulatory, legal, and fiscal constraints. These issues are further complicated by the fact that both of the major contractors involved have a different contract type with DOE, and neither has a contract with the other. This combination of technical and programmatic drivers, constraints, and requirements will continue to provide challenges and opportunities for improvement and optimization. The Bechtel National, Inc. team is under contract to engineer, procure, construct, commission and test the Waste Treatment Plant on or ahead of schedule, at or under cost, and with a throughput capacity equal to or better than specified. The Department of Energy is tasked with the long term mission of waste retrieval, treatment, and disposal. While each mission is a compliment and inextricably linked to one another, they are also at opposite ends of the spectrum, in terms of expectations of one another. These mission requirements, that are seemingly in opposition to one another, pose the single largest challenge and opportunity for optimization: one of balance. While it is recognized that design maturation and optimization are the normal responsibility of any engineering firm responsible for any given project, the aspects of integrating requirements and the management

  18. Optimal treatment of Alzheimer’s disease psychosis: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Koppel J

    2014-11-01

    Full Text Available Jeremy Koppel,1,2 Blaine S Greenwald2 1The Feinstein Institute for Medical Research, North Shore–Long Island Jewish Health System, Manhasset, NY, USA; 2Zucker Hillside Hospital, Hofstra North Shore-Long Island Jewish School of Medicine, Glen Oaks, NY, USA Abstract: Psychotic symptoms emerging in the context of neurodegeneration as a consequence of Alzheimer’s disease was recognized and documented by Alois Alzheimer himself in his description of the first reported case of the disease. Over a quarter of a century ago, in the context of attempting to develop prognostic markers of disease progression, psychosis was identified as an independent predictor of a more-rapid cognitive decline. This finding has been subsequently well replicated, rendering psychotic symptoms an important area of exploration in clinical history taking – above and beyond treatment necessity – as their presence has prognostic significance. Further, there is now a rapidly accreting body of research that suggests that psychosis in Alzheimer’s disease (AD+P is a heritable disease subtype that enjoys neuropathological specificity and localization. There is now hope that the elucidation of the neurobiology of the syndrome will pave the way to translational research eventuating in new treatments. To date, however, the primary treatments employed in alleviating the suffering caused by AD+P are the atypical antipsychotics. These agents are approved by the US Food and Drug Administration for the treatment of schizophrenia, but they have only marginal efficacy in treating AD+P and are associated with troubling levels of morbidity and mortality. For clinical approaches to AD+P to be optimized, this syndrome must be disentangled from other primary psychotic disorders, and recent scientific advances must be translated into disease-specific therapeutic interventions. Here we provide a review of atypical antipsychotic efficacy in AD+P, followed by an overview of critical

  19. Optimizing Fracture Treatments in a Mississippian "Chat" Reservoir, South-Central Kansas

    Energy Technology Data Exchange (ETDEWEB)

    K. David Newell; Saibal Bhattacharya; Alan Byrnes; W. Lynn Watney; Willard Guy

    2005-10-01

    This project is a collaboration of Woolsey Petroleum Corporation (a small independent operator) and the Kansas Geological Survey. The project will investigate geologic and engineering factors critical for designing hydraulic fracture treatments in Mississippian ''chat'' reservoirs. Mississippian reservoirs, including the chat, account for 159 million m3 (1 billion barrels) of the cumulative oil produced in Kansas. Mississippian reservoirs presently represent {approx}40% of the state's 5.6*106m3 (35 million barrels) annual production. Although geographically widespread, the ''chat'' is a heterogeneous reservoir composed of chert, cherty dolomite, and argillaceous limestone. Fractured chert with micro-moldic porosity is the best reservoir in this 18- to 30-m-thick (60- to 100-ft) unit. The chat will be cored in an infill well in the Medicine Lodge North field (417,638 m3 [2,626,858 bbls] oil; 217,811,000 m3 [7,692,010 mcf] gas cumulative production; discovered 1954). The core and modern wireline logs will provide geological and petrophysical data for designing a fracture treatment. Optimum hydraulic fracturing design is poorly defined in the chat, with poor correlation of treatment size to production increase. To establish new geologic and petrophysical guidelines for these treatments, data from core petrophysics, wireline logs, and oil-field maps will be input to a fracture-treatment simulation program. Parameters will be established for optimal size of the treatment and geologic characteristics of the predicted fracturing. The fracturing will be performed and subsequent wellsite tests will ascertain the results for comparison to predictions. A reservoir simulation program will then predict the rate and volumetric increase in production. Comparison of the predicted increase in production with that of reality, and the hypothetical fracturing behavior of the reservoir with that of its actual behavior, will serve as tests of

  20. Evaluation of the generalized gamma as a tool for treatment planning optimization

    Directory of Open Access Journals (Sweden)

    Emmanouil I Petrou

    2014-12-01

    independent software. Furthermore, it was proved that after a small change in dose, the organ that is being affected most is the organ with the highest Generalized Gamma. Apart from that, the validity of the theoretical expressions that describe the change in response and the associated Generalized Gamma was verified but only for the case of small change in dose. Especially for the case of 50% TCP and NTCP, the theoretical values (ΔPapprox. and those calculated by the RayStation show close agreement, which proves the high importance of the D50 parameter in specifying clinical response levels. Finally, the presented findings show that the behavior of ΔPapprox. looks sensible because, for both of the models that were used (Poisson and Probit, it significantly approaches the real ΔP around the region of 37% and 50% response. The present study managed to evaluate the mathematical expression of Generalized Gamma for the case of non-uniform dose delivery and the accuracy of the RayStation to calculate its values for different organs. Conclusion: A very important finding of this work is the establishment of the usefulness and clinical relevance of Generalized Gamma. That is because it gives the planner the opportunity to precisely determine which organ will be affected most after a small increase in dose and as a result an optimal treatment plan regarding tumor control and normal tissue complications can be found.

  1. Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection.

    Science.gov (United States)

    Wagh, Kshitij; Bhattacharya, Tanmoy; Williamson, Carolyn; Robles, Alex; Bayne, Madeleine; Garrity, Jetta; Rist, Michael; Rademeyer, Cecilia; Yoon, Hyejin; Lapedes, Alan; Gao, Hongmei; Greene, Kelli; Louder, Mark K; Kong, Rui; Karim, Salim Abdool; Burton, Dennis R; Barouch, Dan H; Nussenzweig, Michel C; Mascola, John R; Morris, Lynn; Montefiori, David C; Korber, Bette; Seaman, Michael S

    2016-03-01

    The identification of a new generation of potent broadly neutralizing HIV-1 antibodies (bnAbs) has generated substantial interest in their potential use for the prevention and/or treatment of HIV-1 infection. While combinations of bnAbs targeting distinct epitopes on the viral envelope (Env) will likely be required to overcome the extraordinary diversity of HIV-1, a key outstanding question is which bnAbs, and how many, will be needed to achieve optimal clinical benefit. We assessed the neutralizing activity of 15 bnAbs targeting four distinct epitopes of Env, including the CD4-binding site (CD4bs), the V1/V2-glycan region, the V3-glycan region, and the gp41 membrane proximal external region (MPER), against a panel of 200 acute/early clade C HIV-1 Env pseudoviruses. A mathematical model was developed that predicted neutralization by a subset of experimentally evaluated bnAb combinations with high accuracy. Using this model, we performed a comprehensive and systematic comparison of the predicted neutralizing activity of over 1,600 possible double, triple, and quadruple bnAb combinations. The most promising bnAb combinations were identified based not only on breadth and potency of neutralization, but also other relevant measures, such as the extent of complete neutralization and instantaneous inhibitory potential (IIP). By this set of criteria, triple and quadruple combinations of bnAbs were identified that were significantly more effective than the best double combinations, and further improved the probability of having multiple bnAbs simultaneously active against a given virus, a requirement that may be critical for countering escape in vivo. These results provide a rationale for advancing bnAb combinations with the best in vitro predictors of success into clinical trials for both the prevention and treatment of HIV-1 infection.

  2. Single versus multichannel applicator in high-dose-rate vaginal brachytherapy optimized by inverse treatment planning.

    Science.gov (United States)

    Bahadur, Yasir A; Constantinescu, Camelia; Hassouna, Ashraf H; Eltaher, Maha M; Ghassal, Noor M; Awad, Nesreen A

    2015-01-01

    To retrospectively compare the potential dosimetric advantages of a multichannel vaginal applicator vs. a single channel one in intracavitary vaginal high-dose-rate (HDR) brachytherapy after hysterectomy, and evaluate the dosimetric advantage of fractional re-planning. We randomly selected 12 patients with endometrial carcinoma, who received adjuvant vaginal cuff HDR brachytherapy using a multichannel applicator. For each brachytherapy fraction, two inverse treatment plans (for central channel and multichannel loadings) were performed and compared. The advantage of fractional re-planning was also investigated. Dose-volume-histogram (DVH) analysis showed limited, but statistically significant difference (p = 0.007) regarding clinical-target-volume dose coverage between single and multichannel approaches. For the organs-at-risk rectum and bladder, the use of multichannel applicator demonstrated a noticeable dose reduction, when compared to single channel, but statistically significant for rectum only (p = 0.0001). For D2cc of rectum, an average fractional dose of 6.1 ± 0.7 Gy resulted for single channel vs. 5.1 ± 0.6 Gy for multichannel. For D2cc of bladder, an average fractional dose of 5 ± 0.9 Gy occurred for single channel vs. 4.9 ± 0.8 Gy for multichannel. The dosimetric benefit of fractional re-planning was demonstrated: DVH analysis showed large, but not statistically significant differences between first fraction plan and fractional re-planning, due to large inter-fraction variations for rectum and bladder positioning and filling. Vaginal HDR brachytherapy using a multichannel vaginal applicator and inverse planning provides dosimetric advantages over single channel cylinder, by reducing the dose to organs at risk without compromising the target volume coverage, but at the expense of an increased vaginal mucosa dose. Due to large inter-fraction dose variations, we recommend individual fraction treatment plan optimization.

  3. Optimal treatment of chronic angina in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Kaur H

    2014-07-01

    Full Text Available Harjinder Kaur,1 Kully Sandhu,2 Awais Jabbar,3 Azfar G Zaman3,4 1City Hospitals Sunderland, Sunderland, UK; 2University Hospital of North Staffordshire, Stoke-on-Trent, UK; 3Freeman Hospital, Newcastle-upon-Tyne, UK; 4Institute of Cellular Medicine, Newcastle University, Newcastle, UK Abstract: Type 2 diabetes mellitus (T2DM trebles the risk of developing coronary artery disease (CAD; once CAD has developed, the risk of acute coronary syndromes (ACS and clinical risk associated with a coronary event, both double in diabetic patients. Patients with T2DM have more extensive CAD and present at a younger age; therefore, identification and management of chronic angina in these patients presents an opportunity to limit both cardiovascular symptoms and adverse outcomes. This article reviews the role of screening and treatment for chronic angina in patients with T2DM. There is a strong evidence base for modifying lifestyle as a way of reducing adverse cardiovascular outcomes in the diabetic population and this article reviews evidence of lifestyle modification as an important and necessary adjunct to pharmacologic intervention. Management of chronic stable angina is addressed by looking at treatments that reduce ischemic symptoms and those that reduce adverse cardiovascular outcomes. Trials specific to the diabetic population are limited, with information largely obtained from the diabetic subgroup analysis of large intervention trials. The growing diabetic population with increased propensity to cardiovascular disease mandates trials specifically in this patient population. Revascularization in patients with diabetes is associated with more complications than in the non-diabetic population. Recent trials specific to this population suggest surgical revascularization to be associated with better long-term outcomes and therefore, this article reviews the evidence for the optimal mode of revascularization in this population. Keywords: type 2 diabetes

  4. Mixed matrix membrane application for olive oil wastewater treatment: process optimization based on Taguchi design method.

    Science.gov (United States)

    Zirehpour, Alireza; Rahimpour, Ahmad; Jahanshahi, Mohsen; Peyravi, Majid

    2014-01-01

    Olive oil mill wastewater (OMW) is a concentrated effluent with a high organic load. It has high levels of organic chemical oxygen demand (COD) and phenolic compounds. This study presents a unique process to treat OMW. The process uses ultrafiltration (UF) membranes modified by a functionalized multi wall carbon nano-tube (F-MWCNT). The modified tube has an inner diameter of 15-30 nm and is added to the OMW treatment process to improve performance of the membrane. Tests were done to evaluate the following operating parameters of the UF system; pressure, pH and temperature; also evaluated parameters of permeate flux, flux decline, COD removal and total phenol rejection. The Taguchi robust design method was applied for an optimization evaluation of the experiments. Variance (ANOVA) analysis was used to determine the most significant parameters affecting permeate flux, flux decline, COD removal and total phenols rejection. Results demonstrated coagulation and pH as the most important factors affecting permeate flux of the UF. Moreover, pH and F-MWCNT UF had significant positive effects on flux decline, COD removal and total phenols rejection. Based on the optimum conditions determined by the Taguchi method, evaluations for permeate flux tests; flux decline, COD removal and total phenols rejection were about 21.2 (kg/m(2) h), 12.6%, 72.6% and 89.5%, respectively. These results were in good agreement with those predicted by the Taguchi method (i.e.; 22.8 (kg/m(2) h), 11.9%, 75.8 and 94.7%, respectively). Mechanical performance of the membrane and its application for high organic wastewater treatment were determined as strong.

  5. Optimization of a full-scale Unitank wastewater treatment plant for biological phosphorus removal.

    Science.gov (United States)

    Zhou, Zhen; Xing, Can; Wu, Zhichao; Tong, Fei; Wang, Junru

    2014-01-01

    The Unitank process combines the advantages of traditional continuous-flow activated sludge processes and sequencing batch reactors, and has been extensively employed in many wastewater treatment plants (WWTPs) in China. Biological phosphorus removal (BPR) of a full-scale Unitank WWTP was optimized by increasing anaerobic time from 80 to 120 min in an operation cycle of 360 min and reducing solid retention time (SRT) from 21.3 to 13.1 d. The BPR efficiency of the full-scale Unitank system increased from 63.8% (SRT of 21.3 d) to 83.2% for a SRT of 13.1 d. When the anaerobic time increased from 80 to 120 min, the net anaerobic phosphorus release amount increased from 0.25 to 1.06 mg L(-1), and sludge phosphorus content rose from 13.8 to 15.0 mgP x (gSS)(-1). During half an operation cycle, the average specific phosphorus release rate increased from 0.097mgP x (gVSS x h)(-1) in 0-40 min to 0.825 mgP x (gVSS x h)(-1) in 40-60 min. Reducing SRT and increasing anaerobic time account for 84.6% and 15.4% in the total increment of phosphorus removal of 1.15 mgL(-1).

  6. Design and optimization of aspartate N-acetyltransferase inhibitors for the potential treatment of Canavan disease.

    Science.gov (United States)

    Thangavelu, Bharani; Mutthamsetty, Vinay; Wang, Qinzhe; Viola, Ronald E

    2017-02-01

    Canavan disease is a fatal neurological disorder caused by defects in the metabolism of N-acetyl-l-aspartate (NAA). Recent work has shown that the devastating symptoms of this disorder are correlated with the elevated levels of NAA observed in these patients, caused as a consequence of the inability of mutated forms of aspartoacylase to adequately catalyze its breakdown. The membrane-associated enzyme responsible for the synthesis of NAA, aspartate N-acetyltransferase (ANAT), has recently been purified and examined (Wang et al., Prot Expr Purif. 2016;119:11). With the availability, for the first time, of a stable and soluble form of ANAT we can now report the identification of initial inhibitors against this biosynthetic enzyme, obtained from the screening of several focused compound libraries. Two core structures of these moderate binding compounds have subsequently been optimized, with the most potent inhibitors in these series possessing sub-micromolar inhibition constants (Ki values) against ANAT. Slowing the production of NAA via the inhibition of ANAT will lower the elevated levels of this metabolite and can potentially serve as a treatment option to moderate the symptoms of Canavan disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Intermittent cryogen spray cooling for optimal heat extraction during dermatologic laser treatment

    Science.gov (United States)

    Majaron, Boris; Svaasand, Lars O.; Aguilar, Guillermo; Nelson, J. Stuart

    2002-09-01

    Fast heat extraction is critically important to obtain the maximal benefit of cryogen spray cooling (CSC) during laser therapy of shallow skin lesions, such as port wine stain birthmarks. However, a film of liquid cryogen can build up on the skin surface, impairing heat transfer due to the relatively low thermal conductivity and higher temperature of the film as compared to the impinging spray droplets. In an attempt to optimize the cryogen mass flux, while minimally affecting other spray characteristics, we apply a series of 10 ms spurts with variable duty cycles. Heat extraction dynamics during such intermittent cryogen sprays were measured using a custom-made metal-disc detector. The highest cooling rates were observed at moderate duty cycle levels. This confirms the presence, and offers a practical way to eliminate the adverse effect of liquid cryogen build-up on the sprayed surface. On the other hand, lower duty cycles allow a substantial reduction in the average rate of heat extraction, enabling less aggressive and more efficient CSC for treatment of deeper targets, such as hair follicles.

  8. Nano-precipitation Strengthened G91 by Thermo-mechanical Treatment Optimization

    Science.gov (United States)

    Vivas, J.; Celada-Casero, C.; San Martín, D.; Serrano, M.; Urones-Garrote, E.; Adeva, P.; Aranda, M. M.; Capdevila, C.

    2016-11-01

    The increase of thermal efficiency in power plants has been the main driving force to develop Ferritic/Martensitic steels for structural applications capable of operating at 923 K (650 °C) and higher. It has been clarified in previous works that nano-sized precipitates and its distribution are the key factors controlling the stability of the microstructure at high operating temperatures. Based on the science of precipitate strengthening, the aim of this work is to optimize the thermo-mechanical treatment in a commercial creep-resistant steel (G91) to achieve a microstructure where MX precipitates present a suitable size and distribution. The alternative processing route proposed here allows gaining an increase up to 40 pct in yield strength at 973 K (700 °C) compared to the commercial steel. The results of small punch test carried out at room temperature showed that the improvement in strength was obtained without loss of ductility. This fact was attributed to a finer and more homogeneous dispersion of MX precipitates in comparison to the commercial steel.

  9. A study of remitted and treatment-resistant depression using MMPI and including pessimism and optimism scales.

    Directory of Open Access Journals (Sweden)

    Masatoshi Suzuki

    Full Text Available The psychological aspects of treatment-resistant and remitted depression are not well documented.We administered the Minnesota Multiphasic Personality Inventory (MMPI to patients with treatment-resistant depression (n = 34, remitted depression (n = 25, acute depression (n = 21, and healthy controls (n = 64. Pessimism and optimism were also evaluated by MMPI.ANOVA and post-hoc tests demonstrated that patients with treatment-resistant and acute depression showed similarly high scores for frequent scale (F, hypochondriasis, depression, conversion hysteria, psychopathic device, paranoia, psychasthenia and schizophrenia on the MMPI compared with normal controls. Patients with treatment-resistant depression, but not acute depression registered high on the scale for cannot say answer. Using Student's t-test, patients with remitted depression registered higher on depression and social introversion scales, compared with normal controls. For pessimism and optimism, patients with treatment-resistant depression demonstrated similar changes to acutely depressed patients. Remitted depression patients showed lower optimism than normal controls by Student's t-test, even though these patients were deemed recovered from depression using HAM-D.The patients with remitted depression and treatment-resistant depression showed subtle alterations on the MMPI, which may explain the hidden psychological features in these cohorts.

  10. A study of remitted and treatment-resistant depression using MMPI and including pessimism and optimism scales.

    Science.gov (United States)

    Suzuki, Masatoshi; Takahashi, Michio; Muneoka, Katsumasa; Sato, Koichi; Hashimoto, Kenji; Shirayama, Yukihiko

    2014-01-01

    The psychological aspects of treatment-resistant and remitted depression are not well documented. We administered the Minnesota Multiphasic Personality Inventory (MMPI) to patients with treatment-resistant depression (n = 34), remitted depression (n = 25), acute depression (n = 21), and healthy controls (n = 64). Pessimism and optimism were also evaluated by MMPI. ANOVA and post-hoc tests demonstrated that patients with treatment-resistant and acute depression showed similarly high scores for frequent scale (F), hypochondriasis, depression, conversion hysteria, psychopathic device, paranoia, psychasthenia and schizophrenia on the MMPI compared with normal controls. Patients with treatment-resistant depression, but not acute depression registered high on the scale for cannot say answer. Using Student's t-test, patients with remitted depression registered higher on depression and social introversion scales, compared with normal controls. For pessimism and optimism, patients with treatment-resistant depression demonstrated similar changes to acutely depressed patients. Remitted depression patients showed lower optimism than normal controls by Student's t-test, even though these patients were deemed recovered from depression using HAM-D. The patients with remitted depression and treatment-resistant depression showed subtle alterations on the MMPI, which may explain the hidden psychological features in these cohorts.

  11. Optimization of beam angles for intensity modulated radiation therapy treatment planning using genetic algorithm on a distributed computing platform.

    Science.gov (United States)

    Nazareth, Daryl P; Brunner, Stephen; Jones, Matthew D; Malhotra, Harish K; Bakhtiari, Mohammad

    2009-07-01

    Planning intensity modulated radiation therapy (IMRT) treatment involves selection of several angle parameters as well as specification of structures and constraints employed in the optimization process. Including these parameters in the combinatorial search space vastly increases the computational burden, and therefore the parameter selection is normally performed manually by a clinician, based on clinical experience. We have investigated the use of a genetic algorithm (GA) and distributed-computing platform to optimize the gantry angle parameters and provide insight into additional structures, which may be necessary, in the dose optimization process to produce optimal IMRT treatment plans. For an IMRT prostate patient, we produced the first generation of 40 samples, each of five gantry angles, by selecting from a uniform random distribution, subject to certain adjacency and opposition constraints. Dose optimization was performed by distributing the 40-plan workload over several machines running a commercial treatment planning system. A score was assigned to each resulting plan, based on how well it satisfied clinically-relevant constraints. The second generation of 40 samples was produced by combining the highest-scoring samples using techniques of crossover and mutation. The process was repeated until the sixth generation, and the results compared with a clinical (equally-spaced) gantry angle configuration. In the sixth generation, 34 of the 40 GA samples achieved better scores than the clinical plan, with the best plan showing an improvement of 84%. Moreover, the resulting configuration of beam angles tended to cluster toward the patient's sides, indicating where the inclusion of additional structures in the dose optimization process may avoid dose hot spots. Additional parameter selection in IMRT leads to a large-scale computational problem. We have demonstrated that the GA combined with a distributed-computing platform can be applied to optimize gantry angle

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

    Science.gov (United States)

    Yarmand, Hamed; Winey, Brian; Craft, David

    2013-09-07

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

  13. Optimal dosage and duration of pivmecillinam treatment for uncomplicated lower urinary tract infections: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Mariona Pinart

    2017-05-01

    Conclusions: There is insufficient evidence to support the use of an optimal combination of dosage, frequency, and duration of PIV therapy for the treatment of uncomplicated lower UTI. Evidence is limited due to the high risk of bias, poor reporting, and heterogeneous study data.

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

    Energy Technology Data Exchange (ETDEWEB)

    Chi, Y; Li, Y; Tian, Z; Gu, X; Jiang, S; Jia, X [UT Southwestern Medical Center, Dallas, TX (United States)

    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 was 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.

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

    Science.gov (United States)

    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.

  16. Optimal injection volume of epinephrine for endoscopic treatment of peptic ulcer bleeding

    Institute of Scientific and Technical Information of China (English)

    Tai-Cherng Liou; Shee-Chan Lin; Horng-Yuan Wang; Wen-Hsiung Chang

    2006-01-01

    bleeding with a low rate of complications. The optimal injection volume of epinephrine for endoscopic treatment of an actively bleeding ulcer (spurting or oozing) is 30 mL.

  17. An integrative view of mechanisms underlying generalized spike-and-wave epileptic seizures and its implication on optimal therapeutic treatments.

    Directory of Open Access Journals (Sweden)

    Boyuan Yan

    Full Text Available Many types of epileptic seizures are characterized by generalized spike-and-wave discharges. In the past, notable effort has been devoted to understanding seizure dynamics and various hypotheses have been proposed to explain the underlying mechanisms. In this paper, by taking an integrative view of the underlying mechanisms, we demonstrate that epileptic seizures can be generated by many different combinations of synaptic strengths and intrinsic membrane properties. This integrative view has important medical implications: the specific state of a patient characterized by a set of biophysical characteristics ultimately determines the optimal therapeutic treatment. Through the same view, we further demonstrate the potentiation effect of rational polypharmacy in the treatment of epilepsy and provide a new angle to resolve the debate on polypharmacy. Our results underscore the need for personalized medicine and demonstrate that computer modeling and simulation may play an important role in assisting the clinicians in selecting the optimal treatment on an individual basis.

  18. HIV treatment optimism and sexual risk behaviors among HIV positive African American men who have sex with men.

    Science.gov (United States)

    Peterson, John L; Miner, Michael H; Brennan, David J; Rosser, B R Simon

    2012-04-01

    The association between HIV treatment optimism--beliefs about susceptibility to transmit HIV, motivation to use condoms, and severity of HIV--and sexual risk behavior was examined among HIV-positive African American men who have sex with men (MSM). Participants were 174 men recruited in four major metropolitan areas of the United States to participate in a weekend HIV risk reduction intervention. Baseline results revealed that beliefs in less susceptibility to transmit HIV and less motivation to use condoms were significantly associated with more unprotected anal intercourse among serodiscordant casual partners. Less motivation to use condoms also predicted more unprotected insertive and receptive anal sex and was more important than susceptibility beliefs in predicting these behaviors. Suggestions are offered of ways to better inform HIV-positive African American MSM about their misperceptions about HIV treatment and how their level of optimism about HIV treatment may diminish or encourage condom use.

  19. Multi-response optimization of Fenton process for applicability assessment in landfill leachate treatment.

    Science.gov (United States)

    Amiri, Allahyar; Sabour, Mohammad Reza

    2014-12-01

    Fenton process, as a pretreatment method, was found to be effective in the primary treatment of mature/medium landfill leachate. However, the main problem of the process is the large amount of produced sludge that requires an accurate feasibility evaluation for operational applications. In this study, the response surface methodology was applied for the modeling and optimization of Fenton process in three target responses, (1) overall COD removal, (2) sludge to iron ratio (SIR) and (3) organics removal to sludge ratio (ORSR), where the latter two were new self-defined responses for prediction of sludge generation and applicability assessment of the process, respectively. The effective variables included the initial pH, [H2O2]/[Fe(2+)] ratio and Fe(2+) dosage. According to the statistical analysis, all the proposed models were adequate (with adjusted R(2) of 0.9116-0.9512) and had considerable predictive capability (with prediction R(2) up to 0.9092 and appropriate adequate precision). It was found that all the variables had significant effects on the responses, specifically by their observed role in dominant oxidation mechanism. The optimum operational conditions obtained by overlay plot, were found to be initial pH of 5.7, [H2O2]/[Fe(2+)] ratio of 17.72 and [Fe(2+)] of 195 mM, which led to 69% COD removal, 2.4 (l sludge/consumed mole Fe(2+)) of SIR and 16.5 (gCOD removed/l produced sludge) for ORSR in verification test, in accordance with models-predicted values. Finally, it was observed that [H2O2]/[Fe(2+)] ratio and Fe(2+) dosage had significant influence on COD removal, while Fe(2+) dosage and [H2O2]/[Fe(2+)] ratio had remarkable effects on SIR and ORSR responses, respectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Optimizing hepatitis C virus treatment through pharmacist interventions: Identification and management of drug-drug interactions

    Science.gov (United States)

    Langness, Jacob A; Nguyen, Matthew; Wieland, Amanda; Everson, Gregory T; Kiser, Jennifer J

    2017-01-01

    AIM To quantify drug-drug-interactions (DDIs) encountered in patients prescribed hepatitis C virus (HCV) treatment, the interventions made, and the time spent in this process. METHODS As standard of care, a clinical pharmacist screened for DDIs in patients prescribed direct acting antiviral (DAA) HCV treatment between November 2013 and July 2015 at the University of Colorado Hepatology Clinic. HCV regimens prescribed included ledipasvir/sofosbuvir (LDV/SOF), paritaprevir/ritonavir/ombitasvir/dasabuvir (OBV/PTV/r + DSV), simeprevir/sofosbuvir (SIM/SOF), and sofosbuvir/ribavirin (SOF/RBV). This retrospective analysis reviewed the work completed by the clinical pharmacist in order to measure the aims identified for the study. The number and type of DDIs identified were summarized with descriptive statistics. RESULTS Six hundred and sixty four patients (83.4% Caucasian, 57% male, average 56.7 years old) were identified; 369 for LDV/SOF, 48 for OBV/PTV/r + DSV, 114 for SIM/SOF, and 133 for SOF/RBV. Fifty-one point five per cent of patients were cirrhotic. Overall, 5217 medications were reviewed (7.86 medications per patient) and 781 interactions identified (1.18 interactions per patient). The number of interactions were fewest for SOF/RBV (0.17 interactions per patient) and highest for OBV/PTV/r + DSV (2.48 interactions per patient). LDV/SOF and SIM/SOF had similar number of interactions (1.28 and 1.48 interactions per patient, respectively). Gastric acid modifiers and vitamin/herbal supplements commonly caused interactions with LDV/SOF. Hypertensive agents, analgesics, and psychiatric medications frequently caused interactions with OBV/PTV/r + DSV and SIM/SOF. To manage these interactions, the pharmacists most often recommended discontinuing the medication (28.9%), increasing monitoring for toxicities (24.1%), or separating administration times (18.2%). The pharmacist chart review for each patient usually took approximately 30 min, with additional time for more complex

  1. Free terminal time optimal control problem for the treatment of HIV infection

    Directory of Open Access Journals (Sweden)

    Amine Hamdache

    2016-01-01

    to provide the explicit formulations of the optimal controls. The corresponding optimality system with the additional transversality condition for the terminal time is derived and solved numerically using an adapted iterative method with a Runge-Kutta fourth order scheme and a gradient method routine.

  2. WE-B-304-02: Treatment Planning Evaluation and Optimization Should Be Biologically and Not Dose/volume Based

    Energy Technology Data Exchange (ETDEWEB)

    Deasy, J. [Memorial Sloan Kettering Cancer Center, New York, NY (United States)

    2015-06-15

    The ultimate goal of radiotherapy treatment planning is to find a treatment that will yield a high tumor control probability (TCP) with an acceptable normal tissue complication probability (NTCP). Yet most treatment planning today is not based upon optimization of TCPs and NTCPs, but rather upon meeting physical dose and volume constraints defined by the planner. It has been suggested that treatment planning evaluation and optimization would be more effective if they were biologically and not dose/volume based, and this is the claim debated in this month’s Point/Counterpoint. After a brief overview of biologically and DVH based treatment planning by the Moderator Colin Orton, Joseph Deasy (for biological planning) and Charles Mayo (against biological planning) will begin the debate. Some of the arguments in support of biological planning include: this will result in more effective dose distributions for many patients DVH-based measures of plan quality are known to have little predictive value there is little evidence that either D95 or D98 of the PTV is a good predictor of tumor control sufficient validated outcome prediction models are now becoming available and should be used to drive planning and optimization Some of the arguments against biological planning include: several decades of experience with DVH-based planning should not be discarded we do not know enough about the reliability and errors associated with biological models the radiotherapy community in general has little direct experience with side by side comparisons of DVH vs biological metrics and outcomes it is unlikely that a clinician would accept extremely cold regions in a CTV or hot regions in a PTV, despite having acceptable TCP values Learning Objectives: To understand dose/volume based treatment planning and its potential limitations To understand biological metrics such as EUD, TCP, and NTCP To understand biologically based treatment planning and its potential limitations.

  3. WE-B-304-01: Treatment Planning Evaluation and Optimization Should Be Dose/volume and Not Biologically Based

    Energy Technology Data Exchange (ETDEWEB)

    Mayo, C. [Mayo Clinic (United States)

    2015-06-15

    The ultimate goal of radiotherapy treatment planning is to find a treatment that will yield a high tumor control probability (TCP) with an acceptable normal tissue complication probability (NTCP). Yet most treatment planning today is not based upon optimization of TCPs and NTCPs, but rather upon meeting physical dose and volume constraints defined by the planner. It has been suggested that treatment planning evaluation and optimization would be more effective if they were biologically and not dose/volume based, and this is the claim debated in this month’s Point/Counterpoint. After a brief overview of biologically and DVH based treatment planning by the Moderator Colin Orton, Joseph Deasy (for biological planning) and Charles Mayo (against biological planning) will begin the debate. Some of the arguments in support of biological planning include: this will result in more effective dose distributions for many patients DVH-based measures of plan quality are known to have little predictive value there is little evidence that either D95 or D98 of the PTV is a good predictor of tumor control sufficient validated outcome prediction models are now becoming available and should be used to drive planning and optimization Some of the arguments against biological planning include: several decades of experience with DVH-based planning should not be discarded we do not know enough about the reliability and errors associated with biological models the radiotherapy community in general has little direct experience with side by side comparisons of DVH vs biological metrics and outcomes it is unlikely that a clinician would accept extremely cold regions in a CTV or hot regions in a PTV, despite having acceptable TCP values Learning Objectives: To understand dose/volume based treatment planning and its potential limitations To understand biological metrics such as EUD, TCP, and NTCP To understand biologically based treatment planning and its potential limitations.

  4. Treatment planning of intensity modulated composite particle therapy with dose and linear energy transfer optimization

    Science.gov (United States)

    Inaniwa, Taku; Kanematsu, Nobuyuki; Noda, Koji; Kamada, Tadashi

    2017-06-01

    The biological effect of charged-particle beams depends on both dose and particle spectrum. As one of the physical quantities describing the particle spectrum of charged-particle beams, we considered the linear energy transfer (LET) throughout this study. We investigated a new therapeutic technique using two or more ion species in one treatment session, which we call an intensity modulated composite particle therapy (IMPACT), for optimizing the physical dose and dose-averaged LET distributions in a patient as its proof of principle. Protons and helium, carbon, and oxygen ions were considered as ion species for IMPACT. For three cubic targets of 4  ×  4  ×  4, 8  ×  8  ×  8, and 12  ×  12  ×  12 cm3, defined at the center of the water phantom of 20  ×  20  ×  20 cm3, we made IMPACT plans of two composite fields with opposing and orthogonal geometries. The prescribed dose to the target was fixed at 1 Gy, while the prescribed LET to the target was varied from 1 keV µm-1 to 120 keV µm-1 to investigate the range of LET valid for prescription. The minimum and maximum prescribed LETs, (L T_min, L T_max), by the opposing-field geometry, were (3 keV µm-1, 115 keV µm-1), (2 keV µm-1, 84 keV µm-1),and (2 keV µm-1, 66 keV µm-1), while those by the orthogonal-field geometry were (8 keV µm-1, 98 keV µm-1), (7 keV µm-1, 72 keV µm-1), and (8 keV µm-1, 57 keV µm-1) for the three targets, respectively. To show the proof of principle of IMPACT in a clinical situation, we made IMPACT plans for a prostate case. In accordance with the prescriptions, the LETs in prostate, planning target volume (PTV), and rectum could be adjusted at 80 keV µm-1, at 50 keV µm-1, and below 30 keV µm-1, respectively, while keeping the dose to the PTV at 2 Gy uniformly. IMPACT enables the optimization of the dose and the LET distributions in a patient, which will maximize the

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

    Energy Technology Data Exchange (ETDEWEB)

    Hosini, M [King Saud University Hospitals, Riyadh (Saudi Arabia); GALAL, M [Hermitage Medical Clinic, Dublin (Ireland); Emam, I [Ain Shams University, Cairo (France); Kamal, G; Algohary, M [Al Azhar University, Cairo (Egypt)

    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 Direct 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.

  6. Combined MV + kV inverse treatment planning for optimal kV dose incorporation in IGRT

    Science.gov (United States)

    Grelewicz, Zachary; Wiersma, Rodney D.

    2014-04-01

    Despite the existence of real-time kV intra-fractional tumor tracking strategies for many years, clinical adoption has been held back by concern over the excess kV imaging dose cost to the patient when imaging in continuous fluoroscopic mode. This work aims to solve this problem by investigating, for the first time, the use of convex optimization tools to optimally integrate this excess kV imaging dose into the MV therapeutic dose in order to make real-time kV tracking clinically feasible. Phase space files modeling both a 6 MV treatment beam and a kV on-board-imaging beam of a commercial LINAC were generated with BEAMnrc, and used to generate dose influence matrices in DOSXYZnrc for ten previously treated lung cancer patients. The dose optimization problem for IMRT, formulated as a quadratic problem, was modified to include additional constraints as required for real-time kV intra-fractional tracking. An interior point optimizer was used to solve the modified optimization problem. It was found that when using large kV imaging apertures during fluoroscopic tracking, combined MV + kV optimization lead to a 0.5%-5.17% reduction in the total number of monitor units assigned to the MV beam due to inclusion of the kV dose over the ten patients. This was accompanied by a reduction of up to 42% of the excess kV dose compared to standard MV IMRT with kV tracking. For all kV field sizes considered, combined MV + kV optimization provided prescription dose to the treatment volume coverage equal to the no-imaging case, yet superior to standard MV IMRT with non-optimized kV fluoroscopic tracking. With combined MV + kV optimization, it is possible to quantify in a patient specific way the dosimetric effect of real-time imaging on the patient. Such information is necessary when substantial kV imaging is performed.

  7. Design and development of a new micro-beam treatment planning system: effectiveness of algorithms of optimization and dose calculations and potential of micro-beam treatment.

    Science.gov (United States)

    Tachibana, Hidenobu; Kojima, Hiroyuki; Yusa, Noritaka; Miyajima, Satoshi; Tsuda, Akihisa; Yamashita, Takashi

    2012-07-01

    A new treatment planning system (TPS) was designed and developed for a new treatment system, which consisted of a micro-beam-enabled linac with robotics and a real-time tracking system. We also evaluated the effectiveness of the implemented algorithms of optimization and dose calculations in the TPS for the new treatment system. In the TPS, the optimization procedure consisted of the pseudo Beam's-Eye-View method for finding the optimized beam directions and the steepest-descent method for determination of beam intensities. We used the superposition-/convolution-based (SC-based) algorithm and Monte Carlo-based (MC-based) algorithm to calculate dose distributions using CT image data sets. In the SC-based algorithm, dose density scaling was applied for the calculation of inhomogeneous corrections. The MC-based algorithm was implemented with Geant4 toolkit and a phase-based approach using a network-parallel computing. From the evaluation of the TPS, the system can optimize the direction and intensity of individual beams. The accuracy of the dose calculated by the SC-based algorithm was less than 1% on average with the calculation time of 15 s for one beam. However, the MC-based algorithm needed 72 min for one beam using the phase-based approach, even though the MC-based algorithm with the parallel computing could decrease multiple beam calculations and had 18.4 times faster calculation speed using the parallel computing. The SC-based algorithm could be practically acceptable for the dose calculation in terms of the accuracy and computation time. Additionally, we have found a dosimetric advantage of proton Bragg peak-like dose distribution in micro-beam treatment.

  8. Optimism, Symptom Distress, Illness Appraisal, and Coping in Patients With Advanced-Stage Cancer Diagnoses Undergoing Chemotherapy Treatment.

    Science.gov (United States)

    Sumpio, Catherine; Jeon, Sangchoon; Northouse, Laurel L; Knobf, M Tish

    2017-05-01

    To explore the relationships between optimism, self-efficacy, symptom distress, treatment complexity, illness appraisal, coping, and mood disturbance in patients with advanced-stage cancer.
. Cross-sectional study.
. Smilow Cancer Hospital at Yale New Haven in Connecticut, an outpatient comprehensive cancer center.
. A convenience sample of 121 adult patients with stages III-IV cancer undergoing active chemotherapy.
. Participants completed common self-report questionnaires to measure variables. Treatment hours and visits were calculated from data retrieved from medical record review. Mediation and path analysis were conducted to identify direct and indirect pathways from the significant antecedent variables to mood disturbance.
. Dispositional optimism, self-efficacy, social support, treatment complexity, symptom distress, illness appraisal, coping, and mood disturbance.
. Greater optimism and self-efficacy were associated with less negative illness appraisal, less avoidant coping, and decreased mood disturbance. Conversely, greater symptom distress was associated with greater negative illness appraisal, greater avoidant coping, and greater mood disturbance. In the final model, optimism and symptom distress had direct and indirect effects on mood disturbance. Indirect effects were partially mediated by illness appraisal.
. Mood disturbance resulted from an interaction of disease stressors, personal resources, and cognitive appraisal of illness. Avoidant coping was associated with greater disturbed mood, but neither avoidant nor active coping had a significant effect on mood in the multivariate model. 
. Illness appraisal, coping style, and symptom distress are important targets for intervention. Optimism is a beneficial trait and should be included, along with coping style, in comprehensive nursing assessments of patients with cancer.

  9. Optimizing Treatment with TNF Inhibitors in Inflammatory Bowel Disease by Monitoring Drug Levels and Antidrug Antibodies

    DEFF Research Database (Denmark)

    Steenholdt, Casper; Bendtzen, Klaus; Brynskov, Jørn

    2016-01-01

    BACKGROUND: Biological tumor necrosis factor (TNF) inhibitors have revolutionized the treatment of inflammatory bowel disease and redefined treatment goals to include mucosal healing. Clinicians are faced with challenges such as inadequate responses, treatment failures, side effects, and high dru....... CONCLUSIONS: TDM-guided anti-TNF therapy at treatment failure has been brought from bench to bedside....

  10. From the risk-stratification of patients with dilated cardiomyopathy to the optimal treatment strategy

    Directory of Open Access Journals (Sweden)

    Frolov A.V.

    2016-03-01

    Conclusions. Application of the original model of risk stratification will allow to optimize the general management in DCM and the strategy of timely selection of potential candidates for implantation of cardioverter- defibrillator for the primary prevention of SCD.

  11. Optimization of Heat Treatment Process for Internal Clutch by Using Taguchi Technique

    Directory of Open Access Journals (Sweden)

    Prof. S. R. Thakare,

    2014-01-01

    Full Text Available Surface engineering and surface engineered materials find wide applications in engineering industries in recent years. Inconsistency in hardness and case depth has resulted in the further optimization of the process variables involved in surface hardening. In the present study, the following operating parameters viz. Carbon potential, holding position, furnace temperature, carburizing time, quenching medium, quenching temperature, quenching time, tempering temperature and tempering time were taken for optimization using the Taguchi and Factorial design of experiment concepts. From the experiments and optimization analysis conducted on EN8 materials it was observed that furnace temperature and quenching time had equal influence in obtaining a better surface integrity of the case hardened components using gas carburizing. In the case of induction hardening process, power potential played a vital role in optimizing the surface hardness and the depth of hardness.

  12. The optimization of electrocoagulation process for treatment of the textile wastewater by Response surface Methodology (RSM

    Directory of Open Access Journals (Sweden)

    Samaneh Ghodrati

    2014-10-01

    Conclusion: The experimental results indicated that the EC process is an efficient and promising process for the decolorization and COD removal of textile effluents. Under the optimized conditions, the experimental values had a good correlation with the predicted ones, indicating suitability of the model and the success of the RSM in optimizing the conditions of EC process in treating the textile wastewater with maximum removals of color and COD under selected conditions of independent variables.

  13. Optimization of the heat treatment schedule for next european dipole (NED) powder in tube $Nb_{3}Sn$ strand

    CERN Document Server

    Boutboul, T; den Ouden, A; Pedrini, D; Volpini, G

    2009-01-01

    A Nb3Sn strand was successfully developed by the company SMI for Next European Dipole (NED) activity and on the basis of Powder-In-Tube (PIT) method. This strand, after the standard reaction recommended by the firm (84 h @ 675 oC), presents attractive performances as a critical current density in the non-copper part of ~ 2500 A/mm2 for 4.2 K and 12 T applied field, an effective filament diameter of ~ 50 μm and limited flux jumps at low magnetic fields. Heat treatment optimization studies are currently performed at CERN to try to optimize the strand electric abilities. For this purpose, various heat treatment schedules were already investigated with a plateau temperature as low as 625 oC. The preliminary results of these studies are summarized here.

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

    Science.gov (United States)

    Seeley, Kaelyn; Cunha, J. Adam; Hong, Tae Min

    2017-01-01

    We discuss an improvement in brachytherapy--a prostate cancer treatment method that directly places radioactive seeds inside target cancerous regions--by optimizing the current standard for delivering dose. Currently, the seeds' spatiotemporal placement is determined by optimizing the dose based on a set of physical, user-defined constraints. One particular approach is the ``inverse planning'' algorithms that allow for tightly fit isodose lines around the target volumes in order to reduce dose to the patient's organs at risk. However, these dose distributions are typically computed assuming the same biological response to radiation for different types of tissues. In our work, we consider radiobiological parameters to account for the differences in the individual sensitivities and responses to radiation for tissues surrounding the target. Among the benefits are a more accurate toxicity rate and more coverage to target regions for planning high-dose-rate treatments as well as permanent implants.

  15. Optimizing Antibiotic Dosing Strategies for the Treatment of Gram-negative Infections in the Era of Resistance.

    Science.gov (United States)

    Monogue, Marguerite L; Kuti, Joseph L; Nicolau, David P

    2016-01-01

    Gram-negative organisms are an increasing source of concern within the healthcare setting due to their common presence as a cause of infection and emerging resistance to current therapies. However, current antimicrobial dosing recommendations may be insufficient for the treatment of gram-negative infections. Applying knowledge of an antibiotic's pharmacokinetic/pharmacodynamic profile when designing a dosing regimen leads to a greater likelihood of achieving optimal exposure, including against gram-negative pathogens with higher MICs. Additionally, administering antibiotics directly to the site of infection, such as via aerosolization for pneumonia, is another method to achieve optimized drug exposure at the site of infection. Incorporating these treatment strategies into clinical practice will assist antimicrobial stewardship programs in successfully treating gram-negative infections.

  16. Optimization of the diabetic nephropathy treatment with attention to the special features of cellular inflammation mechanisms

    Directory of Open Access Journals (Sweden)

    Тетяна Дмитрівна Щербань

    2016-02-01

    Full Text Available Aim. Optimization of the diabetic nephropathy (DN treatment in association with hypertonic disease (HD based on the study of neutrophil chain of pathogenic cellular mechanisms of these diseases development and the special features of its clinical course.Materials and methods. There were complexly examined 86 patients with HD associated with DN and 30 patients with isolated HD. The control group was formed by 30 practically healthy persons. The activity of NO-synthases in neutrophils was detected by Green colorimetric methods using Griess reagent. The expression of ІСАМ-1 (CD54, CD11b-integrin and inducible NO-synthase on neutrophils was detected by the indirect immunocytochemical method. Oxygen-depending activity of neutrophils was assessed in NBT-test.Results. Expression of adhesive molecules of CD54and CD11b-integrin on neutrophils of peripheral blood essentially increases (р <0,001 in patients with DN in association with HD comparing with isolated HD and the control group.At associated pathology on the background of high oxygen-depending activity of neutrophils its functional reserve decreases that results in intensification of inflammatory processes in kidneys (р<0,001.In comorbid patients chronization of pathological process results in imbalance of NO-synthases system in neutrophils: on the background of decrease of activity of constituent NO-synthases the expression and activity of inducible NO-synthase increase (р<0,001 .The use of L-arginine hydrochloride in the complex therapy of patients with DN associated with HD intensifies organoprotective effect of basal therapy, results in facilitation of the clinical course, decreases albuminuria, corrects the functional indices of neutrophils and diminishes imbalance in NO-synthases system.Conclusions. In patients with DN in association with HD the neutrophil chain of cellular inflammation mechanisms are activated: expression of adhesive molecules grows, oxygen-depending metabolism is

  17. A new approach to integrate GPU-based Monte Carlo simulation into inverse treatment plan optimization for proton therapy

    Science.gov (United States)

    Li, Yongbao; Tian, Zhen; Song, Ting; Wu, Zhaoxia; Liu, Yaqiang; Jiang, Steve; Jia, Xun

    2017-01-01

    Monte Carlo (MC)-based spot dose calculation is highly desired for inverse treatment planning in proton therapy because of its accuracy. Recent studies on biological optimization have also indicated the use of MC methods to compute relevant quantities of interest, e.g. linear energy transfer. Although GPU-based MC engines have been developed to address inverse optimization problems, their efficiency still needs to be improved. Also, the use of a large number of GPUs in MC calculation is not favorable for clinical applications. The previously proposed adaptive particle sampling (APS) method can improve the efficiency of MC-based inverse optimization by using the computationally expensive MC simulation more effectively. This method is more efficient than the conventional approach that performs spot dose calculation and optimization in two sequential steps. In this paper, we propose a computational library to perform MC-based spot dose calculation on GPU with the APS scheme. The implemented APS method performs a non-uniform sampling of the particles from pencil beam spots during the optimization process, favoring those from the high intensity spots. The library also conducts two computationally intensive matrix-vector operations frequently used when solving an optimization problem. This library design allows a streamlined integration of the MC-based spot dose calculation into an existing proton therapy inverse planning process. We tested the developed library in a typical inverse optimization system with four patient cases. The library achieved the targeted functions by supporting inverse planning in various proton therapy schemes, e.g. single field uniform dose, 3D intensity modulated proton therapy, and distal edge tracking. The efficiency was 41.6  ±  15.3% higher than the use of a GPU-based MC package in a conventional calculation scheme. The total computation time ranged between 2 and 50 min on a single GPU card depending on the problem size.

  18. Breast cancer regional radiation fields for supraclavicular and axillary lymph node treatment: is a posterior axillary boost field technique optimal?

    Science.gov (United States)

    Wang, Xiaochun; Yu, Tse Kuan; Salehpour, Mohammad; Zhang, Sean X; Sun, Tzouh Liang; Buchholz, Thomas A

    2009-05-01

    To assess whether using an anterior oblique supraclavicular (SCV) field with a posterior axillary boost (PAB) field is an optimal technique for targeting axillary (AX) lymph nodes compared with two computed tomography (CT)-based techniques: (1) an SCV field with an anterior boost field and (2) intensity-modulated radiotherapy (IMRT). Ten patients with CT simulation data treated with postmastectomy radiation that included an SCV field were selected for the study. Supraclavicular nodes and AX Level I-III nodes within the SCV field were contoured and defined as the treatment target. Plans using the three techniques were generated and evaluated for each patient. The anterior axillary boost field and IMRT resulted in superior dose coverage compared with PAB. Namely, treatment volumes that received 105%, 80%, and 30% of prescribed dose for IMRT plans were significantly less than those for the anterior axillary boost plans, which were significantly less than PAB. For PAB and anterior axillary boost plans, there was a linear correlation between treatment volume receiving 105% of prescribed dose and maximum target depth. Furthermore, the IMRT technique resulted in better lung sparing and dose conformity to the target than anterior axillary boost, which again was significantly better than PAB. The maximum cord dose for IMRT was small, but higher than for the other two techniques. More monitor units were required to deliver the IMRT plan than the PAB plan, which was more than the anterior axillary boost plan. The PAB technique is not optimal for treatment of AX lymph nodes in an SCV field. We conclude that CT treatment planning with dose optimization around delineated target volumes should become standard for radiation treatments of supraclavicular and AX lymph nodes.

  19. Optimal control of hepatitis C antiviral treatment programme delivery for prevention amongst a population of injecting drug users.

    Directory of Open Access Journals (Sweden)

    Natasha K Martin

    Full Text Available In most developed countries, HCV is primarily transmitted by injecting drug users (IDUs. HCV antiviral treatment is effective, and deemed cost-effective for those with no re-infection risk. However, few active IDUs are currently treated. Previous modelling studies have shown antiviral treatment for active IDUs could reduce HCV prevalence, and there is emerging interest in developing targeted IDU treatment programmes. However, the optimal timing and scale-up of treatment is unknown, given the real-world constraints commonly existing for health programmes. We explore how the optimal programme is affected by a variety of policy objectives, budget constraints, and prevalence settings. We develop a model of HCV transmission and treatment amongst active IDUs, determine the optimal treatment programme strategy over 10 years for two baseline chronic HCV prevalence scenarios (30% and 45%, a range of maximum annual budgets (£50,000-300,000 per 1,000 IDUs, and a variety of objectives: minimising health service costs and health utility losses; minimising prevalence at 10 years; minimising health service costs and health utility losses with a final time prevalence target; minimising health service costs with a final time prevalence target but neglecting health utility losses. The largest programme allowed for a given budget is the programme which minimises both prevalence at 10 years, and HCV health utility loss and heath service costs, with higher budgets resulting in greater cost-effectiveness (measured by cost per QALY gained compared to no treatment. However, if the objective is to achieve a 20% relative prevalence reduction at 10 years, while minimising both health service costs and losses in health utility, the optimal treatment strategy is an immediate expansion of coverage over 5-8 years, and is less cost-effective. By contrast, if the objective is only to minimise costs to the health service while attaining the 20% prevalence reduction, the

  20. Optimization of Fenton oxidation pre-treatment for B. thuringiensis - based production of value added products from wastewater sludge.

    Science.gov (United States)

    Pham, T T H; Brar, S K; Tyagi, R D; Surampalli, R Y

    2010-08-01

    Fenton oxidation pretreatment was investigated for enhancement of biodegradability of wastewater sludge (WWS) which was subsequently used as substrate for the production of value- added products. The Response surface method with fractional factorial and central composite designs was applied to determine the effects of Fenton parameters on solubilization and biodegradability of sludge and the optimization of the Fenton process. Maximum solubilization and biodegradability were obtained as 70% and 74%, respectively at the optimal conditions: 0.01 ml H(2)O(2)/g SS, 150 [H(2)O(2)](0)/[Fe(2+)](0), 25 g/L TS, at 25 degrees C and 60 min duration. Further, these optimal conditions were tested for the production of a value added product, Bacillus thuringiensis (Bt) which is being used as a biopesticide in the agriculture and forestry sector. It was observed that Bt growth using Fenton oxidized sludge as a substrate was improved with a maximum total cell count of 1.63 x 10(9)CFU ml(-1) and 96% sporulation after 48 h of fermentation. The results were also tested against ultrasonication treatment and the total cell count was found to be 4.08 x 10(8)CFU ml(-1) with a sporulation of 90%. Hence, classic Fenton oxidation was demonstrated to be a rather more promising chemical pre-treatment for Bt - based biopesticide production using WWS when compared to ultrasonication as a physical pre-treatment.

  1. News of Biomedical Advances in HIV: Relationship to Treatment Optimism and Expected Risk Behavior in US MSM.

    Science.gov (United States)

    Zimmerman, Rick S; Kirschbaum, Allison L

    2017-03-14

    HIV treatment optimism and the ways in which news of HIV biomedical advances in HIV is presented to the most at-risk communities interact in ways that affect risk behavior and the incidence of HIV. The goal of the current study was to understand the relationships among HIV treatment optimism, knowledge of HIV biomedical advances, and current and expected increased risk behavior as a result of reading hypothetical news stories of further advances. Most of an online-recruited sample of MSM were quite knowledgeable about current biomedical advances. After reading three hypothetical news stories, 15-24% of those not living with HIV and 26-52% of those living with HIV reported their condom use would decrease if the story they read were true. Results suggest the importance of more cautious reporting on HIV biomedical advances, and for targeting individuals with greater treatment optimism and those living with HIV via organizations where they are most likely to receive their information about HIV.

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

    Science.gov (United States)

    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.

  3. SU-E-T-555: A Protontherapy Inverse Treatment Planning System Prototype with Linear Energy Transfer (LET) Optimization

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez-Parcerisa, D; Carabe-Fernandez, A [Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA (United States)

    2014-06-01

    Purpose: Develop and benchmark an inverse treatment planning system (TPS) for proton radiotherapy integrating fast analytical dose and LET calculations in patient geometries and a dual objective function with both dose and LET components, enabling us to apply optimization techniques to improve the predicted outcome of treatments based on radiobiological models. Methods: The software package was developed in MATLAB and implements a fluence-dose calculation technique based on a pencil beam model for dose calculations and a 3D LET model based on the extension of the LET in the radial direction as a function of the predicted radiological pathway. Both models were benchmarked against commissioning data from our institution, dose calculations performed with a commercial treatment planning system and Monte Carlo simulations. The optimization is based on the adaptive simulated annealing approach . Results: The dose and LET calculations were tested in a water phantom and several real patient treatments. The pass rate for the gamma index analysis (3%/3mm) test was above 90% for all test cases analyzed, and the calculation time was of the order of seconds. The inverse planning module produced plans with a significantly higher mean LET in the target compared to traditional plans, without any loss of target coverage. The clinical relevance of this improvement is under consideration . Conclusion: The developed treatment planning system is a valuable clinical and research tool that enables us to incorporate LET effects into proton radiotherapy planning in a streamlined fashion.

  4. A role for biological optimization within the current treatment planning paradigm

    Energy Technology Data Exchange (ETDEWEB)

    Das, Shiva [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 (United States)

    2009-10-15

    Purpose: Biological optimization using complication probability models in intensity modulated radiotherapy (IMRT) planning has tremendous potential for reducing radiation-induced toxicity. Nevertheless, biological optimization is almost never clinically utilized, probably because of clinician confidence in, and familiarity with, physical dose-volume constraints. The method proposed here incorporates biological optimization after dose-volume constrained optimization so as to improve the dose distribution without detrimentally affecting the important reductions achieved by dose-volume optimization (DVO). Methods: Following DVO, the clinician/planner first identifies ''fixed points'' on the target and organ-at-risk (OAR) dose-volume histograms. These points represent important DVO plan qualities that are not to be violated within a specified tolerance. Biological optimization then maximally reduces a biological metric (illustrated with equivalent uniform dose (EUD) in this work) while keeping the fixed dose-volume points within tolerance limits, as follows. Incremental fluence adjustments are computed and applied to incrementally reduce the OAR EUDs while approximately maintaining the fixed points. This process of incremental fluence adjustment is iterated until the fixed points exceed tolerance. At this juncture, remedial fluence adjustments are computed and iteratively applied to bring the fixed points back within tolerance, without increasing OAR EUDs. This process of EUD reduction followed by fixed-point correction is repeated until no further EUD reduction is possible. The method is demonstrated in the context of a prostate cancer case and olfactory neuroblastoma case. The efficacy of EUD reduction after DVO is evaluated by comparison to an optimizer with purely biological (EUD) OAR objectives. Results: For both cases, EUD reduction after DVO additionally reduced doses, especially high doses, to normal organs. For the prostate case, bladder

  5. Optimizing electrode placement using finite-element models in radiofrequency ablation treatment planning.

    Science.gov (United States)

    Chen, Chun-Cheng R; Miga, Michael I; Galloway, Robert L

    2009-02-01

    Conventional radiofrequency ablation (RFA) planning methods for identifying suitable electrode placements typically use geometric shapes to model ablation outcomes. A method is presented for searching electrode placements that couples finite-element models (FEMs) of RFA together with a novel optimization strategy. The method was designed to reduce the need for model solutions per local search step. The optimization strategy was tested against scenarios requiring single and multiple ablations. In particular, for a scenario requiring multiple ablations, a domain decomposition strategy was described to minimize the complexity of simultaneously searching multiple electrode placements. The effects of nearby vasculature on optimal electrode placement were also studied. Compared with geometric planning approaches, FEMs could potentially deliver electrode placement plans that provide more physically meaningful predictions of therapeutic outcomes.

  6. Improving time to optimal Staphylococcus aureus treatment using a penicillin-binding protein 2a assay.

    Science.gov (United States)

    Rao, Sonia N; Wang, Sheila K; Gonzalez Zamora, Jose; Hanson, Amy P; Polisetty, Radhika S; Singh, Kamaljit

    2016-12-01

    The penicillin-binding protein 2a (PBP2a) assay is a quick, accurate and inexpensive test for determining methicillin susceptibility in Staphylococcus aureus. A pre-post-study design was conducted using a PBP2a assay with and without the impact of an antimicrobial stewardship intervention to improve time to optimal therapy for methicillin-susceptible and methicillin-resistant S. aureus isolates. Our results demonstrate significantly improved time to optimal therapy and support the use of a PBP2a assay as part of an programme for all healthcare facilities, especially those with limited resources.

  7. Three-Dimensional Microwave Hyperthermia for Breast Cancer Treatment in a Realistic Environment Using Particle Swarm Optimization.

    Science.gov (United States)

    Nguyen, Phong Thanh; Abbosh, Amin; Crozier, Stuart

    2017-06-01

    In this paper, a technique for noninvasive microwave hyperthermia treatment for breast cancer is presented. In the proposed technique, microwave hyperthermia of patient-specific breast models is implemented using a three-dimensional (3-D) antenna array based on differential beam-steering subarrays to locally raise the temperature of the tumor to therapeutic values while keeping healthy tissue at normal body temperature. This approach is realized by optimizing the excitations (phases and amplitudes) of the antenna elements using the global optimization method particle swarm optimization. The antennae excitation phases are optimized to maximize the power at the tumor, whereas the amplitudes are optimized to accomplish the required temperature at the tumor. During the optimization, the technique ensures that no hotspots exist in healthy tissue. To implement the technique, a combination of linked electromagnetic and thermal analyses using MATLAB and the full-wave electromagnetic simulator is conducted. The technique is tested at 4.2 GHz, which is a compromise between the required power penetration and focusing, in a realistic simulation environment, which is built using a 3-D antenna array of 4 × 6 unidirectional antenna elements. The presented results on very dense 3-D breast models, which have the realistic dielectric and thermal properties, validate the capability of the proposed technique in focusing power at the exact location and volume of tumor even in the challenging cases where tumors are embedded in glands. Moreover, the models indicate the capability of the technique in dealing with tumors at different on- and off-axis locations within the breast with high efficiency in using the microwave power.

  8. Geographic information system-based healthcare waste management planning for treatment site location and optimal transportation routeing.

    Science.gov (United States)

    Shanmugasundaram, Jothiganesh; Soulalay, Vongdeuane; Chettiyappan, Visvanathan

    2012-06-01

    In Lao People's Democratic Republic (Lao PDR), a growth of healthcare centres, and the environmental hazards and public health risks typically accompanying them, increased the need for healthcare waste (HCW) management planning. An effective planning of an HCW management system including components such as the treatment plant siting and an optimized routeing system for collection and transportation of waste is deemed important. National government offices at developing countries often lack the proper tools and methodologies because of the high costs usually associated with them. However, this study attempts to demonstrate the use of an inexpensive GIS modelling tool for healthcare waste management in the country. Two areas were designed for this study on HCW management, including: (a) locating centralized treatment plants and designing optimum travel routes for waste collection from nearby healthcare facilities; and (b) utilizing existing hospital incinerators and designing optimum routes for collecting waste from nearby healthcare facilities. Spatial analysis paved the way to understand the spatial distribution of healthcare wastes and to identify hotspots of higher waste generating locations. Optimal route models were designed for collecting and transporting HCW to treatment plants, which also highlights constraints in collecting and transporting waste for treatment and disposal. The proposed model can be used as a decision support tool for the efficient management of hospital wastes by government healthcare waste management authorities and hospitals.

  9. State estimation and optimal long period clinical treatment of HIV seropositive patients

    Directory of Open Access Journals (Sweden)

    Juliana M. Grégio

    2009-03-01

    Full Text Available Optimal control theory provides a very interesting quantitative method that can be used to assist the decision making process in several areas of application, such as engineering, biology, economics and sociology. The main idea is to determine the values of the manipulated variables, such as drug doses, so that some cost function is minimized, subject to physical constraints. In this work, the cost function reflects the number of CD4+T cells, viral particles and the drug doses. It is worth noticing that high drug doses are related to more intense side-effects, apart from the impact on the actual cost of the treatment. In a previous paper by the authors, the LQR - Linear Quadratic Regulator approach was proposed for the computation of long period maintenance doses for the drugs, which turns out to be of state feedback form. However, it is not practical to determine all the components of the state vector, due to the fact that infected and uninfected CD4+T cells are not microscopically distinguishable. In order to overcome this difficulty, this work proposes the use of Extended Kalman Filter to estimate the state, even though, because of the nonlinear nature of the involved state equations, the separation principle may not be valid. Extensive simulations were then carried out to investigate numerically if the control strategy consisting of the feedback of estimated states yielded satisfactory clinical results.A teoria de controle ótimo apresenta um método quantitativo muito interessante que pode ajudar no processo de tomada de decisão em algumas áreas de aplicação, tais como engenharia, biologia, economia e sociologia. A principal idéia é determinar os valores das variáveis controladas, tais como doses de medicamentos, onde alguma função-custo é minimizada, sujeito às restrições físicas. Neste trabalho, a função-custo reflete o número de células CD4+T, partículas virais e doses de medicamentos. É fato que altas dosagens de

  10. PART I. STUDY REGARDING THE OPTIMIZATION OF THE BIOSCOURING TREATMENT IN ULTRASOUND ON 60 % COTTON + 40 % COTTONISED FLAX MATERIALS

    Directory of Open Access Journals (Sweden)

    PUSTIANU Monica

    2016-05-01

    Full Text Available In the past years the commercial products for the bioscouring treatment were usually dedicated only for 100 % cotton or only for 100% lignocelluloses fabrics. The development of hemp/cotton or flax/cotton mixtures fabrics leds to the necessity of finding of the most apropiate products that could be used for different enzymatic treatments on these types of fabrics.The usage of the commercial product SERA ZYME C-PE for bioscouring treatment in ultrasound conditions on 60 % cotton + 40 % cottonised flax was studied in this work. The optimization of the Bioscouring treatment in ultrasound on 60 % cotton + 40 % hemp materials using the same commercial product was previous published. In order to assess more accurately the influence of some process parameters of the bioscouring treatment in a mathematical modeling of the process was made and a central compound rotatable program with two independent variable: x1 - the concentration of enzyme (% and x 2 - treatment time (minutes was used. The independent variable considered was y 1 – the weight loss. The aim of this study was to investigate the behaviour of cottonised flax/cotton mixtures for the same conditions of bioscouring treatment used as for hemp/cotton mixtures.

  11. MO-AB-BRA-08: Rapid Treatment Field Uniformity Optimization for Total Skin Electron Beam Therapy Using Cherenkov Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Andreozzi, J; Zhang, R; Glaser, A; Pogue, B [Dartmouth College, Hanover, NH (United States); Jarvis, L [Dartmouth-Hitchcock Medical Center, City Of Lebanon, New Hampshire (United States); Williams, B [Dartmouth Hitchcock Medical Center, Lebanon, NH (Lebanon); Gladstone, D [Dartmouth Hitchcock-Medical Center, Hanover, NH (United States)

    2015-06-15

    Purpose: To evaluate treatment field heterogeneity resulting from gantry angle choice in total skin electron beam therapy (TSEBT) following a modified Stanford dual-field technique, and determine a relationship between source to surface distance (SSD) and optimized gantry angle spread. Methods: Cherenkov imaging was used to image 62 treatment fields on a sheet of 1.2m x 2.2m x 1.2cm polyethylene following standard TSEBT setup at our institution (6 MeV, 888 MU/min, no spoiler, SSD=441cm), where gantry angles spanned from 239.5° to 300.5° at 1° increments. Average Cherenkov intensity and coefficient of variation in the region of interest were compared for the set of composite Cherenkov images created by summing all unique combinations of angle pairs to simulate dual-field treatment. The angle pair which produced the lowest coefficient of variation was further studied using an ionization chamber. The experiment was repeated at SSD=300cm, and SSD=370.5cm. Cherenkov imaging was also implemented during TSEBT of three patients. Results: The most uniform treatment region from a symmetric angle spread was achieved using gantry angles +/−17.5° about the horizontal axis at SSD=441cm, +/−18.5° at SSD=370.5cm, and +/−19.5° at SSD=300cm. Ionization chamber measurements comparing the original treatment spread (+/−14.5°) and the optimized angle pair (+/−17.5°) at SSD=441cm showed no significant deviation (r=0.999) in percent depth dose curves, and chamber measurements from nine locations within the field showed an improvement in dose uniformity from 24.41% to 9.75%. Ionization chamber measurements correlated strongly (r=0.981) with Cherenkov intensity measured concurrently on the flat Plastic Water phantom. Patient images and TLD results also showed modest uniformity improvements. Conclusion: A decreasing linear relationship between optimal angle spread and SSD was observed. Cherenkov imaging offers a new method of rapidly analyzing and optimizing TSEBT setup

  12. Analysis of Various Multi-Objective Optimization Evolutionary Algorithms for Monte Carlo Treatment Planning System

    CERN Document Server

    Tydrichova, Magdalena

    2017-01-01

    In this project, various available multi-objective optimization evolutionary algorithms were compared considering their performance and distribution of solutions. The main goal was to select the most suitable algorithms for applications in cancer hadron therapy planning. For our purposes, a complex testing and analysis software was developed. Also, many conclusions and hypothesis have been done for the further research.

  13. Superstructure development and optimization under uncertainty for design and retrofit of municipal wastewater treatment plants

    DEFF Research Database (Denmark)

    Bozkurt, Hande; Quaglia, Alberto; Gernaey, Krist

    2014-01-01

    Programming (sMI (N) LP) problem and solve it to determine the optimal process selection and flow diagram that meet s a set of performance criteria including effluent quality requirements , cost and technical requirements. The application of the framework is highlighted using a case study aiming at des igning...

  14. Nd: YAG laser treatment of aluminium-TiB2 coated: optimization of corrosion properties

    CSIR Research Space (South Africa)

    Popoola, PAI

    2011-06-01

    Full Text Available As the reports in the literature regarding corrosion performance of Al/TiB2 MMC are rather contradictory, the optimization of laser surface alloying parameters for these composite coatings seems to be necessary. The characterization of the MMC...

  15. Optimization and modelling of synthetic azo dye wastewater treatment using Graphene oxide nanoplatelets: Characterization toxicity evaluation and optimization using Artificial Neural Network.

    Science.gov (United States)

    Banerjee, Priya; Sau, Shubhra; Das, Papita; Mukhopadhayay, Aniruddha

    2015-09-01

    Azo dyes pose a major threat to current civilization by appearing in almost all streams of wastewater. The present investigation was carried out to examine the potential of Graphene oxide (GO) nanoplatelets as an efficient, cost-effective and non-toxic azo dye adsorbent for efficient wastewater treatment. The treatment process was optimized using Artificial Neural Network for maximum percentage dye removal and evaluated in terms of varying operational parameters, process kinetics and thermodynamics. A brief toxicity assay was also designed using fresh water snail Bellamya benghalensis to analyze the quality of the treated solution. 97.78% removal of safranin dye was obtained using GO as adsorbent. Characterization of GO nanoplatelets (using SEM, TEM, AFM and FTIR) reported the changes in its structure as well as surface morphology before and after use and explained its prospective as a good and environmentally benign adsorbent in very low quantities. The data recorded when subjected to different isotherms best fitted the Temkin isotherm. Further analysis revealed the process to be endothermic and chemisorption in nature. The verdict of the toxicity assay rendered the treated permeate as biologically safe for discharge or reuse in industrial and domestic purposes.

  16. Multiple response optimization of the coagulation process for upgrading the quality of effluent from municipal wastewater treatment plant

    Science.gov (United States)

    Li, Na; Hu, Yi; Lu, Yong-Ze; Zeng, Raymond J.; Sheng, Guo-Ping

    2016-05-01

    To meet the high quality standard of receiving water, the coagulation process using polyferric chloride (PFC) was used to further improve the water quality of effluent from wastewater treatment plants. Uniform design (UD) coupled with response surface methodology (RSM) was adopted to assess the effects of the main influence factors: coagulant dosage, pH and basicity, on the removal of total organic carbon (TOC), NH4+-N and PO43--P. A desirability function approach was used to effectively optimize the coagulation process for the comprehensive removal of TOC, NH4+-N and PO43--P to upgrade the effluent quality in practical application. The optimized operating conditions were: dosage 28 mg/L, pH 8.5 and basicity 0.001. The corresponding removal efficiencies for TOC, NH4+-N and PO43--P were 77.2%, 94.6% and 20.8%, respectively. More importantly, the effluent quality could upgrade to surface water Class V of China through coagulation under optimal region. In addition, grey relational analysis (GRA) prioritized these three factors as: pH > basicity > dosage (for TOC), basicity > dosage > pH (for NH4+-N), pH > dosage > basicity (for PO43--P), which would help identify the most important factor to control the treatment efficiency of various effluent quality indexes by PFC coagulation.

  17. Effect of optimal aging treatment on magnetic performance and mechanical properties of sintered Nd-Fe-B permanent magnets

    Institute of Scientific and Technical Information of China (English)

    DING Xia; DING Kai-hong; CUI Sheng-li; SUN Yong-cong; LI Mu-sen

    2016-01-01

    The magnetic performance and mechanical properties including hardness, brittleness, fracture toughness and strength characteristics of the as-sintered and the optimal aged Nd-Fe-B magnets were examined in this work. A new method of Vickers hardness indentation combined with acoustic emission was used to test the brittleness of the magnets.The results show that the magnetic properties of the magnets could be improved through aging treatment, especially the intrinsic coercive force. But it is accompanied by a decrease of strength and fracture toughness. Theoretical calculation confirms that acoustic emission energy accumulated count value could be used to characterize the material brittleness. The bending fracture morphologies of the as-sintered and the optimal aged NdFeB magnets were investigated with the emphasis on the relationship between mechanical properties and microstructure using a field emission scanning electron microscopy (FE-SEM). The research results indicate that the intergranular fracture is the primary fracture mechanism for both as-sintered and optimal aged NdFeB magnets. Aging treatment changes the morphology and distribution of the Nd-rich phases, reducing the sliding resistance between Nd2Fe14B main crystal grains and lowers the grain boundary strength, which is the main reason for the strength and fracture toughness decrease of the aged Nd-Fe-B magnets.

  18. Performance Optimization of Cold Rolled Type 316L Stainless Steel by Sand Blasting and Surface Linishing Treatment

    Science.gov (United States)

    Krawczyk, B.; Heine, B.; Engelberg, D. L.

    2016-03-01

    Sand blasting followed by a surface linishing treatment was applied to optimize the near-surface microstructure of cold rolled type 316L stainless steel. The introduction of cold rolling led to the formation of α-martensite. Specimens with large thickness reductions (40, 53%) were more susceptible to localized corrosion. The application of sand blasting produced a near-surface deformation layer containing compressive residual stresses with significantly increased surface roughness, resulting in reduced corrosion resistance. The most resistant microstructure was obtained with the application of a final linishing treatment after sand blasting. This treatment produced microstructures with compressive near-surface residual stresses, reduced surface roughness, and increased resistance to localized corrosion.

  19. [Systematization of diseases and lesions of the endometrium by etiological and pathogenetical mechanisms of development to choose an optimal treatment].

    Science.gov (United States)

    Boroda, A M

    2004-03-01

    Current clinical gynecology considers pathological states of endometrium (PSE) as one of the most challenging issue of the day. Many questions of etiology, pathogenesis, diagnostics, and treatment of PSE are still under discussion. Nowadays there isn't a whole agreed classification of PSE. Morphological classification remains the most widely used one, but morphological changes occurring in the endometrium don't show a wide variety of disorders related to these pathological states. A new clinicopathogenetic classification of PSE was proposed, which is based on choosing the optimal treatment with functional state of the disease taken into account. This classification helps us to perceive the problem as a whole with choosing functionally based treatment for each patient.

  20. Identifying Sub-Optimal Responses to Ivermectin in the Treatment of River Blindness

    National Research Council Canada - National Science Library

    Thomas S. Churcher; Sébastien D. S. Pion; Mike Y. Osei-Atweneboana; Roger K. Prichard; Kwablah Awadzie; Michel Boussinesq; Richard C. Collins; James A. Whitwort; Maria-Gloria Basanez; David Cox

    2009-01-01

    .... The variability in the rate at which Onchocerca volvulus microfilariae repopulate host's skin following ivermectin treatment is quantified using an individual-based onchocerciasis mathematical model...

  1. Optimizing treatment scheme for stereotatic treatment with cyberknife in lung cancer patients by analyzing radiobiological parameters determined by tumour locations

    OpenAIRE

    Chan, Chun-lun; 陳俊麟

    2015-01-01

    Objectives: Lung cancer is the leading cause of cancer mortality in the world. Stereotactic Body Radiation Therapy (SBRT) is a novel technique in treatment of inoperable Non-Small Cell Lung Cancer (NSCLC) in which a high dose delivery of 8-30Gy radiation to the lung tumour with one to five fractions precisely, simultaneously, avoiding as much normal tissue as possible. In the present pilot study, lungs were evenly divided into three parts in cranio–caudal direction, namely Upper Lung,...

  2. A Tool to Support Optimal Industrial Wastewater Treatment Design and Analysis

    DEFF Research Database (Denmark)

    Quaglia, Alberto; Pennati, Alessandra; Bozkurt, Hande;

    2013-01-01

    Industrial Wastewater Treatment Plant (IWWTP) design is often based on in-house expert knowledge and experience. Because of time and resources constraints, only a small number of alternative treatment configurations and ideas are evaluated while designing an IWWTP. Consequently, the selected design...

  3. Optimization of the Process of Carburizing and Heat Treatment of Low-Carbon Martensitic Steels

    Science.gov (United States)

    Ivanov, A. S.; Greben'kov, S. K.; Bogdanova, M. V.

    2016-05-01

    Steel 24Kh2G2NMFB is studied after carburizing and different heat treatments. The hardness and microhardness of the surface layer and of the matrix are measured. The content of retained austenite is determined by the method of x-ray diffraction analysis. Heat treatment modes improving the structure of the surface layer after carburizing are suggested.

  4. OPTIMAL ERYTHROID CELL PRODUCTION DURING ERYTHROPOIETIN TREATMENT OF MICE OCCURS BY EXPLOITING THE SPLENIC MICROENVIRONMENT

    NARCIS (Netherlands)

    NIJHOF, W; GORIS, H; DONTJE, B; DRESZ, J; LOEFFLER, M

    1993-01-01

    In this study, quantitative effects on erythroid cell production by a prolonged recombinant human erythropoietin (rhEpo) treatment of mice are presented. Epo treatments, given subcutaneously (s.c.) twice per day in doses of 0.5 to 500 U per day, were performed under steady-state production condition

  5. Physical design optimization of an urban runoff treatment system using Stormwater Management Model (SWMM).

    Science.gov (United States)

    Tobio, J A S; Maniquiz-Redillas, M C; Kim, L H

    2015-01-01

    The study presented the application of Stormwater Management Model (SWMM) in determining the optimal physical design properties of an established low impact development (LID) system treating road runoff. The calibration of the model was based on monitored storm events occurring from May 2010 to July 2013. It was found that the total suspended solids was highly correlated with stormwater runoff volume and dominant heavy metal constituents in stormwater runoff, such lead, zinc and copper, with a Pearson correlation coefficient ranging from 0.88 to 0.95 (P<0.05). Reducing the original ratio of the storage volume to surface area (SV/SA) of the facility and depth by 25% could match the satisfactory performance efficiency achieved in the original design. The smaller SV/SA and depth would mean a less costly system, signifying the importance of optimization in designing LID systems.

  6. Optimizing Oily Wastewater Treatment Via Wet Peroxide Oxidation Using Response Surface Methodology

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Jianzhong; Wang, Xiuqing; Wang, Xiaoyin [Wuhan Textile Univ., Wuhan (China)

    2014-02-15

    The process of petroleum involves in a large amount of oily wastewater that contains high levels of chemical oxygen demand (COD) and toxic compounds. So they must be treated before their discharge into the receptor medium. In this paper, wet peroxide oxidation (WPO) was adopted to treat the oily wastewater. Central composite design, an experimental design for response surface methodology (RSM), was used to create a set of 31 experimental runs needed for optimizing of the operating conditions. Quadratic regression models with estimated coefficients were developed to describe the COD removals. The experimental results show that WPO could effectively reduce COD by 96.8% at the optimum conditions of temperature 290 .deg. C, H{sub 2}O{sub 2} excess (HE) 0.8, the initial concentration of oily wastewater 3855 mg/L and reaction time 9 min. RSM could be effectively adopted to optimize the operating multifactors in complex WPO process.

  7. An optimization model and solution for radiation shielding design of radiotherapy treatment vaults.

    Science.gov (United States)

    Newman, Francis; Asadi-Zeydabadi, Masoud

    2008-01-01

    In radiation shielding design, one is usually faced with a set of conflicting goals that are navigated by an experienced physicist. If one has abundant space, the task is simplified because concrete is relatively inexpensive and will provide adequate shielding for high energy photons and neutrons, when applicable. However, if space is constrained (which is usually the case), the design becomes more difficult since one will likely have to employ combinations of steel, lead, and concrete, or other new materials--each with different properties and costs. Very experienced shielding designers can draw upon previous plans, but they do not know if their design is optimal in any sense. We have constructed a linear program that minimizes the cost of the shielding materials and minimizes the dose at the protection point or the shielding thickness subject to space constraints and to Federal or State regulations regarding the allowable exposure to individuals adjacent to the radiotherapy vault. In spite of what appears to be a simple model, the solution may require iterations of the optimization to arrive at the optimal solution.

  8. Optimization of activator solution and heat treatment of ground lignite type fly ash geopolymers

    Science.gov (United States)

    Molnár, Z.; Szabó, R.; Rácz, Á.; Lakatos, J.; Debreczeni, Á.; Mucsi, G.

    2017-02-01

    Geopolymers are inorganic polymers which can be produced by the reaction between silico aluminate oxides and alkali silicates in alkaline medium. Materialscontaining silica and alumina compounds are suitable for geopolymer production. These can beprimary materials or industrial wastes, i. e. fly ash, metallurgical slag and red mud. In this paper, the results of the systematic experimental series are presented which were carried out in order to optimize the geopolymer preparation process. Fly ash was ground for different residence time (0, 5, 10, 30, 60 min) in order to investigate the optimal specific surface area. NaOH activator solution concentration also varied (6, 8, 10, 12, 14 M). Furthermore, sodium silicate was added to NaOH as a network builder solution. In this last serie different heat curing temperatures (30, 60, 90°C) were also applied. After seven days of ageing the physical properties of the geopolymer(compressive strength and specimen density)were measured. Chemical leaching tests on the rawmaterial and the geopolymers were carried out to determine the elements which can be mobilized by different leaching solutions. It was found that the above mentioned parameters (fly ash fineness, molar concentration and composition of activator solution, heat curing) has great effect on the physical and chemical properties of geopolymer specimens. Optimal conditions were as follows: specific surface area of the fly ash above 2000 cm2/g, 10 M NaOH, 30°C heat curing temperature which resulted in 21 MPa compressive strength geopolymer.

  9. SU-E-T-628: A Cloud Computing Based Multi-Objective Optimization Method for Inverse Treatment Planning.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  11. An optimization model for collection, haul, transfer, treatment and disposal of infectious medical waste: Application to a Greek region.

    Science.gov (United States)

    Mantzaras, Gerasimos; Voudrias, Evangelos A

    2017-09-05

    The objective of this work was to develop an optimization model to minimize the cost of a collection, haul, transfer, treatment and disposal system for infectious medical waste (IMW). The model calculates the optimum locations of the treatment facilities and transfer stations, their design capacities (t/d), the number and capacities of all waste collection, transport and transfer vehicles and their optimum transport path and the minimum IMW management system cost. Waste production nodes (hospitals, healthcare centers, peripheral health offices, private clinics and physicians in private practice) and their IMW production rates were specified and used as model inputs. The candidate locations of the treatment facilities, transfer stations and sanitary landfills were designated, using a GIS-based methodology. Specifically, Mapinfo software with exclusion criteria for non-appropriate areas was used for siting candidate locations for the construction of the treatment plant and calculating the distance and travel time of all possible vehicle routes. The objective function was a non-linear equation, which minimized the total collection, transport, treatment and disposal cost. Total cost comprised capital and operation costs for: (1) treatment plant, (2) waste transfer stations, (3) waste transport and transfer vehicles and (4) waste collection bins and hospital boxes. Binary variables were used to decide whether a treatment plant and/or a transfer station should be constructed and whether a collection route between two or more nodes should be followed. Microsoft excel software was used as installation platform of the optimization model. For the execution of the optimization routine, two completely different software were used and the results were compared, thus, resulting in higher reliability and validity of the results. The first software was Evolver, which is based on the use of genetic algorithms. The second one was Crystal Ball, which is based on Monte Carlo

  12. Acceleration of high resolution temperature based optimization for hyperthermia treatment planning using element grouping.

    Science.gov (United States)

    Kok, H P; de Greef, M; Bel, A; Crezee, J

    2009-08-01

    In regional hyperthermia, optimization is useful to obtain adequate applicator settings. A speed-up of the previously published method for high resolution temperature based optimization is proposed. Element grouping as described in literature uses selected voxel sets instead of single voxels to reduce computation time. Elements which achieve their maximum heating potential for approximately the same phase/amplitude setting are grouped. To form groups, eigenvalues and eigenvectors of precomputed temperature matrices are used. At high resolution temperature matrices are unknown and temperatures are estimated using low resolution (1 cm) computations and the high resolution (2 mm) temperature distribution computed for low resolution optimized settings using zooming. This technique can be applied to estimate an upper bound for high resolution eigenvalues. The heating potential of elements was estimated using these upper bounds. Correlations between elements were estimated with low resolution eigenvalues and eigenvectors, since high resolution eigenvectors remain unknown. Four different grouping criteria were applied. Constraints were set to the average group temperatures. Element grouping was applied for five patients and optimal settings for the AMC-8 system were determined. Without element grouping the average computation times for five and ten runs were 7.1 and 14.4 h, respectively. Strict grouping criteria were necessary to prevent an unacceptable exceeding of the normal tissue constraints (up to approximately 2 degrees C), caused by constraining average instead of maximum temperatures. When strict criteria were applied, speed-up factors of 1.8-2.1 and 2.6-3.5 were achieved for five and ten runs, respectively, depending on the grouping criteria. When many runs are performed, the speed-up factor will converge to 4.3-8.5, which is the average reduction factor of the constraints and depends on the grouping criteria. Tumor temperatures were comparable. Maximum exceeding

  13. Recommendations for Optimizing Tuberculosis Treatment: Therapeutic Drug Monitoring, Pharmacogenetics, and Nutritional Status Considerations.

    Science.gov (United States)

    Choi, Rihwa; Jeong, Byeong Ho; Koh, Won Jung; Lee, Soo Youn

    2017-03-01

    Although tuberculosis is largely a curable disease, it remains a major cause of morbidity and mortality worldwide. Although the standard 6-month treatment regimen is highly effective for drug-susceptible tuberculosis, the use of multiple drugs over long periods of time can cause frequent adverse drug reactions. In addition, some patients with drug-susceptible tuberculosis do not respond adequately to treatment and develop treatment failure and drug resistance. Response to tuberculosis treatment could be affected by multiple factors associated with the host-pathogen interaction including genetic factors and the nutritional status of the host. These factors should be considered for effective tuberculosis control. Therefore, therapeutic drug monitoring (TDM), which is individualized drug dosing guided by serum drug concentrations during treatment, and pharmacogenetics-based personalized dosing guidelines of anti-tuberculosis drugs could reduce the incidence of adverse drug reactions and increase the likelihood of successful treatment outcomes. Moreover, assessment and management of comorbid conditions including nutritional status could improve anti-tuberculosis treatment response.

  14. International Study to Predict Optimized Treatment for Depression (iSPOT-D, a randomized clinical trial: rationale and protocol

    Directory of Open Access Journals (Sweden)

    Cooper Nicholas J

    2011-01-01

    Full Text Available Abstract Background Clinically useful treatment moderators of Major Depressive Disorder (MDD have not yet been identified, though some baseline predictors of treatment outcome have been proposed. The aim of iSPOT-D is to identify pretreatment measures that predict or moderate MDD treatment response or remission to escitalopram, sertraline or venlafaxine; and develop a model that incorporates multiple predictors and moderators. Methods/Design The International Study to Predict Optimized Treatment - in Depression (iSPOT-D is a multi-centre, international, randomized, prospective, open-label trial. It is enrolling 2016 MDD outpatients (ages 18-65 from primary or specialty care practices (672 per treatment arm; 672 age-, sex- and education-matched healthy controls. Study-eligible patients are antidepressant medication (ADM naïve or willing to undergo a one-week wash-out of any non-protocol ADM, and cannot have had an inadequate response to protocol ADM. Baseline assessments include symptoms; distress; daily function; cognitive performance; electroencephalogram and event-related potentials; heart rate and genetic measures. A subset of these baseline assessments are repeated after eight weeks of treatment. Outcomes include the 17-item Hamilton Rating Scale for Depression (primary and self-reported depressive symptoms, social functioning, quality of life, emotional regulation, and side-effect burden (secondary. Participants may then enter a naturalistic telephone follow-up at weeks 12, 16, 24 and 52. The first half of the sample will be used to identify potential predictors and moderators, and the second half to replicate and confirm. Discussion First enrolment was in December 2008, and is ongoing. iSPOT-D evaluates clinical and biological predictors of treatment response in the largest known sample of MDD collected worldwide. Trial registration International Study to Predict Optimised Treatment - in Depression (iSPOT-D ClinicalTrials.gov Identifier

  15. Pharmacogenomics and Pancreatic Cancer Treatment. Optimizing Current Therapy and Individualizing Future Therapy

    Directory of Open Access Journals (Sweden)

    Soonmo Peter Kang

    2008-05-01

    Full Text Available Each year, more than 30,000 Americans are diagnosed with pancreatic cancer. We have only made incremental advancements in treatment of pancreatic cancer despite our best efforts. Research has revealed that pancreatic cancer is a genetic disease which is associated with various forms of cancer associated genetic alterations. Identification and understanding of these carcinogenic gene alterations is the base upon which we can overcome drug resistance and develop novel treatment approaches. In this paper, we review current understanding of pharmacogenomics of pancreatic cancer treatment and address future direction of the field.

  16. What is the optimal treatment for appendiceal mass formed after acute perforated appendicitis?

    Institute of Scientific and Technical Information of China (English)

    Enver Zerem; Goran Imamovi(c); Farid Ljuca; Jasmina Alid(z)anovi(c)

    2012-01-01

    We read with great interest the editorial article by Meshikhes AWN published in issue 25 of World J Gastroenterol 2011.The article described the advantages of emergency laparoscopic appendectomy compared with interval appendectomy as a new safe treatment modality for the appendiceal mass.The author concluded that the emergency laparoscopic appendectomy was a safe treatment modality for the appendiceal mass,and might prove to be more cost-effective than conservative treatment,with no need for interval appendectomy.However,we would like to highlight certain issues regarding the possibility of percutaneous catheter drainage to successfully treat the appendiceal mass,with no need for appendectomy,too.

  17. Optimizing management of treatment-naïve and treatment-experienced HIV+ patients: the role of maraviroc

    Directory of Open Access Journals (Sweden)

    Eva Poveda

    2010-03-01

    Full Text Available Eva Poveda, Vincent SorianoDepartment of Infectious Diseases, Hospital Carlos III, Madrid, SpainAbstract: Maraviroc is the first CCR5 antagonist approved for the treatment of HIV-1 infection. It specifically inhibits the replication of R5 viruses by blocking viral entry. HIV-1 tropism can be estimated accurately and predict viral response to maraviroc. Genotypic tools are increasingly replacing phenotypic assays in most places. The favorable pharmacokinetic properties and the good safety profile of maraviroc may support an earlier use of the drug in HIV-1 infection, as well as favor its consideration as part of switch strategies in patients under suppressive antiretroviral regimens containing less-well-tolerated drugs. Moreover, a particular immune benefit of maraviroc might encourage its use as part of intensification strategies in HIV-infected patients with impaired CD4 gains despite prolonged suppression of HIV replication with antiretroviral therapy. However, the long-term consequences of using maraviroc must be carefully checked, given its particular mechanism of action, blocking a physiologic cell receptor.Keywords: maraviroc, tropism, HIV, antiretroviral therapy, treatment strategies

  18. Optimization of imaging and treatment of patients with focal liver lesions

    NARCIS (Netherlands)

    van Kessel, C.S.

    2012-01-01

    The incidence of focal liver lesions (either benign or malignant) has increased drastically the last decades. Treatment possibilities have extended significantly due to improved chemotherapeutic agents, extended eligibility criteria for partial liver resection, the introduction of radiofrequency abl

  19. Researches on optimizing treatment of Chinese cleft lip and/or palate

    Institute of Scientific and Technical Information of China (English)

    Bing Shi; Qian Zheng; Yang Li; Sheng Li; Yan Wang; Heng Yin; Wei Zheng

    2008-01-01

    @@ We all know that the development of the sequential therapy ameliorates the clefts treatment. Modes and methods of the sequential therapy differ among different countries and places because of the differences of economy, medical system and sanitary status.

  20. Treatment of wastewater effluents from paper-recycling plants by coagulation process and optimization of treatment conditions with response surface methodology

    Science.gov (United States)

    Birjandi, Noushin; Younesi, Habibollah; Bahramifar, Nader

    2016-11-01

    In the present study, a coagulation process was used to treat paper-recycling wastewater with alum coupled with poly aluminum chloride (PACl) as coagulants. The effect of each four factors, viz. the dosages of alum and PACl, pH and chemical oxygen demand (COD), on the treatment efficiency was investigated. The influence of these four parameters was described using response surface methodology under central composite design. The efficiency of reducing turbidity, COD and the sludge volume index (SVI) were considered the responses. The optimum conditions for high treatment efficiency of paper-recycling wastewater under experimental conditions were reached with numerical optimization of coagulant doses and pH, with 1,550 mg/l alum and 1,314 mg/l PACl and 9.5, respectively, where the values for reduction of 80.02 % in COD, 83.23 % in turbidity, and 140 ml/g in SVI were obtained.

  1. Computational Intelligence Techniques for Control and Optimization of Wastewater Treatment Plants

    OpenAIRE

    2016-01-01

    The development of novel, practice-oriented and reliable instrumentation and control strategies for wastewater treatment plants in order to improve energy efficiency, while guaranteeing process stability and maintenance of high cleaning capacity, has become a priority for WWTP operators due to increasing treatment costs. To achieve these ambitious and even contradictory objectives, this thesis investigates a combination of online measurement systems, computational intelligence and...

  2. Duration of untreated bipolar disorder: missed opportunities on the long road to optimal treatment.

    OpenAIRE

    Drancourt, Noëmie; Etain, Bruno; Lajnef, Mohamed; Henry, Chantal; Raust, Aurélie; Cochet, Barbara; Mathieu, Flavie; Gard, Sébastien; M'Bailara, Katia; Zanouy, L.; Kahn, Jean-Pierre; Cohen, Renaud,; Wajsbrot-Elgrabli, O.; Leboyer, Marion; SCOTT, J.

    2013-01-01

    International audience; OBJECTIVE: Duration of untreated illness represents a potentially modifiable component of any diagnosis-treatment pathway. In bipolar disorder (BD), this concept has rarely been systematically defined or not been applied to large clinically representative samples. METHOD: In a well-characterized sample of 501 patients with BD, we estimated the duration of untreated bipolar disorder (DUB: the interval between the first major mood episode and first treatment with a mood ...

  3. Identifying sub-optimal responses to ivermectin in the treatment of River Blindness.

    Science.gov (United States)

    Churcher, Thomas S; Pion, Sébastien D S; Osei-Atweneboana, Mike Y; Prichard, Roger K; Awadzi, Kwablah; Boussinesq, Michel; Collins, Richard C; Whitworth, James A; Basáñez, María-Gloria

    2009-09-29

    Identification of drug resistance before it becomes a public health concern requires a clear distinction between what constitutes a normal and a suboptimal treatment response. A novel method of analyzing drug efficacy studies in human helminthiases is proposed and used to investigate recent claims of atypical responses to ivermectin in the treatment of River Blindness. The variability in the rate at which Onchocerca volvulus microfilariae repopulate host's skin following ivermectin treatment is quantified using an individual-based onchocerciasis mathematical model. The model estimates a single skin repopulation rate for every host sampled, allowing reports of suboptimal responses to be statistically compared with responses from populations with no prior exposure to ivermectin. Statistically faster rates of skin repopulation were observed in 3 Ghanaian villages (treated 12-17 times), despite the wide variability in repopulation rates observed in ivermectin-naïve populations. Another village previously thought to have high rates of skin repopulation was shown to be indistinguishable from the normal treatment response. The model is used to generate testable hypotheses to identify whether atypical rates of skin repopulation by microfilariae could result from low treatment coverage alone or provide evidence of decreased ivermectin efficacy. Further work linking phenotypic poor responses to treatment with parasite molecular genetics markers will be required to confirm drug resistance. Limitations of the skin-snipping method for estimating parasite load indicates that changes in the distribution of microfilarial repopulation rates, rather than their absolute values, maybe a more sensitive indicator of emerging ivermectin resistance.

  4. Pregnancy Research on Osteopathic Manipulation Optimizing Treatment Effects: The PROMOTE Study A Randomized Controlled Trial

    Science.gov (United States)

    HENSEL, Kendi L.; BUCHANAN, Steve; BROWN, Sarah K.; RODRIGUEZ, Mayra; CRUSER, des Anges

    2014-01-01

    Objective To evaluate the efficacy of Osteopathic Manipulative Treatment (OMT) to reduce low back pain and improve functioning during the third trimester in pregnancy and improve selected outcomes of labor and delivery. Study Design PROMOTE was a randomized, placebo-controlled trial of 400 women in their third trimester. Women were randomized to usual care only (UCO), usual care plus OMT (OMT), or usual care plus placebo ultrasound treatment (PUT). The study included seven treatments over nine weeks. The OMT protocol included specific techniques administered by board-certified OMT specialists. Outcomes were assessed using self-report measures for pain and back-related functioning, and medical records for delivery outcomes. Results There were 136 women in the OMT group, 131 in PUT, and 133 in UCO. Characteristics at baseline were similar across groups. Findings indicate significant treatment effects for pain and back related functioning (POMT group similar to that of the PUT, but both groups were significantly improved compared to UCO. For secondary outcome of meconium- stained amniotic fluid there were no differences between the groups. Conclusion OMT was effective for mitigating pain and functional deterioration compared to the UCO group; however OMT did not differ significantly from PUT. This may be attributed to PUT being a more active treatment than intended. There was no higher likelihood of conversion to high risk status based on treatment group. Therefore, OMT is a safe, effective adjunctive modality to improve pain and functioning during their third trimester. PMID:25068560

  5. Estimation of the optimal regime in treatment of prostate cancer recurrence from observational data using flexible weighting models.

    Science.gov (United States)

    Shen, Jincheng; Wang, Lu; Taylor, Jeremy M G

    2017-06-01

    Prostate cancer patients are closely followed after the initial therapy and salvage treatment may be prescribed to prevent or delay cancer recurrence. The salvage treatment decision is usually made dynamically based on the patient's evolving history of disease status and other time-dependent clinical covariates. A multi-center prostate cancer observational study has provided us data on longitudinal prostate specific antigen (PSA) measurements, time-varying salvage treatment, and cancer recurrence time. These data enable us to estimate the best dynamic regime of salvage treatment, while accounting for the complicated confounding of time-varying covariates present in the data. A Random Forest based method is used to model the probability of regime adherence and inverse probability weights are used to account for the complexity of selection bias in regime adherence. The optimal regime is then identified by the largest restricted mean survival time. We conduct simulation studies with different PSA trends to mimic both simple and complex regime adherence mechanisms. The proposed method can efficiently accommodate complex and possibly unknown adherence mechanisms, and it is robust to cases where the proportional hazards assumption is violated. We apply the method to data collected from the observational study and estimate the best salvage treatment regime in managing the risk of prostate cancer recurrence. © 2016, The International Biometric Society.

  6. Immunomodulators for the treatment of Crohn's disease in adults: optimal use and prospects for future drug treatments.

    Science.gov (United States)

    Allen, Patrick B; Peyrin-Biroulet, Laurent

    2016-07-01

    Crohn's disease (CD) requires treatment beyond symptoms by enabling and maintaining mucosal healing and therefore clinical remission. However, with the increasing use of biologics there have been safety concerns and there is a significant cost implication with the early use of biologics. Therefore, it is imperative that patients with severe/complicated disease or poor prognostic factors are treated with an aggressive strategy while all remaining patients should be treated in a step-up strategy. The potential for disease modification with thiopurines and methotrexate is debated in CD when they are used as a monotherapy. In this review we discuss existing and newer therapies that have recently been developed for CD. We will also provide an algorithm for current management of adult CD patients in routine clinical practice.

  7. Optimizing the Use of Aripiprazole Augmentation in the Treatment of Major Depressive Disorder: From Clinical Trials to Clinical Practice

    Science.gov (United States)

    Han, Changsu; Wang, Sheng-Min; Lee, Soo-Jung; Jun, Tae-Youn

    2015-01-01

    Major depressive disorder (MDD) is a recurrent, chronic, and devastating disorder leading to serious impairment in functional capacity as well as increasing public health care costs. In the previous decade, switching therapy and dose adjustment of ongoing antidepressants was the most frequently chosen subsequent treatment option for MDD. However, such recommendations were not based on firmly proven efficacy data from well-designed, placebo-controlled, randomized clinical trials (RCTs) but on practical grounds and clinical reasoning. Aripiprazole augmentation has been dramatically increasing in clinical practice owing to its unique action mechanisms as well as proven efficacy and safety from adequately powered and well-controlled RCTs. Despite the increased use of aripiprazole in depression, limited clinical information and knowledge interfere with proper and efficient use of aripiprazole augmentation for MDD. The objective of the present review was to enhance clinicians' current understanding of aripiprazole augmentation and how to optimize the use of this therapy in the treatment of MDD. PMID:26306301

  8. Optimization of pharmaceutical wastewater treatment by solar/ferrioxalate photo-catalysis.

    Science.gov (United States)

    Monteagudo, J M; Durán, A; Culebradas, R; San Martín, I; Carnicer, A

    2013-10-15

    The degradation of a pharmaceutical wastewater using a ferrioxalate-assisted solar/photo-Fenton system has been studied. The photochemical reaction was carried out in a pilot plant consisting of a compound parabolic collector (CPC) solar reactor. An optimization study was performed combining a multivariate experimental design and Neuronal Networks that included the following variables: initial concentrations of H2O2, catalyst Fe (II) and oxalic acid (H2C2O4), temperature and solar power. Under optimal conditions, 84% TOC (Total Organic Carbon) removal was achieved in 115 min. Oxalic acid had a positive effect on mineralization when solar power was above 30 W m(-2). The minimum amount of H2O2 to degrade 1 mol of TOC was found to be 3.57 mol. Both the H2O2 conversion efficiency and the degree of mineralization were highest when the oxalic/Fe(II) initial molar relation was close to 3. HO radicals were the main oxidative intermediate species in the process, although hydroperoxyl radicals (HO(2)(·)) also played a role.

  9. Multi-GPU implementation of a VMAT treatment plan optimization algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Zhen, E-mail: Zhen.Tian@UTSouthwestern.edu, E-mail: Xun.Jia@UTSouthwestern.edu, E-mail: Steve.Jiang@UTSouthwestern.edu; Folkerts, Michael; Tan, Jun; Jia, Xun, E-mail: Zhen.Tian@UTSouthwestern.edu, E-mail: Xun.Jia@UTSouthwestern.edu, E-mail: Steve.Jiang@UTSouthwestern.edu; Jiang, Steve B., E-mail: Zhen.Tian@UTSouthwestern.edu, E-mail: Xun.Jia@UTSouthwestern.edu, E-mail: Steve.Jiang@UTSouthwestern.edu [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 (United States); Peng, Fei [Computer Science Department, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213 (United States)

    2015-06-15

    Purpose: Volumetric modulated arc therapy (VMAT) optimization is a computationally challenging problem due to its large data size, high degrees of freedom, and many hardware constraints. High-performance graphics processing units (GPUs) have been used to speed up the computations. However, GPU’s relatively small memory size cannot handle cases with a large dose-deposition coefficient (DDC) matrix in cases of, e.g., those with a large target size, multiple targets, multiple arcs, and/or small beamlet size. The main purpose of this paper is to report an implementation of a column-generation-based VMAT algorithm, previously developed in the authors’ group, on a multi-GPU platform to solve the memory limitation problem. While the column-generation-based VMAT algorithm has been previously developed, the GPU implementation details have not been reported. Hence, another purpose is to present detailed techniques employed for GPU implementation. The authors also would like to utilize this particular problem as an example problem to study the feasibility of using a multi-GPU platform to solve large-scale problems in medical physics. Methods: The column-generation approach generates VMAT apertures sequentially by solving a pricing problem (PP) and a master problem (MP) iteratively. In the authors’ method, the sparse DDC matrix is first stored on a CPU in coordinate list format (COO). On the GPU side, this matrix is split into four submatrices according to beam angles, which are stored on four GPUs in compressed sparse row format. Computation of beamlet price, the first step in PP, is accomplished using multi-GPUs. A fast inter-GPU data transfer scheme is accomplished using peer-to-peer access. The remaining steps of PP and MP problems are implemented on CPU or a single GPU due to their modest problem scale and computational loads. Barzilai and Borwein algorithm with a subspace step scheme is adopted here to solve the MP problem. A head and neck (H and N) cancer case is

  10. Selection of candidate wells and optimization of conformance treatment design in the Barrancas Field using a 3D conformance simulator

    Energy Technology Data Exchange (ETDEWEB)

    Crosta, Dante; Elitseche, Luis [Repsol YPF (Argentina); Gutierrez, Mauricio; Ansah, Joe; Everett, Don [Halliburton Argentina S.A., Buenos Aires (Argentina)

    2004-07-01

    Minimizing the amount of unwanted water production is an important goal at the Barrancas field. This paper describes a selection process for candidate injection wells that is part of a pilot conformance project aimed at improving vertical injection profiles, reducing water cut in producing wells, and improving ultimate oil recovery from this field. The well selection process is based on a review of limited reservoir information available for this field to determine inter-well communications. The methodology focuses on the best use of available information, such as production and injection history, well intervention files, open hole logs and injectivity surveys. After the candidate wells were selected and potential water injection channels were identified, conformance treatment design and future performance of wells in the selected pilot area were evaluated using a new 3 -D conformance simulator, developed specifically for optimization of the design and placement of unwanted fluid shut-off treatments. Thus, when acceptable history match ing of the pilot area production was obtained, the 3 -D simulator was used to: evaluate the required volume of selected conformance treatment fluid; review expected pressures and rates during placement;. model temperature behavior; evaluate placement techniques, and forecast water cut reduction and incremental oil recovery from the producers in this simulated section of the pilot area. This paper outlines a methodology for selecting candidate wells for conformance treatments. The method involves application of several engineering tools, an integral component of which is a user-friendly conformance simulator. The use of the simulator has minimized data preparation time and allows the running of sensitivity cases quickly to explore different possible scenarios that best represent the reservoir. The proposed methodology provides an efficient means of identifying conformance problems and designing optimized solutions for these individual

  11. Optimal management of pulmonary arterial hypertension: prognostic indicators to determine treatment course

    Directory of Open Access Journals (Sweden)

    Baldi F

    2014-10-01

    Full Text Available Fabiana Baldi, Leonello Fuso, Eugenio Arrighi, Salvatore Valente Pulmonary Medicine Unit, Catholic University, Rome, Italy Abstract: Pulmonary arterial hypertension (PAH is a rapidly progressive pulmonary vascular disease with a multifactorial etiopathogenesis that can result in right-sided heart failure and death. A number of studies indicate that an early therapeutic intervention yields better results on disease progression as compared to delayed treatment. In this review, we will analyze treatment strategies that may be used for monitoring disease progression and for guiding treatment decisions. Several factors (ie, symptoms, functional class, exercise capacity as assessed by a walking test and cardiopulmonary stress testing, hemodynamic parameters, cardiac magnetic resonance imaging, and plasma levels of biochemical markers have been prognostic of survival. These indicators may be used both at the time of diagnosis and during treatment follow-up. No resolutive therapy is currently available for PAH; however, in the last decade, the advent of specific pharmacological treatments has given new hope to patients suffering from this debilitating disease with a poor prognosis. Combination drug therapies offer increased benefits over monotherapy, and current guidelines recommend a sequential “add on” design approach for patients in functional class II–IV. The goal-oriented “treat to target” therapy sets the timing for treatment escalation in case of inadequate response to currently known prognostic indicators. To date, further longitudinal studies should be urgently conducted to identify new goals that may improve therapeutic strategies in order to optimize personalized treatment in PAH patients. Keywords: pulmonary hypertension, prognostic indicators, specific drug therapy, disease progression

  12. Optimization of surgical treatment of diabetic foot syndrome in Saratov region

    Directory of Open Access Journals (Sweden)

    Osintsev E.Yu.

    2012-03-01

    Full Text Available The research goal is to estimate the results of multidisciplinary approach to treatment of diabetic foot syndrome in the conditions of specialized hospital centre. Materials and methods: The clinical part of work is based on the study of surgical assistance range, recurrence of infectious complications of diabetes mellitus and mortality rate in 226 diabetic foot syndrome patients. Optimum results of treatment have been received in a group of patients with neuropathic forms of lower extremities damage. Conclusion: Use of multidisciplinary approach to the treatment of patients with complications of diabetes mellitus has improved survival rate (x2=12,1; p=0,002 and quality of life of patients with diabetic foot syndrome in Saratov region

  13. Hair dryer use to optimize pulsed dye laser treatment in rosacea patients.

    Science.gov (United States)

    Kashlan, Lana; Graber, Emmy M; Arndt, Kenneth A

    2012-06-01

    Rosacea is a common chronic inflammatory condition characterized by erythema, telangiectasias, papules, and pustules. While there are many effective treatment options for the papulopustular type, laser therapy remains the most effective modality to treat erythematotelangiectatic rosacea. Erythema and flushing associated with rosacea remains an uncomfortable and socially embarrassing problem for patients. Unfortunately, patients often do not have significant erythema or flushing when they present for laser treatment. With this in mind, we propose a novel technique aimed at enhancing the response of rosacea patients being treated for erythema with pulsed dye laser. Specifically, we present a split-face example of our clinical observation that pre-treatment with forced heated air prior to pulsed-dye laser leads to a greater response in rosacea patients with erythema and flushing.

  14. Photodynamic characterization and optimization using multifunctional nanoparticles for brain cancer treatment

    Science.gov (United States)

    Herrmann, Kristen; Lee Koo, Yong-Eun; Orringer, Daniel A.; Sagher, Oren; Philbert, Martin; Kopelman, Raoul

    2013-03-01

    Photosensitizer-conjugated polyacrylamide nanoparticles were prepared for in vivo characterization of the minimally invasive and localized treatment of photodynamic therapy (PDT) on brain tumors. By incorporating a variety of nanoparticle matrixes, choosing methylene blue as a photosensitizer, and targeting the nanoparticle by the use of F3 peptide we have made nanoparticle-based PDT improvements to current PDT efficiency. Quantitative growth patterns were determined through visual observation of the tumorigenic response to various treatments by the use of an animal cranial window model. PDT treatments with methylene blue-polyacrylamide (MB-PAA) nanoparticles produced significant adjournment of tumor growth over control groups, clearly demonstrating the advantages of nanoparticle-based PDT agents for the eradication of local tumors, leading to the potential palliation of the advancing disease.

  15. Optimization of urban wastewater treatment plants process with low C/N ratio

    Science.gov (United States)

    Zheng, L.; Xu, G. M.; Chen, J.; Chen, B.; Lv, Z.; Yang, Y. A.

    2016-08-01

    In southern China, the inflow of water to wastewater treatment plants has a lower concentration of organic matter. This causes treatment plants to face issues in the denitrification and phosphorus removal processes such as deficient carbon sources, high energy consumption, and unstable nitrogen removal. To resolve these issues, we propose the reconstruction of the internal reflux port, improvement of the internal reflux ratio to 200%, the addition of carbon source to anoxic zone, and the addition of phosphorus removal agents in secondary settling tank. The results of study show significantly improved efficiency of nitrogen and phosphorus removal, which ensures the stability of subsequent supply of reused water.

  16. SU-D-BRD-01: Cloud-Based Radiation Treatment Planning: Performance Evaluation of Dose Calculation and Plan Optimization

    Energy Technology Data Exchange (ETDEWEB)

    Na, Y; Kapp, D; Kim, Y; Xing, L [Stanford University School of Medicine, Stanford, CA (United States); Suh, T [Catholic UniversityMedical College, Seoul, Seoul (Korea, Republic of)

    2014-06-01

    Purpose: To report the first experience on the development of a cloud-based treatment planning system and investigate the performance improvement of dose calculation and treatment plan optimization of the cloud computing platform. Methods: A cloud computing-based radiation treatment planning system (cc-TPS) was developed for clinical treatment planning. Three de-identified clinical head and neck, lung, and prostate cases were used to evaluate the cloud computing platform. The de-identified clinical data were encrypted with 256-bit Advanced Encryption Standard (AES) algorithm. VMAT and IMRT plans were generated for the three de-identified clinical cases to determine the quality of the treatment plans and computational efficiency. All plans generated from the cc-TPS were compared to those obtained with the PC-based TPS (pc-TPS). The performance evaluation of the cc-TPS was quantified as the speedup factors for Monte Carlo (MC) dose calculations and large-scale plan optimizations, as well as the performance ratios (PRs) of the amount of performance improvement compared to the pc-TPS. Results: Speedup factors were improved up to 14.0-fold dependent on the clinical cases and plan types. The computation times for VMAT and IMRT plans with the cc-TPS were reduced by 91.1% and 89.4%, respectively, on average of the clinical cases compared to those with pc-TPS. The PRs were mostly better for VMAT plans (1.0 ≤ PRs ≤ 10.6 for the head and neck case, 1.2 ≤ PRs ≤ 13.3 for lung case, and 1.0 ≤ PRs ≤ 10.3 for prostate cancer cases) than for IMRT plans. The isodose curves of plans on both cc-TPS and pc-TPS were identical for each of the clinical cases. Conclusion: A cloud-based treatment planning has been setup and our results demonstrate the computation efficiency of treatment planning with the cc-TPS can be dramatically improved while maintaining the same plan quality to that obtained with the pc-TPS. This work was supported in part by the National Cancer Institute (1

  17. Evaluation of plan quality assurance models for prostate cancer patients based on fully automatically generated Pareto-optimal treatment plans

    Science.gov (United States)

    Wang, Yibing; Breedveld, Sebastiaan; Heijmen, Ben; Petit, Steven F.

    2016-06-01

    IMRT planning with commercial Treatment Planning Systems (TPSs) is a trial-and-error process. Consequently, the quality of treatment plans may not be consistent among patients, planners and institutions. Recently, different plan quality assurance (QA) models have been proposed, that could flag and guide improvement of suboptimal treatment plans. However, the performance of these models was validated using plans that were created using the conventional trail-and-error treatment planning process. Consequently, it is challenging to assess and compare quantitatively the accuracy of different treatment planning QA models. Therefore, we created a golden standard dataset of consistently planned Pareto-optimal IMRT plans for 115 prostate patients. Next, the dataset was used to assess the performance of a treatment planning QA model that uses the overlap volume histogram (OVH). 115 prostate IMRT plans were fully automatically planned using our in-house developed TPS Erasmus-iCycle. An existing OVH model was trained on the plans of 58 of the patients. Next it was applied to predict DVHs of the rectum, bladder and anus of the remaining 57 patients. The predictions were compared with the achieved values of the golden standard plans for the rectum D mean, V 65, and V 75, and D mean of the anus and the bladder. For the rectum, the prediction errors (predicted-achieved) were only  -0.2  ±  0.9 Gy (mean  ±  1 SD) for D mean,-1.0  ±  1.6% for V 65, and  -0.4  ±  1.1% for V 75. For D mean of the anus and the bladder, the prediction error was 0.1  ±  1.6 Gy and 4.8  ±  4.1 Gy, respectively. Increasing the training cohort to 114 patients only led to minor improvements. A dataset of consistently planned Pareto-optimal prostate IMRT plans was generated. This dataset can be used to train new, and validate and compare existing treatment planning QA models, and has been made publicly available. The OVH model was highly accurate

  18. Performance analysis and optimization of an advanced pharmaceutical wastewater treatment plant through a visual basic software tool (PWWT.VB).

    Science.gov (United States)

    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.

  19. Calibrating an optimal condition model for solar water disinfection in peri-urban household water treatment in Kampala, Uganda.

    Science.gov (United States)

    Okurut, Kenan; Wozei, Eleanor; Kulabako, Robinah; Nabasirye, Lillian; Kinobe, Joel

    2013-03-01

    In low income settlements where the quality of drinking water is highly contaminated due to poor hygienic practices at community and household levels, there is need for appropriate, simple, affordable and environmentally sustainable household water treatment technology. Solar water disinfection (SODIS) that utilizes both the thermal and ultra-violet effect of solar radiation to disinfect water can be used to treat small quantities of water at household level to improve its bacteriological quality for drinking purposes. This study investigated the efficacy of the SODIS treatment method in Uganda and determined the optimal condition for effective disinfection. Results of raw water samples from the study area showed deterioration in bacteriological quality of water moved from source to the household; from 3 to 36 cfu/100 mL for tap water and 75 to 126 cfu/100 mL for spring water, using thermotolerant coliforms (TTCs) as indicator microorganisms. SODIS experiments showed over 99.9% inactivation of TTCs in 6 h of exposure, with a threshold temperature of 39.5 ± 0.7°C at about 12:00 noon, in the sun during a clear sunny day. A mathematical optimal condition model for effective disinfection has been calibrated to predict the decline of the number of viable microorganisms over time.

  20. [Baseline characteristics and changes in treatment after a period of optimization of the patients included in the study EFICAR].

    Science.gov (United States)

    Gómez-Marcos, Manuel A; Agudo-Conde, Cristina; Torcal, Jesús; Echevarria, Pilar; Domingo, Mar; Arietaleanizbeascoa, María; Sanz-Guinea, Aitor; de la Torre, Maria M; Ramírez, Jose I; García-Ortiz, Luis

    2016-03-01

    To describe the baseline date and drugs therapy changes during treatment optimization in patients with heart failure with depressed systolic function included in the EFICAR study. Multicenter randomized clinical trial. Seven Health Centers. 150 patients (ICFSD) age 68±10 years, 77% male. Sociodemographic variables, comorbidities (Charlson index), functional capacity and quality of life. Drug therapy optimization was performed. The main etiology was ischemic heart disease (45%), with 89% in functional class II. The Charlson index was 2.03±1.05. The ejection fraction mean was 37%±8, 19% with ejection fraction <30%. With the stress test 6.3±1.6 mean was reached, with the 6 minutes test 446±78 meters and the chair test 13.7±4.4 seconds. The overall quality of life with ejection fraction was 22.8±18.7 and with the Short Form-36 Health Survey, physical health 43.3±8.4 and mental health 50.1±10.6. After optimizing the treatment, the percentage of patients on drugs therapy and the dose of angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists and beta-blockers were not changed. The majority of the subjects are in functional class II, with functional capacity and quality of life decreased and comorbidity index high. A protocolized drug therapy adjustment did not increase the dose or number of patients with effective drugs for heart failure with depressed systolic function. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  1. Critical appraisal of clinical prediction rules that aim to optimize treatment selection for musculoskeletal conditions

    NARCIS (Netherlands)

    T.R. Stanton (Tasha); M.J. Hancock (Mark J.); C. Maher (Chris); B.W. Koes (Bart)

    2010-01-01

    textabstractBackground. Clinical prediction rules (CPRs) for treatment selection in musculoskeletal conditions have become increasingly popular. Purpose. The purposes of this review are: (1) to critically appraise studies evaluating CPRs and (2) to consider the clinical utility and stage of developm

  2. Optimal treatment of partial thickness burns in children: a systematic review.

    Science.gov (United States)

    Vloemans, A F P M; Hermans, M H E; van der Wal, M B A; Liebregts, J; Middelkoop, E

    2014-03-01

    A large part of the patient population of a burn centre consists of children, most of whom are younger than four years. The majority of these young children suffer from superficial and deep partial thickness scald burns that may easily deepen to full thickness burns. A proper wound therapy, that prevents infection and ensures a moist wound condition, might prevent the deterioration of the wound. Therefore, we performed a systematic review of wound management and dressing materials to select the best treatment option for children with burns. A search in Medline and Embase revealed 51 articles for a critical appraisal. The articles were divided into randomized controlled trials, cohort studies and a group of case-reports. Total appraisal did not differ much amongst the groups; the level of evidence was highest in the randomized controlled trials and lowest in the case-reports. In 16 out of 34 comparative studies, silver sulfadiazine or a silver sulfadiazine/chlorhexidine-gluconate combination was the standard of wound care treatment. The competitor dressing was Biobrane(®) in six studies and amnion membrane in three. Tulle gauze, or tulle gauze impregnated with an antibacterial addition were the standard of care treatment in seven studies. In general, membranous dressings like Biobrane(®) and amnion membrane performed better than the standard of care on epithelialization rate, length of hospital stay and pain for treatment of partial thickness burns in children. However, hardly any of the studies investigated long-term results like scar formation.

  3. Optimizing Methotrexate Treatment in Rheumatoid Arthritis: The Case for Subcutaneous Methotrexate Prior to Biologics.

    Science.gov (United States)

    Sharma, Poonam; Scott, David G I

    2015-11-01

    Methotrexate is the most common disease-modifying antirheumatic drug (DMARD) used in the treatment of rheumatoid arthritis (RA). Current evidence supports its efficacy in the treatment of RA, resulting in improved short-term disease control and long-term outcomes in terms of radiographic progression. Oral methotrexate has traditionally been used first-line due to various reasons, including ease of administration, low cost and easy availability. A methotrexate dose of >15 mg/week is generally required for disease control but oral methotrexate may be only partially effective or poorly tolerated in some patients. The rationale for using subcutaneous (SC) methotrexate is based on its improved bioavailability at higher doses and better tolerability in some patients who have side effects when receiving oral methotrexate. Current guidance advocates 'treating to target', with the aim of inducing remission in RA patients. In some patients, this can be achieved using methotrexate alone or in combination with other traditional DMARDs. Patients who have not responded to two DMARDs, including methotrexate, are eligible for biological therapy as per current National Institute for Health and Care Excellence (NICE) guidance in the UK. Biological treatments are expensive and using SC methotrexate can improve disease control in RA patients, thus potentially avoiding or delaying the requirement for future biological treatment.

  4. Pediatric pulmonary arterial hypertension : Towards optimal classification, treatment strategies and outcome

    NARCIS (Netherlands)

    Zijlstra, Willemijn

    2017-01-01

    Pulmonary arterial hypertension (PAH) is a rare, progressive disease of the small pulmonary arteries and has a poor prognosis. Median survival of children with PAH is <3 years if untreated. The development of PAH-targeted drugs and the introduction of evidence-based treatment guidelines have greatly

  5. Targeted pre-treatment of hemp bast fibres for optimal performance in biocomposite materials: A review

    DEFF Research Database (Denmark)

    Liu, Ming; Thygesen, Anders; Summerscales, John

    2017-01-01

    composite matrix material. Targeted modification of natural fibres for NFCs must also be targeted to optimize the fibre surface properties. Consequently, improved interfacial bonding between fibres and hydrophobic polymers, reduced moisture uptake, increased microbial degradation resistance, and prolonged......Global interest in the use of plant fibres in natural fibre reinforced composites (NFCs) is growing rapidly. The increased interest is primarily due to the advantageous properties of natural fibres including biodegradability, low cost, low density and high stiffness and strength to weight ratio....... In order to achieve strong NFCs, well separated and cellulose-rich fibres are required. Hemp is taking a center stage in this regard as a source of suitable natural plant cellulose fibres because natural hemp bast fibres are long and inherently possess high strength. Classical field and water retting...

  6. Optimal Treatment for Intermediate- and High-Risk, Nonmuscle-Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    A.P.M. van der Meijden

    2006-01-01

    Full Text Available According to clinical and pathological factors the prognosis of a patient with non-muscle invasive bladder tumors can be assessed. The prognosis is determined by the likelihood of recurrence(30-70% and/or progression to muscle invasive bladder cancer(1-15%.Trans urethral resection of bladder tumors remains the initial therapy but adjuvant intravesical instillations are necessary.All patients benefit from a single immediate post operative instillation with a chemotherapeutic agent and for low risk tumors this is the optimal therapy.Patients with intermediate and high risk tumors need more intravesical chemo-or immunotherapy. Chemotherapy reduces recurrences but not progression. Intravesical immunotherapy(BCG prevents or delays progression. Patients at high risk for progression may need upfront cystectomy.

  7. Some aspects of optimization of an invasive microwave antenna for local hyperthermia treatment of cancer.

    Science.gov (United States)

    de Sieyes, D C; Douple, E B; Strohbehn, J W; Trembly, B S

    1981-01-01

    Hyperthermia has emerged as a promising alternative or adjunct to other forms of cancer therapy. In order to utilize hyperthermia in very localized volumes immersed in regions of vital normal tissue, an invasive microwave coaxial monopole antenna has been developed. An experimental approach has been taken to characterize and optimize the electromagnetic properties and heating capabilities of bare and insulated antennas imbedded in tissue equivalent phantoms and dog brain. Four methods have been used to visualize the thermal profiles of the microwave probes: the liquid crystal technique, the gelatin technique, and the direct measurement of temperature with thermistor probes in phantom and dog brain. Among the parameters studied are: antenna impedance, insertion depth, antenna insulation (dielectric constant and thickness), shaft insulation, and frequency.

  8. An evidence-based review on urate-lowering treatments: implications for optimal treatment of chronic hyperuricemia

    Directory of Open Access Journals (Sweden)

    Bove M

    2017-02-01

    Full Text Available Marilisa Bove, Arrigo Francesco Giuseppe Cicero, Maddalena Veronesi, Claudio Borghi Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy Abstract: Several studies suggest that chronic hyperuricemia, the main precursor of gout, is involved in the pathogenesis of different systemic disorders that affect cardiovascular and renal systems, such as hypertension, obesity, hypercholesterolemia, atherosclerosis, metabolic syndrome, chronic heart failure, and chronic kidney disease. Recent epidemiological evidence has shown an increasing trend in the prevalence of hyperuricemia and gout in the Western world: a number of population-based studies estimate a prevalence of up to 21% for hyperuricemia and 1%–4% for gout. As such, early detection and careful management of this pathological condition is required, starting from lifestyle changes (mainly based on a diet low in red meat, sugars, and alcoholic beverages, with increased intake of vegetables, water, and vitamin C sources, adding specific drugs to lead serum uric acid (SUA levels under the target value of 7 mg/dL. In particular, nonselective and selective XO inhibitors (allopurinol, oxypurinol, febuxostat reduce SUA levels and the overproduction of reactive oxygen species, mainly related to XO overactivity that often causes inflammatory damage to the vascular endothelium. The effect of lowering SUA levels via XO inhibition includes an attenuation of oxidative stress and related endothelial dysfunction that largely contribute to the pathophysiology of metabolic syndrome and cardiovascular diseases. Therefore, the inhibition of XO overactivation seems to be an excellent therapeutic option to limit the harmful effects of excess UA and reactive oxygen species. In conclusion, rapid diagnosis and correct therapy for hyperuricemia may also improve the prevention and/or treatment of serious and multifactorial diseases. The available evidence supports the importance of

  9. Optimization and control in deep hyperthermia: Clinical implementation of hyperthermia treatment planning in cervical cancer treatment to obtain a higher treatment quality

    NARCIS (Netherlands)

    R.A.M. Canters (Richard)

    2013-01-01

    textabstractDeep hyperthermia is a treatment used in concurrence with radiation therapy or chemotherapy in the treatment of deep seated tumors. In hyperthermia, tumor temperatures are elevated 3 to 7oC above normal body temperature, up to a temperature of 44oC. In a randomized trial, the 3 year over

  10. Optimization and control in deep hyperthermia: Clinical implementation of hyperthermia treatment planning in cervical cancer treatment to obtain a higher treatment quality

    NARCIS (Netherlands)

    R.A.M. Canters (Richard)

    2013-01-01

    textabstractDeep hyperthermia is a treatment used in concurrence with radiation therapy or chemotherapy in the treatment of deep seated tumors. In hyperthermia, tumor temperatures are elevated 3 to 7oC above normal body temperature, up to a temperature of 44oC. In a randomized trial, the 3 year

  11. The main factors influencing canine demodicosis treatment outcome and determination of optimal therapy.

    Science.gov (United States)

    Arsenović, Milica; Pezo, Lato; Vasić, Nebojša; Ćirić, Rodoljub; Stefanović, Milan

    2015-07-01

    The main idea of this research was to evaluate the efficacy of canine demodicosis conventional treatments using mathematical analyses. All available papers published between 1980 and 2014 were used in this study. One hundred six clinical trials enrolling 3414 cases of generalized demodicosis in dogs are studied. Dogs entered in the analysis were only the ones in which the disease occurred naturally, excluding the studies in which transplantation of Demodex canis mites was done from other animals. In conventional acaricide treatments, sorted according to active substances (moxidectin, amitraz, doramectin, ivermectin, and milbemycin oxime), the way of application (spot-on, dips, orally, or subcutaneous), concentration, and interval of application were used as input parameters in mathematical modeling. Data of interest were the treatment outcome, the number of dogs that went into remission, the number of animals not responding to treatment microscopically, the average duration of therapy, the follow-up period, the number of patients with disease recurrence, the number of adverse effects, and the number of animals with side effects. Dogs lost to follow-up or when the treatment was discontinued, due to various reasons not in connection with the therapy protocol, were not considered. Statistical and mathematical analyses were applied for prediction of the drugs' effectiveness. Developed mathematical models showed satisfactorily r (2), higher than 0.87. Good evidence for recommending the use of milbemycin oxime PO (0.5 mg/kg, daily) and moxidectin spot-on (Advocate®, Bayer) weekly is found. A bit less effective therapies were based on ivermectin PO (0.5 mg/kg, daily), moxidectin PO (0.35 mg/kg, daily), and amitraz dips (0.05 % solution, weekly), respectively. It is important to keep in mind that Advocate® is recommended by the manufacturer for use in milder cases.

  12. Optimal control and sensitivity analysis of an influenza model with treatment and vaccination.

    Science.gov (United States)

    Tchuenche, J M; Khamis, S A; Agusto, F B; Mpeshe, S C

    2011-03-01

    We formulate and analyze the dynamics of an influenza pandemic model with vaccination and treatment using two preventive scenarios: increase and decrease in vaccine uptake. Due to the seasonality of the influenza pandemic, the dynamics is studied in a finite time interval. We focus primarily on controlling the disease with a possible minimal cost and side effects using control theory which is therefore applied via the Pontryagin's maximum principle, and it is observed that full treatment effort should be given while increasing vaccination at the onset of the outbreak. Next, sensitivity analysis and simulations (using the fourth order Runge-Kutta scheme) are carried out in order to determine the relative importance of different factors responsible for disease transmission and prevalence. The most sensitive parameter of the various reproductive numbers apart from the death rate is the inflow rate, while the proportion of new recruits and the vaccine efficacy are the most sensitive parameters for the endemic equilibrium point.

  13. Data Mining and Electronic Health Records: Selecting Optimal Clinical Treatments in Practice

    CERN Document Server

    Bennett, Casey

    2011-01-01

    Electronic health records (EHR's) are only a first step in capturing and utilizing health-related data - the problem is turning that data into useful information. Models produced via data mining and predictive analysis profile inherited risks and environmental/behavioral factors associated with patient disorders, which can be utilized to generate predictions about treatment outcomes. This can form the backbone of clinical decision support systems driven by live data based on the actual population. The advantage of such an approach based on the actual population is that it is "adaptive". Here, we evaluate the predictive capacity of a clinical EHR of a large mental healthcare provider (~75,000 distinct clients a year) to provide decision support information in a real-world clinical setting. Initial research has achieved a 70% success rate in predicting treatment outcomes using these methods.

  14. Optimizing the treatment of anemia in cancer patients. The role of a new erythropoietic agent.

    Science.gov (United States)

    Henry, David H

    2002-10-01

    Cancer-related anemia, in addition to having detrimental effects on quality of life and adding the risk and inconvenience of blood transfusions, may also be associated with decreased survival or time to progression. Yet despite increasing awareness of the value of treating cancer-related anemia, over 60% of US cancer patients receiving chemotherapy who have hemoglobin values below 10 g/dL are not treated for this condition. Current treatment options include red blood cell transfusions, iron supplementation for iron deficiency, or erythropoietic agents, including recombinant human erythropoietin (rHuEPO) and darbepoetin alfa (Aranesp). The articles in this supplement describe the basic scientific research and clinical development of darbepoetin alfa--another safe, effective, and approved treatment for chemotherapy-induced anemia.

  15. Treatment of automotive industry oily wastewater by electrocoagulation: statistical optimization of the operational parameters.

    Science.gov (United States)

    GilPavas, Edison; Molina-Tirado, Kevin; Gómez-García, Miguel Angel

    2009-01-01

    An electrocoagulation process was used for the treatment of oily wastewater generated from an automotive industry in Medellín (Colombia). An electrochemical cell consisting of four parallel electrodes (Fe and Al) in bipolar configuration was implemented. A multifactorial experimental design was used for evaluating the influence of several parameters including: type and arrangement of electrodes, pH, and current density. Oil and grease removal was defined as the response variable for the statistical analysis. Additionally, the BOD(5), COD, and TOC were monitored during the treatment process. According to the results, at the optimum parameter values (current density = 4.3 mA/cm(2), distance between electrodes = 1.5 cm, Fe as anode, and pH = 12) it was possible to reach a c.a. 95% oils removal, COD and mineralization of 87.4% and 70.6%, respectively. A final biodegradability (BOD(5)/COD) of 0.54 was reached.

  16. [Optimization of treatment of children with acute intestinal infections by application of Russian biological microbial preparations].

    Science.gov (United States)

    Feklisova, L V

    2005-01-01

    The article presents the results of long-term (several years) use of Russian bifido- and lactocontaing probiotics and data on the clinicolaboratory effectiveness of bifidumbacterin forte, probifor, bifidin, bifilis, calcidum, florin forte, acipol and acilact in children with various intestinal infections of known and unknown etiology. The presented results were obtained by studies conducted according to the requirements of The Governmental Program of L. A. Tarasevich State Institute of Standartization and Medical Biological Preparation Control, which included randomization of groups of patients receiving codified preparations or placebo according to their age, nosology, the degree of the process severity, premorbid status, and the time when the treatment was started. Each of the programs included several hundreds of children, receiving probiotics; in which of the programs the studies were multicentered. The courses of treatment with probiotics were short (1 to 2 weeks). No significant adverse effects were observed.

  17. [Benefits of spironolactone as the optimal treatment for drug resistant hypertension. Pathway-2 trial review].

    Science.gov (United States)

    Prado, J C; Ruilope, L M; Segura, J

    Pathway-2 is the first randomised, double-blind and crossover trial that compares spironolactone as a fourth drug with alfa-blocker, beta-blocker and placebo. This study shows that spironolactone is the drug with more possibilities of success for the management of patients with difficult-to-treat hypertension in patients with a combination of three drugs and poor control. The results validate the widespread treatment with mineralocorticoid receptor antagonists in resistant hypertension.

  18. Tinnitus treatment with precise and optimal electric stimulation: opportunities and challenges

    OpenAIRE

    Zeng, FG; Djalilian, H; LIN, H.

    2015-01-01

    © 2015 Wolters Kluwer Health, Inc. All rights reserved. PURPOSE OF REVIEW: Electric stimulation is a potent means of neuromodulation that has been used to restore hearing and minimize tremor, but its application on tinnitus symptoms has been limited. We examine recent evidence to identify the knowledge gaps in the use of electric stimulation for tinnitus treatment. RECENT FINDINGS: Recent studies using electric stimulation to suppress tinnitus in humans are categorized according to their poin...

  19. Optimizing water treatment practices for the removal of actinomycetes and earthy odor in water of Bovilla reservoir

    Directory of Open Access Journals (Sweden)

    ADELA KULLAJ

    2014-06-01

    Full Text Available Bovilla reservoir, which is situated 15 km North-East of Tirana the capital city of Albania is one of the major hidrotechnical works of this country. This reservoir is a warm monomictic water body and stratifies higher in the summer season. The predominant trophic state of Bovilla reservoir is oligotrophy. From autumn 2001 this reservoir repeatedly manifests an unpleasant taste and odor which is defined as musty- earthy. Taste and odor control has become an important issue for drinking water suppliers worldwide. Consumers react very sensitively to changes in the organoleptic quality of their drinking water. The reason is that odor compounds present a very low threshold of perception (10–20 ng/L. Bovilla water treatment plant treats 1800 L/s raw water taken from Bovilla reservoir, using oxidation, coagulation and flocculation, sedimentation, filtration and disinfection process. In cases of bad odor powdered activated carbon (PAC is added at the rapid mix section. Throughout the monitoring period were done: quality and sensory analysis of raw water on a weekly frequency, analysis of treated water after coagulation, laboratory scale experiments using different doses of chemicals, applying optimized doses in full scale and PAC adsorption experiments. The aims of this study were: to predict the PAC doses required to treat water of Bovilla reservoir containing bad taste and odor, to establish the removal efficiency of taste and odor by three types of activated carbons with different iodine number and to assess the impact of NaOCl and other chemical in the treatment process of the plant in removing actinomycetes and bad odor. Results have shown that traditional treatment processes are usually inadequate in removing taste and odor and optimization of plant practices is required. Powdered activated carbon (PAC can effectively remove taste and odor when the correct dose is applied.

  20. Nonlinear optimization

    CERN Document Server

    Ruszczynski, Andrzej

    2011-01-01

    Optimization is one of the most important areas of modern applied mathematics, with applications in fields from engineering and economics to finance, statistics, management science, and medicine. While many books have addressed its various aspects, Nonlinear Optimization is the first comprehensive treatment that will allow graduate students and researchers to understand its modern ideas, principles, and methods within a reasonable time, but without sacrificing mathematical precision. Andrzej Ruszczynski, a leading expert in the optimization of nonlinear stochastic systems, integrates t

  1. Optimization of the route of platinum drugs administration to optimize the concomitant treatment with radiotherapy for glioblastoma implanted in the Fischer rat brain

    Science.gov (United States)

    Charest, Gabriel; Sanche, Léon; Fortin, David; Mathieu, David; Paquette, Benoit

    2013-01-01

    Treatment of glioblastoma with platinum compounds modestly improves progression-free survival and may cause toxic effects which prevent use at higher dose that would otherwise improve the antineoplastic effect. To reduce toxicity, we propose to encapsulate the platinum drug in a liposome. We have also tested three methods of drug administration (intra-venous, intra-arterial and intra-arterial combined with blood brain barrier disruption) to determine which one optimizes the tumor cell uptake, limits the toxicity and delivers the best concomitance effect with radiotherapy. Cisplatin, oxaliplatin, their respective liposomal formulations, Lipoplatin™ and Lipoxal™, and carboplatin were assessed in F98 glioma, orthotopically implanted in Fischer rats. We found that the modest accumulation of drugs in tumor cells after intra-venous injection was significantly improved when the intra-arterial route was used and further increased after the transient opening of the blood brain barrier with mannitol. The liposomal formulations have largely reduced the toxicity and have allowed a better exploitation of the anti-cancer activity of platinum agent. Although the liposomes Lipoplatin™ and Lipoxal™ have shown a similar ability to that of carboplatin, to accumulate in brain tumors, the highest additive effect with radiotherapy was obtained with carboplatin. We conclude that the intra-arterial infusion of carboplatin or Lipoxal™ in concomitance with radiation therapy leads to the best tumor control as measured by an increase of mean survival time in Fischer rats implanted with the F98 glioma with a benefit in survival time of 13.4 and 6.5 days respectively compared to intra-venous. PMID:24026531

  2. Multi-GPU implementation of a VMAT treatment plan optimization algorithm

    CERN Document Server

    Tian, Zhen; Folkerts, Michael; Tan, Jun; Jia, Xun; Jiang, Steve B

    2015-01-01

    VMAT optimization is a computationally challenging problem due to its large data size, high degrees of freedom, and many hardware constraints. High-performance graphics processing units have been used to speed up the computations. However, its small memory size cannot handle cases with a large dose-deposition coefficient (DDC) matrix. This paper is to report an implementation of our column-generation based VMAT algorithm on a multi-GPU platform to solve the memory limitation problem. The column-generation approach generates apertures sequentially by solving a pricing problem (PP) and a master problem (MP) iteratively. The DDC matrix is split into four sub-matrices according to beam angles, stored on four GPUs in compressed sparse row format. Computation of beamlet price is accomplished using multi-GPU. While the remaining steps of PP and MP problems are implemented on a single GPU due to their modest computational loads. A H&N patient case was used to validate our method. We compare our multi-GPU implemen...

  3. Biogas production from synthetic sago wastewater by anaerobic digestion: Optimization and treatment

    Directory of Open Access Journals (Sweden)

    Sangeetha V.

    2016-01-01

    Full Text Available Sago processing industries generate a voluminous amount of wastewater with extremely high concentration of organic pollutants, resulting in water pollution. Anaerobic digestion has employed for reduction of COD and maximization of biogas production using synthetic sago wastewater by batch process. Mixed culture obtained from sago industry sludge was used as a source for microorganism. Response surface methodology was used to optimize the variables, such as pH, initial BOD, temperature and retention time. Statistical results were assessed with various descriptive, such as p value, lack of fit (F-test, coefficient of R2 determination, and adequate precision values. Pareto Analysis of Variance revealed that the coefficients of determination value (R2 of % COD removal, % BOD removal and biogas production were 0.994, 0.993 and 0.988. The optimum condition in which maximum COD removal (81.85%, BOD removal (91.61% and biogas production of 99.4 ml/day was achieved at pH 7 with an initial BOD of 1374 mg/l, and with the retention time of 10 days at 32oC.

  4. Optimization of megavoltage CT scan registration settings for brain cancer treatments on tomotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Woodford, Curtis; Yartsev, Slav; Van Dyk, Jake [London Regional Cancer Program, London Health Sciences Centre, 790 Commissioners Road East, London, Ontario (Canada)

    2007-04-21

    This study aims to determine the settings that provide the optimal clinical accuracy and consistency for the registration of megavoltage CT (MVCT) with planning kilovoltage CT image sets on the Hi-ART tomotherapy system. The systematic offset between the MVCT and the planning kVCT was determined by registration of multiple MVCT scans of a head phantom aligned with the planning isocentre. Residual error vector lengths and components were used to quantify the alignment quality for the phantom shifted by 5 mm in different directions obtained by all 27 possible combinations of MVCT inter-slice spacing, registration techniques and resolution. MVCT scans with normal slices are superior to coarse slices for registration of shifts in the superior-inferior, lateral and anterior-posterior directions. Decreasing the scan length has no detrimental effect on registration accuracy as long as the scan lengths are larger than 24 mm. In the case of bone technique and fine resolution, normal and fine MVCT scan slice spacing options give similar accuracy, so normal mode is preferable due to shorter procedure and less delivered dose required for patient set-up. A superior-inferior field length of 24-30 mm, normal slice spacing, bone technique, and fine resolution is the optimum set of registration settings for MVCT scans of a Rando head phantom acquired with the Hi-ART tomotherapy system, provided the registration shifts are less than 5 mm. (note)

  5. Optimizing control of acromegaly: integrating a growth hormone receptor antagonist into the treatment algorithm.

    Science.gov (United States)

    Clemmons, David R; Chihara, Kazuo; Freda, Pamela U; Ho, Ken K Y; Klibanski, Anne; Melmed, Shlomo; Shalet, Stephen M; Strasburger, Christian J; Trainer, Peter J; Thorner, Michael O

    2003-10-01

    Acromegaly is associated with significant morbidities and a 2- to 3-fold increase in mortality because of the excessive metabolic action of GH and IGF-I, a marker of GH output. Reductions in morbidity correspond with decreases in IGF-I, and mortality is lowered following normalization of IGF-I or GH levels. Therefore, this has become an important end point. Current guidelines for the treatment of acromegaly have not considered recent advances in medical therapy, in particular, the place of pegvisomant, a GH receptor antagonist. Treatment goals include normalizing biochemical markers, controlling tumor mass, preserving pituitary function, and relieving signs and symptoms. Surgery reduces tumor volume and is considered first-line therapy. Radiation reduces tumor volume and GH and IGF-I levels, but the onset of action is slow and hypopituitarism typically develops. Therefore, pharmacotherapy is often used following surgery or as first-line therapy for nonresectable tumors. Dopamine agonists can be considered in patients exhibiting minimal disease or those with GH-prolactin-cosecreting tumors but will not achieve hormone normalization in most patients. Somatostatin analogs effectively suppress GH and IGF-I in most patients, but intolerance (e.g. diarrhea, cramping, gallstones) can occur. Pegvisomant, the newest therapeutic option, blocks GH action at peripheral receptors, normalizes IGF-I levels, reduces signs and symptoms, and corrects metabolic defects. Pegvisomant does not appear to affect tumor size and has few adverse effects. Pegvisomant is the most effective drug treatment for acromegaly in normalizing IGF-I and producing a clinical response; it is the preferred agent in patients resistant to or intolerant of somatostatin analogs.

  6. Diabetic Patients are often Sub-Optimally Aware about their Disease and its Treatment

    Directory of Open Access Journals (Sweden)

    Ioannis Kyriazis

    2013-01-01

    Full Text Available Background: Diabetes mellitus (DM represents a continuously growing worldwide threat with major financial impact on the healthcare systems. The importance of tight glycaemic control in patients with DM type II is well established and is most effectively accomplished with the proper cooperation of both the treating physicians aswell as the treated subjects.Aims: The aim of our study was to evaluate the level of awareness of patients with DM type II about the various aspects of DM, including the nature of the disease, its precipitating factors and complications, as well as its treatment.Methodology: The patients were asked to complete anonymously a questionnaire concerning their knowledge about diabetes, its basic pathophysiology and complications, the treatment options and possible side-effects. Data were analyzed using STATA statistical software (Version 9.0.Results: Eighty patients were on oral hypoglycaemic agents (OHA, 34 on insulin while 4 were under a hybrid treatment. Among patients on OHA, 40 patients (50% were taking a combination of them. 13.4% of the sample was aware of what DM stands for, 84.9% did not know the type of DM they were suffering from, while (85.7% considered that obesity plays a major role in the pathogenesis of DM. Concerning the therapy of DM, only 54.83% of the patients were aware of the brand names of their antidiabetic medication, 88.2% did not know theirway of action, while 60.5% did not know the possible side effects. The majority of the sample, 60.5%, assumed that blood glucose should be measured only before meals.Conclusions: The knowledge of the subjects visiting the center for the first time was found to be inadequate. This is probably due to inadequate information, non-availability of educational material and improper guidance.

  7. Optimizing the Treatment of Gastrointestinal Disorders in Food Intolerance in Infants

    Directory of Open Access Journals (Sweden)

    O.H. Shadrin

    2016-06-01

    Full Text Available Advisability of including the polyenzyme dietary supplement Sanzyme syrup in the combination treatment of gastrointestinal manifestations of food intolerance in infants has been studied. It is proved that taking polyenzyme dietary supplement by 70 infants with lactose deficiency and gastrointestinal food allergy leads to positive dynamics of clinical symptoms in terms of a decrease in abdominal pain syndrome, colic, posseting, flatulency in 91.1 % of children and the improved digestion according to the results of coprological survey in terms of the disappearance of steatorrhea in 43 patients (95.5 %, creatorrhea — in 40 children (88.9 %, amylorrhea — in 37 (82.2 %.

  8. Kinetics of phase growth in Nb3Sn formation for heat treatment optimization

    Energy Technology Data Exchange (ETDEWEB)

    Emanuela Barzi; Sara Mattafirri

    2002-10-25

    The kinetics of growth and superconducting properties of Nb{sub 3}Sn are investigated as a function of the heat treatment (HT) duration and temperature for Internal Tin and Powder-in-Tube strands at 650, 700 and 750 C. For all times and temperatures, the Nb{sub 3}Sn layer thickness is measured, the critical current at 4.2 K is tested as a function of magnetic field, and the upper critical field is evaluated. Results of the layer critical current density are also shown as a function of HT duration and temperature.

  9. Optimization of the extent of surgical treatment in patients with stage I in cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chernyshova, A. L.; Lyapunov, A. Yu., E-mail: Lyapunov1720.90@mail.ru [Tomsk Cancer Research Institute, Kooperativny Street 5, Tomsk, 634050 (Russian Federation); Kolomiets, L. A. [Tomsk Cancer Research Institute, Kooperativny Street 5, Tomsk, 634050 (Russian Federation); Siberian State Medical University, Moskovsky Trakt 2, Tomsk, 634050 (Russian Federation); Sinilkin, I. G.; Chernov, V. I. [Tomsk Cancer Research Institute, Kooperativny Street 5, Tomsk, 634050 (Russian Federation); Tomsk Polytechnic University, Lenin Avenue 30, Tomsk, 634050 (Russian Federation)

    2016-08-02

    The study included 26 patients with FIGO stage Ia1–Ib1 cervical cancer who underwent fertility-sparing surgery (transabdominaltrachelectomy). To visualize sentinel lymph nodes, lymphoscintigraphy with injection of 99mTc-labelled nanocolloid was performed the day before surgery. Intraoperative identification of sentinel lymph nodes using hand-held gamma probe was carried out to determine the radioactive counts over the draining lymph node basin. The sentinel lymph node detection in cervical cancer patients contributes to the accurate clinical assessment of the pelvic lymph node status, precise staging of the disease and tailoring of surgical treatment to individual patient.

  10. Optimal Use of Combined Modality Therapy in the Treatment of Esophageal Cancer.

    Science.gov (United States)

    Shaikh, Talha; Meyer, Joshua E; Horwitz, Eric M

    2017-07-01

    Esophageal cancer is associated with a poor prognosis with 5-year survival rates of approximately 15% to 20%. Although patients with early stage disease may adequately be treated with a single modality, combined therapy typically consisting of neoadjuvant chemoradiation followed by esophagectomy is being adopted increasingly in patients with locally advanced disease. In patients who are not surgical candidates, definitive chemoradiation is the preferred treatment approach. All patients with newly diagnosed esophageal cancer should be evaluated in the multidisciplinary setting by a surgeon, radiation oncologist, and medical oncologist owing to the importance of each specialty in the management of these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Optimization of the extent of surgical treatment in patients with stage I in cervical cancer

    Science.gov (United States)

    Chernyshova, A. L.; Kolomiets, L. A.; Sinilkin, I. G.; Chernov, V. I.; Lyapunov, A. Yu.

    2016-08-01

    The study included 26 patients with FIGO stage Ia1-Ib1 cervical cancer who underwent fertility-sparing surgery (transabdominaltrachelectomy). To visualize sentinel lymph nodes, lymphoscintigraphy with injection of 99mTc-labelled nanocolloid was performed the day before surgery. Intraoperative identification of sentinel lymph nodes using hand-held gamma probe was carried out to determine the radioactive counts over the draining lymph node basin. The sentinel lymph node detection in cervical cancer patients contributes to the accurate clinical assessment of the pelvic lymph node status, precise staging of the disease and tailoring of surgical treatment to individual patient.

  12. Multi-objective Optimization for the Robust Performance of Drinking Water Treatment Plants under Climate Change and Climate Extremes

    Science.gov (United States)

    Raseman, W. J.; Kasprzyk, J. R.; Rosario-Ortiz, F.; Summers, R. S.; Stewart, J.; Livneh, B.

    2016-12-01

    To promote public health, the United States Environmental Protection Agency (US EPA), and similar entities around the world enact strict laws to regulate drinking water quality. These laws, such as the Stage 1 and 2 Disinfectants and Disinfection Byproducts (D/DBP) Rules, come at a cost to water treatment plants (WTPs) which must alter their operations and designs to meet more stringent standards and the regulation of new contaminants of concern. Moreover, external factors such as changing influent water quality due to climate extremes and climate change, may force WTPs to adapt their treatment methods. To grapple with these issues, decision support systems (DSSs) have been developed to aid WTP operation and planning. However, there is a critical need to better address long-term decision making for WTPs. In this poster, we propose a DSS framework for WTPs for long-term planning, which improves upon the current treatment of deep uncertainties within the overall potable water system including the impact of climate on influent water quality and uncertainties in treatment process efficiencies. We present preliminary results exploring how a multi-objective evolutionary algorithm (MOEA) search can be coupled with models of WTP processes to identify high-performing plans for their design and operation. This coupled simulation-optimization technique uses Borg MOEA, an auto-adaptive algorithm, and the Water Treatment Plant Model, a simulation model developed by the US EPA to assist in creating the D/DBP Rules. Additionally, Monte Carlo sampling methods were used to study the impact of uncertainty of influent water quality on WTP decision-making and generate plans for robust WTP performance.

  13. Tricuspid regurgitation following left-sided valve surgery: echocardiographic evaluation and optimal timing of surgical treatment.

    Science.gov (United States)

    Izumi, Chisato

    2015-03-01

    Severe tricuspid regurgitation may often appear and progress late after left-sided valve surgery without left-sided valve dysfunction, significant left heart failure, and pulmonary hypertension. The clinical features, echocardiographic evaluation, treatment, and prognosis of this disease entity have been discussed, but data is limited compared with left-sided valve diseases. Tricuspid annular dilatation associated with atrial fibrillation and right ventricular dysfunction strongly relate to development of isolated tricuspid regurgitation late after left-sided valve surgery. Three-dimensional evaluation may be useful in evaluating tricuspid valve anatomy in more detail. Better prognosis in patients undergoing surgical treatment for severe isolated tricuspid regurgitation than those who were treated medically has been reported; however, the timing of isolated tricuspid valve surgery is often too late. Right ventricular function is a key word for determining the timing of isolated tricuspid valve surgery; however, it is difficult to evaluate by conventional echocardiography. One of the serious issues in the future will be how to accurately evaluate right ventricular function.

  14. Technological Advances in the Treatment of Cancer: Combining Modalities to Optimize Outcomes.

    Science.gov (United States)

    Wong, Eric T; Toms, Steven A; Ahluwalia, Manmeet S

    2015-11-01

    The anticancer treatment modality tumor treating fields (TTFields; Optune, Novocure) use the lower frequency range of the electromagnetic spectrum to destroy tumor cells during mitosis. This treatment has been evaluated in several trials of patients with glioblastoma. In these patients, TTFields are delivered through 4 transducer arrays applied to the scalp. In a phase 3 clinical trial of patients with recurrent glioblastoma, TTFields were as effective as chemotherapy, and were associated with fewer and milder systemic toxicities. Data from a phase 3 trial in newly diagnosed glioblastoma suggested that the addition of TTFields to postoperative radiation therapy and chemotherapy represents an important advance in the management of newly diagnosed glioblastoma. Ongoing clinical trials are investigating the efficacy and safety of TTFields in other tumor types, including pancreatic cancer, mesothelioma, ovarian cancer, and non–small cell lung cancer. Other recent advances in the management of cancer have been seen with immunomodulatory therapy, including immune checkpoint inhibitors. Further study will be necessary to evaluate whether TTFields will enhance or impair other established and newly emerging therapies.

  15. Optimization of Anaerobic Treatment of Petroleum Refinery Wastewater Using Artificial Neural Networks

    Directory of Open Access Journals (Sweden)

    H.A. Gasim

    2013-07-01

    Full Text Available Treatment of petroleum refinery wastewater using anaerobic treatment has many advantages over other biological method particularly when used to treat complex wastewater. In this study, accumulated data of Up-flow Anaerobic Sludge Blanket (UASB reactor treating petroleum refinery wastewater under six different volumetric organic loads (0.58, 1.21, 0.89, 2.34, 1.47 and 4.14 kg COD/m3.d, respectively were used for developing mathematical model that could simulate the process pattern. The data consist of 160 entries and were gathered over approximately 180 days from two UASB reactors that were continuously operating in parallel. Artificial neural network software was used to model the reactor behavior during different loads applied. Two transfer functions were compared and different number of neurons was tested to find the optimum model that predicts the reactor pattern. The tangent sigmoid transfer function (tansig at hidden layer and a linear transfer function (purelin at output layer with 12 neurons were selected as the optimum best model.

  16. Selection of Steady-State Process Simulation Software to Optimize Treatment of Radioactive and Hazardous Waste

    Energy Technology Data Exchange (ETDEWEB)

    Nichols, Todd Travis; Barnes, Charles Marshall; Lauerhass, Lance; Taylor, Dean Dalton

    2001-06-01

    The process used for selecting a steady-state process simulator under conditions of high uncertainty and limited time is described. Multiple waste forms, treatment ambiguity, and the uniqueness of both the waste chemistries and alternative treatment technologies result in a large set of potential technical requirements that no commercial simulator can totally satisfy. The aim of the selection process was two-fold. First, determine the steady-state simulation software that best, albeit not completely, satisfies the requirements envelope. And second, determine if the best is good enough to justify the cost. Twelve simulators were investigated with varying degrees of scrutiny. The candidate list was narrowed to three final contenders: ASPEN Plus 10.2, PRO/II 5.11, and CHEMCAD 5.1.0. It was concluded from "road tests" that ASPEN Plus appears to satisfy the project's technical requirements the best and is worth acquiring. The final software decisions provide flexibility: they involve annual rather than multi-year licensing, and they include periodic re-assessment.

  17. Selection of Steady-State Process Simulation Software to Optimize Treatment of Radioactive and Hazardous Waste

    Energy Technology Data Exchange (ETDEWEB)

    Nichols, T. T.; Barnes, C. M.; Lauerhass, L.; Taylor, D. D.

    2001-06-01

    The process used for selecting a steady-state process simulator under conditions of high uncertainty and limited time is described. Multiple waste forms, treatment ambiguity, and the uniqueness of both the waste chemistries and alternative treatment technologies result in a large set of potential technical requirements that no commercial simulator can totally satisfy. The aim of the selection process was two-fold. First, determine the steady-state simulation software that best, albeit not completely, satisfies the requirements envelope. And second, determine if the best is good enough to justify the cost. Twelve simulators were investigated with varying degrees of scrutiny. The candidate list was narrowed to three final contenders: ASPEN Plus 10.2, PRO/II 5.11, and CHEMCAD 5.1.0. It was concluded from ''road tests'' that ASPEN Plus appears to satisfy the project's technical requirements the best and is worth acquiring. The final software decisions provide flexibility: they involve annual rather than multi-year licensing, and they include periodic re-assessment.

  18. Optimal treatment of cervical necrotizing fasciitis associated with descending necrotizing mediastinitis.

    Science.gov (United States)

    Karkas, A; Chahine, K; Schmerber, S; Brichon, P-Y; Righini, C A

    2010-04-01

    Cervical necrotizing fasciitis (CNF) associated with descending necrotizing mediastinitis (DNM) is a rapidly evolving and life-threatening condition. The aim of this retrospective study was to describe a treatment strategy for CNF with DNM and present a management algorithm for mediastinal extensions of CNF. Patients diagnosed and treated for CNF with DNM over 14 years in a tertiary referral centre were included. Seventeen adult patients were included. The origin of infection was mainly oropharyngeal. The diagnosis of CNF/DNM was based on clinical and computed tomography findings. All patients underwent cervicotomy for CNF. In ten patients, DNM was located above the carina and could be accessed by a cervical approach. In seven patients, DNM was below the carina, and necessitated sternotomy for anteroinferior mediastinal involvement and posterolateral thoracotomy for posteroinferior mediastinal involvement. All patients received broad-spectrum antibiotics. One patient died 3 days after surgery. The median hospital stay was 30 days. There was no recurrence during long-term follow-up. Prompt diagnosis and early surgical treatment are essential for reducing mortality in CNF/DNM. All patients should undergo extensive cervicotomy. The surgical approach to the mediastinum depends on the supracarinal or infracarinal location of the disease. Copyright (c) 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

  19. How to optimize excisional procedures for the treatment of CIN? The role of colposcopy.

    Science.gov (United States)

    Grisot, Céline; Mancini, Julien; Giusiano, Sophie; Houvenaeghel, Gilles; Agostini, Aubert; d'Ercole, Claude; Boubli, Léon; Prendiville, Walter; Carcopino, Xavier

    2012-05-01

    To evaluate the value of colposcopy during excisional treatment of cervical intraepithelial neoplasia (CIN). Data from 469 women who underwent excisional treatment for CIN in three different hospitals between January 2005 and December 2009 were reviewed. Margins status and surgical specimen dimensions were analyzed according to the use of colposcopy during procedure. The rate of negative margins was not significantly different between women who had excision performed without colposcopic examination, with colposcopy immediately before excision and with direct colposcopic vision (DCV): 74 (62.2%), 186 (72.9%) and 25 (67.6%), respectively (p = 0.107). DCV allowed for significantly higher probability to achieve both negative margins and depth of specimen of less than 10 mm: 22 (18.5%) versus 70 (27.5%) versus 14 (37.8%), respectively (p = 0.039). In multivariate analysis, compared to women who had excision without any use of colposcopy, DCV allowed for significant and independent reduction in both depth (ß: -2.46; 95%CI: -4.45 to -0.47; p = 0.015) and diameter (ß: -4.80; 95%CI: -7.14 to -2.47; p CIN, allows for smaller surgical specimen without jeopardizing the margins status.

  20. Optimization of Bromelain Treatment pH with Wool for Antifelting and Reduced Pilling Behaviour: Objective Assessment Approach

    Directory of Open Access Journals (Sweden)

    Amandeep Kaur

    2015-01-01

    Full Text Available Wool fabric possesses unique properties like resiliency, warmth, wide aesthetic qualities, and comfort. However, felting-shrinkage and pilling tendency of wool after wear and repeated launderings are its inherent limitations. Proteolytic enzymes are extensively used as biocatalysts for eco-friendly wool antifelting treatments. However, uncontrolled wool protein hydrolysis by protease may lead to excessive weight loss leading to weakening of fiber and reduction in its tensile value, which further have detrimental effect on the pilling propensity of protease treated wool during use of woolen textiles. Optimum selection of protease treatment parameters like concentration, pH, temperature, and so forth can help in controlled reaction to achieve the desired effect, which generally involves cumbersome sampling and analysis. Optimization for pH of bromelain (proteolytic enzyme having activity in acidic conditions treatment with wool has been done while aiming at the desired areawise shrinkage value, minimum weight loss, and reduced pilling by using standard methods and objective fast Fourier transformation technique for pilling evaluation specifically.

  1. The use of a realistic VMAT delivery emulator to optimize dynamic machine parameters for improved treatment efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Boylan, C J; Rowbottom, C G; Mackay, R I, E-mail: Christopher.Boylan@physics.cr.man.ac.uk [North Western Medical Physics, Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX (United Kingdom)

    2011-07-07

    The delivery of volumetric modulated arc therapy (VMAT) requires the simultaneous movement of the linear accelerator gantry, multi-leaf collimators and jaws while the dose rate is varied. In this study, a VMAT delivery emulator was developed to accurately predict the characteristics of a given treatment plan, incorporating realistic parameters for gantry inertia and the variation in leaf speed with respect to gravity. The emulator was used to assess the impact of dynamic machine parameters on the delivery efficiency, using a set of prostate and head and neck VMAT plans. Initially, assuming a VMAT system with fixed dose rate bins, the allowable leaf and jaw speeds were increased and a significant improvement in treatment time and average dose rate was observed. The software was then adapted to simulate a VMAT system with continuously varying dose rate, and the increase in delivery efficiency was quantified, along with the impact of an increased leaf and jaw speed. Finally, a set of optimal dynamic machine parameters was derived assuming an idealized scenario in which the treatment is delivered in a single arc at constant maximum gantry speed.

  2. Optimal management of testicular cancer: from self-examination to treatment of advanced disease

    Directory of Open Access Journals (Sweden)

    Stephen DW Beck

    2010-08-01

    Full Text Available Stephen DW BeckDepartment of Urology, Indiana University, Indianapolis, Indiana, USAAbstract: Germ-cell cancer is the most common solid tumor in men aged 15 to 35 years and has become the model for curable neoplasm. Over the last 3 decades, the cure rate has increased from 15% to 85%. This improved cure rate has been largely attributed to the ­introduction of cisplatin-based chemotherapy. In stage I seminoma and nonseminoma, cure rates approach 100% and treatment is governed by patient choice based on the perceived morbidities of each therapy and personal preferences. For seminoma, treatments include surveillance, radiotherapy, and single course carboplatin. For nonseminoma, treatments include surveillance, retroperitoneal lymph node dissection (RPLND, and adjuvant chemotherapy. Low volume (<3 cm stage II seminoma is typically managed with radiotherapy while higher volume (>3 cm stage II and stage III disease treated with chemotherapy. Positron emission tomography (PET imaging can differentiate active cancer versus necrosis for postchemotherapy residual masses. PET-positive masses are managed with either surgery or second-line chemotherapy. Low volume (<5 cm stage II nonseminoma with normal serum tumor markers may be managed with either RPLND or chemotherapy. Patients with persistently elevated serum tumor markers and larger volume stage II and stage III disease are managed with systemic chemotherapy. As with ­seminoma, good risk patients are typically treated with 3 courses of bleomycin, etoposide, and ­cisplatin (BEP and intermediate and poor risk patients are treated with 4 courses. Residual postchemotherapy masses should be resected due to the uncertainty of the histology with 50% to 60% harboring residual teratoma or active cancer. The majority of patients completing initial therapy who relapse do so within 2 years. A minority of patients (2%–3% recur after 2 years and this phenomenon is termed late relapse. Excluding chemona

  3. Plasma treatment of bulk niobium surface for superconducting rf cavities: Optimization of the experimental conditions on flat samples

    Directory of Open Access Journals (Sweden)

    M. Rašković

    2010-11-01

    Full Text Available Accelerator performance, in particular the average accelerating field and the cavity quality factor, depends on the physical and chemical characteristics of the superconducting radio-frequency (SRF cavity surface. Plasma based surface modification provides an excellent opportunity to eliminate nonsuperconductive pollutants in the penetration depth region and to remove the mechanically damaged surface layer, which improves the surface roughness. Here we show that the plasma treatment of bulk niobium (Nb presents an alternative surface preparation method to the commonly used buffered chemical polishing and electropolishing methods. We have optimized the experimental conditions in the microwave glow discharge system and their influence on the Nb removal rate on flat samples. We have achieved an etching rate of 1.7  μm/min⁡ using only 3% chlorine in the reactive mixture. Combining a fast etching step with a moderate one, we have improved the surface roughness without exposing the sample surface to the environment. We intend to apply the optimized experimental conditions to the preparation of single cell cavities, pursuing the improvement of their rf performance.

  4. Optimizing the coagulation process in a drinking water treatment plant -- comparison between traditional and statistical experimental design jar tests.

    Science.gov (United States)

    Zainal-Abideen, M; Aris, A; Yusof, F; Abdul-Majid, Z; Selamat, A; Omar, S I

    2012-01-01

    In this study of coagulation operation, a comparison was made between the optimum jar test values for pH, coagulant and coagulant aid obtained from traditional methods (an adjusted one-factor-at-a-time (OFAT) method) and with central composite design (the standard design of response surface methodology (RSM)). Alum (coagulant) and polymer (coagulant aid) were used to treat a water source with very low pH and high aluminium concentration at Sri-Gading water treatment plant (WTP) Malaysia. The optimum conditions for these factors were chosen when the final turbidity, pH after coagulation and residual aluminium were within 0-5 NTU, 6.5-7.5 and 0-0.20 mg/l respectively. Traditional and RSM jar tests were conducted to find their respective optimum coagulation conditions. It was observed that the optimum dose for alum obtained through the traditional method was 12 mg/l, while the value for polymer was set constant at 0.020 mg/l. Through RSM optimization, the optimum dose for alum was 7 mg/l and for polymer was 0.004 mg/l. Optimum pH for the coagulation operation obtained through traditional methods and RSM was 7.6. The final turbidity, pH after coagulation and residual aluminium recorded were all within acceptable limits. The RSM method was demonstrated to be an appropriate approach for the optimization and was validated by a further test.

  5. The optimal duration and delay of first aid treatment for deep partial thickness burn injuries.

    Science.gov (United States)

    Cuttle, Leila; Kempf, Margit; Liu, Pei-Yun; Kravchuk, Olena; Kimble, Roy M

    2010-08-01

    Using our porcine model of deep dermal partial thickness burn injury, various durations (10min, 20min, 30min or 1h) and delays (immediate, 10min, 1h, 3h) of 15 degrees C running water first aid were applied to burns and compared to untreated controls. The subdermal temperatures were monitored during the treatment and wounds observed weekly for 6 weeks, for re-epithelialisation, wound surface area and cosmetic appearance. At 6 weeks after the burn, tissue biopsies were taken of the scar for histological analysis. Results showed that immediate application of cold running water for 20min duration is associated with an improvement in re-epithelialisation over the first 2 weeks post-burn and decreased scar tissue at 6 weeks. First aid application of cold water for as little as 10min duration or up to 1h delay still provides benefit.

  6. Optimal treatment strategies for community-acquired pneumonia: high-risk patients (geriatric and with comorbidity).

    Science.gov (United States)

    Carbon, C

    2001-01-01

    The four major factors predisposing individuals to community-acquired pneumonia (CAP) are chronic obstructive pulmonary disease, congestive heart failure, diabetes, and a high alcohol intake. The elderly are also at increased risk of severe infection. The introduction of fluoroquinolones with increased activity against Streptococcus pneumoniae and other CAP pathogens has been an important development, with recent guidelines recommending the use of respiratory fluoroquinolones as a first-line choice in outpatients with modifying factors, nursing home residents, and hospitalised patients in medical wards. Of the fluoroquinolones currently available that have antipneumococcal activity, levofloxacin is well tolerated and effective. It has been approved by the Food and Drug Administration (FDA) for treatment of CAP and widespread use has shown it to be very safe.

  7. Convergence analysis of particle swarm optimization (PSO) method on the with-in host dengue infection treatment model

    Science.gov (United States)

    Handayani, D.; Nuraini, N.; Tse, O.; Saragih, R.; Naiborhu, J.

    2016-04-01

    PSO is a computational optimization method motivated by the social behavior of organisms like bird flocking, fish schooling and human social relations. PSO is one of the most important swarm intelligence algorithms. In this study, we analyze the convergence of PSO when it is applied to with-in host dengue infection treatment model simulation in our early research. We used PSO method to construct the initial adjoin equation and to solve a control problem. Its properties of control input on the continuity of objective function and ability of adapting to the dynamic environment made us have to analyze the convergence of PSO. With the convergence analysis of PSO we will have some parameters that ensure the convergence result of numerical simulations on this model using PSO.

  8. [Promising directions of optimization of providing radiological safety in large-scale treatment-and-preventive institutions].

    Science.gov (United States)

    Tsvetkov, S V; Petreev, I V; Greben'kov, S V

    2011-09-01

    The article contains results of fulfilled studies that allowed finding main features of radiology safety, working out academic and research recommendations to perfect radiology safety in treatment-and-preventive institutions (TPI) and creating a method of calculation of authorized staffing needed by radiological safety services. It was established that the following actions are least fulfilled: radiation control, organization of radiation safety education, authorization for work with ionizing radiation both for military men and civil staff, maintenance of documentation. We suggest that promising direction of optimization of providing radiological safety in large-scale TPI is the following: allotment of special structure that will provide comprehensive fulfillment of regulatory documents demands, it may be, e. g. radiological safety service.

  9. Discovery and Optimization of Small Molecule Splicing Modifiers of Survival Motor Neuron 2 as a Treatment for Spinal Muscular Atrophy.

    Science.gov (United States)

    Woll, Matthew G; Qi, Hongyan; Turpoff, Anthony; Zhang, Nanjing; Zhang, Xiaoyan; Chen, Guangming; Li, Chunshi; Huang, Song; Yang, Tianle; Moon, Young-Choon; Lee, Chang-Sun; Choi, Soongyu; Almstead, Neil G; Naryshkin, Nikolai A; Dakka, Amal; Narasimhan, Jana; Gabbeta, Vijayalakshmi; Welch, Ellen; Zhao, Xin; Risher, Nicole; Sheedy, Josephine; Weetall, Marla; Karp, Gary M

    2016-07-14

    The underlying cause of spinal muscular atrophy (SMA) is a deficiency of the survival motor neuron (SMN) protein. Starting from hits identified in a high-throughput screening campaign and through structure-activity relationship investigations, we have developed small molecules that potently shift the alternative splicing of the SMN2 exon 7, resulting in increased production of the full-length SMN mRNA and protein. Three novel chemical series, represented by compounds 9, 14, and 20, have been optimized to increase the level of SMN protein by >50% in SMA patient-derived fibroblasts at concentrations of <160 nM. Daily administration of these compounds to severe SMA Δ7 mice results in an increased production of SMN protein in disease-relevant tissues and a significant increase in median survival time in a dose-dependent manner. Our work supports the development of an orally administered small molecule for the treatment of patients with SMA.

  10. Optimization of the treatment of wheat samples for the determination of phytic acid by HPLC with refractive index detection.

    Science.gov (United States)

    Amaro, Rosa; Murillo, Miguel; González, Zurima; Escalona, Andrés; Hernández, Luís

    2009-01-01

    The treatment of wheat samples was optimized before the determination of phytic acid by high-performance liquid chromatography with refractive index detection. Drying by lyophilization and oven drying were studied; drying by lyophilization gave better results, confirming that this step is critical in preventing significant loss of analyte. In the extraction step, washing of the residue and collection of this water before retention of the phytates in the NH2 Sep-Pak cartridge were important. The retention of phytates in the NH2 Sep-Pak cartridge and elimination of the HCI did not produce significant loss (P = 0.05) in the phytic acid content of the sample. Recoveries of phytic acid averaged 91%, which is a substantial improvement with respect to values reported by others using this methodology.

  11. Update on optimal use of lisdexamfetamine in the treatment of ADHD

    Directory of Open Access Journals (Sweden)

    Madaan V

    2013-07-01

    Full Text Available Vishal Madaan, Venkata Kolli, Durga P Bestha, Manan J ShahDepartment of Psychiatry and Neurobehavioral Sciences, Division of Child and Family Psychiatry, University of Virginia Health System, Charlottesville, VA, USAAbstract: Lisdexamfetamine (LDX has been a recent addition to the treatment armamentarium for Attention Deficit Hyperactivity Disorder (ADHD. It is unique among stimulants as it is a prodrug, and has been found to be safe and well-tolerated medication in children older than 6 years, adolescents and adults. It has a smooth onset of action, exerts its action up to 13 hours and may have less rebound symptoms. LDX has proven to be effective in the treatment of ADHD in placebo controlled trials, and improved performance in simulated academic and work environments have been noticed. Both stimulant naïve and stimulant-exposed patients with ADHD appear to benefit from LDX. It has also shown some promise in improving emotional expression and executive function of patients with ADHD. Adverse effects such as decrease in sleep, loss of appetite and others have been reported with LDX use, just as with other stimulant formulations. Since most such studies exclude subjects with preexisting cardiac morbidity, prescribing precautions should be taken with LDX in such subjects, as with any other stimulant. Study subjects on LDX have been reported to have low scores on drug likability scales, even with intravenous use; as a result, LDX may have somewhat less potential for abuse and diversion. There is a need for future studies comparing other long acting stimulants with LDX in ADHD; in fact clinical trials comparing LDX with OROS (osmotic controlled-release oral delivery system methylphenidate are currently underway. Furthermore, the utility of this medication in other psychiatric disorders and beyond ADHD is being investigated.Keywords: lisdexamfetamine, ADHD, functional impairment, pharmacotherapy

  12. Optimizing human hepatocyte models for metabolic phenotype and function: effects of treatment with dimethyl sulfoxide (DMSO).

    Science.gov (United States)

    Nikolaou, Nikolaos; Green, Charlotte J; Gunn, Pippa J; Hodson, Leanne; Tomlinson, Jeremy W

    2016-11-01

    Primary human hepatocytes are considered to be the "gold standard" cellular model for studying hepatic fatty acid and glucose metabolism; however, they come with limitations. Although the HepG2 cell line retains many of the primary hepatocyte metabolic functions they have a malignant origin and low rates of triglyceride secretion. The aim of this study was to investigate whether dimethyl sulfoxide supplementation in the media of HepG2 cells would enhance metabolic functionality leading to the development of an improved in vitro cell model that closely recapitulates primary human hepatocyte metabolism. HepG2 cells were cultured in media containing 1% dimethyl sulfoxide for 2, 4, 7, 14, and 21 days. Gene expression, protein levels, intracellular triglyceride, and media concentrations of triglyceride, urea, and 3-hydroxybutyrate concentrations were measured. Dimethyl sulfoxide treatment altered the expression of genes involved in lipid (FAS, ACC1, ACC2, DGAT1, DGAT2, SCD) and glucose (PEPCK, G6Pase) metabolism as well as liver functionality (albumin, alpha-1-antitrypsin, AFP). mRNA changes were paralleled by alterations at the protein level. DMSO treatment decreased intracellular triglyceride content and lactate production and increased triglyceride and 3-hydroxybutyrate concentrations in the media in a time-dependent manner. We have demonstrated that the addition of 1% dimethyl sulfoxide to culture media changes the metabolic phenotype of HepG2 cells toward a more primary human hepatocyte phenotype. This will enhance the currently available in vitro model systems for the study of hepatocyte biology related to pathological processes that contribute to disease and their response to specific therapeutic interventions. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  13. Efficacy of Venlafaxine in Neuropathic Pain: A Narrative Review of Optimized Treatment.

    Science.gov (United States)

    Trouvin, Anne-Priscille; Perrot, Serge; Lloret-Linares, Célia

    2017-06-01

    The prevalence of neuropathic pain is high in the general population, and high priority is given to the management of this pain condition. The treatment of neuropathic pain remains challenging, despite the publication of national and international recommendations. The purpose of this narrative review of venlafaxine (VLX) is to provide a better knowledge of the pharmacology of this drug and a clearer view of its efficacy and tolerability in neuropathic pain. Two independent reviewers searched PubMed with the following search terms: serotonin and noradrenalin reuptake inhibitors OR VLX hydrochloride AND pain. The reviewers included all clinical studies that investigated VLX in neuropathic pain conditions and excluded animal studies, studies on fibromyalgia, studies that focused on the prevention of neuropathic pain, case reports, and studies that did not clearly describe neuropathic pain in the included patients. We describe the 13 studies that we analyzed. Eleven were randomized clinical trials, and the comparator was placebo in 8 studies. Nine studies reported that VLX was effective against neuropathic pain. However, among the trials, only one against placebo included a large number of patients with >200 participants and one against prégabaline and carbamazepine had >200 patients. Most of the adverse events reported in the selected studies were consistent with known adverse events of VLX, and most were mild to moderate. However, most studies were of very short duration. Most of the clinical studies found that VLX was effective and well tolerated. However, given the limited number of study and the limitations of all these studies, further large clinical trials are needed. Currently, considering the limited therapeutic options for treating neuropathic pain and the highly variable nature of responses to all drugs, VLX has a place as a treatment option for neuropathic pain. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  14. Gamma-knife radiosurgery as an optimal treatment modality for brain metastases from epithelial ovarian cancer.

    Science.gov (United States)

    Lee, Yoo-Kyung; Park, Noh-Hyun; Kim, Jae Weon; Song, Yong-Sang; Kang, Soon-Beom; Lee, Hyo-Pyo

    2008-03-01

    The objectives of this study are to analyze the clinical feature and overall survival rate of patients with brain metastases from epithelial ovarian cancer (EOC) and to compare the treatment outcomes of gamma-knife radiosurgery (GKS) and whole-brain radiation therapy (WBRT). A retrospective chart review of patients diagnosed with brain metastases from EOC in a single institution between 1983 and 2005 was performed. Of 1413 patients with EOC, 18 (1.3%) developed brain metastases. Fifteen patients who were treated with GKS or WBRT were enrolled for this study. Seven patients were treated with GKS, and the remaining patients were treated with WBRT as a primary treatment modality. The median age at the time of diagnosis of the primary cancer and brain metastases was 55 and 56 years, respectively. The median interval between the diagnosis of the primary cancer and brain metastases was 28 months. It was significantly associated with the overall survival rate after the diagnosis of ovarian cancer (p=0.017). There were 5 patients (33.3%) with extracranial metastases. Five patients (33.3%) had a solitary brain lesion. The median survival time after the diagnosis of brain metastases was 14 months (range, 1-59 months). Patients who were treated with GKS after brain metastasis had a longer survival time (median, 29 months) than those treated with WBRT (median, 6 months) (p=0.0061). For the control of brain metastases, GKS seems to be an effective modality. GKS improves the overall survival of the patients with brain metastases from EOC.

  15. What is the Optimal Treatment of Atrophic Scaphoid Non-Union?

    Directory of Open Access Journals (Sweden)

    Alper Cirakli

    2016-09-01

    Full Text Available Aim: To evaluate the efficacy of the treatment method of autogenous iliac wing or radius bone graft and fixation with screw applied to cases of scaphoid non-union. Material and Method: A retrospective evaluation was made of 89 cases between 2000 and 2014. Postoperative measurements were taken of both wrists%u2019 movement with a goniometer and muscle strength was assessed with a dynamometer. Fractures were evaluated radiologically according to the Herbert-Fisher System and the functional results according to the Herbert-Fisher Classification System and the Mayo Clinic Modified Wrist Scoring System. The data were input to the SPSS system and evaluated with the Shapiro-Wilk test. Results: Non-union were on the right side in 47 and the left side in 42 cases. The fracture was seen to be in the waist in 60 cases (67.5%, in the proximal third in 27 cases (30.3% and in the distal third in two cases (2.2%. The mean follow-up period was 16.4 months (range, 5-72 months. Definitive findings of union were observed in 71 cases. The mean time to union was 14.9 weeks (range, 8-40 weeks. Discussion: The grafting procedure applied is an invasive technique but if it is considered that there are negative effects of open surgery on the feeding of the scaphoid bone, then in the treatment of scaphoid non-union which is atrophic non-union, ultimately autogenous bone grafting and screw fixation is a safe and successful method and because of the pain created by an iliac wing graft, radius distal bone graft can be considered more appropriate.

  16. Imatinib in the treatment of chronic myeloid leukemia: current perspectives on optimal dose

    Directory of Open Access Journals (Sweden)

    Waclaw J

    2015-09-01

    Full Text Available Joanna Waclaw,1 Tomasz Sacha,1 Tomasz Stoklosa,21Department of Hematology, Jagiellonian University Collegium Medicum, Kraków, 2Department of Immunology, Medical University of Warsaw, Warsaw, Poland Abstract: Imatinib was the first tyrosine kinase inhibitor (TKI, successfully used in a clinical setting. It inhibits activity of BCR-ABL1 oncogenic tyrosine kinase which is crucial in the pathogenesis of chronic myeloid leukemia (CML. The safety and efficacy of imatinib dose 400 mg daily was established in several clinical studies. Nevertheless, imatinib dose escalation (≥600 mg daily has been widely explored as an option to improve clinical outcomes. Results of the meta-analysis comparing frontline therapy with imatinib 400 mg daily vs high dose (HD, ≥600 mg daily in patients with chronic phase CML (CML-CP showed that the rate of complete cytogenetic response as well as major molecular response (MMR at 12 months was significantly higher in HD imatinib group. However, HD imatinib does not improve overall survival and progression-free survival. Thus, the routine use of HD imatinib as frontline treatment for CML-CP is not recommended. In patients with CML-CP resistant to standard dose, HD imatinib does not significantly improve patient outcomes without a prior cytogenetic response. Therefore, in second-line therapy, the current CML-CP treatment guidelines do not recommend imatinib dose escalation but the use of second-or third-generation TKIs. In the therapy of TKI-naïve patients with accelerated or blastic phase of CML, HD imatinib (400 mg twice daily is one of the recommended standards. In case of disease progression while on imatinib, second- or third-generation TKIs should be administered. Keywords: imatinib, standard dose, dose escalation, chronic myeloid leukemia, BCR-ABL1, high dose

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

    Science.gov (United States)

    Wu, Qixue; Snyder, Karen Chin; Liu, Chang; Huang, Yimei; Zhao, Bo; Chetty, Indrin J.; Wen, Ning

    2016-01-01

    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. PMID:27688047

  18. What Is the Optimal Treatment of Large Brain Metastases? An Argument for a Multidisciplinary Approach

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Clara Y.H.; Chang, Steven D. [Department of Neurosurgery, Stanford University Medical Center, Stanford, California (United States); Gibbs, Iris C. [Department of Radiation Oncology, Stanford University Medical Center, Stanford, California (United States); Adler, John R.; Harsh, Griffith R. [Department of Neurosurgery, Stanford University Medical Center, Stanford, California (United States); Atalar, Banu [Department of Radiation Oncology, Acibadem University School of Medicine, Istanbul (Turkey); Lieberson, Robert E. [Department of Neurosurgery, Stanford University Medical Center, Stanford, California (United States); Soltys, Scott G., E-mail: sgsoltys@stanford.edu [Department of Radiation Oncology, Stanford University Medical Center, Stanford, California (United States)

    2012-11-01

    Purpose: Single-modality treatment of large brain metastases (>2 cm) with whole-brain irradiation, stereotactic radiosurgery (SRS) alone, or surgery alone is not effective, with local failure (LF) rates of 50% to 90%. Our goal was to improve local control (LC) by using multimodality therapy of surgery and adjuvant SRS targeting the resection cavity. Patients and Methods: We retrospectively evaluated 97 patients with brain metastases >2 cm in diameter treated with surgery and cavity SRS. Local and distant brain failure (DF) rates were analyzed with competing risk analysis, with death as a competing risk. The overall survival rate was calculated by the Kaplain-Meier product-limit method. Results: The median imaging follow-up duration for all patients was 10 months (range, 1-80 months). The 12-month cumulative incidence rates of LF, with death as a competing risk, were 9.3% (95% confidence interval [CI], 4.5%-16.1%), and the median time to LF was 6 months (range, 3-17 months). The 12-month cumulative incidence rate of DF, with death as a competing risk, was 53% (95% CI, 43%-63%). The median survival time for all patients was 15.6 months. The median survival times for recursive partitioning analysis classes 1, 2, and 3 were 33.8, 13.7, and 9.0 months, respectively (p = 0.022). On multivariate analysis, Karnofsky Performance Status ({>=}80 vs. <80; hazard ratio 0.54; 95% CI 0.31-0.94; p = 0.029) and maximum preoperative tumor diameter (hazard ratio 1.41; 95% CI 1.08-1.85; p = 0.013) were associated with survival. Five patients (5%) required intervention for Common Terminology Criteria for Adverse Events v4.02 grade 2 and 3 toxicity. Conclusion: Surgery and adjuvant resection cavity SRS yields excellent LC of large brain metastases. Compared with other multimodality treatment options, this approach allows patients to avoid or delay whole-brain irradiation without compromising LC.

  19. Current idea of an algorithm for drug treatment and optimal succession of using targeted drugs

    Directory of Open Access Journals (Sweden)

    D. A. Nosov

    2014-11-01

    Full Text Available The application of targeted and pathogenetically sound medicational approaches could considerably improve the results of therapy in patients with metastatic renal-cell carcinoma (mRCC. To date, VEGF/VEGFR inhibitors continue to remain a basic and most effective drug treatment in patients with mRCC and the choice of a drug for first-line therapy is based on the following factors: disease prognosis, a patient’s general somatic state, and the understanding of immediate therapy goals, anticipated toxicity and tolerability.Most patients develop resistance to VEGFR inhibitors within 6–11 months after treatment initiation. The basis for resistance development may be the following mechanisms: activation of alternative proangiogenic signaling pathways, that of angiogenesis-independent progression pathways, a microenvironment-induced phenotypic change of tumor cells to form their resistance to targeted drugs, and pharmacokinetic and pharmacodynamic changes in the drug itself during therapy. To overcome resistance to VEGFR inhibitors, there are 2 possible options: 1 switching to a drug having another mechanism of action (the mTOR inhibitor everolimus; 2 that to a more selective and potent tyrosine kinase inhibitor (axitinib that selectively affects and suppresses the activityof the same targets – VEGFR (Vascular Endothelial Growth Factor Receptor 1–3. As before, there is scanty convincing evidence for unique benefits in a particular succession of targeted drugs: a VEGFR inhibitor – a VEGFR inhibitor or a VEGFR inhibitor – an mТOR inhibitor. In a number of cases, the succession of prescribing of targeted drugs may be practically determined by clinical criteria, specifically by the possibility of controlling toxic complications that may be typical for VEFGR inhibitors and may accumulate in case of their successive use. It must be also remembered that VEGFR inhibitors may be successfully reused in patients who have received second- or

  20. Current idea of an algorithm for drug treatment and optimal succession of using targeted drugs

    Directory of Open Access Journals (Sweden)

    D. A. Nosov

    2014-01-01

    Full Text Available The application of targeted and pathogenetically sound medicational approaches could considerably improve the results of therapy in patients with metastatic renal-cell carcinoma (mRCC. To date, VEGF/VEGFR inhibitors continue to remain a basic and most effective drug treatment in patients with mRCC and the choice of a drug for first-line therapy is based on the following factors: disease prognosis, a patient’s general somatic state, and the understanding of immediate therapy goals, anticipated toxicity and tolerability.Most patients develop resistance to VEGFR inhibitors within 6–11 months after treatment initiation. The basis for resistance development may be the following mechanisms: activation of alternative proangiogenic signaling pathways, that of angiogenesis-independent progression pathways, a microenvironment-induced phenotypic change of tumor cells to form their resistance to targeted drugs, and pharmacokinetic and pharmacodynamic changes in the drug itself during therapy. To overcome resistance to VEGFR inhibitors, there are 2 possible options: 1 switching to a drug having another mechanism of action (the mTOR inhibitor everolimus; 2 that to a more selective and potent tyrosine kinase inhibitor (axitinib that selectively affects and suppresses the activityof the same targets – VEGFR (Vascular Endothelial Growth Factor Receptor 1–3. As before, there is scanty convincing evidence for unique benefits in a particular succession of targeted drugs: a VEGFR inhibitor – a VEGFR inhibitor or a VEGFR inhibitor – an mТOR inhibitor. In a number of cases, the succession of prescribing of targeted drugs may be practically determined by clinical criteria, specifically by the possibility of controlling toxic complications that may be typical for VEFGR inhibitors and may accumulate in case of their successive use. It must be also remembered that VEGFR inhibitors may be successfully reused in patients who have received second- or

  1. Optimal dose of gemcitabine for the treatment of biliary tract or pancreatic cancer in patients with liver dysfunction.

    Science.gov (United States)

    Shibata, Takashi; Ebata, Tomoki; Fujita, Ken-ichi; Shimokata, Tomoya; Maeda, Osamu; Mitsuma, Ayako; Sasaki, Yasutsuna; Nagino, Masato; Ando, Yuichi

    2016-02-01

    A clear consensus does not exist about whether the initial dose of gemcitabine, an essential anticancer antimetabolite, should be reduced in patients with liver dysfunction. Adult patients with biliary tract or pancreatic cancer were divided into three groups according to whether they had mild, moderate, or severe liver dysfunction, evaluated on the basis of serum bilirubin and liver transaminase levels at baseline. As anticancer treatment, gemcitabine at a dose of 800 or 1000 mg/m(2) was given as an i.v. infusion once weekly for 3 weeks of a 4-week cycle. The patients were prospectively evaluated for adverse events during the first cycle, and the pharmacokinetics of gemcitabine and its inactive metabolite, difluorodeoxyuridine, were studied to determine the optimal initial dose of gemcitabine as monotherapy according to the severity of liver dysfunction. A total of 15 patients were studied. Liver dysfunction was mild in one patient, moderate in six, and severe in eight. All 15 patients had been undergoing biliary drainage for obstructive jaundice when they received gemcitabine. Grade 3 cholangitis developed in one patient with moderate liver dysfunction who received gemcitabine at the dose level of 1000 mg/m(2). No other patients had severe treatment-related adverse events resulting in the omission or discontinuation of gemcitabine treatment. The plasma concentrations of gemcitabine and difluorodeoxyuridine were similar among the groups. An initial dose reduction of gemcitabine as monotherapy for the treatment of biliary tract or pancreatic cancers is not necessary for patients with hyperbilirubinemia, provided that obstructive jaundice is well managed. (Clinical trial registration no. UMIN000005363.)

  2. Optimization of photocatalytic degradation of meloxicam using titanium dioxide nanoparticles: application to pharmaceutical wastewater analysis, treatment, and cleaning validation.

    Science.gov (United States)

    Nadim, Ahmed H; Al-Ghobashy, Medhat A; Nebsen, Marianne; Shehata, Mostafa A

    2015-10-01

    Meloxicam is a commonly prescribed nonsteroidal anti-inflammatory drug with analgesic and fever-reducing effects. In this study, photocatalytic degradation of meloxicam in the presence of TiO2 nanoparticles (TiO2NP) was optimized and applied for pharmaceutical wastewater treatment. A validated stability-indicating orthogonal testing protocol (reversed-phase (RP)-HPLC and capillary zone electrophoresis) was developed and validated for monitoring of meloxicam concentration in the presence of its photodegradation products. Fractional factorial design was employed in order to investigate the effects of pH, irradiation time, UV light intensity, TiO2NP loading, and initial meloxicam concentration on the efficiency of the process. The light intensity was found as the most significant parameter followed by irradiation time and concentration, respectively. The most influencing interactions were noted between irradiation time-concentration and irradiation time-light intensity. The kinetics of meloxicam degradation was investigated at the optimum set of experimental conditions. The protocol was successfully applied for treatment of incurred water samples collected during various cleaning validation cycles. A percentage degradation of 77.34 ± 0.02 % was achieved upon irradiation of samples containing 64.57 ± 0.09 μg/mL with UV light (1012 μW/cm(2), 8 h) in the presence of 0.4 mg/mL TiO2NP at pH 9.0 ± 0.05. Treatment of wastewaters collected during the cleaning validation of each product separately rather than the combined waste should result in a significant improvement in the economics of pharmaceutical wastewater treatment. This could be attributed to the relatively small waste volumes and the ability to tailor the experimental conditions to achieve maximum efficiency.

  3. Optimal vitamin D status for the prevention and treatment of osteoporosis.

    Science.gov (United States)

    Holick, Michael F

    2007-01-01

    Vitamin D(3) (cholecalciferol) sufficiency is essential for maximising bone health. Vitamin D enhances intestinal absorption of calcium and phosphorus. The major source of vitamin D for both children and adults is exposure of the skin to sunlight. Season, latitude, skin pigmentation, sunscreen use, clothing and aging can dramatically influence the synthesis of vitamin D in the skin. Very few foods naturally contain vitamin D or are fortified with vitamin D. Serum 25-hydroxyvitamin D [25(OH)D; calcifediol] is the best measure of vitamin D status. Vitamin D deficiency [as defined by a serum 25(OH)D level of causes osteopenia, osteoporosis and osteomalacia, increasing the risk of fracture. Unlike osteoporosis, which is a painless disease, osteomalacia causes aching bone pain that is often misdiagnosed as fibromyalgia or chronic pain syndrome or is simply dismissed as depression. Vitamin D deficiency causes muscle weakness, increasing the risk of falls and fractures, and should be aggressively treated with pharmacological doses of vitamin D. Vitamin D sufficiency can be sustained by sensible sun exposure or ingesting at least 800-1000 IU of vitamin D(3) daily. Patients being treated for osteoporosis should be adequately supplemented with calcium and vitamin D to maximise the benefit of treatment.

  4. Optimal duration of percutaneous microballoon compression for treatment of trigeminal nerve injury

    Institute of Scientific and Technical Information of China (English)

    Fuyong Li; Shuai Han; Yi Ma; Fuxin Yi; Xinmin Xu; Yunhui Liu

    2014-01-01

    Percutaneous microballoon compression of the trigeminal ganglion is a brand new operative technique for the treatment of trigeminal neuralgia. However, it is unclear how the procedure mediates pain relief, and there are no standardized criteria, such as compression pressure, com-pression time or balloon shape, for the procedure. In this study, percutaneous microballoon compression was performed on the rabbit trigeminal ganglion at a mean inlfation pressure of 1,005 ± 150 mmHg for 2 or 5 minutes. At 1, 7 and 14 days after percutaneous microballoon compression, the large-diameter myelinated nerves displayed axonal swelling, rupture and demy-elination under the electron microscope. Fragmentation of myelin and formation of digestion chambers were more evident after 5 minutes of compression. Image analyzer results showed that the diameter of trigeminal ganglion cells remained unaltered after compression. These experi-mental ifndings indicate that a 2-minute period of compression can suppress pain transduction. Immunohistochemical staining revealed that vascular endothelial growth factor expression in the ganglion cells and axons was signiifcantly increased 7 days after trigeminal ganglion compression, however, the changes were similar after 2-minute compression and 5-minute compression. The upregulated expression of vascular endothelial growth factor in the ganglion cells after percu-taneous microballoon compression can promote the repair of the injured nerve. These ifndings suggest that long-term compression is ideal for patients with recurrent trigeminal neuralgia.

  5. Optimal choice of acetylcholinesterase reactivators for antidotal treatment of nerve agent intoxication.

    Science.gov (United States)

    Bajgar, Jirí

    2010-01-01

    The studies dealing with mechanism of organophosphates (OP)/nerve agent action, prophylaxis and treatment of intoxications is a very hot topic at present. Though the research is very intensive, unfortunately, up to now, there is not universal or significantly better reactivator sufficiently effective against all nerve agents/OP when compared with presently available oximes (pralidoxime, methoxime, obidoxime, trimedoxime, HI-6). The use of the most effective reactivator (HI-6) using simple type of autoinjector (e.g. ComboPen) is strictly limited because of decomposition of HI-6 in solution. Thanks to better solubility it is clear that another salt of HI-6 (dimethanesulfonate, HI-6 DMS) is more convenient for the use as antidote against nerve agents in the autoinjector than HI-6 chloride (Cl). It was clearly demonstrated that reactivation potency of HI-6 DMS in comparison with HI-6 Cl in vivo was the same and bioavailability of HI-6 DMS is better than that of HI-6 Cl. Three chambered autoinjector allows administration of all three antidotes (atropine, reactivator, diazepam) simultaneously. Moreover, the content of chambers can be changed according to proposed requirements. Possible way to solve the problem of universal reactivator could be the use of two reactivators. Three chambered autoinjector is an ideal device for this purpose.

  6. Tinnitus treatment with precise and optimal electric stimulation: opportunities and challenges.

    Science.gov (United States)

    Zeng, Fan-Gang; Djalilian, Hamid; Lin, Harrison

    2015-10-01

    Electric stimulation is a potent means of neuromodulation that has been used to restore hearing and minimize tremor, but its application on tinnitus symptoms has been limited. We examine recent evidence to identify the knowledge gaps in the use of electric stimulation for tinnitus treatment. Recent studies using electric stimulation to suppress tinnitus in humans are categorized according to their points of attacks. First, noninvasive, direct current stimulation uses an active electrode in the ear canal, tympanic membrane, or temporal scalp. Second, inner ear stimulation uses charge-balanced biphasic stimulation by placing an active electrode on the promontory or round window, or a cochlear implant array in the cochlea. Third, intraneural implants can provide targeted stimulation of specific sites along the auditory pathway. Although these studies demonstrated some success in tinnitus suppression, none established a link between tinnitus suppression efficacy and tinnitus-generating mechanisms. Electric stimulation provides a unique opportunity to suppress tinnitus. Challenges include matching electric stimulation sites and patterns to tinnitus locus and type, meeting the oftentimes-contradictory demands between tinnitus suppression and other indications, such as speech understanding, and justifying the costs and risks of electric stimulation for tinnitus symptoms.

  7. Optimizing treatments for nicotine dependence by increasing cognitive performance during withdrawal

    Science.gov (United States)

    Ashare, Rebecca L; Schmidt, Heath D

    2014-01-01

    Introduction Current FDA-approved smoking cessation pharmacotherapies have limited efficacy and are associated with high rates of relapse. Therefore, there is a clear need to develop novel antismoking medications. Nicotine withdrawal is associated with cognitive impairments that predict smoking relapse. It has been proposed that these cognitive deficits are a hallmark of nicotine withdrawal that could be targeted in order to prevent smoking relapse. Thus, pharmacotherapies that increase cognitive performance during nicotine withdrawal may represent potential smoking cessation agents. Areas covered The authors review the clinical literature demonstrating that nicotine withdrawal is associated with deficits in working memory, attention and response inhibition. They then briefly summarize different classes of compounds and strategies to increase cognitive performance during nicotine withdrawal. Particular emphasis has been placed on translational research in order to highlight areas for which there is strong rationale for pilot clinical trials of potential smoking cessation medications. Expert opinion There is emerging evidence that supports deficits in cognitive function as a plausible nicotine withdrawal phenotype. The authors furthermore believe that the translational paradigms presented here may represent efficient and valid means for the evaluation of cognitive-enhancing medications as possible treatments for nicotine dependence. PMID:24707983

  8. TREATMENT OPTIMIZATION IN PATIENTS WITH STABLE ANGINA PECTORIS: FOCUS ON VERAPAMIL SR

    Directory of Open Access Journals (Sweden)

    I. M. Sokolov

    2011-01-01

    Full Text Available Possibilities of angina pectoris pharmacotherapy are analyzed. Achievement of target heart rate (HR 55-60 beats per minute in these patients is possible due to three classes of antianginal medications that slow down HR: beta blockers (BB, If-channel inhibitors, nondihydropyridine calcium channel blockers (CCB. Nondihydropyridine CCB verapamil in slow release (SR formulation is focused. The main results of randomized clinical trials (APSIS, VHAS, CRIS, EVERESTH, VAMPHYRE, INVEST, VESPA, DAVIT-1, DAVIT-2, which have proven efficacy and safety, are presented. Verapamil SR is indicated for the treatment of angina pectoris in patients without history of myocardial infarction (MI; angina patients experienced MI without systolic heart failure and with contraindications to BB; angina with arterial hypertension; left ventricular diastolic dysfunction; peripheral arteries obliterating atherosclerosis; silent myocardial ischemia; vasospastic angina; angina associated with supraventricular cardiac arrhythmias (especially in permanent atrial fibrillation except Wolff-Parkinson-White and Lown-Ganong-Levine syndromes; after coronary angioplasty and the placement of bare metal stents.

  9. Optimizing outcome in SLE: treating-to-target and definition of treatment goals.

    Science.gov (United States)

    Doria, Andrea; Gatto, Mariele; Zen, Margherita; Iaccarino, Luca; Punzi, Leonardo

    2014-07-01

    Patients affected with systemic lupus erythematosus (SLE) display poor-long term prognosis and increased mortality in respect of general population. This may be due to continuous organ damage accrual which is fostered both by persistent disease activity (mainly in the short term) and prolonged corticosteroid exposure (mainly in the long term). The effort of defining novel therapeutic goals to which patients should be treated in order to have their prognosis improved is named treat-to-target. Remission in SLE was shown to be associated with better outcome and prolonged survival; in clinical practice, patients may experience either complete or clinical remission, which are defined as complete clinical/serological healing or no clinical signs of lupus with active serology, respectively. The main treat-to-target in SLE is complete remission, however since longitudinal observations suggest that clinical remission or low disease activity even with minimal corticosteroid intake do improve patients prognosis and survival as well, they may be assumed as acceptable alternative targets. Suitable therapeutic strategies have to be defined in order for these goals to be achieved including early diagnosis, effective treatment and proper corticosteroid tapering which in turn require development of more reliable serum biomarkers for early disease detection and less toxic targeted therapies with a steroid-sparing potential.

  10. Selection of optimal antisense accessible sites of survivin and its application in treatment of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Qiang-Song Tong; Li-Duan Zheng; Fang-Min Chen; Fu-Qing Zeng; Liang Wang; Ji-Hua Dong; Gong-Cheng Lu

    2005-01-01

    AIM: To select the optimal antisense accessible sites of survivin, a highly expressed gene in tumor tissues, in order to explore a novel approach to improve biological therapy of gastric cancer.METHODS: The 20 mer random oligonucleotide library was synthesized, hybridized with in vitro transcribed total survivin cRNA, then digested by RNase H. After primer extension and autoradiography, the antisense accessible sites (AAS) of survivin were selected. Then RNADraw software was used to analyze and choose the AAS with obvious stem-loop structures, according to which the complementary antisense oligonucleotides (AS-ODNs) were synthesized and transferred into survivin highly- expressing gastric cancer cell line MKN-45. Survivin expression was detected by RT-PCR and Western Blotting. Cellular growth activities were assayed by tetrazolium bromide (MTT)colorimetry. Cellular ultrastructure was observed by electronic microscopy, while apoptosis was detected by annexin V-FITC and propidium iodide staining flow cytometry.RESULTS: Thirteen AAS of survivin were selected in vitro.Four AAS with stem-loop structures were chosen, locating at 207-226 bp, 187-206 bp, 126-145 bp and 44-63 bp of survivin cDNA respectively. When compared with nontranfection controls, their corresponding AS-ODNs (AS-ODN1,AS-ODN2, AS-ODN3 and AS-ODN4) could reduce Survivin mRNA levels in MKN-45 cells by 54.3±1.1% (t= 6.12, P<0.01),86.1±1.0% (t= 5.27, P<0.01), 32.2±1.3% (t= 7.34, P<0.01)and 56.2±0.9% (t= 6.45, P<0.01) respectively, while survivin protein levels were decreased by 42.2±2.5% (t = 6.26,P<0.01), 75.4±3.1% (t= 7.11, P<0.01), 28.3±2.0% (t= 6.04,P<0.01) and 45.8±1.2% (t = 6.38, P<0.01) respectively.After transfection with 600 nmol/L AS-ODN1~AS-ODN4 for24 h, cell growth was inhibited by 28.12±1.54% (t= 7.62,P<0.01), 38.42±3.12% (t = 7.75, P<0.01), 21.46±2.63%(t= 5.94, P<0.01) and 32.12±1.77% (t= 6.17, P<0.01)respectively. Partial cancer cells presented the

  11. Temperature simulations in hyperthermia treatment planning of the head and neck region. Rigorous optimization of tissue properties

    Energy Technology Data Exchange (ETDEWEB)

    Verhaart, Rene F.; Rijnen, Zef; Verduijn, Gerda M.; Paulides, Margarethus M. [Erasmus MC - Cancer Institute, Department of Radiation Oncology, Hyperthermia Unit, Rotterdam (Netherlands); Fortunati, Valerio; Walsum, Theo van; Veenland, Jifke F. [Erasmus MC, Departments of Medical Informatics and Radiology, Biomedical Imaging Group Rotterdam, Rotterdam (Netherlands)

    2014-12-15

    Hyperthermia treatment planning (HTP) is used in the head and neck region (H and N) for pretreatment optimization, decision making, and real-time HTP-guided adaptive application of hyperthermia. In current clinical practice, HTP is based on power-absorption predictions, but thermal dose-effect relationships advocate its extension to temperature predictions. Exploitation of temperature simulations requires region- and temperature-specific thermal tissue properties due to the strong thermoregulatory response of H and N tissues. The purpose of our work was to develop a technique for patient group-specific optimization of thermal tissue properties based on invasively measured temperatures, and to evaluate the accuracy achievable. Data from 17 treated patients were used to optimize the perfusion and thermal conductivity values for the Pennes bioheat equation-based thermal model. A leave-one-out approach was applied to accurately assess the difference between measured and simulated temperature (∇T). The improvement in ∇T for optimized thermal property values was assessed by comparison with the ∇T for values from the literature, i.e., baseline and under thermal stress. The optimized perfusion and conductivity values of tumor, muscle, and fat led to an improvement in simulation accuracy (∇T: 2.1 ± 1.2 C) compared with the accuracy for baseline (∇T: 12.7 ± 11.1 C) or thermal stress (∇T: 4.4 ± 3.5 C) property values. The presented technique leads to patient group-specific temperature property values that effectively improve simulation accuracy for the challenging H and N region, thereby making simulations an elegant addition to invasive measurements. The rigorous leave-one-out assessment indicates that improvements in accuracy are required to rely only on temperature-based HTP in the clinic. (orig.) [German] Die Hyperthermiebehandlungsplanung (HTP, ''hyperthermia treatment planning'') wird in der Kopf- und Halsregion zur Optimierung der

  12. Optimization of ultraviolet ozone treatment process for improvement of polycaprolactone (PCL) microcarrier performance.

    Science.gov (United States)

    Samsudin, Nurhusna; Hashim, Yumi Zuhanis Has-Yun; Arifin, Mohd Azmir; Mel, Maizirwan; Salleh, Hamzah Mohd; Sopyan, Iis; Jimat, Dzun Noraini

    2017-08-01

    Growing cells on microcarriers may have overcome the limitation of conventional cell culture system. However, the surface functionality of certain polymeric microcarriers for effective cell attachment and growth remains a challenge. Polycaprolactone (PCL), a biodegradable polymer has received considerable attention due to its good mechanical properties and degradation rate. The drawback is the non-polar hydrocarbon moiety which makes it not readily suitable for cell attachment. This report concerns the modification of PCL microcarrier surface (introduction of functional oxygen groups) using ultraviolet irradiation and ozone (UV/O3) system and investigation of the effects of ozone concentration, the amount of PCL and exposure time; where the optimum conditions were found to be at 60,110.52 ppm, 5.5 g PCL and 60 min, respectively. The optimum concentration of carboxyl group (COOH) absorbed on the surface was 1495.92 nmol/g and the amount of gelatin immobilized was 320 ± 0.9 µg/g on UV/O3 treated microcarriers as compared to the untreated (26.83 ± 3 µg/g) microcarriers. The absorption of functional oxygen groups on the surface and the immobilized gelatin was confirmed with the attenuated total reflectance Fourier transformed infrared spectroscopy (ATR-FTIR) and the enhancement of hydrophilicity of the surface was confirmed using water contact angle measurement which decreased (86.93°-49.34°) after UV/O3 treatment and subsequently after immobilization of gelatin. The attachment and growth kinetics for HaCaT skin keratinocyte cells showed that adhesion occurred much more rapidly for oxidized surfaces and gelatin immobilized surface as compared to untreated PCL.

  13. High-voltage electrode optimization towards uniform surface treatment by a pulsed volume discharge

    Science.gov (United States)

    Ponomarev, A. V.; Pedos, M. S.; Scherbinin, S. V.; Mamontov, Y. I.; Ponomarev, S. V.

    2015-11-01

    In this study, the shape and material of the high-voltage electrode of an atmospheric pressure plasma generation system were optimised. The research was performed with the goal of achieving maximum uniformity of plasma treatment of the surface of the low-voltage electrode with a diameter of 100 mm. In order to generate low-temperature plasma with the volume of roughly 1 cubic decimetre, a pulsed volume discharge was used initiated with a corona discharge. The uniformity of the plasma in the region of the low-voltage electrode was assessed using a system for measuring the distribution of discharge current density. The system's low-voltage electrode - collector - was a disc of 100 mm in diameter, the conducting surface of which was divided into 64 radially located segments of equal surface area. The current at each segment was registered by a high-speed measuring system controlled by an ARM™-based 32-bit microcontroller. To facilitate the interpretation of results obtained, a computer program was developed to visualise the results. The program provides a 3D image of the current density distribution on the surface of the low-voltage electrode. Based on the results obtained an optimum shape for a high-voltage electrode was determined. Uniformity of the distribution of discharge current density in relation to distance between electrodes was studied. It was proven that the level of non-uniformity of current density distribution depends on the size of the gap between electrodes. Experiments indicated that it is advantageous to use graphite felt VGN-6 (Russian abbreviation) as the material of the high-voltage electrode's emitting surface.

  14. Formulation and PEGylation optimization of the therapeutic PEGylated phenylalanine ammonia lyase for the treatment of phenylketonuria

    Science.gov (United States)

    Bell, Sean M.; Wendt, Dan J.; Zhang, Yanhong; Long, Shinong; Tsuruda, Laurie; Zhao, Bin; Laipis, Phillip; Fitzpatrick, Paul A.

    2017-01-01

    Phenylketonuria (PKU) is a genetic metabolic disease in which the decrease or loss of phenylalanine hydroxylase (PAH) activity results in elevated, neurotoxic levels of phenylalanine (Phe). Due to many obstacles, PAH enzyme replacement therapy is not currently an option. Treatment of PKU with an alternative enzyme, phenylalanine ammonia lyase (PAL), was first proposed in the 1970s. However, issues regarding immunogenicity, enzyme production and mode of delivery needed to be overcome. Through the evaluation of PAL enzymes from multiple species, three potential PAL enzymes from yeast and cyanobacteria were chosen for evaluation of their therapeutic potential. The addition of polyethylene glycol (PEG, MW = 20,000), at a particular ratio to modify the protein surface, attenuated immunogenicity in an animal model of PKU. All three PEGylated PAL candidates showed efficacy in a mouse model of PKU (BTBR Pahenu2) upon subcutaneous injection. However, only PEGylated Anabaena variabilis (Av) PAL-treated mice demonstrated sustained low Phe levels with weekly injection and was the only PAL evaluated that maintained full enzymatic activity upon PEGylation. A PEGylated recombinant double mutant version of AvPAL (Cys503Ser/Cys565Ser), rAvPAL-PEG, was selected for drug development based on its positive pharmacodynamic profile and favorable expression titers. PEGylation was shown to be critical for rAvPAL-PEG efficacy as under PEGylated rAvPAL had a lower pharmacodynamic effect. rAvPAL and rAvPAL-PEG had poor stability at 4°C. L-Phe and trans-cinnamate were identified as activity stabilizing excipients. rAvPAL-PEG is currently in Phase 3 clinical trials to assess efficacy in PKU patients. PMID:28282402

  15. Decision support system for the optimal location of electrical and electronic waste treatment plants: a case study in greece.

    Science.gov (United States)

    Achillas, Ch; Vlachokostas, Ch; Moussiopoulos, Nu; Banias, G

    2010-05-01

    Environmentally sound end-of-life management of Electrical and Electronic Equipment has been realised as a top priority issue internationally, both due to the waste stream's continuously increasing quantities, as well as its content in valuable and also hazardous materials. In an effort to manage Waste Electrical and Electronic Equipment (WEEE), adequate infrastructure in treatment and recycling facilities is considered a prerequisite. A critical number of such plants are mandatory to be installed in order: (i) to accommodate legislative needs, (ii) decrease transportation cost, and (iii) expand reverse logistics network and cover more areas. However, WEEE recycling infrastructures require high expenditures and therefore the decision maker need to be most precautious. In this context, special care should be given on the viability of infrastructure which is heavily dependent on facilities' location. To this end, a methodology aiming towards optimal location of Units of Treatment and Recycling is developed, taking into consideration economical together with social criteria, in an effort to interlace local acceptance and financial viability. For the decision support system's needs, ELECTRE III is adopted as a multicriteria analysis technique. The methodology's applicability is demonstrated with a real-world case study in Greece.

  16. Optimizing non-invasive radiofrequency hyperthermia treatment for improving drug delivery in 4T1 mouse breast cancer model

    Science.gov (United States)

    Ware, Matthew J.; Krzykawska-Serda, Martyna; Chak-Shing Ho, Jason; Newton, Jared; Suki, Sarah; Law, Justin; Nguyen, Lam; Keshishian, Vazrik; Serda, Maciej; Taylor, Kimberly; Curley, Steven A.; Corr, Stuart J.

    2017-03-01

    Interactions of high-frequency radio waves (RF) with biological tissues are currently being investigated as a therapeutic platform for non-invasive cancer hyperthermia therapy. RF delivers thermal energy into tissues, which increases intra-tumoral drug perfusion and blood-flow. Herein, we describe an optical-based method to optimize the short-term treatment schedules of drug and hyperthermia administration in a 4T1 breast cancer model via RF, with the aim of maximizing drug localization and homogenous distribution within the tumor microenvironment. This method, based on the analysis of fluorescent dyes localized into the tumor, is more time, cost and resource efficient, when compared to current analytical methods for tumor-targeting drug analysis such as HPLC and LC-MS. Alexa-Albumin 647 nm fluorphore was chosen as a surrogate for nab-paclitaxel based on its similar molecular weight and albumin driven pharmacokinetics. We found that RF hyperthermia induced a 30–40% increase in Alexa-Albumin into the tumor micro-environment 24 h after treatment when compared to non-heat treated mice. Additionally, we showed that the RF method of delivering hyperthermia to tumors was more localized and uniform across the tumor mass when compared to other methods of heating. Lastly, we provided insight into some of the factors that influence the delivery of RF hyperthermia to tumors.

  17. Key signaling pathways in the muscle-invasive bladder carcinoma: Clinical markers for disease modeling and optimized treatment.

    Science.gov (United States)

    Kiselyov, Alex; Bunimovich-Mendrazitsky, Svetlana; Startsev, Vladimir

    2016-06-01

    In this review, we evaluate key molecular pathways and markers of muscle-invasive bladder cancer (MIBC). Overexpression and activation of EGFR, p63, and EMT genes are suggestive of basal MIBC subtype generally responsive to chemotherapy. Alterations in PPARγ, ERBB2/3, and FGFR3 gene products and their signaling along with deregulated p53, cytokeratins KRT5/6/14 in combination with the cellular proliferation (Ki-67), and cell cycle markers (p16) indicate the need for more radical treatment protocols. Similarly, the "bell-shape" dynamics of Shh expression levels may suggest aggressive MIBC. A panel of diverse biological markers may be suitable for simulation studies of MIBC and development of an optimized treatment protocol. We conducted a critical evaluation of PubMed/Medline and SciFinder databases related to MIBC covering the period 2009-2015. The free-text search was extended by adding the following keywords and phrases: bladder cancer, metastatic, muscle-invasive, basal, luminal, epithelial-to-mesenchymal transition, cancer stem cell, mutations, immune response, signaling, biological markers, molecular markers, mathematical models, simulation, epigenetics, transmembrane, transcription factor, kinase, predictor, prognosis. The resulting selection of ca 500 abstracts was further analyzed in order to select the latest publications relevant to MIBC molecular markers of immediate clinical significance. © 2015 UICC.

  18. Heat Treatment Parameters to Optimize Friction and Wear behavior of Novel Hybrid Aluminium Composites Using Taguchi Technique

    Directory of Open Access Journals (Sweden)

    V.C.Uvaraja

    2014-05-01

    Full Text Available In the present study, an Al 7075 alloy is used as the matrix and varying weight percentage of Silicon Carbide (SiC and constant weight percentage of Boron Carbide (B4C as the reinforcing material. The composite is produced using stir casting technique. The composite thus formed is termed as hybrid composite. The samples are prepared for heat treatment process by subjecting to solutionizing temperature of 530o C for 1 hr followed by quenching in water. Further the specimens are subjected to artificial aging for durations of 4, 6 and 8 hr at a temperature of 175°C. The mechanical and tribological properties of composites before and after heat treatment are examined by Vickers hardness test machine and pin-on-disc test machine respectively. The wear rate and friction co-efficient of heat treatment parameters are evaluated based on Taguchi technique. The analysis is further extended to the optimization of test parameters using Design of Experiment (DoE based on L9 orthogonal array. The developed Analysis of Variance (ANOVA and the regression equations is obtained through MINITAB R16 are used to investigate the influence of parameters like sliding speed, applied load, sliding time, and percentage of reinforcement on the dry sliding wear and friction co-efficient of the composites. The wear surface morphology and wear mechanism of the pins are investigated using Scanning Electron Microscope (SEM and are correlated them with wear test results. Finally, confirmation tests are carried out to verify the experimental results.

  19. Nanomedicines in the treatment of hepatitis C virus infection in Asian patients: optimizing use of peginterferon alfa

    Directory of Open Access Journals (Sweden)

    Liu CH

    2014-04-01

    Full Text Available Chen-Hua Liu,1–3 Jia-Horng Kao1–3 1Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 2Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; 3Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan Abstract: Asia is endemic for hepatitis C virus (HCV infection, which is the leading cause of cirrhosis, hepatic decompensation, hepatocellular carcinoma , and liver transplantation worldwide. HCV has six major genotypes and each HCV genotype has its specific geographic distribution. HCV genotypes 1, 2, 3, and 6 are common in Asia. The aim of HCV treatment is to eradicate the virus by effective therapeutic agents; viral clearance is durable after long-term post-treatment follow-up. In most Asian countries, peginterferon alfa (PEG-IFN α in combination with ribavirin remains the standard of care, and the overall sustained viral response (SVR rate in Asian HCV patients is higher than that in Western patients. The differences are most significant in patients with HCV genotype 1 (HCV-1 infection, which is attributed to the higher frequency of IFN-responsive or favorable interleukin-28B (IL-28B genotype in Asian populations than in other ethnic populations. In addition, the introduction of response-guided therapy, where the optimized treatment duration is based on the early viral kinetics during the first 12 weeks of treatment, increases the SVR rate. Recently, telaprevir or boceprevir-based triple therapy was found to further improve the SVR rate in treated and untreated HCV-1 patients and has become the new standard of care in Western and some Asian countries. Many novel direct-acting antiviral agents, either in combination with PEG-IFN α plus ribavirin or used as IFN-free regimens are under active investigation. At the time of this writing, simeprevir and sofosbuvir have been approved in the US. Because the SVR rates in Asian HCV patients

  20. Accessibility of opioid analgesics and barriers to optimal chronic pain treatment in Poland in 2000-2015.

    Science.gov (United States)

    Dzierżanowski, Tomasz; Ciałkowska-Rysz, Aleksandra

    2017-03-01

    Based on the international reports, consumption of opioid analgesics in Poland is relatively low. There is limited information on possible impediments to optimal opioid use. This study was aimed to identify possible barriers to access to opioid analgesics and causes of failure to comply with current clinical guidelines. Consumption data per capita in 2000-2015 were analyzed in terms of oral morphine equivalents in total, per prescription type, per reimbursement status, to identify the impact of regulations specific for Poland. The consumption of opioid analgesics has been consistently growing from 36.0 in 2000 to 103.4 mg oral morphine equivalents (OME) per capita in 2015, mainly thanks to strong opioid consumption growth. Tramadol is the most commonly used opioid in Poland. Fentanyl and buprenorphine transdermal formulations are the most frequently used strong opioid analgesics in terms of OME. The vast majority (92.8 %) of opioids were distributed upon for outpatient use in 2015, with a almost fourfold growth of consumption of strong opioids and almost threefold of weak opioids between 2000 and 2015. Strong opioids were 41 % of OME used upon prescription in 2015. Acceleration of consumption growth has been observed since 2013. The prescription pattern does not abide by the current clinical guidelines for pain treatment, and the most often used opioids in Poland are tramadol, buprenorphine, and fentanyl. The use of opioids in Poland grows fast, with acceleration since 2013. The most important legal impediments of optimal opioid analgesics use have been lack of reimbursement, special prescription forms, and complicated prescribing rules.

  1. Synthesis and optimization of Ag–TiO{sub 2} composite nanofibers for photocatalytic treatment of impaired water sources

    Energy Technology Data Exchange (ETDEWEB)

    Nalbandian, Michael J.; Zhang, Miluo; Sanchez, Joel [Department of Chemical and Environmental Engineering, University of California, Riverside, Riverside, CA 92521 (United States); Kim, Seil; Choa, Yong-Ho [Department of Fusion Chemical Engineering, Hanyang University, Ansan, Kyeonggi-do 426-791 (Korea, Republic of); Cwiertny, David M., E-mail: david-cwiertny@uiowa.edu [Department of Civil and Environmental Engineering, University of Iowa, Iowa, IA 52242 (United States); Myung, Nosang V., E-mail: myung@engr.ucr.edu [Department of Chemical and Environmental Engineering, University of California, Riverside, Riverside, CA 92521 (United States)

    2015-12-15

    Highlights: • We synthesized tunable Ag–TiO{sub 2} nanofibers via electrospinning. • We examined property changes due to the addition of the co-catalyst Ag. • Photocatalytic activity against phenol was studied under UV irradiation. • The 0.5 at.% Ag–TiO{sub 2} showed optimal photocatalytic activity. • The enhanced performance was associated with electron trap mechanism. - Abstract: In this work, Ag–TiO{sub 2} composite nanofibers were fabricated by electrospinning, where the composition and crystallinity were tuned by controlling the precursor composition and annealing conditions. Characterization revealed that bulk–embedded Ag nanoparticles inhibited anatase-to-rutile phase transformation and a decrease in band gap from 3.2 down to 2.8 eV with increase in the Ag content. The photocatalytic activity of 0.5 at.% Ag–TiO{sub 2} nanofibers toward phenol degradation was the greatest, outperforming both unmodified TiO{sub 2} nanofibers and commercially available TiO{sub 2} Aeroxide{sup ®} P25 by a factor of ∼3. The high reactivity of the low content Ag–TiO{sub 2} nanofibers can be attributed to the addition of electron traps, which provide efficient carrier separation and, therefore, decreased recombination. However, further increase in Ag content led to lower photoreactivity, most likely due to the growth of the Ag nanoparticles, which suggests an optimal size of 2 to 3 nm for the Ag nanoparticles at 0.5 at.% provided the greatest photoreactivity. Ag–TiO{sub 2} nanofibers show great promise as innovative and highly performing nanomaterials for future nanotechnology-based treatment systems, particularly when the photoreactivity demonstrate herein is used in synergy with the established antimicrobial activity of nano-Ag.

  2. Direct colposcopic vision used with the LLETZ procedure for optimal treatment of CIN: results of joint cohort studies.

    Science.gov (United States)

    Carcopino, Xavier; Mancini, Julien; Charpin, Colette; Grisot, Céline; Maycock, Joan Annette; Houvenaeghel, Gilles; Agostini, Aubert; Boubli, Léon; Prendiville, Walter

    2013-11-01

    To assess the value of direct colposcopic vision (DCV) for optimizing large loop excision of the transformation zone (LLETZ) for the treatment of cervical intraepithelial neoplasia (CIN). Data from 648 patients who underwent excisional procedures for CIN and were included in two previously published cohort studies were retrospectively reviewed. Women who had a LLETZ were included for analysis (n = 436). Margin status, surgical specimen dimensions and volume were analysed according to the use of colposcopy during procedure. Compared to LLETZ guided by previous colposcopy report only, and to LLETZ performed immediately after colposcopy, DCV allowed for a significantly higher rate of clear margins: 33 (52.4 %), 104 (68.0 %) and 142 (84.5 %), respectively (p < 0.001). It also allowed for a significantly higher probability of achieving both negative margins and depth of specimen <10 mm: 10 (15.9 %) cases, 47 (30.7 %) cases and 125 (74.4 %) cases, respectively (p < 0.001). In multivariate analysis, when compared with the use of previous colposcopy report or with colposcopy immediately before the LLETZ, DCV allowed for a significantly higher probability of negative margins (AOR: 4.61; 95 % CI: 2.37-8.99 and AOR: 2.55; 95 % CI: 1.47-4.41), combined negative margins and depth <75th percentile (AOR: 3.67; 95 % CI: 1.97-6.86 and AOR: 3.05; 95 % CI: 1.91-4.87) and combined negative margins and volume <75th percentile (AOR: 12.96; 95 % CI: 5.99-28.05 and AOR: 6.16; 95 % CI: 3.75-10.14), respectively. When used with the LLETZ procedure, DCV allows for optimal outcomes in terms of negative resection margins, and minimized depth and volume of the excised specimen; and should therefore be recommended.

  3. The optimized acupuncture treatment for neck pain caused by cervical spondylosis: a study protocol of a multicentre randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Liang Zhao-Hui

    2012-07-01

    Full Text Available Abstract Background Neck pain is one of the chief symptoms of cervical spondylosis (CS. Acupuncture is a well-accepted and widely used complementary therapy for the management of neck pain caused by CS. In this paper, we present a randomized controlled trial protocol evaluating the use of acupuncture for CS neck pain, comparing the effects of the optimized acupuncture therapy in real practice compared with sham and shallow acupuncture. Methods/Design This trial uses a multicentre, parallel-group, randomized, sham acupuncture and shallow acupuncture, controlled single-blind design. Nine hospitals are involved as trial centres. 945 patients who meet inclusion criteria are randomly assigned to receive optimized acupuncture therapy, sham acupuncture or shallow acupuncture by a computerized central randomization system. The interventions past for 4 weeks with eight to ten treatments in total. The group allocations and interventions are concealed to patients and statisticians. The Northwick Park Neck Pain Questionnaire (NPQ is used as the primary outcome measure, and the McGill Pain Questionnaire (MPQ and The Short Form (36 Health Survey (SF-36 are applied as secondary outcome measures. The evaluation is performed at baseline, at the end of the intervention, and at the end of the first month and the third month during follow-up. The statistical analyses will include baseline data comparison and repeated measures of analysis of variance (ANOVA for primary and secondary outcomes of group and time differences. Adverse events (AEs will be reported if they occur. Discussion This trial is a multicentre randomized control trial (RCT on the efficacy of acupuncture for CS neck pain and has a large sample size and central randomization in China. It will strictly follow the CONSORT statement and STRICTA extension guideline to report high-quality study results. By setting the control groups as sham and shallow acupuncture, this study attempts to reveal the

  4. Development of a methodology to determine optimized therapeutic doses of {sup 131}I for the treatment of hyperthyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Araujo, F.; Moura, M.B.; Pereira, A.C., E-mail: faraujo@ird.gov.br [Instituto de Medicna Nuclear (IMEN), Goiania, GO (Brazil); Dantas, B.M.; Dantas, A.L.A.; Lucena, E.A. [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Melo, R.C.; Rebelo, A.M.O. [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil). Faculdade de Medicina

    2008-07-01

    Several methods can be used to determine the activity of {sup 131}I to be administered for the treatment of hyperthyroidism. However, some of them do not take into consideration the dose absorbed by the thyroid, while others do not consider all the parameters necessary for dose calculation. The relationship between the dose absorbed by the thyroid and the activity administered depends basically on three parameters: mass of the organ, iodine uptake and effective half-life of iodine in the thyroid. Such parameters should be individually determined for each patient in order to optimize the administered activity. The objective of this work is to develop a methodology for individualized treatment with {sup 131}I in patients with hyperthyroidism of the Grave's Disease. A neck-thyroid phantom developed at the In Vivo Monitoring Laboratory of IRD, containing a known amount of {sup 131}I, was used to calibrate a scintillation camera and a uptake probe available at the Nuclear Medicine Center of the University Hospital of Rio de Janeiro and Instituto de Medicina Nuclear - IMEN, of Goiania. The optimization of the counting geometry was carried out by the determination of the characteristic curves of the view angle of the collimator-detector assembly. The view angle of the collimator-detector assembly presented values compatible with the size of the organ for distances of 25 cm (uptake probe) and 45.8 cm (scintillation camera). The calibration factors (in cpm/kBq) and the associated uncertainty related to these distances were (39.3 ± 0.78), (58.1 ± 2.38) to uptake probe SCT-13004 e 13002, respectively and 4.3 ± 0.17 to scintillation camera. The time period between 14 and 30 hours of the retention curve allows the calculation of the activity between those two points. It is concluded that the use of diagnose equipment available at the hospital (scintillation camera and uptake probe) has shown to be a suitable procedure in terms of effectiveness, simplicity and cost

  5. Development of a methodology to determine optimized therapeutic doses of {sup 131}I for the treatment of hyperthyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Araujo, Francisco de; Santas, Bernardo Maranhao; Dantas, Ana Leticia Almeida; Lucena, Eder Augusto [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)]. E-mail: faraujo@ird.gov.br; Melo, Rossana Corbo de; Rebelo, Ana Maria de Oliveira [Universidade Federal, Rio de Janeiro, RJ (Brazil). Faculdade de Medicina

    2007-07-01

    Several methods can be used to determine the activity of {sup 131}I to be administered for the treatment of hyperthyroidism. However, some of them do not take into consideration the dose absorbed by the thyroid, while others do not consider all the parameters necessary for dose calculation. The relationship between the dose absorbed by the thyroid and the activity administered depends basically on three parameters: mass of the organ, iodine uptake and effective half-life of iodine in the thyroid. Such parameters should be individually determined for each patient in order to optimize the administered activity. The objective of this work is to develop a methodology to evaluate therapeutic doses through the determination of biokinetic parameters and the activity of {sup 131}I deposited in the thyroid of patients submitted to the treatment of hyperthyroidism with {sup 131}I. A neck-thyroid phantom developed at the In Vivo Monitoring Laboratory of IRD, containing a known amount of {sup 131}I, was used to calibrate a scintillation camera and a uptake probe available at the Nuclear Medicine Center of the University Hospital of Rio de Janeiro. The optimization of the counting geometry was carried out by the determination of the characteristic curves of the view angle of the collimator-detector assembly. The calculation of the calibration factor of the scintillation camera allows the determination of activities in the thyroid of patients in pre-established time periods through a 48-hours uptake curve. The view angle of the collimator-detector assembly presented values compatible with the size of the organ for distances of 25 cm (uptake probe) and 45.8 cm (scintillation camera). The calibration factors (in cpm/kBq) and the associated uncertainty related to these distances were 39.3 {+-} 0.8 and 4.3 {+-} 0.2 respectively. The time period between 14 and 30 hours of the retention curve allows the calculation of the activity between those two points. It is concluded that the use

  6. SU-E-J-113: The Influence of Optimizing Pediatric CT Simulator Protocols On the Treatment Dose Calculation in Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Y; Zhang, J; Hu, Q; Tie, J; Wu, H [Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiotherapy, Peking University Cancer Hospital ' Institute, Beijing (China); Deng, J [Department of Therapeutic Radiology, Yale University, New Haven, CT (United States)

    2014-06-01

    Purpose: To investigate the possibility of applying optimized scanning protocols for pediatric CT simulation by quantifying the dosimetric inaccuracy introduced by using a fixed HU to density conversion. Methods: The images of a CIRS electron density reference phantom (Model 062) were acquired by a Siemens CT simulator (Sensation Open) using the following settings of tube voltage and beam current: 120 kV/190mA (the reference protocol used to calibrate CT for our treatment planning system (TPS)); Fixed 190mA combined with all available kV: 80, 100, and 140; fixed 120 kV and various current from 37 to 444 mA (scanner extremes) with interval of 30 mA. To avoid the HU uncertainty of point sampling in the various inserts of known electron densities, the mean CT numbers of the central cylindrical volume were calculated using DICOMan software. The doses per 100 MU to the reference point (SAD=100cm, Depth=10cm, Field=10X10cm, 6MV photon beam) in a virtual cubic phantom (30X30X30cm) were calculated using Eclipse TPS (calculation model: AcurosXB-11031) by assigning the CT numbers to HU of typical materials acquired by various protocols. Results: For the inserts of densities less than muscle, CT number fluctuations of all protocols were within the tolerance of 10 HU as accepted by AAPM-TG66. For more condensed materials, fixed kV yielded stable HU with any mA combination where largest disparities were found in 1750mg/cc insert: HU{sub reference}=1801(106.6cGy), HU{sub minimum}=1799 (106.6cGy, error{sub dose}=0.00%), HU{sub maximum}=1815 (106.8cGy, error{sub dose}=0.19%). Yet greater disagreements were observed with increasing density when kV was modified: HU{sub minimum}=1646 (104.5cGy, error{sub dose}=- 1.97%), HU{sub maximum}=2487 (116.4cGy, error{sub dose}=9.19%) in 1750mg/cc insert. Conclusion: Without affecting treatment dose calculation, personalized mA optimization of CT simulator can be conducted by fixing kV for a better cost-effectiveness of imaging dose and quality

  7. Optimization of the geometry and composition of a neutron system for treatment by Boron Neutron Capture Therapy

    Directory of Open Access Journals (Sweden)

    Rohollah Gheisari

    2015-01-01

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