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Sample records for modelling treatment effects

  1. Effective operator treatment of the Lipkin model

    International Nuclear Information System (INIS)

    Abraham, K.J.; Vary, J.P.

    2004-01-01

    We analyze the Lipkin model in the strong coupling limit using effective operator techniques. We present both analytical and numerical results for low energy effective Hamiltonians. We investigate the reliability of various approximations used to simplify the nuclear many body problem, such as the cluster approximation. We demonstrate, in explicit examples, certain limits to the validity of the cluster approximation but caution that these limits may be particular to this model where the interactions are of unlimited range

  2. Enhancing treatment effectiveness through social modelling: A pilot study.

    Science.gov (United States)

    Faasse, Kate; Perera, Anna; Loveys, Kate; Grey, Andrew; Petrie, Keith J

    2017-05-01

    Medical treatments take place in social contexts; however, little research has investigated how social modelling might influence treatment outcomes. This experimental pilot study investigated social modelling of treatment effectiveness and placebo treatment outcomes. Fifty-nine participants took part in the study, ostensibly examining the use of beta-blockers (actually placebos) for examination anxiety. Participants were randomly assigned to observe a female confederate report positive treatment effects (reduced heart rate, relaxed, calm) or feeling no different. Heart rate, anxiety and blood pressure were assessed, as were symptoms and attributed side effects. Heart rate decreased significantly more in the social modelling compared to control condition, p = .027 (d = .63), and there were trends towards effects in the same direction for both anxiety, p = .097 (d = .46), and systolic blood pressure, p = .077 (d = .51). Significant pre-post placebo differences in heart rate, anxiety and diastolic blood pressure were found in the social modelling group, ps  .28 (ds = .09-.59). Social observation of medication effectiveness enhanced placebo effectiveness in heart rate, and showed a trend towards enhancing treatment effectiveness in both anxiety and systolic blood pressure. Social modelling may have utility in enhancing the effectiveness of many active medical treatments.

  3. Modelling the effects of treatment and quarantine on measles

    Science.gov (United States)

    Beay, Lazarus Kalvein

    2018-03-01

    Treatment and quarantine are efforts to cure as well as to overcome the spread of diseases including measles. The spread of measles can be expressed by mathematical modelling in the form of nonlinear dynamical systems. In this study was conducted on the spread of measles by considering the effect of treatment and quarantine on the infected individuals. By using the basic reproduction number of the model, can be analyzed the effects of treatment and quarantine to reduce the spread of measles. Basic reproduction number of models is monotonically descreasing as treatment and quarantine increasing. Numerical simulations conducted on the analysis of the results. The results showed that treatment and quarantine was given to infected individuals who were infectious has a major influence to eliminate measles from the system.

  4. Treatment Effects

    DEFF Research Database (Denmark)

    Heckman, James J.; Lopes, Hedibert F.; Piatek, Rémi

    2014-01-01

    This paper contributes to the emerging Bayesian literature on treatment effects. It derives treatment parameters in the framework of a potential outcomes model with a treatment choice equation, where the correlation between the unobservable components of the model is driven by a low-dimensional v...... easily be applied....

  5. Treatment of cloud radiative effects in general circulation models

    Energy Technology Data Exchange (ETDEWEB)

    Wang, W.C.; Dudek, M.P.; Liang, X.Z.; Ding, M. [State Univ. of New York, Albany, NY (United States)] [and others

    1996-04-01

    We participate in the Atmospheric Radiation Measurement (ARM) program with two objectives: (1) to improve the general circulation model (GCM) cloud/radiation treatment with a focus on cloud verticle overlapping and layer cloud optical properties, and (2) to study the effects of cloud/radiation-climate interaction on GCM climate simulations. This report summarizes the project progress since the Fourth ARM Science Team meeting February 28-March 4, 1994, in Charleston, South Carolina.

  6. [Treatment of cloud radiative effects in general circulation models

    International Nuclear Information System (INIS)

    Wang, W.C.

    1993-01-01

    This is a renewal proposal for an on-going project of the Department of Energy (DOE)/Atmospheric Radiation Measurement (ARM) Program. The objective of the ARM Program is to improve the treatment of radiation-cloud in GCMs so that reliable predictions of the timing and magnitude of greenhouse gas-induced global warming and regional responses can be made. The ARM Program supports two research areas: (I) The modeling and analysis of data related to the parameterization of clouds and radiation in general circulation models (GCMs); and (II) the development of advanced instrumentation for both mapping the three-dimensional structure of the atmosphere and high accuracy/precision radiometric observations. The present project conducts research in area (I) and focuses on GCM treatment of cloud life cycle, optical properties, and vertical overlapping. The project has two tasks: (1) Development and Refinement of GCM Radiation-Cloud Treatment Using ARM Data; and (2) Validation of GCM Radiation-Cloud Treatment

  7. Using Dirichlet Processes for Modeling Heterogeneous Treatment Effects across Sites

    Science.gov (United States)

    Miratrix, Luke; Feller, Avi; Pillai, Natesh; Pati, Debdeep

    2016-01-01

    Modeling the distribution of site level effects is an important problem, but it is also an incredibly difficult one. Current methods rely on distributional assumptions in multilevel models for estimation. There it is hoped that the partial pooling of site level estimates with overall estimates, designed to take into account individual variation as…

  8. Modeling nonlinear time-dependent treatment effects: an application of the generalized time-varying effect model (TVEM).

    Science.gov (United States)

    Shiyko, Mariya P; Burkhalter, Jack; Li, Runze; Park, Bernard J

    2014-10-01

    The goal of this article is to introduce to social and behavioral scientists the generalized time-varying effect model (TVEM), a semiparametric approach for investigating time-varying effects of a treatment. The method is best suited for data collected intensively over time (e.g., experience sampling or ecological momentary assessments) and addresses questions pertaining to effects of treatment changing dynamically with time. Thus, of interest is the description of timing, magnitude, and (nonlinear) patterns of the effect. Our presentation focuses on practical aspects of the model. A step-by-step demonstration is presented in the context of an empirical study designed to evaluate effects of surgical treatment on quality of life among early stage lung cancer patients during posthospitalization recovery (N = 59; 61% female, M age = 66.1 years). Frequency and level of distress associated with physical symptoms were assessed twice daily over a 2-week period, providing a total of 1,544 momentary assessments. Traditional analyses (analysis of covariance [ANCOVA], repeated-measures ANCOVA, and multilevel modeling) yielded findings of no group differences. In contrast, generalized TVEM identified a pattern of the effect that varied in time and magnitude. Group differences manifested after Day 4. Generalized TVEM is a flexible statistical approach that offers insight into the complexity of treatment effects and allows modeling of nonnormal outcomes. The practical demonstration, shared syntax, and availability of a free set of macros aim to encourage researchers to apply TVEM to complex data and stimulate important scientific discoveries. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  9. Effective field treatment of the annealed bond-dilute transverse Ising model

    International Nuclear Information System (INIS)

    Silva, P.R.; Sa Barreto, F.C. de

    1983-01-01

    The dilution of the spin-1/2 transverse Ising Model is studied by means of an effective field type treatment based on an extension of Callen's relation to the present model. The thermodynamics of the diluted model is obtained and the results are shown to be an improvement over the standard mean field treatment. The results are also compared with the Monte Carlo calculation for the spin-infinite transverse Ising Model. (Author) [pt

  10. Model averaging in the presence of structural uncertainty about treatment effects: influence on treatment decision and expected value of information.

    Science.gov (United States)

    Price, Malcolm J; Welton, Nicky J; Briggs, Andrew H; Ades, A E

    2011-01-01

    Standard approaches to estimation of Markov models with data from randomized controlled trials tend either to make a judgment about which transition(s) treatments act on, or they assume that treatment has a separate effect on every transition. An alternative is to fit a series of models that assume that treatment acts on specific transitions. Investigators can then choose among alternative models using goodness-of-fit statistics. However, structural uncertainty about any chosen parameterization will remain and this may have implications for the resulting decision and the need for further research. We describe a Bayesian approach to model estimation, and model selection. Structural uncertainty about which parameterization to use is accounted for using model averaging and we developed a formula for calculating the expected value of perfect information (EVPI) in averaged models. Marginal posterior distributions are generated for each of the cost-effectiveness parameters using Markov Chain Monte Carlo simulation in WinBUGS, or Monte-Carlo simulation in Excel (Microsoft Corp., Redmond, WA). We illustrate the approach with an example of treatments for asthma using aggregate-level data from a connected network of four treatments compared in three pair-wise randomized controlled trials. The standard errors of incremental net benefit using structured models is reduced by up to eight- or ninefold compared to the unstructured models, and the expected loss attaching to decision uncertainty by factors of several hundreds. Model averaging had considerable influence on the EVPI. Alternative structural assumptions can alter the treatment decision and have an overwhelming effect on model uncertainty and expected value of information. Structural uncertainty can be accounted for by model averaging, and the EVPI can be calculated for averaged models. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights

  11. Quality of data computational models and telemedicine treatment effects

    NARCIS (Netherlands)

    Larburu Rubio, Nekane; Widya, I.A.; Bults, Richard G.A.; Hermens, Hermanus J.

    2014-01-01

    Clinical decision-support functions of telemedicine systems use patient's monitored clinical data to support treatment of outpatients. However, the quality of monitored clinical data may vary due to performance variations of technological resources inside a deployed telemedicine system. This paper

  12. Do different methods of modeling statin treatment effectiveness influence the optimal decision?

    NARCIS (Netherlands)

    B.J.H. van Kempen (Bob); B.S. Ferket (Bart); A. Hofman (Albert); S. Spronk (Sandra); E.W. Steyerberg (Ewout); M.G.M. Hunink (Myriam)

    2012-01-01

    textabstractPurpose. Modeling studies that evaluate statin treatment for the prevention of cardiovascular disease (CVD) use different methods to model the effect of statins. The aim of this study was to evaluate the impact of using different modeling methods on the optimal decision found in such

  13. Applying a Treatment Effects Model to Investigate Public Amenity Effect on Physical Activity of the Elderly.

    Science.gov (United States)

    Yeh, Chia-Yu; Chang, Chen-Kang; Yang, Feng-An

    2018-01-01

    The increasing elderly population puts significant health, economic, and social burdens on society. Physical activity is one of the most cost-effective ways to maintain the health of the elderly. This study adopts a treatment effects model to investigate the causal relationship between environment attributes and physical activity among the elderly, while taking endogeneity into account. The data were collected from 274 participants by face-to-face interviews in Taichung, Taiwan. Performing physical activity regularly in parks is the most important measure of the amount of physical activity by the elderly. Providing sufficient and accessible parks in metropolitan residential neighborhoods could be one of the most cost-effective ways to promote physical activity for the elderly living in midsize Asian cities.

  14. Visualization of laser tattoo removal treatment effects in a mouse model by two-photon microscopy.

    Science.gov (United States)

    Jang, Won Hyuk; Yoon, Yeoreum; Kim, Wonjoong; Kwon, Soonjae; Lee, Seunghun; Song, Duke; Choi, Jong Woon; Kim, Ki Hean

    2017-08-01

    Laser tattoo removal is an effective method of eliminating tattoo particles in the skin. However, laser treatment cannot always remove the unwanted tattoo completely, and there are risks of either temporary or permanent side effects. Studies using preclinical animal models could provide detailed information on the effects of laser treatment in the skin, and might help to minimize side effects in clinical practices. In this study, two-photon microscopy (TPM) was used to visualize the laser treatment effects on tattoo particles in both phantom specimens and in vivo mouse models. Fluorescent tattoo ink was used for particle visualization by TPM, and nanosecond (ns) and picosecond (ps) lasers at 532 nm were used for treatment. In phantom specimens, TPM characterized the fragmentation of individual tattoo particles by tracking them before and after the laser treatment. These changes were confirmed by field emission scanning electron microscopy (FE-SEM). TPM was used to measure the treatment efficiency of the two lasers at different laser fluences. In the mouse model, TPM visualized clusters of tattoo particles in the skin and detected their fragmentation after the laser treatment. Longitudinal TPM imaging observed the migration of cells containing tattoo particles after the laser treatment. These results show that TPM may be useful for the assessment of laser tattoo removal treatment in preclinical studies.

  15. Detecting treatment-subgroup interactions in clustered data with generalized linear mixed-effects model trees.

    Science.gov (United States)

    Fokkema, M; Smits, N; Zeileis, A; Hothorn, T; Kelderman, H

    2017-10-25

    Identification of subgroups of patients for whom treatment A is more effective than treatment B, and vice versa, is of key importance to the development of personalized medicine. Tree-based algorithms are helpful tools for the detection of such interactions, but none of the available algorithms allow for taking into account clustered or nested dataset structures, which are particularly common in psychological research. Therefore, we propose the generalized linear mixed-effects model tree (GLMM tree) algorithm, which allows for the detection of treatment-subgroup interactions, while accounting for the clustered structure of a dataset. The algorithm uses model-based recursive partitioning to detect treatment-subgroup interactions, and a GLMM to estimate the random-effects parameters. In a simulation study, GLMM trees show higher accuracy in recovering treatment-subgroup interactions, higher predictive accuracy, and lower type II error rates than linear-model-based recursive partitioning and mixed-effects regression trees. Also, GLMM trees show somewhat higher predictive accuracy than linear mixed-effects models with pre-specified interaction effects, on average. We illustrate the application of GLMM trees on an individual patient-level data meta-analysis on treatments for depression. We conclude that GLMM trees are a promising exploratory tool for the detection of treatment-subgroup interactions in clustered datasets.

  16. Cost-effectiveness models for chronic obstructive pulmonary disease : cross-model comparison of hypothetical treatment scenarios

    NARCIS (Netherlands)

    Hoogendoorn, Martine; Feenstra, Talitha L; Asukai, Yumi; Borg, Sixten; Hansen, Ryan N; Jansson, Sven-Arne; Samyshkin, Yevgeniy; Wacker, Margarethe; Briggs, Andrew H; Lloyd, Adam; Sullivan, Sean D; Rutten-van Mölken, Maureen P M H

    OBJECTIVES: To compare different chronic obstructive pulmonary disease (COPD) cost-effectiveness models with respect to structure and input parameters and to cross-validate the models by running the same hypothetical treatment scenarios. METHODS: COPD modeling groups simulated four hypothetical

  17. A bootstrap test for instrument validity in heterogeneous treatment effect models

    OpenAIRE

    Kitagawa, Toru

    2013-01-01

    This paper develops a specification test for the instrument validity conditions in the heterogeneous treatment effect model with a binary treatment and a discrete instrument. A necessary testable implication for the joint restriction of instrument exogeneity and instrument monotonicity is given by nonnegativity of point-identifiable complier's outcome densities. Our specification test infers this testable implication using a Kolmogorov-Smirnov type test statistic. We provide a bootstrap algor...

  18. A pharmacokinetic/viral kinetic model to evaluate the treatment effectiveness of danoprevir against chronic HCV.

    Science.gov (United States)

    Canini, Laetitia; Chatterjee, Anushree; Guedj, Jeremie; Lemenuel-Diot, Annabelle; Brennan, Barbara; Smith, Patrick F; Perelson, Alan S

    2015-01-01

    Viral kinetic models have proven useful to characterize treatment effectiveness during HCV therapy with interferon (IFN) or with direct-acting antivirals. We use a pharmacokinetic/viral kinetic (PK/VK) model to describe HCV RNA kinetics during treatment with danoprevir, a protease inhibitor. In a Phase I study, danoprevir monotherapy was administered for 14 days in ascending doses ranging from 200 to 600 mg per day to 40 patients of whom 32 were treatment-naive and 8 were non-responders to prior pegylated IFN-α/ribavirin treatment. In all patients, a biphasic decline of HCV RNA during therapy was observed. A two-compartment PK model and a VK model that considered treatment effectiveness to vary with the predicted danoprevir concentration inside the second compartment provided a good fit to the viral load data. A time-varying effectiveness model was also used to fit the viral load data. The antiviral effectiveness increased in a dose-dependent manner, with a 14-day time-averaged effectiveness of 0.95 at the lowest dose (100 mg twice daily) and 0.99 at the highest dose (200 mg three times daily). Prior IFN non-responders exhibited a 14-day time-averaged effectiveness of 0.98 (300 mg twice daily). The second phase decline showed two different behaviours, with 30% of patients exhibiting a rapid decline of HCV RNA, comparable to that seen with other protease inhibitors (>0.3 day(-1)), whereas the viral decline was slower in the other patients. Our results are consistent with the modest SVR rates from the INFORM-SVR study where patients were treated with a combination of mericitabine and ritonavir-boosted danoprevir.

  19. Fuel treatment effects on tree-based forest carbon storage and emissions under modeled wildfire scenarios

    Science.gov (United States)

    M. Hurteau; M. North

    2009-01-01

    Forests are viewed as a potential sink for carbon (C) that might otherwise contribute to climate change. It is unclear, however, how to manage forests with frequent fire regimes to maximize C storage while reducing C emissions from prescribed burns or wildfire. We modeled the effects of eight different fuel treatments on treebased C storage and release over a century,...

  20. Effects of monopolar radiofrequency treatment over soft-tissue fillers in an animal model.

    Science.gov (United States)

    England, Laura J; Tan, Mei-Heng; Shumaker, Peter R; Egbert, Barbara M; Pittelko, Kim; Orentreich, David; Pope, Karl

    2005-12-01

    Monopolar radiofrequency (RF) treatment is used by physicians to tighten and contour the skin of their patients. In many cases, patients have received prior treatment with other aesthetic modalities such as soft-tissue augmentation or they may wish to receive these treatment modalities simultaneously. Together, soft-tissue augmentation and monopolar RF treatment have the potential to restore tissue volume and improve facial laxity. To date, no published studies have documented the effects of RF treatment directly over soft-tissue fillers. We examined the tissue interactions of monopolar RF heating with five commonly injected fillers in a juvenile pig model. This is the first part of a two-part study. In this study, the interaction of monopolar RF and filler substances was examined over a period of 4 months. The five soft-tissue fillers examined were cross-linked human collagen (Cosmoplast), hyaluronic acid (Restylane), calcium hydroxylapatite (Radiesse), polylactic acid (Sculptra), and liquid injectable silicone (Silikon 1000). There was no apparent increase in the risk of local burns and no observable effect of RF treatment on filler persistence in the tissue. With monopolar RF treatment, an increase in fibroplasia and collagen deposition surrounding Restylane, Radiesse, and Sculptra was observed. When scored in a blinded fashion, the increase in collagen deposition was statistically significant for Radiesse. In this animal study, RF treatment had no observed adverse effect on filler collagen responses or persistence. Filler presence did not increase the risk of undesirable thermal effects with monopolar RF treatment. Further clinical studies are required to evaluate the effect of monopolar RF treatment over dermal fillers with respect to aesthetic outcome. (c) 2005 Wiley-Liss, Inc.

  1. Accounting for Heterogeneity in Relative Treatment Effects for Use in Cost-Effectiveness Models and Value-of-Information Analyses.

    Science.gov (United States)

    Welton, Nicky J; Soares, Marta O; Palmer, Stephen; Ades, Anthony E; Harrison, David; Shankar-Hari, Manu; Rowan, Kathy M

    2015-07-01

    Cost-effectiveness analysis (CEA) models are routinely used to inform health care policy. Key model inputs include relative effectiveness of competing treatments, typically informed by meta-analysis. Heterogeneity is ubiquitous in meta-analysis, and random effects models are usually used when there is variability in effects across studies. In the absence of observed treatment effect modifiers, various summaries from the random effects distribution (random effects mean, predictive distribution, random effects distribution, or study-specific estimate [shrunken or independent of other studies]) can be used depending on the relationship between the setting for the decision (population characteristics, treatment definitions, and other contextual factors) and the included studies. If covariates have been measured that could potentially explain the heterogeneity, then these can be included in a meta-regression model. We describe how covariates can be included in a network meta-analysis model and how the output from such an analysis can be used in a CEA model. We outline a model selection procedure to help choose between competing models and stress the importance of clinical input. We illustrate the approach with a health technology assessment of intravenous immunoglobulin for the management of adult patients with severe sepsis in an intensive care setting, which exemplifies how risk of bias information can be incorporated into CEA models. We show that the results of the CEA and value-of-information analyses are sensitive to the model and highlight the importance of sensitivity analyses when conducting CEA in the presence of heterogeneity. The methods presented extend naturally to heterogeneity in other model inputs, such as baseline risk. © The Author(s) 2015.

  2. Autoregressive transitional ordinal model to test for treatment effect in neurological trials with complex endpoints

    Directory of Open Access Journals (Sweden)

    Lorenzo G. Tanadini

    2016-11-01

    Full Text Available Abstract Background A number of potential therapeutic approaches for neurological disorders have failed to provide convincing evidence of efficacy, prompting pharmaceutical and health companies to discontinue their involvement in drug development. Limitations in the statistical analysis of complex endpoints have very likely had a negative impact on the translational process. Methods We propose a transitional ordinal model with an autoregressive component to overcome previous limitations in the analysis of Upper Extremity Motor Scores, a relevant endpoint in the field of Spinal Cord Injury. Statistical power and clinical interpretation of estimated treatment effects of the proposed model were compared to routinely employed approaches in a large simulation study of two-arm randomized clinical trials. A revisitation of a key historical trial provides further comparison between the different analysis approaches. Results The proposed model outperformed all other approaches in virtually all simulation settings, achieving on average 14 % higher statistical power than the respective second-best performing approach (range: -1 %, +34 %. Only the transitional model allows treatment effect estimates to be interpreted as conditional odds ratios, providing clear interpretation and visualization. Conclusion The proposed model takes into account the complex ordinal nature of the endpoint under investigation and explicitly accounts for relevant prognostic factors such as lesion level and baseline information. Superior statistical power, combined with clear clinical interpretation of estimated treatment effects and widespread availability in commercial software, are strong arguments for clinicians and trial scientists to adopt, and further extend, the proposed approach.

  3. Limited Effect of Chronic Valproic Acid Treatment in a Mouse Model of Machado-Joseph Disease.

    Science.gov (United States)

    Esteves, Sofia; Duarte-Silva, Sara; Naia, Luana; Neves-Carvalho, Andreia; Teixeira-Castro, Andreia; Rego, Ana Cristina; Silva-Fernandes, Anabela; Maciel, Patrícia

    2015-01-01

    Machado-Joseph disease (MJD) is an inherited neurodegenerative disease, caused by a CAG repeat expansion within the coding region of ATXN3 gene, and which currently lacks effective treatment. In this work we tested the therapeutic efficacy of chronic treatment with valproic acid (VPA) (200mg/kg), a compound with known neuroprotection activity, and previously shown to be effective in cell, fly and nematode models of MJD. We show that chronic VPA treatment in the CMVMJD135 mouse model had limited effects in the motor deficits of these mice, seen mostly at late stages in the motor swimming, beam walk, rotarod and spontaneous locomotor activity tests, and did not modify the ATXN3 inclusion load and astrogliosis in affected brain regions. However, VPA chronic treatment was able to increase GRP78 protein levels at 30 weeks of age, one of its known neuroprotective effects, confirming target engagement. In spite of limited results, the use of another dosage of VPA or of VPA in a combined therapy with molecules targeting other pathways, cannot be excluded as potential strategies for MJD therapeutics.

  4. Modelling of ultrasonic impact treatment (UIT of welded joints and its effect on fatigue strength

    Directory of Open Access Journals (Sweden)

    K.L. Yuan

    2015-10-01

    Full Text Available Ultrasonic impact treatment (UIT is a remarkable post-weld technique applying mechanical impacts in combination with ultrasound into the welded joints. In the present work, a 3D simulation method including welding simulation, numerical modelling of UIT-process and an evaluation of fatigue crack growth has been developed. In the FE model, the actual treatment conditions and local mechanical characteristics due to acoustic softening are set as input parameters. The plastic deformation and compressive stress layer are found to be more pronounced when acoustic softening takes place. The predicted internal residual stress distributions of welded joint before and after UIT are compared with experimental results, showing a fairly good agreement with each other. Finally, simulated results of fatigue crack growth in various residual stress fields are well compared with test results, so that the proposed model may provide an effective tool to simulate UIT-process in engineering structures.

  5. Some consequences of assuming simple patterns for the treatment effect over time in a linear mixed model.

    Science.gov (United States)

    Bamia, Christina; White, Ian R; Kenward, Michael G

    2013-07-10

    Linear mixed models are often used for the analysis of data from clinical trials with repeated quantitative outcomes. This paper considers linear mixed models where a particular form is assumed for the treatment effect, in particular constant over time or proportional to time. For simplicity, we assume no baseline covariates and complete post-baseline measures, and we model arbitrary mean responses for the control group at each time. For the variance-covariance matrix, we consider an unstructured model, a random intercepts model and a random intercepts and slopes model. We show that the treatment effect estimator can be expressed as a weighted average of the observed time-specific treatment effects, with weights depending on the covariance structure and the magnitude of the estimated variance components. For an assumed constant treatment effect, under the random intercepts model, all weights are equal, but in the random intercepts and slopes and the unstructured models, we show that some weights can be negative: thus, the estimated treatment effect can be negative, even if all time-specific treatment effects are positive. Our results suggest that particular models for the treatment effect combined with particular covariance structures may result in estimated treatment effects of unexpected magnitude and/or direction. Methods are illustrated using a Parkinson's disease trial. Copyright © 2012 John Wiley & Sons, Ltd.

  6. Effect of sclerostin antibody treatment in a mouse model of severe osteogenesis imperfecta.

    Science.gov (United States)

    Roschger, Andreas; Roschger, Paul; Keplingter, Petra; Klaushofer, Klaus; Abdullah, Sami; Kneissel, Michaela; Rauch, Frank

    2014-09-01

    Osteogenesis imperfecta (OI) is a heritable bone fragility disorder that is usually caused by mutations affecting collagen type I production in osteoblasts. Stimulation of bone formation through sclerostin antibody treatment (Sost-ab) has shown promising results in mouse models of relatively mild OI. We assessed the effect of once-weekly intravenous Sost-ab injections for 4weeks in male Col1a1(Jrt)/+mice, a model of severe dominant OI, starting either at 4weeks (growing mice) or at 20weeks (adult mice) of age. Sost-ab had no effect on weight or femur length. In OI mice, no significant treatment-associated differences in serum markers of bone formation (alkaline phosphatase activity, procollagen type I N-propeptide) or resorption (C-telopeptide of collagen type I) were found. Micro-CT analyses at the femur showed that Sost-ab treatment was associated with higher trabecular bone volume and higher cortical thickness in wild type mice at both ages and in growing OI mice, but not in adult OI mice. Three-point bending tests of the femur showed that in wild type but not in OI mice, Sost-ab was associated with higher ultimate load and work to failure. Quantitative backscattered electron imaging of the femur did not show any effect of Sost-ab on CaPeak (the most frequently occurring calcium concentration in the bone mineral density distribution), regardless of genotype, age or measurement location. Thus, Sost-ab had a larger effect in wild type than in Col1a1(Jrt)/+mice. Previous studies had found marked improvements of Sost-ab on bone mass and strength in an OI mouse model with a milder phenotype. Our data therefore suggest that Sost-ab is less effective in a more severely affected OI mouse model. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Inhalational Gentamicin Treatment Is Effective Against Pneumonic Plague in a Mouse Model

    Directory of Open Access Journals (Sweden)

    David Gur

    2018-04-01

    Full Text Available Pneumonic plague is an infectious disease characterized by rapid and fulminant development of acute pneumonia and septicemia that results in death within days of exposure. The causative agent of pneumonic plague, Yersinia pestis (Y. pestis, is a Tier-1 bio-threat agent. Parenteral antibiotic treatment is effective when given within a narrow therapeutic window after symptom onset. However, the non-specific “flu-like” symptoms often lead to delayed diagnosis and therapy. In this study, we evaluated inhalational gentamicin therapy in an infected mouse model as a means to improve antibiotic treatment efficacy. Inhalation is an attractive route for treating lung infections. The advantages include directly dosing the main infection site, the relative accessibility for administration and the lack of extensive enzymatic drug degradation machinery. In this study, we show that inhalational gentamicin treatment administered 24 h post-infection, prior to the appearance of symptoms, protected against lethal intranasal challenge with the fully virulent Y. pestis Kimberley53 strain (Kim53. Similarly, a high survival rate was demonstrated in mice treated by inhalation with another aminoglycoside, tobramycin, for which an FDA-approved inhaled formulation is clinically available for cystic fibrosis patients. Inhalational treatment with gentamicin 48 h post-infection (to symptomatic mice was also successful against a Y. pestis challenge dose of 10 i.n.LD50. Whole-body imaging using IVIS technology demonstrated that adding inhalational gentamicin to parenteral therapy accelerated the clearance of Y. pestis from the lungs of infected animals. This may reduce disease severity and the risk of secondary infections. In conclusion, our data suggest that inhalational therapy with aerosolized gentamicin may be an effective prophylactic treatment against pneumonic plague. We also demonstrate the benefit of combining this treatment with a conventional parenteral

  8. Mitotane effects in a H295R xenograft model of adjuvant treatment of adrenocortical cancer.

    Science.gov (United States)

    Lindhe, O; Skogseid, B

    2010-09-01

    Adrenocortical cancer is one of the most aggressive endocrine malignancies. Growth through the capsule or accidental release of cancer cells during surgery frequently results in metastatic disease. We investigated the antitumoral effect of 2 adrenocorticolytic compounds, O, P'-DDD and MeSO2-DDE, in the adrenocortical cell line H295R both in vitro and as a xenograft model in vivo. H295R cells were injected s. c. in nude mice. O, P'-DDD, MeSO2-DDE, or oil (control) was administered i. p., either simultaneously with cell injection at day 0 (mimicking adjuvant treatment), or at day 48 (established tumors). Accumulation of PET tracers [ (11)C]methionine (MET), [ (11)C] metomidate (MTO), 2-deoxy-2-[ (18)F]fluoro-d-glucose (FDG), and [ (18)F]-l-tyrosine (FLT) in the aggregates were assessed +/- drug treatment in vitro. Tumor growth was significantly inhibited when O, P'-DDD was given at the same time as injection of tumor cells. No significant growth inhibition was observed after treatment with O, P'-DDD at day 48. A significant reduction in FLT uptake and an increased FDG uptake, compared to control, were observed following treatment with 15 microM O, P'-DDD (p<0.01) in vitro. MeSO2-DDE (15 microM) treatment gave rise to a reduced MET and an increased FLT uptake (p<0.01). Both compounds reduced the uptake of MTO compared to control (p<0.01). Treatment with O, P'-DDD simultaneously to inoculation of H295R cells in mice, imitating release of cells during surgery, gave a markedly better effect than treatment of established H295R tumors. We suggest that FLT may be a potential PET biomarker when assessing adrenocortical cancer treatment with O,P'-DDD. Further studies in humans are needed to investigate this.

  9. A mathematical model for CTL effect on a latently infected cell inclusive HIV dynamics and treatment

    Science.gov (United States)

    Tarfulea, N. E.

    2017-10-01

    This paper investigates theoretically and numerically the effect of immune effectors, such as the cytotoxic lymphocyte (CTL), in modeling HIV pathogenesis (via a newly developed mathematical model); our results suggest the significant impact of the immune response on the control of the virus during primary infection. Qualitative aspects (including positivity, boundedness, stability, uncertainty, and sensitivity analysis) are addressed. Additionally, by introducing drug therapy, we analyze numerically the model to assess the effect of treatment consisting of a combination of several antiretroviral drugs. Our results show that the inclusion of the CTL compartment produces a higher rebound for an individual's healthy helper T-cell compartment than drug therapy alone. Furthermore, we quantitatively characterize successful drugs or drug combination scenarios.

  10. Microwave thermal ablation: Effects of tissue properties variations on predictive models for treatment planning.

    Science.gov (United States)

    Lopresto, Vanni; Pinto, Rosanna; Farina, Laura; Cavagnaro, Marta

    2017-08-01

    Microwave thermal ablation (MTA) therapy for cancer treatments relies on the absorption of electromagnetic energy at microwave frequencies to induce a very high and localized temperature increase, which causes an irreversible thermal damage in the target zone. Treatment planning in MTA is based on experimental observations of ablation zones in ex vivo tissue, while predicting the treatment outcomes could be greatly improved by reliable numerical models. In this work, a fully dynamical simulation model is exploited to look at effects of temperature-dependent variations in the dielectric and thermal properties of the targeted tissue on the prediction of the temperature increase and the extension of the thermally coagulated zone. In particular, the influence of measurement uncertainty of tissue parameters on the numerical results is investigated. Numerical data were compared with data from MTA experiments performed on ex vivo bovine liver tissue at 2.45GHz, with a power of 60W applied for 10min. By including in the simulation model an uncertainty budget (CI=95%) of ±25% in the properties of the tissue due to inaccuracy of measurements, numerical results were achieved in the range of experimental data. Obtained results also showed that the specific heat especially influences the extension of the thermally coagulated zone, with an increase of 27% in length and 7% in diameter when a variation of -25% is considered with respect to the value of the reference simulation model. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

  11. Effects of an Immunosuppressive Treatment in the GRMD Dog Model of Duchenne Muscular Dystrophy

    Science.gov (United States)

    Barthélémy, Inès; Uriarte, Ane; Drougard, Carole; Unterfinger, Yves; Thibaud, Jean-Laurent; Blot, Stéphane

    2012-01-01

    The GRMD (Golden retriever muscular dystrophy) dog has been widely used in pre-clinical trials targeting DMD (Duchenne muscular dystrophy), using in many cases a concurrent immune-suppressive treatment. The aim of this study is to assess if such a treatment could have an effect on the disease course of these animals. Seven GRMD dogs were treated with an association of cyclosporine A (immunosuppressive dosage) and prednisolone (2 mg/kg/d) during 7 months, from 2 to 9 months of age. A multi-parametric evaluation was performed during this period which allowed us to demonstrate that this treatment had several significant effects on the disease progression. The gait quality as assessed by 3D-accelerometry was dramatically improved. This was consistent with the evolution of other parameters towards a significant improvement, such as the clinical motor score, the post-tetanic relaxation and the serum CK levels. In contrast the isometric force measurement as well as the histological evaluation argued in favor of a more severe disease progression. In view of the disease modifying effects which have been observed in this study it should be concluded that immunosuppressive treatments should be used with caution when carrying out pre-clinical studies in this canine model of DMD. They also highlight the importance of using a large range of multi-parametric evaluation tools to reliably draw any conclusion from trials involving dystrophin-deficient dogs, which reproduce the complexity of the human disease. PMID:23185260

  12. Effectivity of pazopanib treatment in orthotopic models of human testicular germ cell tumors

    International Nuclear Information System (INIS)

    Juliachs, Mercè; Viñals, Francesc; Vidal, August; Muro, Xavier Garcia del; Piulats, Josep M; Condom, Enric; Casanovas, Oriol; Graupera, Mariona; Germà, Jose R; Villanueva, Alberto

    2013-01-01

    Cisplatin (CDDP) resistance in testicular germ cell tumors (GCTs) is still a clinical challenge, and one associated with poor prognosis. The purpose of this work was to test pazopanib, an anti-tumoral and anti-angiogenic multikinase inhibitor, and its combination with lapatinib (an anti-ErbB inhibitor) in mouse orthotopic models of human testicular GCTs. We used two different models of human testicular GCTs orthotopically grown in nude mice; a CDDP-sensitive choriocarcinoma (TGT38) and a new orthotopic model generated from a metastatic GCT refractory to first-line CDDP chemotherapy (TGT44). Nude mice implanted with these orthotopic tumors were treated with the inhibitors and the effect on tumoral growth and angiogenesis was evaluated. TGT44 refractory tumor had an immunohistochemical profile similar to the original metastasis, with characteristics of yolk sac tumor. TGT44 did not respond when treated with cisplatin. In contrast, pazopanib had an anti-angiogenic effect and anti-tumor efficacy in this model. Pazopanib in combination with lapatinib in TGT38, an orthotopic model of choriocarcinoma had an additive effect blocking tumor growth. We present pazopanib as a possible agent for the alternative treatment of CDDP-sensitive and CDDP-refractory GCT patients, alone or in combination with anti-ErbB therapies

  13. Synergistic effect of lidocaine with pingyangmycin for treatment of venous malformation using a mouse spleen model

    Science.gov (United States)

    Bai, Nan; Chen, Yuan-Zheng; Mao, Kai-Ping; Fu, Yanjie; Lin, Qiang; Xue, Yan

    2014-01-01

    Aims: To explore whether lidocaine has the synergistic effect with pingyangmycin (PYM) in the venous malformations (VMs) treatment. Methods: The mouse spleen was chosen as a VM model and injected with different concentration of lidocaine or PYM or jointly treated with lidocaine and PYM. After 2, 5, 8 or 14 days, the mouse spleen tissues were acquired for hematoxylin-eosin (HE) staining, transmission electron microscopy (TEM) analysis, TUNEL assay and quantitative RT-PCR analysis to examine the toxicological effects of lidocaine and PYM on splenic vascular endothelial cells. Results: 0.4% of lidocaine mildly promoted the apoptosis of endothelial cells, while 2 mg/ml PYM significantly elevated the apoptotic ratios. However, the combination of 0.2% lidocaine and 0.5 mg/ml PYM notably elevated the apoptotic ratios of splenic cells and severely destroyed the configuration of spleen, compared to those of treatment with 0.5 mg/ml PYM alone. Conclusion: Lidocaine exerts synergistic effects with PYM in promoting the apoptosis of mouse splenic endothelial cells, indicating that lidocaine possibly promotes the therapeutic effects of PYM in VMs treatment via synergistically enhancing the apoptosis of endothelial cells of malformed venous lesions. PMID:24966943

  14. Negative Effects of Chronic Rapamycin Treatment on Behavior in a Mouse Model of Fragile X Syndrome

    Directory of Open Access Journals (Sweden)

    Rachel M. Saré

    2018-01-01

    Full Text Available Fragile X syndrome (FXS, the most common form of inherited intellectual disability, is also highly associated with autism spectrum disorders (ASD. It is caused by expansion of a CGG repeat sequence on the X chromosome resulting in silencing of the FMR1 gene. This is modeled in the mouse by deletion of Fmr1 (Fmr1 KO. Fmr1 KO mice recapitulate many of the behavioral features of the disorder including seizure susceptibility, hyperactivity, impaired social behavior, sleep problems, and learning and memory deficits. The mammalian target of rapamycin pathway (mTORC1 is upregulated in Fmr1 KO mice and is thought to be important for the pathogenesis of this disorder. We treated Fmr1 KO mice chronically with an mTORC1 inhibitor, rapamycin, to determine if rapamycin treatment could reverse behavioral phenotypes. We performed open field, zero maze, social behavior, sleep, passive avoidance, and audiogenic seizure testing. We found that pS6 was upregulated in Fmr1 KO mice and normalized by rapamycin treatment, but, except for an anxiogenic effect, it did not reverse any of the behavioral phenotypes examined. In fact, rapamycin treatment had an adverse effect on sleep and social behavior in both control and Fmr1 KO mice. These results suggest that targeting the mTOR pathway in FXS is not a good treatment strategy and that other pathways should be considered.

  15. Study on the treatment effect of Bx decoction on rat models of reflux esophagitis

    International Nuclear Information System (INIS)

    Liu Xiaoni; Jin Xiudong; Li Yuezhen; Liu Guilian; Sun Wei

    2008-01-01

    Objective: To explore the mechanism of BAN-XIA-XIE-XIN Decoction (Bx Decoction) treatment in rat models of reflux esophagitis. Methods: Rat models of reflux esophagitis were prepared with the method previously reported from this laboratory. Twenty-five models each were left untreated, treated with cisapride (2.5 mg/kg/d) or treated with BAN-XIA-XIE-XIN Decoction (BX) 5.78m/kg/d) respectively. All the models were sacrificed after 4 weeks, acid contents in gastric juice, cholic acid contents in duodenal juice as well as calcitonin-gene-related peptide (CGRP) (with RIA) contents in lower esophageal tissue and plasma were measured. Histologic examination of lower esophageal tissue for degree of esophagitis was also performed in all the models. Besides, 25 animals underwent sham operation only and served as controls. Results: The positive rates of pathologic changes (mucosal inflammation, squamous cell hyperplasia, lamina propria extension and mucosal erosion) were all significantly higher in the non-treated models than those in the BX treated models (P<0.01). Acid contents in gastric juice were significantly lowered with pH significantly increased in the BX treated group (P<0.01). The CGRP contents in esophageal tissue in the BX treated models, though remains lower than those in the 25 animals with sham operation only, were significantly higher than those in non-treated models (P<0.01). The plasma contents of CGRP in the BX-treated models remained significantly higher than those in sham-operation animals (P<0.01), decrease from the very high levels in untreated model was not large enough to be significant. Conclusion: BX-decoction might exert its protective effect on esophageal mucosa through lowering of gastric acidity with modulation of CGRP synthesis. (authors)

  16. Effects of combination treatment with alendronate and raloxifene on skeletal properties in a beagle dog model.

    Science.gov (United States)

    Allen, Matthew R; McNerny, Erin; Aref, Mohammad; Organ, Jason M; Newman, Christopher L; McGowan, Brian; Jang, Tim; Burr, David B; Brown, Drew M; Hammond, Max; Territo, Paul R; Lin, Chen; Persohn, Scott; Jiang, Lei; Riley, Amanda A; McCarthy, Brian P; Hutchins, Gary D; Wallace, Joseph M

    2017-01-01

    A growing number of studies have investigated combination treatment as an approach to treat bone disease. The goal of this study was to investigate the combination of alendronate and raloxifene with a particular focus on mechanical properties. To achieve this goal we utilized a large animal model, the beagle dog, used previously by our laboratory to study both alendronate and raloxifene monotherapies. Forty-eight skeletally mature female beagles (1-2 years old) received daily oral treatment: saline vehicle (VEH), alendronate (ALN), raloxifene (RAL) or both ALN and RAL. After 6 and 12 months of treatment, all animals underwent assessment of bone material properties using in vivo reference point indentation (RPI) and skeletal hydration using ultra-short echo magnetic resonance imaging (UTE-MRI). End point measures include imaging, histomorphometry, and mechanical properties. Bone formation rate was significantly lower in iliac crest trabecular bone of animals treated with ALN (-71%) and ALN+RAL (-81%) compared to VEH. In vivo assessment of properties by RPI yielded minimal differences between groups while UTE-MRI showed a RAL and RAL+ALN treatment regimens resulted in significantly higher bound water compared to VEH (+23 and +18%, respectively). There was no significant difference among groups for DXA- or CT-based measures lumbar vertebra, or femoral diaphysis. Ribs of RAL-treated animals were smaller and less dense compared to VEH and although mechanical properties were lower the material-level properties were equivalent to normal. In conclusion, we present a suite of data in a beagle dog model treated for one year with clinically-relevant doses of alendronate and raloxifene monotherapies or combination treatment with both agents. Despite the expected effects on bone remodeling, our study did not find the expected benefit of ALN to BMD or structural mechanical properties, and thus the viability of the combination therapy remains unclear.

  17. Effects of combination treatment with alendronate and raloxifene on skeletal properties in a beagle dog model.

    Directory of Open Access Journals (Sweden)

    Matthew R Allen

    Full Text Available A growing number of studies have investigated combination treatment as an approach to treat bone disease. The goal of this study was to investigate the combination of alendronate and raloxifene with a particular focus on mechanical properties. To achieve this goal we utilized a large animal model, the beagle dog, used previously by our laboratory to study both alendronate and raloxifene monotherapies. Forty-eight skeletally mature female beagles (1-2 years old received daily oral treatment: saline vehicle (VEH, alendronate (ALN, raloxifene (RAL or both ALN and RAL. After 6 and 12 months of treatment, all animals underwent assessment of bone material properties using in vivo reference point indentation (RPI and skeletal hydration using ultra-short echo magnetic resonance imaging (UTE-MRI. End point measures include imaging, histomorphometry, and mechanical properties. Bone formation rate was significantly lower in iliac crest trabecular bone of animals treated with ALN (-71% and ALN+RAL (-81% compared to VEH. In vivo assessment of properties by RPI yielded minimal differences between groups while UTE-MRI showed a RAL and RAL+ALN treatment regimens resulted in significantly higher bound water compared to VEH (+23 and +18%, respectively. There was no significant difference among groups for DXA- or CT-based measures lumbar vertebra, or femoral diaphysis. Ribs of RAL-treated animals were smaller and less dense compared to VEH and although mechanical properties were lower the material-level properties were equivalent to normal. In conclusion, we present a suite of data in a beagle dog model treated for one year with clinically-relevant doses of alendronate and raloxifene monotherapies or combination treatment with both agents. Despite the expected effects on bone remodeling, our study did not find the expected benefit of ALN to BMD or structural mechanical properties, and thus the viability of the combination therapy remains unclear.

  18. Orlistat for the treatment of obesity: rapid review and cost-effectiveness model.

    Science.gov (United States)

    Foxcroft, D R; Milne, R

    2000-10-01

    The aim of this study is to clarify the potential benefits, disbenefits and costs of Orlistat for the treatment of obesity. The method was a search for relevant systematic reviews and randomized controlled trials, in Medline, Pre-Medline, Embase and the Cochrane Library, using Orlistat and its synonyms. Identified trials were appraised using a standard appraisal checklist and trial data were extracted for use in cost-effectiveness modelling. Three large multicentre, randomized placebo controlled trials were included in the rapid review. On average, Orlistat results in obese people losing an additional 3-4% of their initial body weight over diet alone during a 2 year period. There was no strong evidence that this short-term weight loss would have a longer-term impact on morbidity and mortality. The cost utility of Orlistat treatment was estimated at around 46,000 Pounds per Quality Adjusted Life Year gained (extreme values sensitivity analysis 14,000 Pounds to 132,000 Pounds). This rapid review raises some important questions about the potential value of Orlistat in the treatment of obesity. Further research is needed, not only to clarify the longer-term impact of Orlistat treatment, but also to uncover the longer-term impact on mortality and morbidity from short-term weight loss.

  19. Hypericum perforatum treatment: effect on behaviour and neurogenesis in a chronic stress model in mice

    Directory of Open Access Journals (Sweden)

    Cuzzocrea Salvatore

    2011-01-01

    Full Text Available Abstract Background Extracts of Hypericum perforatum (St. John's wort have been traditionally recommended for a wide range of medical conditions, in particular mild-to-moderate depression. The present study was designed to investigate the effect of Hypericum perforatum treatment in a mouse model of anxiety/depressive-like behavior, induced by chronic corticosterone administration. Methods CD1 mice were submitted to 7 weeks corticosterone administration and then behavioral tests as Open Field (OF, Novelty-Suppressed Feeding (NSF, Forced Swim Test (FST were performed. Cell proliferation in hippocampal dentate gyrus (DG was investigated by both 5-bromo-2'-deoxyuridine (BrdU and doublecortin (DCX immunohistochemistry techniques and stereological procedure was used to quantify labeled cells. Golgi-impregnation method was used to evaluate changes in dendritic spines in DG. Hypericum perforatum (30 mg/Kg has been administered for 3 weeks and then neural development in the adult hippocampus and behavioral changes have been examined. Results The anxiety/depressive-like state due to chronic corticosterone treatment was reversed by exogenous administration of Hypericum perforatum; the proliferation of progenitor cells in mice hippocampus was significantly reduced under chronic corticosterone treatment, whereas a long term treatment with Hypericum perforatum prevented the corticosterone-induced decrease in hippocampal cell proliferation. Corticosterone-treated mice exhibited a reduced spine density that was ameliorated by Hypericum perforatum administration. Conclusion These results provide evidence of morphological adaptations occurring in mature hippocampal neurons that might underlie resilient responses to chronic stress and contribute to the therapeutic effects of chronic Hypericum perforatum treatment.

  20. Simple, efficient estimators of treatment effects in randomized trials using generalized linear models to leverage baseline variables.

    Science.gov (United States)

    Rosenblum, Michael; van der Laan, Mark J

    2010-04-01

    Models, such as logistic regression and Poisson regression models, are often used to estimate treatment effects in randomized trials. These models leverage information in variables collected before randomization, in order to obtain more precise estimates of treatment effects. However, there is the danger that model misspecification will lead to bias. We show that certain easy to compute, model-based estimators are asymptotically unbiased even when the working model used is arbitrarily misspecified. Furthermore, these estimators are locally efficient. As a special case of our main result, we consider a simple Poisson working model containing only main terms; in this case, we prove the maximum likelihood estimate of the coefficient corresponding to the treatment variable is an asymptotically unbiased estimator of the marginal log rate ratio, even when the working model is arbitrarily misspecified. This is the log-linear analog of ANCOVA for linear models. Our results demonstrate one application of targeted maximum likelihood estimation.

  1. Wastewater treatment models

    DEFF Research Database (Denmark)

    Gernaey, Krist; Sin, Gürkan

    2011-01-01

    The state-of-the-art level reached in modeling wastewater treatment plants (WWTPs) is reported. For suspended growth systems, WWTP models have evolved from simple description of biological removal of organic carbon and nitrogen in aeration tanks (ASM1 in 1987) to more advanced levels including...... of WWTP modeling by linking the wastewater treatment line with the sludge handling line in one modeling platform. Application of WWTP models is currently rather time consuming and thus expensive due to the high model complexity, and requires a great deal of process knowledge and modeling expertise...

  2. Wastewater Treatment Models

    DEFF Research Database (Denmark)

    Gernaey, Krist; Sin, Gürkan

    2008-01-01

    The state-of-the-art level reached in modeling wastewater treatment plants (WWTPs) is reported. For suspended growth systems, WWTP models have evolved from simple description of biological removal of organic carbon and nitrogen in aeration tanks (ASM1 in 1987) to more advanced levels including...... the practice of WWTP modeling by linking the wastewater treatment line with the sludge handling line in one modeling platform. Application of WWTP models is currently rather time consuming and thus expensive due to the high model complexity, and requires a great deal of process knowledge and modeling expertise...

  3. Intensive treatment models and coercion

    DEFF Research Database (Denmark)

    Ohlenschlaeger, Johan; Thorup, Anne; Petersen, Lone

    2007-01-01

    Little evidence exists concerning the optimal treatment for patients with first-episode schizophrenia-spectrum disorders and the effect on traditional outcomes. The aim was to investigate whether optimal treatment models have an effect on the level of use of coercion and on traditional outcomes. ...

  4. Performance of the marginal structural cox model for estimating individual and joined effects of treatments given in combination.

    Science.gov (United States)

    Lusivika-Nzinga, Clovis; Selinger-Leneman, Hana; Grabar, Sophie; Costagliola, Dominique; Carrat, Fabrice

    2017-12-04

    The Marginal Structural Cox Model (Cox-MSM), an alternative approach to handle time-dependent confounder, was introduced for survival analysis and applied to estimate the joint causal effect of two time-dependent nonrandomized treatments on survival among HIV-positive subjects. Nevertheless, Cox-MSM performance in the case of multiple treatments has not been fully explored under different degree of time-dependent confounding for treatments or in case of interaction between treatments. We aimed to evaluate and compare the performance of the marginal structural Cox model (Cox-MSM) to the standard Cox model in estimating the treatment effect in the case of multiple treatments under different scenarios of time-dependent confounding and when an interaction between treatment effects is present. We specified a Cox-MSM with two treatments including an interaction term for situations where an adverse event might be caused by two treatments taken simultaneously but not by each treatment taken alone. We simulated longitudinal data with two treatments and a time-dependent confounder affected by one or the two treatments. To fit the Cox-MSM, we used the inverse probability weighting method. We illustrated the method to evaluate the specific effect of protease inhibitors combined (or not) to other antiretroviral medications on the anal cancer risk in HIV-infected individuals, with CD4 cell count as time-dependent confounder. Overall, Cox-MSM performed better than the standard Cox model. Furthermore, we showed that estimates were unbiased when an interaction term was included in the model. Cox-MSM may be used for accurately estimating causal individual and joined treatment effects from a combination therapy in presence of time-dependent confounding provided that an interaction term is estimated.

  5. Modeling the Cost Effectiveness of Neuroimaging-Based Treatment of Acute Wake-Up Stroke.

    Directory of Open Access Journals (Sweden)

    Ankur Pandya

    Full Text Available Thrombolytic treatment (tissue-type plasminogen activator [tPA] is only recommended for acute ischemic stroke patients with stroke onset time 4.5 hours, 46.3% experienced a good stroke outcome. Lifetime discounted QALYs and costs were 5.312 and $88,247 for the no treatment strategy and 5.342 and $90,869 for the MRI-based strategy, resulting in an ICER of $88,000/QALY. Results were sensitive to variations in patient- and provider-specific factors such as sleep duration, hospital travel and door-to-needle times, as well as onset probability distribution, MRI specificity, and mRS utility values.Our model-based findings suggest that an MRI-based treatment strategy for this population could be cost-effective and quantifies the impact that patient- and provider-specific factors, such as sleep duration, hospital travel and door-to-needle times, could have on the optimal decision for wake-up stroke patients.

  6. Model for Simulating Fasting Glucose in Type 2 Diabetes and the Effect of Adherence to Treatment

    DEFF Research Database (Denmark)

    Aradóttir, Tinna Björk; Boiroux, Dimitri; Bengtsson, Henrik

    2017-01-01

    The primary goal of this paper is to predict fasting glucose levels in type 2 diabetes (T2D) in long-acting insulin treatment. The paper presents a model for simulating insulin-glucose dynamics in T2D patients. The model combines a physiological model of type 1 diabetes (T1D) and an endogenous in...

  7. Effect of sodium aescinate treatment on PCOS rat model with insulin resistance.

    Science.gov (United States)

    Chen, L; Hu, L M; Wang, Y F; Yang, H Y; Huang, X Y; Zhou, W; Sun, H X

    2017-01-01

    Recent studies indicated that insulin resistance may contribute to the pathogenesis of polycystic ovary syndrome (PCOS); however, the specific mechanism is still unclear. To investigate the effect of sodium aescinate (SA) on PCOS-IR rat models. Sixty rats were randomly divided into the five groups: un-treated rats (n = 12), PCOS-IR group (n = 12), PCOS-IR group plus 50 mg/kg SA (n = 12), PCOS-IR group plus 10 mg/kg SA (n = 12), PCOS-IR group plus 150 mg/kg metformin (n = 12). On day 21, rats were sacrificed, and H(and)E staining was performed for histopathologic examination of the ovaries; moreover, the serum level of follicle-stimulating hormone (FSH), testosterone, and luteotropic hormone (LH) were measured, and the expression as well as phosphorylation of PI3K, Akt and Gsk-3β were examined using western blot assay. High dosage of SA treatment improved the morphological features of the ovaries in PCOS rats, and also induced significant decrease in serum expression of testosterone and LH/FSH ratio and significant decrease in the expression of p-PI3K, p-Akt and p-Gsk-3β. Our results demonstrated that SA treatment could alleviate the symptom of PCOS in rat model through regulating the PI3K/Akt/GSK3-β pathway (Fig. 4, Ref. 22).

  8. An Exponential Tilt Mixture Model for Time-to-Event Data to Evaluate Treatment Effect Heterogeneity in Randomized Clinical Trials.

    Science.gov (United States)

    Wang, Chi; Tan, Zhiqiang; Louis, Thomas A

    2014-01-01

    Evaluating the effect of a treatment on a time-to-event outcome is the focus of many randomized clinical trials. It is often observed that the treatment effect is heterogeneous, where only a subgroup of the patients may respond to the treatment due to some unknown mechanism such as genetic polymorphism. In this paper, we propose a semiparametric exponential tilt mixture model to estimate the proportion of patients who respond to the treatment and to assess the treatment effect. Our model is a natural extension of parametric mixture models to a semiparametric setting with a time-to-event outcome. We propose a nonparametric maximum likelihood estimation approach for inference and establish related asymptotic properties. Our method is illustrated by a randomized clinical trial on biodegradable polymer-delivered chemotherapy for malignant gliomas patients.

  9. Intensive treatment models and coercion

    DEFF Research Database (Denmark)

    Ohlenschlaeger, Johan; Thorup, Anne; Petersen, Lone

    2007-01-01

    Little evidence exists concerning the optimal treatment for patients with first-episode schizophrenia-spectrum disorders and the effect on traditional outcomes. The aim was to investigate whether optimal treatment models have an effect on the level of use of coercion and on traditional outcomes...... and on client satisfaction. Integrated Treatment had fewer bed-days, more patients living in non-supervised accommodation, and better score on quality of life. No differences were found as to the use of coercion. This study adds to the evidence that intensified treatment models are superior to standard...

  10. Effect of Antihypertensive Drug Treatment on Oxidative Stress Markers in Heart of Spontaneously Hypertensive Rat Models.

    Science.gov (United States)

    Yusoff, Nik Syamimi Nik; Mustapha, Zulkarnain; Sharif, Sharifah Emilia Tuan; Govindasamy, Chandran; Sirajudeen, Kuttulebbai Nainamohamed Salam

    2017-01-01

    Oxidative stress has been suggested to play a role in hypertension- and hypertension-induced organ damage. The effect of antihypertensive drug treatments on oxidative stress markers has not been well assessed. Therefore, in this study we investigated the effect of enalapril on oxidative stress markers in hearts of hypertensive rat models such as spontaneously hypertensive rats (SHR) and SHRs administered N-nitro-L-arginine methyl ester (SHR+L-NAME rats). Male rats were divided into four groups: SHRs, SHR+enalapril (SHR-E) rats, SHR+L-NAME rats, SHR+enalapril+L-NAME (SHRE+L-NAME) rats. Rats (SHREs) were administered enalapril (30 mg kg-1 day-1) in drinking water from week 4 to week 28 and L-NAME (25 mg kg-1 day-1) from week 16 to week 28 in drinking water. At the end of 28 weeks, animals were sacrificed, and their hearts were collected for the assessment of oxidative stress markers and histological examination. Enalapril treatment significantly enhanced the total antioxidant status (TAS) (P heart. The fibrosis areas in SHRs and SHR+L-NAME rats were also markedly reduced. These findings suggest that enalapril might play a protective role in hypertension- and hypertension-induced organ damage.

  11. Effect of human milk as a treatment for dry eye syndrome in a mouse model.

    Science.gov (United States)

    Diego, Jose L; Bidikov, Luke; Pedler, Michelle G; Kennedy, Jeffrey B; Quiroz-Mercado, Hugo; Gregory, Darren G; Petrash, J Mark; McCourt, Emily A

    Dry eye syndrome (DES) affects millions of people worldwide. Homeopathic remedies to treat a wide variety of ocular diseases have previously been documented in the literature, but little systematic work has been performed to validate the remedies' efficacy using accepted laboratory models of disease. The purpose of this study was to evaluate the efficacy of human milk and nopal cactus (prickly pear), two widely used homeopathic remedies, as agents to reduce pathological markers of DES. The previously described benzalkonium chloride (BAK) dry eye mouse model was used to study the efficacy of human milk and nopal cactus (prickly pear). BAK (0.2%) was applied to the mouse ocular surface twice daily to induce dry eye pathology. Fluorescein staining was used to verify that the animals had characteristic signs of DES. After induction of DES, the animals were treated with human milk (whole and fat-reduced), nopal, nopal extract derivatives, or cyclosporine four times daily for 7 days. Punctate staining and preservation of corneal epithelial thickness, measured histologically at the end of treatment, were used as indices of therapeutic efficacy. Treatment with BAK reduced the mean corneal epithelial thickness from 36.77±0.64 μm in the control mice to 21.29±3.2 μm. Reduction in corneal epithelial thickness was largely prevented by administration of whole milk (33.2±2.5 μm) or fat-reduced milk (36.1±1.58 μm), outcomes that were similar to treatment with cyclosporine (38.52±2.47 μm), a standard in current dry eye therapy. In contrast, crude or filtered nopal extracts were ineffective at preventing BAK-induced loss of corneal epithelial thickness (24.76±1.78 μm and 27.99±2.75 μm, respectively), as were solvents used in the extraction of nopal materials (26.53±1.46 μm for ethyl acetate, 21.59±5.87 μm for methanol). Epithelial damage, as reflected in the punctate scores, decreased over 4 days of treatment with whole and fat-reduced milk but continued to

  12. Antiepileptogenic Effect of Subchronic Palmitoylethanolamide Treatment in a Mouse Model of Acute Epilepsy

    Directory of Open Access Journals (Sweden)

    Julia M. Post

    2018-03-01

    Full Text Available Research on the antiepileptic effects of (endo-cannabinoids has remarkably progressed in the years following the discovery of fundamental role of the endocannabinoid (eCB system in controlling neural excitability. Moreover, an increasing number of well-documented cases of epilepsy patients exhibiting multi-drug resistance report beneficial effects of cannabis use. Pre-clinical and clinical research has increasingly focused on the antiepileptic effectiveness of exogenous administration of cannabinoids and/or pharmacologically induced increase of eCBs such as anandamide (also known as arachidonoylethanolamide [AEA]. Concomitant research has uncovered the contribution of neuroinflammatory processes and peripheral immunity to the onset and progression of epilepsy. Accordingly, modulation of inflammatory pathways such as cyclooxygenase-2 (COX-2 was pursued as alternative therapeutic strategy for epilepsy. Palmitoylethanolamide (PEA is an endogenous fatty acid amide related to the centrally and peripherally present eCB AEA, and is a naturally occurring nutrient that has long been recognized for its analgesic and anti-inflammatory properties. Neuroprotective and anti-hyperalgesic properties of PEA were evidenced in neurodegenerative diseases, and antiepileptic effects in pentylenetetrazol (PTZ, maximal electroshock (MES and amygdaloid kindling models of epileptic seizures. Moreover, numerous clinical trials in chronic pain revealed that PEA treatment is devoid of addiction potential, dose limiting side effects and psychoactive effects, rendering PEA an appealing candidate as antiepileptic compound or adjuvant. In the present study, we aimed at assessing antiepileptic properties of PEA in a mouse model of acute epileptic seizures induced by systemic administration of kainic acid (KA. KA-induced epilepsy in rodents is assumed to resemble to different extents human temporal lobe epilepsy (TLE depending on the route of KA administration; intracerebral (i

  13. Fluctuations induced extinction and stochastic resonance effect in a model of tumor growth with periodic treatment

    International Nuclear Information System (INIS)

    Li Dongxi; Xu Wei; Guo, Yongfeng; Xu Yong

    2011-01-01

    We investigate a stochastic model of tumor growth derived from the catalytic Michaelis-Menten reaction with positional and environmental fluctuations under subthreshold periodic treatment. Firstly, the influences of environmental fluctuations on the treatable stage are analyzed numerically. Applying the standard theory of stochastic resonance derived from the two-state approach, we derive the signal-to-noise ratio (SNR) analytically, which is used to measure the stochastic resonance phenomenon. It is found that the weak environmental fluctuations could induce the extinction of tumor cells in the subthreshold periodic treatment. The positional stability is better in favor of the treatment of the tumor cells. Besides, the appropriate and feasible treatment intensity and the treatment cycle should be highlighted considered in the treatment of tumor cells.

  14. Correcting for Test Score Measurement Error in ANCOVA Models for Estimating Treatment Effects

    Science.gov (United States)

    Lockwood, J. R.; McCaffrey, Daniel F.

    2014-01-01

    A common strategy for estimating treatment effects in observational studies using individual student-level data is analysis of covariance (ANCOVA) or hierarchical variants of it, in which outcomes (often standardized test scores) are regressed on pretreatment test scores, other student characteristics, and treatment group indicators. Measurement…

  15. The effectiveness of the Minnesota Model approach in the treatment of adolescent drug abusers.

    Science.gov (United States)

    Winters, K C; Stinchfield, R D; Opland, E; Weller, C; Latimer, W W

    2000-04-01

    The treatment outcome of drug-abusing adolescents treated with a 12-Step approach. The study compares drug use outcome data at 6 and 12 months post-treatment among three groups of adolescents: those who completed treatment, those who did not and those on a waiting list. Also, among treatment completers, residential and outpatient samples were compared on outcome. The treatment site is located in the Minneapolis/St Paul area of Minnesota. Two hundred and forty-five drug clinic-referred adolescents (12-18 years old), all of whom met at least one DSM-III-R substance dependence disorder. One hundred and seventy-nine subjects received either complete or incomplete 12-Step, Minnesota Model treatment and 66 were waiting list subjects. In addition to demographics and clinical background variables, measures included treatment involvement, treatment setting and drug use frequency at intake and follow-up. Absolute and relative outcome analyses indicated that completing treatment was associated with far superior outcome compared to those who did not complete treatment or receive any at all. The percentage of treatment completers who reported either abstinence or a minor lapse for the 12 months following treatment was 53%, compared to 15 and 28% for the incompleter and waiting list groups, respectively. Favorable treatment outcome for drug abuse was about two to three times more likely if treatment was completed. Also, there were no outcome differences between residential and outpatient groups. Alcohol was the most common drug used during the follow-up period, despite cannabis being the preferred drug at intake.

  16. Effect of monopolar radiofrequency treatment over soft-tissue fillers in an animal model: part 2.

    Science.gov (United States)

    Shumaker, Peter R; England, Laura J; Dover, Jeffrey S; Ross, E Victor; Harford, Robert; Derienzo, Damian; Bogle, Melissa; Uebelhoer, Nathan; Jacoby, Mark; Pope, Karl

    2006-03-01

    Monopolar radiofrequency (RF) treatment is used by physicians to heat skin and promote tissue tightening and contouring. Cosmetic fillers are used to soften deep facial lines and wrinkles. Patients who have had dermal fillers implanted may also benefit from or are candidates for monopolar RF skin tightening. This study examined the effect of RF treatment on various dermal filler substances. This is the second part of a two-part study. A juvenile farm pig was injected with dermal fillers including cross-linked human collagen (Cosmoplast), polylactic acid (PLA) (Sculptra), liquid injectable silicone (Silikon 1000), calcium hydroxylapatite (CaHA) (Radiesse), and hyaluronic acid (Restylane). Skin injected with dermal fillers was RF-treated using a 1.5-cm2 treatment tip and treatment levels typically used in the clinical setting. Fillers were examined histologically 5 days, 2 weeks, or 1 month after treatment. Histological specimens were scored for inflammatory response, foreign body response, and fibrosis in order to assess the effect of treatment on early filler processes, such as inflammation and encapsulation. Each filler substance produced a characteristic inflammatory response. No immediate thermal effect of RF treatment was observed histologically. RF treatment resulted in statistically significant increases in the inflammatory, foreign body, and fibrotic responses associated with the filler substances. Monopolar RF treatment levels that are typically used in the clinical setting were employed in this animal study. RF treatment resulted in measurable and statistically significant histological changes associated with the various filler materials. Additional clinical and histological studies are required to determine the optimal timing of monopolar RF treatment and filler placement for maximal potential aesthetic outcome. 2006 Wiley-Liss, Inc.

  17. In silico modelling of radiation effects towards personalised treatment in radiotherapy

    Science.gov (United States)

    Marcu, Loredana G.; Marcu, David

    2017-12-01

    In silico models applied in medical physics are valuable tools to assist in treatment optimization and personalization, which represent the ultimate goal of today's radiotherapy. Next to several biological and biophysical factors that influence tumour response to ionizing radiation, hypoxia and cancer stem cells are critical parameters that dictate the final outcome. The current work presents the results of an in silico model of tumour growth and response to radiation developed using Monte Carlo techniques. We are presenting the impact of partial oxygen tension and repopulation via cancer stem cells on tumour control after photon irradiation, highlighting some of the gaps that clinical research needs to fill for better customized treatment.

  18. Effects of prolonged treatment with memantine in the MRL model of CNS lupus.

    Science.gov (United States)

    Marcinko, Katarina; Parsons, Tiffany; Lerch, Jason P; Sled, John G; Sakic, Boris

    2012-09-01

    Neuropsychiatric manifestations and brain atrophy of unknown etiology are common and severe complications of systemic lupus erythematosus (SLE). An autoantibody that binds to N-methyl-D-aspartate (NMDA) receptor NR2 has been proposed as a key factor in the etiology of central nervous system (CNS) SLE. This hypothesis was supported by evidence suggesting memantine (MEM), an uncompetitive NMDA receptor antagonist, prevents behavioral dysfunction and brain pathology in healthy mice immunized with a peptide similar to an epitope on the NR2 receptor. Given that SLE is a chronic condition, we presently examine the effects of MEM in MRL/lpr mice, which develop behavioral deficits alongside SLE-like disease. A broad behavioral battery and 7-Tesla MRI were used to examine whether prolonged treatment with MEM (~25 mg/kg b.w. in drinking water) prevents CNS involvement in this spontaneous model of SLE. Although MEM increased novel object exploration in MRL/lpr mice, it did not show other beneficial, substrain-specific effects. Conversely, MEM was detrimental to spontaneous activity in control MRL +/+ mice and had a negative effect on body mass gain. Similarly, MRI revealed comparable increases in the volume of periventricular structures in MEM-treated groups. Sustained exposure to MEM affects body growth, brain morphology, and behavior primarily by pharmacological, and not autoimmunity-dependant mechanisms. Substrain-specific improvement in exploratory behavior of MEM-treated MRL/lpr mice may indicate that the NMDA system is merely a constituent of a complex pathogenenic cascade. However, it was evident that chronic administration of MEM is unable to completely prevent the development of a CNS SLE-like syndrome.

  19. Effects of Vitamin D Treatment on Skeletal Muscle Histology and Ultrastructural Changes in a Rodent Model

    Directory of Open Access Journals (Sweden)

    Sobhy M. Yakout

    2012-07-01

    Full Text Available Vitamin D is well known for its role in maintaining calcium and phosphorus homeostasis and in promoting bone mineralization; however, more of its pleiotropic effects have been described recently. The aim of the present investigation was to study the effect of vitamin D treatment on skeletal muscles changes under different dietary conditions using an animal model. Four groups of C57BL/6J mice (n = 11 each were maintained on either low fat diet (LFD or high fat diet ‎‎(HFD with and without 1α,25–dihydroxyvitamin D3 (calcitriol for 16 weeks. Animal weigh was recorded at baseline and then regular intervals, and at the end of the study, skeletal muscle tissues were harvested for the evaluation of the histopathological and ultrastructural changes. When control C57BL/6J mice were fed high-fat diet for 12 weeks, body weight gain was significantly increased compared with mice fed a LFD. (30.2% vs. 8.4%, p < 0.01. There was a significant gradual decrease in the weight of HFD fed mice that were treated with vitamin D as compared with a steady increase in the weights of controls (6.8% vs. 28.7%, p < 0.01. While the LFD group showed some ultrastructural changes, HDF fed on mice showed great muscle structural abnormalities. The whole sarcosome along with its membrane and cristae were severely damaged with scattered myocytes in HFD group. Furthermore, the mitochondria appeared weak and were on the verge of degenerations. The bands were diminished with loss of connections among myofibrils. These changes were attenuated in the HFD group treated with vitamin D with tissues have regained their normal structural appearance. The current findings indicate an important effect of vitamin D on skeletal muscle histology under HFD conditions.

  20. The Effectiveness of Holistic Multi-dimensional Treatment Model (HMTM in the Treatment of Children with Autism Spectrum Disorder (ASD

    Directory of Open Access Journals (Sweden)

    Maryam Hojati

    2014-04-01

    Full Text Available Introduction: Autism spectrum disorders (ASD belong to the pervasive neurodevelopmental disorders. The prevalence of ASD has increased significantly throughout recent decades, bringing the overall estimated prevalence to 11.3 per 1000 children. ASD is characterized by severe difficulties in reciprocal social interaction, stereotyped patterns of behavior and profound impairments in verbal and nonverbal communication. Materials and Method: In this experimental study, 150 children with ASD, who referred to psychiatry clinics of children in two Mashhad academic Hospitals-Iran, were enrolled. At the first, they divided into 3 groups (N=50 patients in each group. All groups were educated and treated with Holistic Multidimensional Treatment Model (HMTM method but for different periods: one, two, and three years. Data analysis was done using ANOVA and ANCOVA test. Results: 78% of participants were boys. According to the results, 26% of participants after one year treatment, 44% after two years and 52% after three years treatment improved. The participants’ symptoms of behavioral, cognitive and physical function declined in 3 groups significantly (p

  1. Treatment effects model for assessing disease management: measuring outcomes and strengthening program management.

    Science.gov (United States)

    Wendel, Jeanne; Dumitras, Diana

    2005-06-01

    This paper describes an analytical methodology for obtaining statistically unbiased outcomes estimates for programs in which participation decisions may be correlated with variables that impact outcomes. This methodology is particularly useful for intraorganizational program evaluations conducted for business purposes. In this situation, data is likely to be available for a population of managed care members who are eligible to participate in a disease management (DM) program, with some electing to participate while others eschew the opportunity. The most pragmatic analytical strategy for in-house evaluation of such programs is likely to be the pre-intervention/post-intervention design in which the control group consists of people who were invited to participate in the DM program, but declined the invitation. Regression estimates of program impacts may be statistically biased if factors that impact participation decisions are correlated with outcomes measures. This paper describes an econometric procedure, the Treatment Effects model, developed to produce statistically unbiased estimates of program impacts in this type of situation. Two equations are estimated to (a) estimate the impacts of patient characteristics on decisions to participate in the program, and then (b) use this information to produce a statistically unbiased estimate of the impact of program participation on outcomes. This methodology is well-established in economics and econometrics, but has not been widely applied in the DM outcomes measurement literature; hence, this paper focuses on one illustrative application.

  2. The effects of modeling contingencies in the treatment of food selectivity in children with autism.

    Science.gov (United States)

    Fu, Sherrene B; Penrod, Becky; Fernand, Jonathan K; Whelan, Colleen M; Griffith, Kristin; Medved, Shannon

    2015-11-01

    The current study investigated the effectiveness of stating and modeling contingencies in increasing food consumption for two children with food selectivity. Results suggested that stating and modeling a differential reinforcement (DR) contingency for food consumption was effective in increasing consumption of two target foods for one child, and stating and modeling a DR plus nonremoval of the spoon contingency was effective in increasing consumption of the remaining food for the first child and all target foods for the second child. © The Author(s) 2015.

  3. Serotonergic Modulation as Effective Treatment for Dravet Syndrome in a Zebrafish Mutant Model.

    Science.gov (United States)

    Sourbron, Jo; Schneider, Henning; Kecskés, Angéla; Liu, Yusu; Buening, Ellen M; Lagae, Lieven; Smolders, Ilse; de Witte, Peter

    2016-05-18

    Dravet syndrome (DS) is a severe epilepsy syndrome that starts within the first year of life. In a clinical study, add-on treatment with fenfluramine, a potent 5-hydroxytryptamine (5-HT) releaser activating multiple 5-HT receptor subtypes, made 70% of DS children seizure free. Others and we recently confirmed the efficacy of fenfluramine as an antiepileptiform compound in zebrafish models of DS. By using a large set of subtype selective agonists, in this study we examined which 5-HT receptor subtypes can be targeted to trigger antiseizure effects in homozygous scn1Lab(-/-) mutant zebrafish larvae that recapitulate DS well. We also provide evidence that zebrafish larvae express the orthologues of all human 5-HT receptor subtypes. Using an automated larval locomotor behavior assay, we were able to show that selective 5-HT1D-, 5-HT1E-, 5-HT2A-, 5-HT2C-, and 5-HT7-agonists significantly decreased epileptiform activity in the mutant zebrafish at 7 days post fertilization (dpf). By measuring local field potentials in the zebrafish larval forebrain, we confirmed the antiepileptiform activity of the 5-HT1D-, 5-HT2C-, and especially the 5-HT2A-agonist. Interestingly, we also found a significant decrease of serotonin in the heads of homozygous scn1Lab(-/-) mutants as compared to the wild type zebrafish, which suggest that neurochemical defects might play a crucial role in the pathophysiology of DS. Taken together, our results emphasize the high conservation of the serotonergic receptors in zebrafish larvae. Modulating certain serotonergic receptors was shown to effectively reduce seizures. Our findings therefore open new avenues for the development of future novel DS therapeutics.

  4. Effectiveness and cost-effectiveness of antidepressants in primary care: a multiple treatment comparison meta-analysis and cost-effectiveness model.

    Directory of Open Access Journals (Sweden)

    Joakim Ramsberg

    Full Text Available OBJECTIVE: To determine effectiveness and cost-effectiveness over a one-year time horizon of pharmacological first line treatment in primary care for patients with moderate to severe depression. DESIGN: A multiple treatment comparison meta-analysis was employed to determine the relative efficacy in terms of remission of 10 antidepressants (citalopram, duloxetine escitalopram, fluoxetine, fluvoxamine mirtazapine, paroxetine, reboxetine, sertraline and venlafaxine. The estimated remission rates were then applied in a decision-analytic model in order to estimate costs and quality of life with different treatments at one year. DATA SOURCES: Meta-analyses of remission rates from randomised controlled trials, and cost and quality-of-life data from published sources. RESULTS: The most favourable pharmacological treatment in terms of remission was escitalopram with an 8- to 12-week probability of remission of 0.47. Despite a high acquisition cost, this clinical effectiveness translated into escitalopram being both more effective and having a lower total cost than all other comparators from a societal perspective. From a healthcare perspective, the cost per QALY of escitalopram was €3732 compared with venlafaxine. CONCLUSION: Of the investigated antidepressants, escitalopram has the highest probability of remission and is the most effective and cost-effective pharmacological treatment in a primary care setting, when evaluated over a one year time-horizon. Small differences in remission rates may be important when assessing costs and cost-effectiveness of antidepressants.

  5. Effectiveness and Cost-Effectiveness of Antidepressants in Primary Care: A Multiple Treatment Comparison Meta-Analysis and Cost-Effectiveness Model

    Science.gov (United States)

    Ramsberg, Joakim; Asseburg, Christian; Henriksson, Martin

    2012-01-01

    Objective To determine effectiveness and cost-effectiveness over a one-year time horizon of pharmacological first line treatment in primary care for patients with moderate to severe depression. Design A multiple treatment comparison meta-analysis was employed to determine the relative efficacy in terms of remission of 10 antidepressants (citalopram, duloxetine escitalopram, fluoxetine, fluvoxamine mirtazapine, paroxetine, reboxetine, sertraline and venlafaxine). The estimated remission rates were then applied in a decision-analytic model in order to estimate costs and quality of life with different treatments at one year. Data Sources Meta-analyses of remission rates from randomised controlled trials, and cost and quality-of-life data from published sources. Results The most favourable pharmacological treatment in terms of remission was escitalopram with an 8- to 12-week probability of remission of 0.47. Despite a high acquisition cost, this clinical effectiveness translated into escitalopram being both more effective and having a lower total cost than all other comparators from a societal perspective. From a healthcare perspective, the cost per QALY of escitalopram was €3732 compared with venlafaxine. Conclusion Of the investigated antidepressants, escitalopram has the highest probability of remission and is the most effective and cost-effective pharmacological treatment in a primary care setting, when evaluated over a one year time-horizon. Small differences in remission rates may be important when assessing costs and cost-effectiveness of antidepressants. PMID:22876296

  6. The effective field treatment of the spin-1 Ashkin–Teller model

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Jander P., E-mail: jander@ufsj.edu.br [Departamento de Ciências Naturais, Universidade Federal de São João del Rei, C.P. 110, CEP 36301-160, São João del Rei, MG (Brazil); Departamento de Matemática, Universidade Federal de São João del Rei, C.P. 110, CEP 36301-160, São João del Rei, MG (Brazil); Sá Barreto, F.C., E-mail: fcsabarreto@gmail.com [Departamento de Ciências Naturais, Universidade Federal de São João del Rei, C.P. 110, CEP 36301-160, São João del Rei, MG (Brazil); Departamento de Física, Universidade Federal de Minas Gerais, C.P. 110, CEP 31270-901, Belo Horizonte, MG (Brazil)

    2016-03-01

    Spin correlation identities for the spin-1 Ashkin–Teller model are derived. From the spin correlation identities and effective field approximation results for the magnetization, the critical frontiers and tricritical points are obtained in the hexagonal lattice. The results of the effective field approximation are compared to those obtained by other methods. - Highlights: • Correlation identities for spin-1 Ashkin–Teller model on a hexagonal lattice are obtained. • From the spin correlation identities the effective-field theory is applied. • The effective-field theory is extended to locate first-order transitions. • Multicritical points are obtained according to this procedure.

  7. A semi-analytical model of biological effectiveness for treatment planning in light ion radiotherapy

    Czech Academy of Sciences Publication Activity Database

    Kundrát, Pavel

    2007-01-01

    Roč. 34, č. 6 (2007), s. 2654-2654 ISSN 0094-2405. [AAPM Annual Meeting. Minneapolis, 22.07.2007-26.07.2007] R&D Projects: GA ČR GA202/05/2728 Institutional research plan: CEZ:AV0Z10100502 Keywords : treatment planning * light-ion therapy * radiobiological models Subject RIV: BF - Elementary Particles and High Energy Physics Impact factor: 3.198, year: 2007

  8. Cost-effectiveness model comparing olanzapine and other oral atypical antipsychotics in the treatment of schizophrenia in the United States

    Directory of Open Access Journals (Sweden)

    Smolen Lee J

    2009-04-01

    Full Text Available Abstract Background Schizophrenia is often a persistent and costly illness that requires continued treatment with antipsychotics. Differences among antipsychotics on efficacy, safety, tolerability, adherence, and cost have cost-effectiveness implications for treating schizophrenia. This study compares the cost-effectiveness of oral olanzapine, oral risperidone (at generic cost, primary comparator, quetiapine, ziprasidone, and aripiprazole in the treatment of patients with schizophrenia from the perspective of third-party payers in the U.S. health care system. Methods A 1-year microsimulation economic decision model, with quarterly cycles, was developed to simulate the dynamic nature of usual care of schizophrenia patients who switch, continue, discontinue, and restart their medications. The model captures clinical and cost parameters including adherence levels, relapse with and without hospitalization, quality-adjusted life years (QALYs, treatment discontinuation by reason, treatment-emergent adverse events, suicide, health care resource utilization, and direct medical care costs. Published medical literature and a clinical expert panel were used to develop baseline model assumptions. Key model outcomes included mean annual total direct cost per treatment, cost per stable patient, and incremental cost-effectiveness values per QALY gained. Results The results of the microsimulation model indicated that olanzapine had the lowest mean annual direct health care cost ($8,544 followed by generic risperidone ($9,080. In addition, olanzapine resulted in more QALYs than risperidone (0.733 vs. 0.719. The base case and multiple sensitivity analyses found olanzapine to be the dominant choice in terms of incremental cost-effectiveness per QALY gained. Conclusion The utilization of olanzapine is predicted in this model to result in better clinical outcomes and lower total direct health care costs compared to generic risperidone, quetiapine, ziprasidone, and

  9. Modelling of volumetric composition and mechanical properties of unidirectional hemp/epoxy composites - Effect of enzymatic fibre treatment

    DEFF Research Database (Denmark)

    Liu, Ming; Thygesen, Anders; Meyer, Anne S.

    2016-01-01

    The objective of the present study is to assess the effect of enzymatic fibre treatments on the fibre performance in unidirectional hemp/epoxy composites by modelling the volumetric composition and mechanical properties of the composites. It is shown that the applied models can well predict...... the changes in volumetric composition and mechanical properties of the composites when differently treated hemp fibres are used. The decrease in the fibre correlated porosity factor with the enzymatic fibre treatments shows that the removal of pectin by pectinolytic enzymes results in a better fibre...

  10. Common and specific effects of couples treatment for alcoholism: a test of the generic model of psychotherapy.

    Science.gov (United States)

    Harwood, T Mark; Beutler, Larry E; Castillo, Salvador; Karno, Mitch

    2006-09-01

    The generic model of psychotherapy (Orlinsky & Howard, 1987) eschews the view that inputs, processes or outputs associated with treatment exert linear and independent effects on outcomes. Variables within these three clusters must be viewed both within the context of time and through their interactions with other variables within a class. This study illustrates the use of this model by identifying common (comprising both traditional relationship factors and shared therapy ingredients) and specific factors in cognitive-behavioural (CB) and family systems (FS) treatments for alcoholic couples and tracking their contributions over two treatment phases - the acute phase, and the follow-up phase. While four process variables (therapy type, intensity of treatment, common elements and FS-specific procedures) contributed to outcomes during the active treatment phase, these variables became more interactive during follow-up. Indeed, high levels of both specific interventions of both treatments were negatively associated with benefit, if common factors were also frequently used during the acute phase. The best effects were obtained when common and specific interventions were counterbalanced, one being frequently used and the other being infrequently used. Implications for future alcohol treatment and recommendations for research on common and specific factors are discussed.

  11. A novel brain trauma model in the mouse : effects of dexamethasone treatment

    NARCIS (Netherlands)

    Hortobágyi, Tibor; Hortobagyi, S; Gorlach, C; Harkany, T; Benbyo, Z; Gorogh, T; Nagel, W; Wahl, M

    2000-01-01

    We describe a novel methodological approach for inducing cold lesion in the mouse as a model of human cortical contusion trauma. To validate its reproducibility and reliability, dexamethasone (Dxm) was repeatedly applied to demonstrate possible antioedematous drug effects. Following tho induction of

  12. The effects of psychotherapy treatment on outcome in bulimia nervosa: Examining indirect effects through emotion regulation, self-directed behavior, and self-discrepancy within the mediation model.

    Science.gov (United States)

    Peterson, Carol B; Berg, Kelly C; Crosby, Ross D; Lavender, Jason M; Accurso, Erin C; Ciao, Anna C; Smith, Tracey L; Klein, Marjorie; Mitchell, James E; Crow, Scott J; Wonderlich, Stephen A

    2017-06-01

    The purpose of this investigation was to examine the indirect effects of Integrative Cognitive-Affective Therapy (ICAT-BN) and Cognitive-Behavioral Therapy-Enhanced (CBT-E) on bulimia nervosa (BN) treatment outcome through three hypothesized maintenance variables: emotion regulation, self-directed behavior, and self-discrepancy. Eighty adults with BN were randomized to 21 sessions of ICAT-BN or CBT-E. A regression-based bootstrapping approach was used to test the indirect effects of treatment on outcome at end of treatment through emotion regulation and self-directed behavior measured at mid-treatment, as well as the indirect effects of treatment at follow-up through emotion regulation, self-directed behavior, and self-discrepancy measured at end of treatment. No significant differences in outcome between treatment conditions were observed, and no significant direct or indirect effects were found. Examination of the individual paths within the indirect effects models revealed comparable treatment effects. Across treatments, improvements in emotion regulation and self-directed behavior between baseline and mid-treatment predicted improvements in global eating disorder scores but not binge eating and purging frequency at end of treatment. Baseline to end of treatment improvements in emotion regulation and self-directed behavior also predicted improvements in global eating disorder scores at follow-up. Baseline to end of treatment improvements in emotion regulation predicted improvements in binge eating and baseline to end of treatment increases in positive self-directed behavior predicted improvements in purging at follow-up. These findings suggest that emotion regulation and self-directed behavior are important treatment targets and that ICAT-BN and CBT-E are comparable in modifying these psychological processes among individuals with BN. © 2017 Wiley Periodicals, Inc.

  13. Population cost-effectiveness of the Triple P parenting programme for the treatment of conduct disorder: an economic modelling study.

    Science.gov (United States)

    Sampaio, Filipa; Barendregt, Jan J; Feldman, Inna; Lee, Yong Yi; Sawyer, Michael G; Dadds, Mark R; Scott, James G; Mihalopoulos, Cathrine

    2017-12-29

    Parenting programmes are the recommended treatments of conduct disorders (CD) in children, but little is known about their longer term cost-effectiveness. This study aimed to evaluate the population cost-effectiveness of one of the most researched evidence-based parenting programmes, the Triple P-Positive Parenting Programme, delivered in a group and individual format, for the treatment of CD in children. A population-based multiple cohort decision analytic model was developed to estimate the cost per disability-adjusted life year (DALY) averted of Triple P compared with a 'no intervention' scenario, using a health sector perspective. The model targeted a cohort of 5-9-year-old children with CD in Australia currently seeking treatment, and followed them until they reached adulthood (i.e., 18 years). Multivariate probabilistic and univariate sensitivity analyses were conducted to incorporate uncertainty in the model parameters. Triple P was cost-effective compared to no intervention at a threshold of AU$50,000 per DALY averted when delivered in a group format [incremental cost-effectiveness ratio (ICER) = $1013 per DALY averted; 95% uncertainty interval (UI) 471-1956] and in an individual format (ICER = $20,498 per DALY averted; 95% UI 11,146-39,470). Evidence-based parenting programmes, such as the Triple P, for the treatment of CD among children appear to represent good value for money, when delivered in a group or an individual face-to-face format, with the group format being the most cost-effective option. The current model can be used for economic evaluations of other interventions targeting CD and in other settings.

  14. The Effect of Treatment Advances on the Mortality Results of Breast Cancer Screening Trials: A Microsimulation Model.

    Science.gov (United States)

    Birnbaum, Jeanette; Gadi, Vijayakrishna K; Markowitz, Elan; Etzioni, Ruth

    2016-02-16

    Mammography trials, which are the primary sources of evidence for screening benefit, were conducted decades ago. Whether advances in systemic therapies have rendered previously observed benefits of screening less significant is unknown. To compare the outcomes of breast cancer screening trials had they been conducted using contemporary systemic treatments with outcomes of trials conducted with previously used treatments. Computer simulation model of 3 virtual screening trials with similar reductions in advanced-stage cancer cases but reflecting treatment patterns in 1975 (prechemotherapy era), 1999, or 2015 (treatment according to receptor status). Meta-analyses of screening and treatment trials; study of dissemination of primary systemic treatments; SEER (Surveillance, Epidemiology, and End Results) registry. U.S. women aged 50 to 74 years. 10 and 25 years. Population. Mammography, chemotherapy, tamoxifen, aromatase inhibitors, and trastuzumab. Breast cancer mortality rate ratio (MRR) and absolute risk reduction (ARR) obtained by the difference in cumulative breast cancer mortality between control and screening groups. At 10 years, screening in a 1975 trial yielded an MRR of 90% and an ARR of 5 deaths per 10,000 women. A 2015 screening trial yielded a 10-year MRR of 90% and an ARR of 3 deaths per 10,000 women. Greater reductions in advanced-stage disease yielded a greater screening effect, but MRRs remained similar across trials. However, ARRs were consistently lower under contemporary treatments. When contemporary treatments were available only for early-stage cases, the MRR was 88%. Disease models simplify reality and cannot capture all breast cancer subtypes. Advances in systemic therapies for breast cancer have not substantively reduced the relative benefits of screening but have likely reduced the absolute benefits because of their positive effect on breast cancer survival. University of Washington and National Cancer Institute.

  15. Ionic imbalance and lack of effect of adjuvant treatment with methylene blue in the hamster model of leptospirosis

    Directory of Open Access Journals (Sweden)

    Cleiton Silva Santos

    2013-06-01

    Full Text Available Leptospirosis in humans usually involves hypokalaemia and hypomagnesaemia and the putative mechanism underlying such ionic imbalances may be related to nitric oxide (NO production. We previously demonstrated the correlation between serum levels of NO and the severity of renal disease in patients with severe leptospirosis. Methylene blue inhibits soluble guanylyl cyclase (downstream of the action of any NO synthase isoforms and was recently reported to have beneficial effects on clinical and experimental sepsis. We investigated the occurrence of serum ionic changes in experimental leptospirosis at various time points (4, 8, 16 and 28 days in a hamster model. We also determined the effect of methylene blue treatment when administered as an adjuvant therapy, combined with late initiation of standard antibiotic (ampicillin treatment. Hypokalaemia was not reproduced in this model: all of the groups developed increased levels of serum potassium (K. Furthermore, hypermagnesaemia, rather than magnesium (Mg depletion, was observed in this hamster model of acute infection. These findings may be associated with an accelerated progression to acute renal failure. Adjuvant treatment with methylene blue had no effect on survival or serum Mg and K levels during acute-phase leptospirosis in hamsters.

  16. Combined Treatment Effects of Radiation and Immunotherapy: Studies in an Autochthonous Prostate Cancer Model

    Energy Technology Data Exchange (ETDEWEB)

    Wada, Satoshi [Department of Oncology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Harris, Timothy J.; Tryggestad, Erik [Department of Radiation Oncology and Molecular Radiation Sciences, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Yoshimura, Kiyoshi [Department of Oncology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Zeng, Jing [Department of Radiation Oncology and Molecular Radiation Sciences, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Yen, Hung-Rong; Getnet, Derese; Grosso, Joseph F.; Bruno, Tullia C. [Department of Oncology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); De Marzo, Angelo M. [Department of Pathology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); and others

    2013-11-15

    Purpose: To optimize the combination of ionizing radiation and cellular immunotherapy using a preclinical autochthonous model of prostate cancer. Methods and Materials: Transgenic mice expressing a model antigen under a prostate-specific promoter were treated using a platform that integrates cone-beam CT imaging with 3-dimensional conformal therapy. Using this technology we investigated the immunologic and therapeutic effects of combining ionizing radiation with granulocyte/macrophage colony-stimulating factor-secreting cellular immunotherapy for prostate cancer in mice bearing autochthonous prostate tumors. Results: The combination of ionizing radiation and immunotherapy resulted in a significant decrease in pathologic tumor grade and gross tumor bulk that was not evident with either single-modality therapy. Furthermore, combinatorial therapy resulted in improved overall survival in a preventive metastasis model and in the setting of established micrometastases. Mechanistically, combined therapy resulted in an increase of the ratio of effector-to-regulatory T cells for both CD4 and CD8 tumor-infiltrating lymphocytes. Conclusions: Our preclinical model establishes a potential role for the use of combined radiation-immunotherapy in locally advanced prostate cancer, which warrants further exploration in a clinical setting.

  17. Combined treatment effects of radiation and immunotherapy: studies in an autochthonous prostate cancer model.

    Science.gov (United States)

    Wada, Satoshi; Harris, Timothy J; Tryggestad, Erik; Yoshimura, Kiyoshi; Zeng, Jing; Yen, Hung-Rong; Getnet, Derese; Grosso, Joseph F; Bruno, Tullia C; De Marzo, Angelo M; Netto, George J; Pardoll, Drew M; DeWeese, Theodore L; Wong, John; Drake, Charles G

    2013-11-15

    To optimize the combination of ionizing radiation and cellular immunotherapy using a preclinical autochthonous model of prostate cancer. Transgenic mice expressing a model antigen under a prostate-specific promoter were treated using a platform that integrates cone-beam CT imaging with 3-dimensional conformal therapy. Using this technology we investigated the immunologic and therapeutic effects of combining ionizing radiation with granulocyte/macrophage colony-stimulating factor-secreting cellular immunotherapy for prostate cancer in mice bearing autochthonous prostate tumors. The combination of ionizing radiation and immunotherapy resulted in a significant decrease in pathologic tumor grade and gross tumor bulk that was not evident with either single-modality therapy. Furthermore, combinatorial therapy resulted in improved overall survival in a preventive metastasis model and in the setting of established micrometastases. Mechanistically, combined therapy resulted in an increase of the ratio of effector-to-regulatory T cells for both CD4 and CD8 tumor-infiltrating lymphocytes. Our preclinical model establishes a potential role for the use of combined radiation-immunotherapy in locally advanced prostate cancer, which warrants further exploration in a clinical setting. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Methodologies used in cost-effectiveness models for evaluating treatments in major depressive disorder: a systematic review

    Directory of Open Access Journals (Sweden)

    Zimovetz Evelina A

    2012-02-01

    Full Text Available Abstract Background Decision makers in many jurisdictions use cost-effectiveness estimates as an aid for selecting interventions with an appropriate balance between health benefits and costs. This systematic literature review aims to provide an overview of published cost-effectiveness models in major depressive disorder (MDD with a focus on the methods employed. Key components of the identified models are discussed and any challenges in developing models are highlighted. Methods A systematic literature search was performed to identify all primary model-based economic evaluations of MDD interventions indexed in MEDLINE, the Cochrane Library, EMBASE, EconLit, and PsycINFO between January 2000 and May 2010. Results A total of 37 studies were included in the review. These studies predominantly evaluated antidepressant medications. The analyses were performed across a broad set of countries. The majority of models were decision-trees; eight were Markov models. Most models had a time horizon of less than 1 year. The majority of analyses took a payer perspective. Clinical input data were obtained from pooled placebo-controlled comparative trials, single head-to-head trials, or meta-analyses. The majority of studies (24 of 37 used treatment success or symptom-free days as main outcomes, 14 studies incorporated health state utilities, and 2 used disability-adjusted life-years. A few models (14 of 37 incorporated probabilities and costs associated with suicide and/or suicide attempts. Two models examined the cost-effectiveness of second-line treatment in patients who had failed to respond to initial therapy. Resource use data used in the models were obtained mostly from expert opinion. All studies, with the exception of one, explored parameter uncertainty. Conclusions The review identified several model input data gaps, including utility values in partial responders, efficacy of second-line treatments, and resource utilisation estimates obtained from

  19. Modelling of volumetric composition and mechanical properties of unidirectional hemp/epoxy composites - Effect of enzymatic fibre treatment

    Science.gov (United States)

    Liu, M.; Thygesen, A.; Meyer, AS; Madsen, B.

    2016-07-01

    The objective of the present study is to assess the effect of enzymatic fibre treatments on the fibre performance in unidirectional hemp/epoxy composites by modelling the volumetric composition and mechanical properties of the composites. It is shown that the applied models can well predict the changes in volumetric composition and mechanical properties of the composites when differently treated hemp fibres are used. The decrease in the fibre correlated porosity factor with the enzymatic fibre treatments shows that the removal of pectin by pectinolytic enzymes results in a better fibre impregnation by the epoxy matrix, and the mechanical properties of the composites are thereby increased. The effective fibre stiffness and strength established from the modelling show that the enzymatic removal of pectin also leads to increased mechanical properties of the fibres. Among the investigated samples, the composites with hydrothermally pre-treated and enzymatically treated fibres have the lowest porosity factor of 0.08 and the highest mechanical properties. In these composites, the effective fibre stiffness and strength are determined to be 83 GPa and 667 MPa, respectively, when the porosity efficiency exponent is set equal to 2. Altogether, it is demonstrated that the applied models provide a concept to be used for the evaluation of performance of treated fibres in composites.

  20. Analysis of the reliability of the local effect model for the use in carbon ion treatment planning systems.

    Science.gov (United States)

    Russo, G; Attili, A; Bourhaleb, F; Marchetto, F; Peroni, C; Schmitt, E; Bertrand, D

    2011-02-01

    In radiotherapy with carbon ions, biological effects of treatments have to be predicted. For this purpose, one of the most used models is the local effect model (LEM) developed at the Gesellschaft für Schwerionenforschung (GSI), Germany. At the Istituto Nazionale di Fisica Nucleare, Italy, the reliability of the last published version of LEM (LEM III) in reproducing radiobiological data has been checked under both monoenergetic and spread-out Bragg peak (SOBP) carbon-ion irradiation. The reproduction of the monoenergetic measurements with the LEM was rather successful for some cell lines, while it failed for the less-radioresistant ones. The SOBP experimental trend was predicted by the LEM, but a large shift between model curves and measured points was observed.

  1. Effective treatment of diverse medulloblastoma models with mebendazole and its impact on tumor angiogenesis.

    Science.gov (United States)

    Bai, Ren-Yuan; Staedtke, Verena; Rudin, Charles M; Bunz, Fred; Riggins, Gregory J

    2015-04-01

    Medulloblastoma is the most common malignant brain tumor in children. Current standard treatments cure 40%-60% of patients, while the majority of survivors suffer long-term neurological sequelae. The identification of 4 molecular groups of medulloblastoma improved the clinical management with the development of targeted therapies; however, the tumor acquires resistance quickly. Mebendazole (MBZ) has a long safety record as antiparasitic in children and has been recently implicated in inhibition of various tyrosine kinases in vitro. Here, we investigated the efficacy of MBZ in various medulloblastoma subtypes and MBZ's impact on vascular endothelial growth factor receptor 2 (VEGFR2) and tumor angiogenesis. The inhibition of MBZ on VEGFR2 kinase was investigated in an autophosphorylation assay and a cell-free kinase assay. Mice bearing orthotopic PTCH1-mutant medulloblastoma allografts, a group 3 medulloblastoma xenograft, and a PTCH1-mutant medulloblastoma with acquired resistance to the smoothened inhibitor vismodegib were treated with MBZ. The survival benefit and the impact on tumor angiogenesis and VEGFR2 kinase function were analyzed. We determined that MBZ interferes with VEGFR2 kinase by competing with ATP. MBZ selectively inhibited tumor angiogenesis but not the normal brain vasculatures in orthotopic medulloblastoma models and suppressed VEGFR2 kinase in vivo. MBZ significantly extended the survival of medulloblastoma models derived from different molecular backgrounds. Our findings support testing of MBZ as a possible low-toxicity therapy for medulloblastomas of various molecular subtypes, including tumors with acquired vismodegib resistance. Its antitumor mechanism may be partially explained by inhibition of tumor angiogenesis. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. A novel convolution-based approach to address ionization chamber volume averaging effect in model-based treatment planning systems

    Science.gov (United States)

    Barraclough, Brendan; Li, Jonathan G.; Lebron, Sharon; Fan, Qiyong; Liu, Chihray; Yan, Guanghua

    2015-08-01

    The ionization chamber volume averaging effect is a well-known issue without an elegant solution. The purpose of this study is to propose a novel convolution-based approach to address the volume averaging effect in model-based treatment planning systems (TPSs). Ionization chamber-measured beam profiles can be regarded as the convolution between the detector response function and the implicit real profiles. Existing approaches address the issue by trying to remove the volume averaging effect from the measurement. In contrast, our proposed method imports the measured profiles directly into the TPS and addresses the problem by reoptimizing pertinent parameters of the TPS beam model. In the iterative beam modeling process, the TPS-calculated beam profiles are convolved with the same detector response function. Beam model parameters responsible for the penumbra are optimized to drive the convolved profiles to match the measured profiles. Since the convolved and the measured profiles are subject to identical volume averaging effect, the calculated profiles match the real profiles when the optimization converges. The method was applied to reoptimize a CC13 beam model commissioned with profiles measured with a standard ionization chamber (Scanditronix Wellhofer, Bartlett, TN). The reoptimized beam model was validated by comparing the TPS-calculated profiles with diode-measured profiles. Its performance in intensity-modulated radiation therapy (IMRT) quality assurance (QA) for ten head-and-neck patients was compared with the CC13 beam model and a clinical beam model (manually optimized, clinically proven) using standard Gamma comparisons. The beam profiles calculated with the reoptimized beam model showed excellent agreement with diode measurement at all measured geometries. Performance of the reoptimized beam model was comparable with that of the clinical beam model in IMRT QA. The average passing rates using the reoptimized beam model increased substantially from 92.1% to

  3. A budget-impact and cost-effectiveness model for second-line treatment of major depression.

    Science.gov (United States)

    Malone, Daniel C

    2007-07-01

    Depressed patients who initially fail to achieve remission when placed on a selective serotonin reuptake inhibitor (SSRI) may require a second treatment. The purpose of this study was to evaluate the effectiveness, cost, cost-effectiveness, and budget impact of second-line pharmacologic treatment for major depressive disorder (MDD). A cost-effectiveness analysis was conducted to evaluate second-line therapies (citalopram, escitalopram, fluoxetine, paroxetine, paroxetine controlled release [CR], sertraline, and venlafaxine extended release [XR]) for the treatment of depression. Effectiveness data were obtained from published clinical studies. The primary outcome was remission defined as a score of 7 or less on the Hamilton Rating Scale for Depression (HAM-D) or a score of 10 or less on the montgomery-Asberg Depression Rating Scale (MADRS) depression rating scales. The wholesale acquisition cost (WAC) for medications and medical treatment costs for depression were included. The perspective was derived from a managed care organization (MCO) with 500,000 members, a 1.9% annual incidence of depression, and treatment duration of 6 months. Assumptions included: second-line treatment is not as effective as first-line treatment, WAC price reflects MCO costs, and side effects were identical. Sensitivity analyses were conducted to determine variables that influenced the results. Second-line remission rates were 20.4% for venlafaxine XR, 16.9% for sertraline, 16.4% for escitalopram, 15.1% for generic SSRIs (weighted average), and 13.6% for paroxetine CR. Pharmacy costs ranged from $163 for generic SSRIs to $319 for venlafaxine SR. Total cost per patient achieving remission was $14,275 for venlafaxine SR, followed by $16,100 for escitalopram. The incremental cost-effectiveness ratio (ICER) for venlafaxine SR compared with generic SSRIs was $2,073 per patient achieving remission, followed by escitalopram with an ICER of $3,566. The model was most sensitive to other therapies

  4. Modeling and optimization of acid dye manufacturing wastewater treatment with Fenton's reagent: comparison with electrocoagulation treatment results and effects on activated sludge inhibition.

    Science.gov (United States)

    Arslan-Alaton, Idil; Gursoy, B Hande; Akyol, Abdurahman; Kobya, Mehmet; Bayramoglu, Mahmut

    2010-01-01

    In the present study, Fenton's oxidation of a chromium complex disazo dye (Acid Blue 193) synthesis wastewater was evaluated, modeled and optimized by employing Central Composite Design. Within this context, the individual and interactive effects of critical process parameters such as Fe(2 + ), H(2)O(2) concentrations, initial chemical oxygen demand (COD) and reaction time was assessed. The process response (output) variables were chosen as percent color, COD and total organic carbon (TOC) removal efficiencies. Optimum working conditions in terms of color and organic carbon removals were established to be Fe(2 + )=3 mM; H(2)O(2)=25 mM; reaction time = 10 min at pH 3 and an initial COD content of 245 mg/L. Under these conditions, 96% color, 82% COD and 51% TOC removals were obtained. The established polynomial regression models describing color, COD and TOC removals satisfactorily fitted the experimental data and could be used to predict Fenton's treatment results at statistically significant rates. Optimized treatment results were compared with those obtained via electrocoagulation treatment under optimized conditions (applied current = 50 A/m(2); reaction time = 15 min; initial pH = 7 for an initial COD content of 245 mg/L). The relative inhibition of heterotrophic oxygen uptake rate was measured to examine the inhibitory effect of azo dye synthesis effluent before and after Fenton's oxidation and electrocoagulation with respect to synthetic domestic wastewater. Untreated azo dye production wastewater exhibited a slightly inhibitory effect that was appreciably reduced but not entirely removed after Fenton's oxidation, whereas no inhibition of mixed bioculture was observed for azo dye synthesis effluent subjected to electrocoagulation treatment.

  5. The modeled cost-effectiveness of family-based and adolescent-focused treatment for anorexia nervosa.

    Science.gov (United States)

    Le, Long Khanh-Dao; Barendregt, Jan J; Hay, Phillipa; Sawyer, Susan M; Hughes, Elizabeth K; Mihalopoulos, Cathrine

    2017-12-01

    Anorexia nervosa (AN) is a prevalent, serious mental disorder. We aimed to evaluate the cost-effectiveness of family-based treatment (FBT) compared to adolescent-focused individual therapy (AFT) or no intervention within the Australian healthcare system. A Markov model was developed to estimate the cost and disability-adjusted life-year (DALY) averted of FBT relative to comparators over 6 years from the health system perspective. The target population was 11-18 year olds with AN of relatively short duration. Uncertainty and sensitivity analyses were conducted to test model assumptions. Results are reported as incremental cost-effectiveness ratios (ICER) in 2013 Australian dollars per DALY averted. FBT was less costly than AFT. Relative to no intervention, the mean ICER of FBT and AFT was $5,089 (95% uncertainty interval (UI): dominant to $16,659) and $51,897 ($21,591 to $1,712,491) per DALY averted. FBT and AFT are 100% and 45% likely to be cost-effective, respectively, at a threshold of AUD$50,000 per DALY averted. Sensitivity analyses indicated that excluding hospital costs led to increases in the ICERs but the conclusion of the study did not change. FBT is the most cost-effective among treatment arms, whereas AFT was not cost-effective compared to no intervention. Further research is required to verify this result. © 2017 Wiley Periodicals, Inc.

  6. Detrimental effects of rat mesenchymal stromal cell pre-treatment in a model of acute kidney rejection

    Directory of Open Access Journals (Sweden)

    Martina eSeifert

    2012-07-01

    Full Text Available Mesenchymal stromal cells (MSC have shown immunomodulatory and tissue repair potential including partial tolerance induction by pre-treatment of donor-specific cells in a rat heart transplantation model. Very recently, we could show that autologous MSC attenuated ischemia reperfusion injury in a highly mismatched donor-recipient rat kidney transplant model. Therefore, we investigated donor-specific MSC pre-treatment in this rat kidney transplantation model to study whether graft function could be improved, or if tolerance could be induced.Donor- and recipient-type MSC or PBS as a control were injected i.v. four days before kidney transplantation. Mycophenolate mofetil (MMF immunosuppression (20 mg/kg body weight was applied for 7 days. Kidney grafts and spleens were harvested between days 8-10 and analyzed by quantitative RT-PCR and immunohistology. In addition, creatinine levels in the blood were measured and serum was screened for the presence of donor-specific antibodies.Surprisingly, application of both donor- and recipient-specific MSC resulted in enhanced humoral immune responses verified by intragraft B cell infiltration and complement factor C4d deposits. Moreover, signs of inflammation and rejection were generally enhanced in both MSC-treated groups relative to PBS control group. Additionally, pre-treatment with donor-specific MSC significantly enhanced the level of donor-specific antibody formation when compared with PBS- or recipient-MSC-treated groups. Pre-treatment with both MSC types resulted in a higher degree of kidney cortex tissue damage and elevated creatinine levels at the time point of rejection. Thus, MSC pre-sensitization in this model impairs the allograft outcome.Our data from this pre-clinical kidney transplantation model indicate that pre-operative MSC administration may not be optimal in kidney transplantation and caution must be exerted before moving forward with clinical studies in order to avoid adverse effects.

  7. Effects of Methadone Maintenance Treatment on Decision-Making Processes in Heroin-Abusers: A Cognitive Modeling Analysis

    Directory of Open Access Journals (Sweden)

    Arash Khodadadi

    2010-05-01

    Full Text Available A B S T R A C TIntroduction: Although decision-making processes have become a principal target of study among addiction researchers, few researches are published according to effects of different treatment methods on the cognitive processes underlying decision making up to now. Utilizing cognitive modeling method, in this paper we examine the effects of Methadone maintenance treatment (MMT on cognitive processes underlying decision-making disorders in heroin-abusers. Methods: For this purpose, for the first time, we use the balloon analog risk task (BART to assess the decision-making ability of heroin-abusers before and after treatment and compare it to the non heroin-dependent subjects. Results: Results demonstrate that heroin-abusers show more risky behavior than other groups. But, there is no difference between the performance of heroin-abusers after 6 months of MMT and control group. Modeling subjects’ behavior in BART reveals that poor performance in heroin-abusers is due to reward-dependency and insensitivity to evaluation. Discussion: Results show that 6 months of MMT decreases reward-dependency and increases sensitivity to evaluation.

  8. Effect of combined treatment with zoledronic acid and propranolol on mechanical strength in an rat model of disuse osteoporosis.

    Science.gov (United States)

    Khajuria, Deepak Kumar; Razdan, Rema; Mahapatra, Debiprosad Roy

    2015-01-01

    A model that uses right hind-limb unloading of rats is used to study the consequences of skeletal unloading during various conditions like space flights and prolonged bed rest in elderly. This study was aimed to investigate the additive effects of antiresorptive agent zoledronic acid (ZOL), alone and in combination with propranolol (PRO) in a rat model of disuse osteoporosis. In the present study, 3-month-old male Wistar rats had their right hind-limb immobilized (RHLI) for 10 weeks to induce osteopenia, then were randomized into four groups: 1- RHLI positive control, 2- RHLI plus ZOL (50 μg/kg, i.v. single dose), 3- RHLI plus PRO (0.1mg/kg, s.c. 5 days per week), 4- RHLI plus PRO (0.1mg/kg, s.c. 5 days per week) plus ZOL (50 μg/kg, i.v. single dose) for another 10 weeks. One group of non-immobilized rats was used as negative control. At the end of treatment, the femurs were removed and tested for bone porosity, bone mechanical properties, and bone dry and ash weight. With respect to improvement in the mechanical strength of the femoral mid-shaft, the combination treatment with ZOL plus PRO was more effective than ZOL or PRO monotherapy. Moreover, combination therapy using ZOL plus PRO was more effective in improving dry bone weight and preserved the cortical bone porosity better than monotherapy using ZOL or PRO in right hind-limb immobilized rats. These data suggest that this combined treatment with ZOL plus PRO should be recommended for the treatment of disuse osteoporosis. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

  9. PET Imaging of Disease Progression and Treatment Effects in the Experimental Autoimmune Encephalomyelitis Rat Model

    NARCIS (Netherlands)

    Faria, Daniele de Paula; Vlaming, Maria L. H.; Copray, Sjef C. V. M.; Tielen, Frans; Anthonijsz, Herma J. A.; Sijbesma, Jurgen W. A.; Buchpiguel, Carlos A.; Dierckx, Rudi A. J. O.; van der Hoorn, Jose W. A.; de Vries, Erik F. J.

    The experimental autoimmune encephalomyelitis model is a model of multiple sclerosis that closely mimics the disease characteristics in humans. The main hallmarks of multiple sclerosis are neuroinflammation (microglia activation, monocyte invasion, and T-cell infiltration) and demyelination. PET

  10. Cervical cancer treatment costs and cost-effectiveness analysis of human papillomavirus vaccination in Vietnam: a PRIME modeling study.

    Science.gov (United States)

    Van Minh, Hoang; My, Nguyen Thi Tuyet; Jit, Mark

    2017-05-15

    Cervical cancer is currently the leading cause of cancer mortality among women in South Vietnam and the second leading cause of cancer mortality in North Vietnam. Human papillomavirus (HPV) vaccination has the potential to substantially decrease this burden. The World Health Organization (WHO) recommends that a cost-effectiveness analysis of HPV vaccination is conducted before nationwide introduction. The Papillomavirus Rapid Interface for Modeling and Economics (PRIME) model was used to evaluate the cost-effectiveness of HPV vaccine introduction. A costing study based on expert panel discussions, interviews and hospital case note reviews was conducted to explore the cost of cervical cancer care. The cost of cervical cancer treatment ranged from US$368 - 11400 depending on the type of hospital and treatment involved. Under Gavi-negotiated prices of US$4.55, HPV vaccination is likely to be very cost-effective with an incremental cost per disability-adjusted life year (DALY) averted in the range US$780 - 1120. However, under list prices for Cervarix and Gardasil in Vietnam, the incremental cost per DALY averted for HPV vaccination can exceed US$8000. HPV vaccine introduction appears to be economically attractive only if Vietnam is able to procure the vaccine at Gavi prices. This highlights the importance of initiating a nationwide vaccination programme while such prices are still available.

  11. Joint distraction in treatment of osteoarthritis (II): effects on cartilage in a canine model

    NARCIS (Netherlands)

    van Valburg, A. A.; van Roermund, P. M.; Marijnissen, A. C.; Wenting, M. J.; Verbout, A. J.; Lafeber, F. P.; Bijlsma, J. W.

    2000-01-01

    From a clinical point of view, joint distraction as a treatment for osteoarthritis (OA) of hip and ankle has been demonstrated to be very promising. Pain, joint mobility and functional ability, the most important factors for a patient with severe OA, all improved. Although radiographic joint space

  12. Different effects of postnatal caffeine treatment on two pentylenetetrazole-induced seizure models persist into adulthood

    Czech Academy of Sciences Publication Activity Database

    Tchekalarova, Jana; Kubová, Hana; Mareš, Pavel

    2013-01-01

    Roč. 65, č. 4 (2013), s. 847-853 ISSN 1734-1140 R&D Projects: GA MŠk(CZ) LC554; GA MZd(CZ) NR9184 Institutional research plan: CEZ:AV0Z50110509 Keywords : caffeine * postnatal treatment * pentylenetetrazole * spike-and-wave episodes Subject RIV: FH - Neurology Impact factor: 2.165, year: 2013

  13. Effects of anti-inflammatory treatments on stroke outcome in animal models

    NARCIS (Netherlands)

    Tiebosch, I.A.C.W.

    2012-01-01

    Background: Stroke is a devastating disease with over 5.5 million yearly casualties worldwide. Acute treatment strategies are limited. The acute inflammatory response following stroke has been demonstrated to be detrimental on stroke outcome, for both ischemic and hemorrhagic stroke subtypes.

  14. Renal effects of long-term ciclosporin A treatment in a large animal model

    DEFF Research Database (Denmark)

    Cibulskyte, Donata; Samsoe Engberg, Anne; Hanefelt Kristensen, Daniel

    2007-01-01

    BACKGROUND: Most experimental studies of chronic ciclosporin A (CsA) nephrotoxicity have been performed in rodents; however, the pig possesses several advantages. The aim of this study was to investigate renal functional and structural changes during CsA treatment with 20 mg/kg/day for 6 months i...

  15. Modeling the Effects of Onsite Wastewater Treatment Systems on Nitrate Loads Using SWAT in an Urban Watershed of Metropolitan Atlanta.

    Science.gov (United States)

    Hoghooghi, Nahal; Radcliffe, David E; Habteselassie, Mussie Y; Jeong, Jaehak

    2017-05-01

    Onsite wastewater treatment systems (OWTSs) can be a source of nitrogen (N) pollution in both surface and ground waters. In metropolitan Atlanta, GA, >26% of homes are on OWTSs. In a previous article, we used the Soil Water Assessment Tool to model the effect of OWTSs on stream flow in the Big Haynes Creek Watershed in metropolitan Atlanta. The objective of this study was to estimate the effect of OWTSs, including failing systems, on nitrate as N (NO-N) load in the same watershed. Big Haynes Creek has a drainage area of 44 km with mainly urban land use (67%), and most of the homes use OWTSs. A USGS gauge station where stream flow was measured daily and NO-N concentrations were measured monthly was used as the outlet. The model was simulated for 12 yr. Overall, the model showed satisfactory daily stream flow and NO-N loads with Nash-Sutcliffe coefficients of 0.62 and 0.58 for the calibration period and 0.67 and 0.33 for the validation period at the outlet of the Big Haynes Watershed. Onsite wastewater treatment systems caused an average increase in NO-N load of 23% at the watershed scale and 29% at the outlet of a subbasin with the highest density of OWTSs. Failing OWTSs were estimated to be 1% of the total systems and did not have a large impact on stream flow or NO-N load. The NO-N load was 74% of the total N load in the watershed, indicating the important effect of OWTSs on stream loads in this urban watershed. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  16. Modeling the cost-effectiveness of ilaprazole versus omeprazole for the treatment of newly diagnosed duodenal ulcer patients in China.

    Science.gov (United States)

    Xuan, J W; Song, R L; Xu, G X; Lu, W Q; Lu, Y J; Liu, Z

    2016-11-01

    To evaluate the cost-effectiveness of 10 mg ilaprazole once-daily vs 20 mg omeprazole once-daily to treat newly-diagnosed duodenal ulcer patients in China. A decision tree model was constructed and the treatment impact was projected up to 1 year. The CYP2C19 polymorphism distribution in the Chinese population, the respective cure rates in the CYP2C19 genotype sub-groups, the impact of Duodenal Ulcer (DU) on utility value and drug-related side-effect data were obtained from the literature. The total costs of medications were calculated to estimate the treatment costs based on current drug retail prices in China. Expert surveys were conducted when published data were not available. Probabilistic sensitivity analysis was performed to gauge the robustness of the results. Ilaprazole, when compared with omeprazole, achieved a better overall clinical efficacy. For the overall population, ilaprazole achieved an incremental cost effectiveness ratio (ICER) of ¥132 056 per QALY gained. This is less than the WHO recommended threshold of 3-times the average GDP per capita in China (2014). Furthermore, sub-group analysis showed that ilaprazole is cost-effective in every province in CYP2C19 hetEM patients and in the most developed provinces in CYP2C19 homEM patients. Probabilistic sensitivity analysis suggests that the results are robust with 97% probability that ilaprozole is considered cost-effective when a threshold of 3-times China's average GDP per capita is considered. This study didn't have the data of ilaprazole combined with Hp eradication therapy. Caution should be taken when extrapolating these findings to DU patients with an Hp eradication therapy. The cost-effectiveness analysis results demonstrated that ilaprazole would be considered a cost-effective therapy, compared with omeprazole, in Chinese DU patients based on the efficacy projections in various CYP2C19 polymorphism types.

  17. The Cost and Cost-Effectiveness of Scaling up Screening and Treatment of Syphilis in Pregnancy: A Model

    Science.gov (United States)

    Kahn, James G.; Jiwani, Aliya; Gomez, Gabriela B.; Hawkes, Sarah J.; Chesson, Harrell W.; Broutet, Nathalie; Kamb, Mary L.; Newman, Lori M.

    2014-01-01

    Background Syphilis in pregnancy imposes a significant global health and economic burden. More than half of cases result in serious adverse events, including infant mortality and infection. The annual global burden from mother-to-child transmission (MTCT) of syphilis is estimated at 3.6 million disability-adjusted life years (DALYs) and $309 million in medical costs. Syphilis screening and treatment is simple, effective, and affordable, yet, worldwide, most pregnant women do not receive these services. We assessed cost-effectiveness of scaling-up syphilis screening and treatment in existing antenatal care (ANC) programs in various programmatic, epidemiologic, and economic contexts. Methods and Findings We modeled the cost, health impact, and cost-effectiveness of expanded syphilis screening and treatment in ANC, compared to current services, for 1,000,000 pregnancies per year over four years. We defined eight generic country scenarios by systematically varying three factors: current maternal syphilis testing and treatment coverage, syphilis prevalence in pregnant women, and the cost of healthcare. We calculated program and net costs, DALYs averted, and net costs per DALY averted over four years in each scenario. Program costs are estimated at $4,142,287 – $8,235,796 per million pregnant women (2010 USD). Net costs, adjusted for averted medical care and current services, range from net savings of $12,261,250 to net costs of $1,736,807. The program averts an estimated 5,754 – 93,484 DALYs, yielding net savings in four scenarios, and a cost per DALY averted of $24 – $111 in the four scenarios with net costs. Results were robust in sensitivity analyses. Conclusions Eliminating MTCT of syphilis through expanded screening and treatment in ANC is likely to be highly cost-effective by WHO-defined thresholds in a wide range of settings. Countries with high prevalence, low current service coverage, and high healthcare cost would benefit most. Future analyses can be

  18. A novel model of lethal Hendra virus infection in African green monkeys and the effectiveness of ribavirin treatment.

    Science.gov (United States)

    Rockx, Barry; Bossart, Katharine N; Feldmann, Friederike; Geisbert, Joan B; Hickey, Andrew C; Brining, Douglas; Callison, Julie; Safronetz, David; Marzi, Andrea; Kercher, Lisa; Long, Dan; Broder, Christopher C; Feldmann, Heinz; Geisbert, Thomas W

    2010-10-01

    The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are emerging zoonotic paramyxoviruses that can cause severe and often lethal neurologic and/or respiratory disease in a wide variety of mammalian hosts, including humans. There are presently no licensed vaccines or treatment options approved for human or veterinarian use. Guinea pigs, hamsters, cats, and ferrets, have been evaluated as animal models of human HeV infection, but studies in nonhuman primates (NHP) have not been reported, and the development and approval of any vaccine or antiviral for human use will likely require efficacy studies in an NHP model. Here, we examined the pathogenesis of HeV in the African green monkey (AGM) following intratracheal inoculation. Exposure of AGMs to HeV produced a uniformly lethal infection, and the observed clinical signs and pathology were highly consistent with HeV-mediated disease seen in humans. Ribavirin has been used to treat patients infected with either HeV or NiV; however, its utility in improving outcome remains, at best, uncertain. We examined the antiviral effect of ribavirin in a cohort of nine AGMs before or after exposure to HeV. Ribavirin treatment delayed disease onset by 1 to 2 days, with no significant benefit for disease progression and outcome. Together our findings introduce a new disease model of acute HeV infection suitable for testing antiviral strategies and also demonstrate that, while ribavirin may have some antiviral activity against the henipaviruses, its use as an effective standalone therapy for HeV infection is questionable.

  19. Effects of Sildenafil Citrate and Heparin Treatments on Placental Cell Morphology in a Murine Model of Pregnancy Loss.

    Science.gov (United States)

    Luna, Rayana Leal; Vasconcelos, Anne Gabrielle; Nunes, Ana Karolina Santana; de Oliveira, Wilma Helena; Barbosa, Karla Patricia de Sousa; Peixoto, Christina Alves

    2016-01-01

    Lipopolysaccharide (LPS) injections during pregnancy are well established as models for pregnancy complications, including fetal growth restriction (FGR), thrombophilia, preterm labor and abortion. Indeed, inflammation, as induced by LPS injection has been described as a pivotal factor in cases of miscarriage related to placental tissue damage. The phosphodiesterase-5 inhibitor sildenafil (Viagra®) is currently used to treat FGR cases in women, while low-molecular weight heparin (Fragmin®) is a standard treatment for recurrent miscarriage (RM). However, the pathways and cellular dynamics involved in RM are not completely understood. The aim of this study was to evaluate the protective effect of sildenafil and dalteparin in a mouse model of LPS-induced abortion. Histopathology, ultrastructural analysis and immunofluorescence for P-selectin were studied in two different placental cell types: trophoblast cells and labyrinth endothelial cells. Treatment with sildenafil either alone or in combination with heparin showed the best response against LPS-induced injury during pregnancy. In conclusion, our results support the use of these drugs as future therapeutic agents that may protect the placenta against inflammatory injury in RM events. Analyses of the ultrastructure and placental immunophysiology are important to understand the mechanism underlying RM. These findings may spark future studies and aid in the development of new therapies in cases of RM. © 2016 S. Karger AG, Basel.

  20. Effects of pulsatile L-DOPA treatment in the double lesion rat model of striatonigral degeneration (multiple system atrophy).

    Science.gov (United States)

    Stefanova, N; Lundblad, M; Tison, F; Poewe, W; Cenci, M A; Wenning, G K

    2004-04-01

    We examined the role of a striatal lesion in the development of L-DOPA-induced abnormal involuntary movements (AIMs) using the double lesion rat model of striatonigral degeneration (SND), the underlying neuropathological substrate of parkinsonism associated with multiple system atrophy (MSA-P), in comparison to a Parkinson's disease (PD) rat model. L-DOPA administration reliably induced AIMs in SND and PD rats in a dose-dependent fashion. AIMs occurred significantly earlier in SND compared to PD rats. There was a mild, but significant, transient increase of orolingual AIMs during the first week of low-dose L-DOPA treatment in SND. Whereas L-DOPA significantly improved contralateral forelimb akinesia in PD rats, there was no beneficial effect in SND rats. Striatal FosB/Delta FosB up-regulation in SND and PD rats correlated with the severity of L-DOPA-induced dyskinesias. Pulsatile L-DOPA administration in the double lesion SND rat model replicates salient features of the human disease MSA-P, including loss of the anti-akinetic L-DOPA response and induction of dyskinesias with transient orolingual predominance.

  1. Atorvastatin treatment is effective when used in combination with mefloquine in an experimental cerebral malaria murine model

    Directory of Open Access Journals (Sweden)

    Souraud Jean-Baptiste

    2012-01-01

    Full Text Available Abstract Background One of the major complications of Plasmodium falciparum infection is cerebral malaria (CM, which causes one million deaths worldwide each year, results in long-term neurological sequelae and the treatment for which is only partially effective. Statins are recognized to have an immunomodulatory action, attenuate sepsis and have a neuroprotective effect. Atorvastatin (AVA has shown in vitro anti-malarial activity and has improved the activity of mefloquine (MQ and quinine. Methods The efficiency of 40 mg/kg intraperitoneal AVA, alone or in association with MQ, was assessed in an experimental Plasmodium berghei ANKA rodent parasite model of CM and performed according to different therapeutic schemes. The effects on experimental CM were assessed through the evaluation of brain histopathological changes and neuronal apoptosis by TUNEL staining. Results AVA alone in the therapeutic scheme show no effect on survival, but the prophylactic scheme employing AVA associated with MQ, rather than MQ alone, led to a significant delay in mouse death and had an effect on the onset of CM symptoms and on the level of parasitaemia. Histopathological findings show a correlation between brain lesions and CM onset. A neuronal anti-apoptotic effect of AVA in the AVA + MQ combination was not shown. Conclusions The combination of AVA and MQ therapy led to a significant delay in mouse mortality. There were differences in the incidence, time to cerebral malaria and the level of parasitaemia when the drug combination was administered to mice. When used in combination with MQ, AVA had a relevant effect on the in vivo growth inhibition and clinical outcome of P. berghei ANKA-infected mice.

  2. Modeling Hepatitis C treatment policy.

    Energy Technology Data Exchange (ETDEWEB)

    Kuypers, Marshall A.; Lambert, Gregory Joseph; Moore, Thomas W.; Glass, Robert John,; Finley, Patrick D.; Ross, David; Chartier, Maggie

    2013-09-01

    Chronic infection with Hepatitis C virus (HCV) results in cirrhosis, liver cancer and death. As the nations largest provider of care for HCV, US Veterans Health Administration (VHA) invests extensive resources in the diagnosis and treatment of the disease. This report documents modeling and analysis of HCV treatment dynamics performed for the VHA aimed at improving service delivery efficiency. System dynamics modeling of disease treatment demonstrated the benefits of early detection and the role of comorbidities in disease progress and patient mortality. Preliminary modeling showed that adherence to rigorous treatment protocols is a primary determinant of treatment success. In depth meta-analysis revealed correlations of adherence and various psycho-social factors. This initial meta-analysis indicates areas where substantial improvement in patient outcomes can potentially result from VA programs which incorporate these factors into their design.

  3. Effect of Cordyceps sinensis on the Treatment of Experimental Autoimmune Encephalomyelitis: A Pilot Study on Mice Model

    Directory of Open Access Journals (Sweden)

    Shan-Shan Zhong

    2017-01-01

    Conclusions: Our preliminary study demonstrated that CS efficiently alleviated EAE severity and EAE-related pathology damage and decreased the number of Th1s in the periphery, indicating its effectiveness in the treatment of murine EAE. Thus, our findings strongly support the therapeutic potential of this agent as a new traditional Chinese medicine approach in MS treatment.

  4. Comparison of acute effect of systemic versus intravitreal infliximab treatment in an experimental model of endotoxin-induced uveitis.

    Science.gov (United States)

    Yuksel, Erdem; Hasanreisoglu, Berati; Yuksel, Nilay; Yilmaz, Guldal; Ercin, Ugur; Bilgihan, Ayse

    2014-02-01

    In this study, we investigated the efficacy of systemic and intravitreal (IV) infliximab treatments and compared these 2 different treatment modalities in an experimental model of endotoxin-induced uveitis (EIU). Twenty-four white New Zealand rabbits were equally divided into 4 groups. Group 1 received IV injection of lipopolysaccharide (LPS), group 2 received IV injections of LPS and saline, group 3 received IV LPS and IV 2 mg/0.1 cc infliximab, and group 4 received IV LPS and 5 mg/kg intravenous infliximab. Inflammation was determined with objective and subjective tests. The subjective test was clinical determination of uveitis, the objective tests were determination of protein concentrations and tumor necrosis factor alpha (TNF-α) levels and histopathology. Clinical examination score was lower in group 3 and group 4 (4±0.6 and 3.5±1.6, respectively) when compared with group 1 (P=0.02; P=0.04, respectively) and group 2. In group 3 and 4, the aqueous and vitreous protein and TNF-α concentration measured significantly lower than group 1 and 2. In histopathologic examination, there was no statistically significant difference between group 1, 2, and 3 (3.5±0.5, 3.6±0.5, 3.6±0.5, respectively). However, the lowest histopathologic inflammation was determined in group 4 (2.5±0.5) (compared with group 1 and group 3, respectively; P=0.03; P=0.014). In a rabbit model of experimental EIU, intravenous administration of infliximab was more effective than IV route in an acute period.

  5. Hippocampal Proteome of Rats Subjected to the Li-Pilocarpine Epilepsy Model and the Effect of Carisbamate Treatment

    Directory of Open Access Journals (Sweden)

    José Eduardo Marques-Carneiro

    2017-07-01

    Full Text Available In adult rats, the administration of lithium–pilocarpine (LiPilo reproduces most clinical and neuropathological features of human temporal lobe epilepsy (TLE. Carisbamate (CRS possesses the property of modifying epileptogenesis in this model. Indeed, about 50% of rats subjected to LiPilo status epilepticus (SE develop non-convulsive seizures (NCS instead of motor seizures when treated with CRS. However, the mechanisms underlying these effects remain unknown. The aim of this study was to perform a proteomic analysis in the hippocampus of rats receiving LiPilo and developing motor seizures or NCS following CRS treatment. Fifteen adult male Sprague–Dawley rats were used. SE was induced by LiPilo injection. CRS treatment was initiated at 1 h and 9 h after SE onset and maintained for 7 days, twice daily. Four groups were studied after video-EEG control of the occurrence of motor seizures: a control group receiving saline (CT n = 3 and three groups that underwent SE: rats treated with diazepam (DZP n = 4, rats treated with CRS displaying NCS (CRS-NCS n = 4 or motor seizures (CRS-TLE n = 4. Proteomic analysis was conducted by 2D-SDS-PAGE. Twenty-four proteins were found altered. In the CRS-NCS group, proteins related to glycolysis and ATP synthesis were down-regulated while proteins associated with pyruvate catabolism were up-regulated. Moreover, among the other proteins differentially expressed, we found proteins related to inflammatory processes, protein folding, tissue regeneration, response to oxidative stress, gene expression, biogenesis of synaptic vesicles, signal transduction, axonal transport, microtubule formation, cell survival, and neuronal plasticity. Our results suggest a global reduction of glycolysis and cellular energy production that might affect brain excitability. In addition, CRS seems to modulate proteins related to many other pathways that could significantly participate in the epileptogenesis-modifying effect observed.

  6. Modeling the effects of different fuel treatment mosaics on wildfire spread and behavior in a Mediterranean agro-pastoral area.

    Science.gov (United States)

    Salis, Michele; Del Giudice, Liliana; Arca, Bachisio; Ager, Alan A; Alcasena-Urdiroz, Fermin; Lozano, Olga; Bacciu, Valentina; Spano, Donatella; Duce, Pierpaolo

    2018-02-20

    Wildfire spread and behavior can be limited by fuel treatments, even if their effects can vary according to a number of factors including type, intensity, extension, and spatial arrangement. In this work, we simulated the response of key wildfire exposure metrics to variations in the percentage of treated area, treatment unit size, and spatial arrangement of fuel treatments under different wind intensities. The study was carried out in a fire-prone 625 km 2 agro-pastoral area mostly covered by herbaceous fuels, and located in Northern Sardinia, Italy. We constrained the selection of fuel treatment units to areas covered by specific herbaceous land use classes and low terrain slope (fuel treatment units for all treatment alternatives. The fuel treatment alternatives were designed create diverse mosaics of disconnected treatment units with different sizes (0.5-10 ha, LOW strategy; 10-25 ha, MED strategy; 25-50 ha, LAR strategy); in addition, treatment units in a 100-m buffer around the road network (ROAD strategy) were tested. We assessed pre- and post-treatment wildfire behavior by the Minimum Travel Time (MTT) fire spread algorithm. The simulations replicated a set of southwestern wind speed scenarios (16, 24 and 32 km h -1 ) and the driest fuel moisture conditions observed in the study area. Our results showed that fuel treatments implemented near the existing road network were significantly more efficient than the other alternatives, and this difference was amplified at the highest wind speed. Moreover, the largest treatment unit sizes were the most effective in containing wildfire growth. As expected, increasing the percentage of the landscape treated and reducing wind speed lowered fire exposure profiles for all fuel treatment alternatives, and this was observed at both the landscape scale and for highly valued resources. The methodology presented in this study can support the design and optimization of fuel management programs and policies in agro

  7. Patient perspectives on breast cancer treatment side effects and the prospective surveillance model for physical rehabilitation for women with breast cancer.

    Science.gov (United States)

    Binkley, Jill M; Harris, Susan R; Levangie, Pamela K; Pearl, Marcia; Guglielmino, Janine; Kraus, Valerie; Rowden, Diana

    2012-04-15

    Women's experience of breast cancer is complex, affecting all aspects of life during and after treatment. Patients' perspectives about common impairments and functional limitations secondary to breast cancer treatment, including upper extremity motion restriction, lymphedema, fatigue, weight gain, pain, and chemotherapy-induced peripheral neuropathy, are addressed. Women often report being uninformed regarding these side effects and surprised that they do not always disappear after treatment, but remain part of their lives. Breast cancer patients express strong, unmet needs for education, information, and intervention for these side effects. Evidence suggests that rehabilitation and exercise are effective in preventing and managing many physical side effects of breast cancer treatment. Nevertheless, few women are referred to rehabilitation during or after treatment, and fewer receive baseline assessments of impairment and function to facilitate early detection of impairment and functional limitations. The prospective surveillance model of rehabilitation will serve the needs of women with breast cancer by providing education and information about treatment side effects, reducing the incidence and burden of side effects through early identification and treatment, and enhancing access to timely rehabilitation. Integration of exercise as a component of the model benefits patients at every phase of survivorship, by addressing individual concerns about exercise during and after treatment and highlighting the important contribution of exercise to overall health and survival. The prospective surveillance model of rehabilitation can meet the evident and often expressed needs of survivors for information, guidance, and intervention--thus addressing, and potentially improving, overall quality of life for individuals diagnosed with and treated for breast cancer. Copyright © 2012 American Cancer Society.

  8. Iatrogenic Effects of Group Treatment on Adolescents with Conduct and Substance Use Problems: A Review of the Literature and a Presentation of a Model

    OpenAIRE

    Macgowan, Mark J.; Wagner, Eric F.

    2005-01-01

    Group therapy is the most popular approach in the treatment of adolescent substance use problems. Recently, concerns have mounted about possible iatrogenic effects of group therapy based on studies on adolescents with conduct disorder. This paper reviews three possible contributors to response to group treatment among adolescents, and proposes a model of the relations among these variables, specifically in regard to how they independently and interactively contribute to outcomes among youth w...

  9. Economic impact of COPD: Empirical and model-based studies on the cost-effectiveness of treatment options

    NARCIS (Netherlands)

    M. Hoogendoorn (Martine)

    2011-01-01

    textabstractChronic obstructive pulmonary disease (COPD) is a disease characterized by progressive airflow limitation that is not fully reversible and is accompanied by extra-pulmonary effects that can lead to important co-morbidities. The treatment of COPD is associated with substantial

  10. A Danish cost-effectiveness model of escitalopram in comparison with citalopram and venlafaxine as first-line treatments for major depressive disorder in primary care

    DEFF Research Database (Denmark)

    Sørensen, Jan; Stage, Kurt B; Damsbo, Niels

    2007-01-01

    The objective of this study was to model the cost-effectiveness of escitalopram in comparison with generic citalopram and venlafaxine in primary care treatment of major depressive disorder (baseline scores 22-40 on the Montgomery-Asberg Depression Rating Scale, MADRS) in Denmark. A three......, ad-hoc survey and expert opinion. Main outcome measures were remission defined as MADRS treatment costs. Analyses were conducted from healthcare system and societal perspectives. The human capital approach was used to estimate societal cost of lost productivity. Costs were reported......-path decision analytic model with a 6-month horizon was used. All patients started at the primary care path and were referred to outpatient or inpatient secondary care in the case of insufficient response to treatment. Model inputs included drug-specific probabilities derived from systematic literature review...

  11. Including the effects of filamentous bulking sludge during the simulation of wastewater treatment plants using a risk assessment model

    DEFF Research Database (Denmark)

    Flores Alsina, Xavier; Comas, J.; Rodriquez-Roda, I.

    2009-01-01

    pollution removal efficiency is observed. Also, a scenario analysis is conducted to examine i) the influence of sludge retention time (SRT), the external recirculation flow rate (Qr) and the air flow rate in the bioreactor (modelled as kLa) as factors promoting bulking sludge, and ii) the effect...

  12. Is bronchial thermoplasty cost-effective as treatment for problematic asthma patients? Singapore's perspective on a global model.

    Science.gov (United States)

    Nguyen, Hai V; Bose, Saideep; Mital, Shweta; Yii, Anthony Chau Ang; Ang, Shin Yuh; Lam, Sean Shao Wei; Anantham, Devanand; Finkelstein, Eric; Koh, Mariko Siyue

    2017-08-01

    Bronchial thermoplasty (BT) has been shown to be effective at reducing asthma exacerbations and improving asthma control for patients with severe persistent asthma but it is also expensive. Evidence on its cost-effectiveness is limited and inconclusive. In this study, we aim to evaluate the incremental cost-effectiveness of BT combined with optimized asthma therapy (BT-OAT) relative to OAT for difficult-to-treat and severe asthma patients in Singapore, and to provide a general framework for determining BT's cost-effectiveness in other healthcare settings. We developed a Markov model to estimate the costs and quality-adjusted life years (QALYs) gained with BT-OAT versus OAT from the societal and health system perspectives. The model was populated using Singapore-specific costs and transition probabilities and utilities from the literature. Sensitivity analyses were conducted to identify the main factors determining cost-effectiveness of BT-OAT. BT-OAT is not cost-effective relative to OAT over a 5-year time horizon with an incremental cost-effectiveness ratio (ICER) of $US138 889 per QALY from the societal perspective and $US139 041 per QALY from the health system perspective. The cost-effectiveness of BT-OAT largely depends on a combination of the cost of the BT procedure and the cost of asthma-related hospitalizations and emergency department (ED) visits. Based on established thresholds for cost-effectiveness, BT-OAT is not cost-effective compared with OAT in Singapore. Given its current clinical efficacy, BT-OAT is most likely to be cost-effective in a setting where the cost of BT procedure is low and costs of hospitalization and ED visits are high. © 2017 Asian Pacific Society of Respirology.

  13. New treatment models for compulsive disorders.

    Science.gov (United States)

    Grant, Jon E; Fineberg, Naomi; van Ameringen, Michael; Cath, Danielle; Visser, Henny; Carmi, Lior; Pallanti, Stefano; Hollander, Eric; van Balkom, Anton J L M

    2016-05-01

    Obsessive compulsive disorder (OCD) as well as related disorders such as body dysmorphic disorder, tic disorder, and trichotillomania are all common and often debilitating. Although treatments are available, more effective approaches to these problems are needed. Thus this review article presents what is currently known about OCD and related disorders and suggests that understanding OCD more broadly as a compulsive disorder may allow for more effective treatment options. Toward that goal, the review presents new models of psychopharmacology and psychotherapy, as well as new brain stimulation strategies. Treatment advances, grounded in the neuroscience, have promise in advancing treatment response for OCD as well as other disorders of compulsivity. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  14. The cost-effectiveness of different feeding patterns combined with prompt treatments for preventing mother-to-child HIV transmission in South Africa: estimates from simulation modeling.

    Directory of Open Access Journals (Sweden)

    Wenhua Yu

    Full Text Available OBJECTIVES: Based on the important changes in South Africa since 2009 and the Antiretroviral Treatment Guideline 2013 recommendations, we explored the cost-effectiveness of different strategy combinations according to the South African HIV-infected mothers' prompt treatments and different feeding patterns. STUDY DESIGN: A decision analytic model was applied to simulate cohorts of 10,000 HIV-infected pregnant women to compare the cost-effectiveness of two different HIV strategy combinations: (1 Women were tested and treated promptly at any time during pregnancy (Promptly treated cohort. (2 Women did not get testing or treatment until after delivery and appropriate standard treatments were offered as a remedy (Remedy cohort. Replacement feeding or exclusive breastfeeding was assigned in both strategies. Outcome measures included the number of infant HIV cases averted, the cost per infant HIV case averted, and the cost per life year (LY saved from the interventions. One-way and multivariate sensitivity analyses were performed to estimate the uncertainty ranges of all outcomes. RESULTS: The remedy strategy does not particularly cost-effective. Compared with the untreated baseline cohort which leads to 1127 infected infants, 698 (61.93% and 110 (9.76% of pediatric HIV cases are averted in the promptly treated cohort and remedy cohort respectively, with incremental cost-effectiveness of $68.51 and $118.33 per LY, respectively. With or without the antenatal testing and treatments, breastfeeding is less cost-effective ($193.26 per LY than replacement feeding ($134.88 per LY, without considering the impact of willingness to pay. CONCLUSION: Compared with the prompt treatments, remedy in labor or during the postnatal period is less cost-effective. Antenatal HIV testing and prompt treatments and avoiding breastfeeding are the best strategies. Although encouraging mothers to practice replacement feeding in South Africa is far from easy and the advantages of

  15. Assessing ballast treatment standards for effect on rate of establishment using a stochastic model of the green crab

    Directory of Open Access Journals (Sweden)

    Cynthia Cooper

    2012-03-01

    Full Text Available This paper describes a stochastic model used to characterize the probability/risk of NIS establishment from ships' ballast water discharges. Establishment is defined as the existence of a sufficient number of individuals of a species to provide for a sustained population of the organism. The inherent variability in population dynamics of organisms in their native or established environments is generally difficult to quantify. Muchqualitative information is known about organism life cycles and biotic and abiotic environmental pressures on the population, but generally little quantitative data exist to develop a mechanistic model of populations in such complex environments. Moreover, there is little quantitative data to characterize the stochastic fluctuations of population size over time even without accounting for systematic responses to biotic and abiotic pressures. This research applies an approach using life-stage density and fecundity measures reported in research to determine a stochastic model of an organism's population dynamics. The model is illustrated withdata from research studies on the green crab that span a range of habitats of the established organism and were collected over some years to represent a range of time-varying biotic and abiotic conditions that are expected to exist in many receiving environments. This model is applied to introductions of NIS at the IMO D-2 and the U.S. ballast water discharge standard levels designated as Phase Two in the United States Coast Guard'sNotice of Proposed Rulemaking. Under a representative range of ballast volumes discharged at U.S. ports, the average rate of establishment of green crabs for ballast waters treated to the IMO-D2 concentration standard (less than 10 organisms/m3 is predicted to be reduced to about a third the average rate from untreated ballast water discharge. The longevity of populations from the untreated ballast water discharges is expected to be reducedby about 90% by

  16. A novel model to study neonatal Escherichia coli sepsis and the effect of treatment on the human immune system using humanized mice.

    Science.gov (United States)

    Schlieckau, Florian; Schulz, Daniela; Fill Malfertheiner, Sara; Entleutner, Kathrin; Seelbach-Goebel, Birgit; Ernst, Wolfgang

    2018-04-19

    Neonatal sepsis is a serious threat especially for preterm infants. As existing in vitro and in vivo models have limitations, we generated a novel neonatal sepsis model using humanized mice and tested the effect of Betamethasone and Indomethacin which are used in the clinic in case of premature birth. Humanized mice were infected with Escherichia coli (E. coli). Subsequently, the effect of the infection itself, and treatment with Betamethasone and Indomethacin on survival, recovery, bacterial burden, leukocyte populations, and cytokine production, was analyzed. The human immune system in the animals responded with leukocyte trafficking to the site of infection and granulopoiesis in the bone marrow. Treatment with Indomethacin had no pronounced effect on the immune system or bacterial burden. Betamethasone induced a decline of splenocytes. The human immune system in humanized mice responds to the infection, making them a suitable model to study neonatal E. coli sepsis and the immune response of the neonatal immune system. Treatment with Betamethasone could have potential negative long-term effects for the immune system of the child. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Effects of Extinction Treatments on the Reduction of Conditioned Responding and Conditioned Hyperarousal in a Rabbit Model of Posttraumatic Stress Disorder (PTSD)

    Science.gov (United States)

    Burhans, Lauren B.; Smith-Bell, Carrie A.; Schreurs, Bernard G.

    2015-01-01

    We have previously characterized a model of posttraumatic stress disorder (PTSD), based on classical conditioning of the rabbit nictitating membrane response (NMR), that focuses on 2 key PTSD-like features: conditioned responses to trauma-associated cues and hyperarousal. In addition to the development of conditioned NMRs (CRs) to a tone conditioned stimulus (CS) associated with a periorbital shock unconditioned stimulus (US), we have observed that rabbits also exhibit a conditioning-specific reflex modification (CRM) of the NMR that manifests as an exaggerated and more complex reflexive NMR to presentations of the US by itself, particularly to intensities that elicited little response prior to conditioning. Previous work has demonstrated that unpaired presentations of the CS and US are successful at extinguishing CRs and CRM simultaneously, even when a significantly weakened version of the US is utilized. In the current study, additional extinction treatments were tested, including continued pairings of the CS with a weakened US and exposure to the training context alone, and these treatments were contrasted with the effects of unpaired extinction with a weakened US and remaining in home cages with no further treatment. Results showed that continued pairings only slightly decreased CRs and CRM, while context exposure had no effect on CRs and marginal effects on reducing CRM. Unpaired extinction was still the most effective treatment for reducing both. Findings are discussed in terms of applications to cognitive–behavioral therapies for treatment of PTSD, such as incorporating mild, innately stressful stimuli into virtual reality therapy. PMID:26348715

  18. The effect of antioxidant treatment on blood lactate and pyruvate concentrations in a rabbit model of obesity

    Directory of Open Access Journals (Sweden)

    N. Grigorova

    2017-03-01

    Full Text Available In the current study, the impact of dietary antioxidant supplementation on fasting blood lactate and pyruvate concentrations in a rabbit model of obesity was investigated. A total of 26 rabbits were randomly divided into 3 groups: castrated and obese animals (CO, n=7; castrated, obese and treated with antioxidants (Immunoprotect, n=7, CIm and non-castrated, non-treated controls (NC, n=12. At the end of the 2-month treatment period blood lactate concentration, lactate to pyruvate and lactate to glucose ratio in CIm were significantly (P<0.05 lower than in NC and tended to be lower than in CO. No group differences in pyruvate and glucose concentrations were found. There was a significant negative (r =–0.53; P<0.05 correlation between lactate and glucose concentrations. On the other hand, lactate was correlated significantly positively with pyruvate (r=0.72; P<0.01, lactate to pyruvate ratio (r=0.94; P<0.001, lactate to glucose ratio (r=0.75; P<0.001 and pyruvate to glucose ratio (r=0.81; P<0.001. In conclusion, the decrease of blood lactate concentration in antioxi-dant treated rabbits could be considered as a mechanism for improvement of skeletal muscle insulin sensitivity. In addition, antioxidant treatment could be used as an alternative tool to counteract lactic acidosis in obesity and diabetes.

  19. Comparing the effects of fluticasone, anti-IgE and anti-TNF treatments in a chronic asthma model.

    Science.gov (United States)

    Ozkars, M Y; Keskin, O; Tokur, M; Ulasli, M; Gogebakan, B; Ciralik, H; Kucukosmanoglu, E; Demirel, C; Oztuzcu, S; Kahraman, H

    2017-11-27

    Corticosteroids are used in the treatment of asthma. The aim of this study was to determine the efficacy of anti-IgE and anti-TNF alpha as asthma treatments. A mouse model of chronic asthma was developed. The fluticasone group was exposed to fluticasone and the anti-IgE and anti-TNF groups were administered anti-IgE or anti-TNF. IL-4, and IgE levels were measured, and histological analysis, pathological analysis and miRNA-126, miRNA-133a analyses were applied. The cell concentration in the BAL fluid decreased in all the treatment groups. The rate of perivascular and peribronchial cell infiltration decreased in the lung in the high-dose anti-IgE and anti-TNF groups. Smooth muscle thickness decreased in the lung tissue in the low-dose anti-IgE and anti-TNF groups. Bronchial wall thickness decreased in the lung tissue in the fluticasone+anti-IgE group. The IL-4 level in BAL fluid decreased in the high-dose anti-IgE, fluticasone+anti-IgE and anti-TNF groups. IgE levels increased in the BAL fluid in the high-dose anti-IgE and anti-TNF groups. The lymphocyte level increased in the BAL fluid in the high-dose anti-IgE group. The macrophage level decreased in the BAL fluid in the anti-TNF group. The relative expression of miRNA-126 increased in all groups. The relative expression of miRNA-133a decreased in the placebo and fluticasone groups. The relative expression of miRNA-133a increased in the low-dose anti-IgE, high-dose anti-IgE, fluticasone+anti-IgE and anti-TNF groups. The results showed that anti-IgE is successful as a treatment. Fluticasone+anti-IgE and anti-TNF were seen to be superior to other therapeutic modalities when used for prophylaxis. Copyright © 2017 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

  20. The Effect of Electromagnetic Field Treatment on Recovery from Ischemic Stroke in a Rat Stroke Model: Clinical, Imaging, and Pathological Findings

    Directory of Open Access Journals (Sweden)

    Y. Segal

    2016-01-01

    Full Text Available Stroke is a leading cause of death and disability. Effects of stroke include significant deficits in sensory-motor skills and cognitive abilities. At present, there are limited effective interventions for postacute stroke patients. In this preliminary research we studied a new noninvasive, very low intensity, low frequency, electromagnetic field treatment (VLIFE, targeting a neural network, on an in vivo stroke rat model. Eighteen rats were divided into three groups: sham (M1 and two treatment groups which were exposed to VLIFE treatment for 4 weeks, one using theta waves (M2 and another using beta waves (M3; all groups were followed up for an additional month. Results indicate that the M2 and M3 treated groups showed recovery of sensorimotor functional deficits, as demonstrated by Modified Neurological Severity Score and forelimb placement tests. Brain MRI imaging results show a decrease in perilesional edema and lateral ventricle widening in the treated groups. Fiber tracts’ imaging, following VLIFE treatment, showed a higher white matter integrity compared to control. Histological findings support neural regeneration processes. Our data suggest that VLIFE treatment, targeting a specific functional neural network by frequency rather than location, promotes neuronal plasticity after stroke and, as a result, improves clinical recovery. Further studies will investigate the full potential of the treatment.

  1. Fatty acids, mercury, and methylmercury bioaccessibility in salmon (Salmo salar) using an in vitro model: Effect of culinary treatment.

    Science.gov (United States)

    Costa, Sara; Afonso, Cláudia; Cardoso, Carlos; Batista, Irineu; Chaveiro, Nádia; Nunes, Maria Leonor; Bandarra, Narcisa Maria

    2015-10-15

    The effect of culinary treatments on the fatty acid profile, mercury (Hg), and methylmercury (MeHg) levels of salmon was studied. The bioaccessibility of fatty acids, Hg, and MeHg in raw and grilled salmon was determined. The most intense thermal treatment (grilling) did not alter the relative fatty acid (FA) profile. There were bioaccessibility differences between FAs. To the authors' knowledge, for the first time, higher bioaccessibility of the long-chain FAs than the short- and medium-chain FAs was measured. Chemical interaction phenomena seemed to play a role. On the other hand, higher levels of unsaturation decreased bioaccessibility. Two main alternative hypotheses were put forward, either lower polarity led to higher incorporation of FAs with longer hydrophobic aliphatic chain and lower number of double bonds in the emulsion present in the bioaccessible fraction or enzymatic selectivity preferentially hydrolyzed some FAs on the basis of their structure or position in the triacylglycerol molecule. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Multivariable modelling for meta-epidemiological assessment of the association between trial quality and treatment effects estimated in randomized clinical trials

    DEFF Research Database (Denmark)

    Siersma, V; Als-Nielsen, B; Chen, Weikeng

    2007-01-01

    Methodological deficiencies are known to affect the results of randomized trials. There are several components of trial quality, which, when inadequately attended to, may bias the treatment effect under study. The extent of this bias, so far only vaguely known, is currently being investigated....... Therefore, a stable multivariable method that allows for heterogeneity is needed for assessing the 'bias coefficients'. We present two general statistical models for analysis of a study of 523 randomized trials from 48 meta-analyses in a random sample of Cochrane reviews: a logistic regression model uses...

  3. Dynamic treatment selection and modification for personalised blood pressure therapy using a Markov decision process model: a cost-effectiveness analysis.

    Science.gov (United States)

    Choi, Sung Eun; Brandeau, Margaret L; Basu, Sanjay

    2017-11-15

    Personalised medicine seeks to select and modify treatments based on individual patient characteristics and preferences. We sought to develop an automated strategy to select and modify blood pressure treatments, incorporating the likelihood that patients with different characteristics would benefit from different types of medications and dosages and the potential severity and impact of different side effects among patients with different characteristics. We developed a Markov decision process (MDP) model to incorporate meta-analytic data and estimate the optimal treatment for maximising discounted lifetime quality-adjusted life-years (QALYs) based on individual patient characteristics, incorporating medication adjustment choices when a patient incurs side effects. We compared the MDP to current US blood pressure treatment guidelines (the Eighth Joint National Committee, JNC8) and a variant of current guidelines that incorporates results of a major recent trial of intensive treatment (Intensive JNC8). We used a microsimulation model of patient demographics, cardiovascular disease risk factors and side effect probabilities, sampling from the National Health and Nutrition Examination Survey (2003-2014), to compare the expected population outcomes from adopting the MDP versus guideline-based strategies. Costs and QALYs for the MDP-based treatment (MDPT), JNC8 and Intensive JNC8 strategies. Compared with the JNC8 guideline, the MDPT strategy would be cost-saving from a societal perspective with discounted savings of US$1187 per capita (95% CI 1178 to 1209) and an estimated discounted gain of 0.06 QALYs per capita (95% CI 0.04 to 0.08) among the US adult population. QALY gains would largely accrue from reductions in severe side effects associated with higher treatment doses later in life. The Intensive JNC8 strategy was dominated by the MDPT strategy. An MDP-based approach can aid decision-making by incorporating meta-analytic evidence to personalise blood pressure

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

    Science.gov (United States)

    Bustillo-Lecompte, Ciro Fernando; Mehrvar, Mehrab

    2016-11-01

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

  5. Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain

    DEFF Research Database (Denmark)

    Hald, Andreas; Ding, Ming; Egerod, Kristoffer Lihme

    2008-01-01

    Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment with can......Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment...... with cannabinoid agonists. However, the use of cannabinoid agonists in humans may be hampered by CNS related side effects and development of tolerance. In the present study, we investigated the effect of repeated low dose administration of the synthetic cannabinoid agonist WIN 55,212-2 on bone cancer pain...... and neuropathic pain in mice. In addition, we investigated the development of CNS related side effects and tolerance. We found that 0.5 mg/kg/day for 18 days reduced pain related behavior and expression of spinal glial fibrillary acidic protein in the bone cancer pain model but not in the neuropathic pain model...

  6. A teacher-consultation approach to social skills training for pre-kindergarten children: treatment model and short-term outcome effects.

    Science.gov (United States)

    Han, Susan S; Catron, Thomas; Weiss, Bahr; Marciel, Kristen K

    2005-12-01

    This study evaluated the post-treatment outcome effects of a classroom-based social skills program for pre-kindergarten children, using a teacher-consultation model. The pre-K RECAP (Reaching Educators, Children, and Parents) program is a semi-structured, cognitive-behavioral skills training program that provides teachers with in-classroom consultation on program implementation and classroom-wide behavior management. Data on children's social skills and behavior problems were collected from parents and teachers at pre- and post-treatment, for 149 children aged 4-5 years (of whom 56% were girls). Significant treatment effects were found for teacher but not parent reports, with treatment group children improving significantly more than comparison group children in their teacher-rated social skills and internalizing and externalizing problems. These results provide some preliminary support for the efficacy of the program on children's social skills and behavior problems, and for a teacher-consultation model for training teachers to implement school-based mental health programs.

  7. Atorvastatin treatment improves effects of implanted mesenchymal stem cells: meta-analysis of animal models with acute myocardial infarction.

    Science.gov (United States)

    Dai, Guo; Xu, Qing; Luo, Rong; Gao, Jianfang; Chen, Hui; Deng, Yun; Li, Yongqing; Wang, Yuequn; Yuan, Wuzhou; Wu, Xiushan

    2015-12-14

    Previous studies reported that Atorvastatin (ATOR) can improve the efficacy of Mesenchymal stem cells (MSCs) transplantation after acute myocardial infarction (AMI). However, the results of those studies were inconsistent. To clarify the beneficial effects of atorvastatin added to the cell therapy with MSCs in animal model of acute myocardial infarction (AMI), we performed a systematic review and meta-analysis of case-control studies. Searches were performed using the PubMed database, the Excerpta Medica Database (Embase), the Science Citation Index, the China National Knowledge Information database, the Wanfang database, and the Chinese Scientific and Technological Journal Database (VIP database). The search term included "Atorvastatin (or Ator)", "Mesenchymal Stem Cells (or Mesenchymal Stem Cell or MSC or MSCs)" and "Acute Myocardial Infarction (or Myocardial Infarction or AMI or MI)". The endpoints were the left ventricular ejection fraction (LVEF) in animal model with AMI. In total, 5 studies were included in the meta-analysis. Pooled analysis indicated a significant LVEF difference at 4 weeks follow-up between MSCs + ATOR combine group and MSCs alone group (95 % CI, 9.09-13.62 %; P 0.05) and inconsistency (I(2): 22 %). Atorvastatin can enhance the existing effects of MSCs transplantation, and this combinational therapy is a superior cell/pharmacological therapeutic approach that merits future preclinical and clinical studies.

  8. [Effects in the adherence treatment and psychological adjustment after the disclosure of HIV/AIDS diagnosis with the "DIRE" clinical model in Colombian children under 17].

    Science.gov (United States)

    Trejos, Ana María; Reyes, Lizeth; Bahamon, Marly Johana; Alarcón, Yolima; Gaviria, Gladys

    2015-08-01

    A study in five Colombian cities in 2006, confirms the findings of other international studies: the majority of HIV-positive children not know their diagnosis, caregivers are reluctant to give this information because they believe that the news will cause emotional distress to the child becoming primary purpose of this study to validate a model of revelation. We implemented a clinical model, referred to as: "DIRE" that hypothetically had normalizing effects on psychological adjustment and adherence to antiretroviral treatment of HIV seropositive children, using a quasi-experimental design. Test were administered (questionnaire to assess patterns of disclosure and non-disclosure of the diagnosis of VIH/SIDA on children in health professionals and participants caregivers, Family Apgar, EuroQol EQ- 5D, MOS Social Support Survey Questionnaire Information treatment for VIH/SIDA and child Symptom Checklist CBCL/6-18 adapted to Latinos) before and after implementation of the model to 31 children (n: 31), 30 caregivers (n: 30) and 41 health professionals. Data processing was performed using the Statistical Package for the Social Science version 21 by applying parametric tests (Friedman) and nonparametric (t Student). No significant differences in adherence to treatment (p=0.392), in the psychological adjustment were found positive significant differences at follow-ups compared to baseline 2 weeks (p: 0.001), 3 months (p: 0.000) and 6 months (p: 0.000). The clinical model demonstrated effectiveness in normalizing of psychological adjustment and maintaining treatment compliance. The process also generated confidence in caregivers and health professionals in this difficult task.

  9. A cost-effectiveness model for the use of a cannabis-derived oromucosal spray for the treatment of spasticity in multiple sclerosis.

    Science.gov (United States)

    Gras, Adrien; Broughton, Julie

    2016-12-01

    Severity of spasticity in multiple sclerosis (MS) directly correlates with the level and cost of care required. This study assessed whether a tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray for treatment of moderate-severe MS spasticity is a cost-effective use of healthcare resources in Wales. A Markov model was developed to compare THC/CBD plus standard of care (SoC) treatments with SoC alone. At 30 years, total incremental cost for THC/CBD plus SoC treatment was estimated at £3,836/patient (ICER: £10,891/quality-adjusted life year [QALY]). Hospital admission costs had the greatest effect on the base case ICER. Inclusion of carer cost led to incremental cost of -£33,609/patient (ICER: -£95,423/QALY). The THC/CBD spray was found to be cost-effective for the treatment of spasticity in MS, and dominant, if home carer costs were included. Use of THC/CBD has the potential to generate cost savings by significantly improving the symptoms of moderate to severe MS spasticity.

  10. Autism Treatment and Family Support Models Review

    Directory of Open Access Journals (Sweden)

    Mehrnoush Esbati

    2009-04-01

    Full Text Available Autism is a lifelong neurological disability of unknown etiology. The criteria for a diagnosis of autism are based on a triad of impairments in social interaction, communication and a lack of flexibility in thinking and behavior There are several factors which are likely to contribute to this variation including the definition of autism and variability in diagnosis amongst professionals, however anecdotally there appears to have been a steadily increasing demand for services. The purpose of this review of research literature relating to the management and treatment of children with autism is to identify the most effective models of best practice. The review includes Comparative evidence supporting a range of treatment and intervention models, across the range of individuals included within autism spectrum disorders, psychodynamic treatment/management which are based on the assumption that autism is the result of emotional damage to the child, usually because of failure to develop a close attachment to parents, especially the mother, biological treatments, educational and behavioral interventions, communication therapies, cost benefits and supporting families.The research is examined for evidence to support best practice models in supporting families at the time of diagnosis and assessment and an overview of the nature of comprehensive supports that help reduce stresses that may be experienced by families of a child with autism and promote inclusion in community activities.

  11. A Danish cost-effectiveness model of escitalopram in comparison with citalopram and venlafaxine as first-line treatments for major depressive disorder in primary care.

    Science.gov (United States)

    Sørensen, Jan; Stage, Kurt B; Damsbo, Niels; Le Lay, Agathe; Hemels, Michiel E

    2007-01-01

    The objective of this study was to model the cost-effectiveness of escitalopram in comparison with generic citalopram and venlafaxine in primary care treatment of major depressive disorder (baseline scores 22-40 on the Montgomery-Asberg Depression Rating Scale, MADRS) in Denmark. A three-path decision analytic model with a 6-month horizon was used. All patients started at the primary care path and were referred to outpatient or inpatient secondary care in the case of insufficient response to treatment. Model inputs included drug-specific probabilities derived from systematic literature review, ad-hoc survey and expert opinion. Main outcome measures were remission defined as MADRS escitalopram (64.1%) than citalopram (58.9%). From both perspectives, the total expected cost per successfully treated patient was lower for escitalopram (DKK 22,323 healthcare, DKK 72,399 societal) than for citalopram (DKK 25,778 healthcare, DKK 87,786 societal). Remission rates and costs were similar for escitalopram and venlafaxine. Robustness of the findings was verified in multivariate sensitivity analyses. For patients in primary care, escitalopram appears to be a cost-effective alternative to (generic) citalopram, with greater clinical benefit and cost-savings, and similar in cost-effectiveness to venlafaxine.

  12. A study of an effective sunitinib–chemotherapeutic combination regimen for bladder cancer treatment using a mouse model

    Directory of Open Access Journals (Sweden)

    Dah-Shyong Yu

    2014-06-01

    Conclusion: Combination of the tyrosine kinase receptor inhibitor sunitinib with gemcitabine chemotherapy synergistically enhances tumor cytotoxicity and may provide a new treatment modality for advanced bladder cancer.

  13. The Trimeric Model: A New Model of Periodontal Treatment Planning

    Science.gov (United States)

    Tarakji, Bassel

    2014-01-01

    Treatment of periodontal disease is a complex and multidisciplinary procedure, requiring periodontal, surgical, restorative, and orthodontic treatment modalities. Several authors attempted to formulate models for periodontal treatment that orders the treatment steps in a logical and easy to remember manner. In this article, we discuss two models of periodontal treatment planning from two of the most well-known textbook in the specialty of periodontics internationally. Then modify them to arrive at a new model of periodontal treatment planning, The Trimeric Model. Adding restorative and orthodontic interrelationships with periodontal treatment allows us to expand this model into the Extended Trimeric Model of periodontal treatment planning. These models will provide a logical framework and a clear order of the treatment of periodontal disease for general practitioners and periodontists alike. PMID:25177662

  14. Treatment of pathological gambling - integrative systemic model.

    Science.gov (United States)

    Mladenović, Ivica; Lažetić, Goran; Lečić-Toševski, Dušica; Dimitrijević, Ivan

    2015-03-01

    Pathological gambling was classified under impulse control disorders within the International Classification of Diseases (ICD-10) (WHO 1992), but the most recent Diagnostic and Statistical Manual, 5th edition (DSM-V), (APA 2013), has recognized pathological gambling as a first disorder within a new diagnostic category of behavioral addictions - Gambling disorder. Pathological gambling is a disorder in progression, and we hope that our experience in the treatment of pathological gambling in the Daily Hospital for Addictions at The Institute of Mental Health, through the original "Integrative - systemic model" would be of use to colleagues, dealing with this pathology. This model of treatment of pathological gambling is based on multi-systemic approach and it primarily represents an integration of family and cognitive-behavioral therapy, with traces of psychodynamic, existential and pharmacotherapy. The model is based on the book "Pathological gambling - with self-help manual" by Dr Mladenovic and Dr Lazetic, and has been designed in the form of a program that lasts 10 weeks in the intensive phase, and then continues for two years in the form of "extended treatment" ("After care"). The intensive phase is divided into three segments: educational, insight with initial changes and analysis of the achieved changes with the definition of plans and areas that need to be addressed in the extended treatment. "Extended treatment" lasts for two years in the form of group therapy, during which there is a second order change of the identified patient, but also of other family members. Pathological gambling has been treated in the form of systemic-family therapy for more than 10 years at the Institute of Mental Health (IMH), in Belgrade. For second year in a row the treatment is carried out by the modern "Integrative-systemic model". If abstinence from gambling witihin the period of one year after completion of the intensive phase of treatment is taken as the main criterion of

  15. Modeling tree-level fuel connectivity to evaluate the effectiveness of thinning treatments for reducing crown fire potential

    Science.gov (United States)

    Marco A. Contreras; Russell A. Parsons; Woodam Chung

    2012-01-01

    Land managers have been using fire behavior and simulation models to assist in several fire management tasks. These widely-used models use average attributes to make stand-level predictions without considering spatial variability of fuels within a stand. Consequently, as the existing models have limitations in adequately modeling crown fire initiation and propagation,...

  16. Investigation on the Effectiveness of Holistic Multi-dimensional Treatment Model (HMTM in Improvement of CARS Test Indicators in Children suffering from Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Maryam Hojjati

    2015-04-01

    Full Text Available Introduction The goal of research is investigation on the effectiveness of Holistic Multi-dimensional Treatment Model (HMTM in improvement of CARS test indicators in children with Autism Spectrum Disorder (ASD and it is done without pharmaceutical interventions, without names and accompanied by parental satisfaction questionnaire. Materials and Methods In this study with purposeful sampling method, 60 autistic children chosen randomly among 6-10 year-old patients were taken under a 12-month observation. At the beginning of this research they were taken the CARS pre-test and then in each month a complete behavioral HMTM checklist and a CARS test was taken. Observing HMTM treatment model, includes intuitive checklist with the aim of intuitive adjustment, abnormal behaviors’ checklist with the aim of decreasing them, individual behaviors’ checklist with the aim of increasing them and emotional interactive behaviors checklist with the aim of improvement that are conducted in statistical tables. Results Results shown a positive impact of HMTM in treatment trend of autism spectrum disorder considering sum of CARS points, also the effect on each CARS test parameters and CARS parameters improvements are meaningful holistic approach in HMTM method has interpreted some vague CARS parameters furthermore (P

  17. Beneficial effect of combined treatment with octreotide and pasireotide in PCK rats, an orthologous model of human autosomal recessive polycystic kidney disease.

    Directory of Open Access Journals (Sweden)

    Masanori Kugita

    Full Text Available Increased intracellular cyclic AMP (cAMP in renal tubular epithelia accelerates the progression of polycystic kidney disease (PKD. Thus, decreasing cAMP levels by an adenylyl cyclase inhibitory G protein activator is considered to be an effective approach in ameliorating PKD. In fact, pasireotide (PAS was effective in reducing disease progression in animal models of PKD. However, hyperglycemia caused by the administration of PAS is an adverse effect in its clinical use. Whereas, co-administration of octreotide (OCT with PAS did not increase serum glucose in normal rats. In the current study, we examined the efficacy of combined treatment with OCT and PAS in PCK rats, an autosomal recessive PKD model. Four-week-old PCK males were treated with the long-acting release type of OCT, PAS, or a combination of both (OCT/PAS for 12 weeks. After termination, serum and renal tissue were used for analyses. Kidney weight, kidney weight per body weight, renal cyst area, renal Ki67 expression, and serum urea nitrogen were significantly decreased either in the PAS or OCT/PAS group, compared with vehicle. Renal tissue cAMP content was significantly decreased by PAS or OCT/PAS treatment, but not OCT, compared with vehicle. As a marker of cellular mTOR signaling activity, renal phospho-S6 kinase expression was significantly decreased by OCT/PAS treatment compared with vehicle, OCT, or PAS. Serum glucose was significantly increased by PAS administration, whereas no difference was shown between vehicle and OCT/PAS, possibly because serum glucagon was decreased either by the treatment of OCT alone or co-application of OCT/PAS. In conclusion, since serum glucose levels are increased by the use of PAS, its combination with OCT may reduce the risk of hyperglycemia associated with PAS monotherapy against PKD progression.

  18. The effectiveness of the anti-CD11d treatment is reduced in rat models of spinal cord injury that produce significant levels of intraspinal hemorrhage.

    Science.gov (United States)

    Geremia, N M; Hryciw, T; Bao, F; Streijger, F; Okon, E; Lee, J H T; Weaver, L C; Dekaban, G A; Kwon, B K; Brown, A

    2017-09-01

    We have previously reported that administration of a CD11d monoclonal antibody (mAb) improves recovery in a clip-compression model of SCI. In this model the CD11d mAb reduces the infiltration of activated leukocytes into the injured spinal cord (as indicated by reduced intraspinal MPO). However not all anti-inflammatory strategies have reported beneficial results, suggesting that success of the CD11d mAb treatment may depend on the type or severity of the injury. We therefore tested the CD11d mAb treatment in a rat hemi-contusion model of cervical SCI. In contrast to its effects in the clip-compression model, the CD11d mAb treatment did not improve forelimb function nor did it significantly reduce MPO levels in the hemi-contused cord. To determine if the disparate results using the CD11d mAb were due to the biomechanical nature of the cord injury (compression SCI versus contusion SCI) or to the spinal level of the injury (12th thoracic level versus cervical) we further evaluated the CD11d mAb treatment after a T12 contusion SCI. In contrast to the T12 clip compression SCI, the CD11d mAb treatment did not improve locomotor recovery or significantly reduce MPO levels after T12 contusion SCI. Lesion analyses revealed increased levels of hemorrhage after contusion SCI compared to clip-compression SCI. SCI that is accompanied by increased intraspinal hemorrhage would be predicted to be refractory to the CD11d mAb therapy as this approach targets leukocyte diapedesis through the intact vasculature. These results suggest that the disparate results of the anti-CD11d treatment in contusion and clip-compression models of SCI are due to the different pathophysiological mechanisms that dominate these two types of spinal cord injuries. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  19. Effects of Combined Simultaneous and Sequential Endostar and Cisplatin Treatment in a Mice Model of Gastric Cancer Peritoneal Metastases

    Directory of Open Access Journals (Sweden)

    Lin Jia

    2017-01-01

    Full Text Available Objective. Aimed to study the effects of endostar and cisplatin using an in vivo imaging system (IVIS in a model of peritoneal metastasis of gastric cancer. Methods. NUGC-4 gastric cancer cells transfected with luciferase gene (NUGC-4-Luc were injected i.p. into nude mice. One week later, mice were randomly injected i.p.: group 1, cisplatin (d1–3 + endostar (d4–7; group 2, endostar (d1–4 + cisplatin (d5–7; group 3, endostar + cisplatin d1, 4, and 7; group 4, saline for two weeks. One week after the final administration, mice were sacrificed. Bioluminescent data, microvessel density (MVD, and lymphatic vessel density (LVD were analyzed. Results. Among the four groups, there were no significant differences in the weights and in the number of cancer cell photons on days 1 and 8 (P>0.05. On day 15, the numbers in groups 3 and 1 were less than that in group 2 (P0.05 or in LVD number among the four groups (P>0.05. Conclusions. IVIS® was more useful than weight, volume of ascites, and number of peritoneal nodules. The simultaneous group was superior to sequential groups in killing cancer cells and inhibiting vascular endothelium. Cisplatin-endostar was superior to endostar-cisplatin in killing cancer cells, while the latter in inhibiting peritoneal vascular endothelium.

  20. Decision analytic cost-effectiveness model to compare prostate cryotherapy to androgen deprivation therapy for treatment of radiation recurrent prostate cancer

    Science.gov (United States)

    Boyd, Kathleen A; Jones, Rob J; Paul, Jim; Birrell, Fiona; Briggs, Andrew H; Leung, Hing Y

    2015-01-01

    Objective To determine the cost-effectiveness of salvage cryotherapy (SC) in men with radiation recurrent prostate cancer (RRPC). Design Cost-utility analysis using decision analytic modelling by a Markov model. Setting and methods Compared SC and androgen deprivation therapy (ADT) in a cohort of patients with RRPC (biopsy proven local recurrence, no evidence of metastatic disease). A literature review captured published data to inform the decision model, and resource use data were from the Scottish Prostate Cryotherapy Service. The model was run in monthly cycles for RRPC men, mean age of 70 years. The model was run over the patient lifetime, to assess changes in patient health states and the associated quality of life, survival and cost impacts. Results are reported in terms of the discounted incremental costs and discounted incremental quality-adjusted life years (QALYs) gained between the 2 alternative interventions. Probabilistic sensitivity analysis used a 10 000 iteration Monte Carlo simulation. Results SC has a high upfront treatment cost, but delays the ongoing monthly cost of ADT. SC is the dominant strategy over the patient lifetime; it is more effective with an incremental 0.56 QALY gain (95% CI 0.28 to 0.87), and less costly with a reduced lifetime cost of £29 719 (€37 619) (95% CI −51 985 to −9243). For a ceiling ratio of £30 000, SC has a 100% probability to be cost-effective. The cost neutral point was at 3.5 years, when the upfront cost of SC (plus any subsequent cumulative cost of side effects and ADT) equates the cumulative cost in the ADT arm. Limitations of our model may arise from its insensitivity to parameter or structural uncertainty. Conclusions The platform for SC versus ADT cost-effective analysis can be employed to evaluate other treatment modalities or strategies in RRPC. SC is the dominant strategy, costing less over a patient's lifetime with improvements in QALYs. Trial registration number This economic analysis

  1. Cost-effectiveness analysis of antimuscarinics in the treatment of patients with overactive bladder in Spain: A decision-tree model

    Directory of Open Access Journals (Sweden)

    Trocio Jeffrey

    2011-05-01

    Full Text Available Abstract Background Fesoterodine, a new once daily antimuscarinic, has proven to be an effective, safe, and well-tolerated treatment in patients with overactive bladder (OAB. To date, no analysis has evaluated the economic costs and benefits associated with fesoterodine, compared to antimuscarinics in Spain. The purpose of this analysis was to assess the economic value of OAB treatment with fesoterodine relative to extended release tolterodine and solifenacin, from the societal perspective. Methods The economic model was based on data from two 12-week, randomized, double-blind, and multicenter trials comparing fesoterodine and tolterodine extended released (ER. Treatment response rates for solifenacin were extracted from the published literature. Discontinuation and efficacy were based on the results of a 12-week multinational randomized clinical trial extrapolated to 52 weeks. Changes in health related quality of life were assessed with the King's Health Questionnaire, which was transformed into preference-based utility values. Medical costs included (expressed in € 2010 were antimuscarinics, physician visits, laboratory tests, incontinence pads and the costs of OAB-related comorbidities, fractures, skin infections, urinary tract infections, depression, and nursing home admissions associated with incontinence. Time lost from work was also considered. Univariate sensitivity analyses were also performed. Results At week 12, continents accounted for 50.6%, 40.6% and 47.2% of patients in the fesoterodine, tolterodine, and solifenacin groups, respectively. By week 52, the projected proportions of patients remaining on therapy were 33.1%, 26.5% and 30.8%, respectively. The projected quality- adjusted life years (QALY gain (compared to baseline over the 52-week simulation period were 0.01014, 0.00846 and 0.00957, respectively. The overall treatment cost was estimated at €1,937, €2,089 and €1,960 for fesoterodine, tolterodine and solifenacin

  2. Empiric antibiotic treatment of erythema migrans-like skin lesions as a function of geography: a clinical and cost effectiveness modeling study.

    Science.gov (United States)

    Lantos, Paul M; Brinkerhoff, R Jory; Wormser, Gary P; Clemen, Robert

    2013-12-01

    The skin lesion of early Lyme disease, erythema migrans (EM), is so characteristic that routine practice is to treat all such patients with antibiotics. Because other skin lesions may resemble EM, it is not known whether presumptive treatment of EM is appropriate in regions where Lyme disease is rare. We constructed a decision model to compare the cost and clinical effectiveness of three strategies for the management of EM: Treat All, Observe, and Serology as a function of the probability that an EM-like lesion is Lyme disease. Treat All was found to be the preferred strategy in regions that are endemic for Lyme disease. Where Lyme disease is rare, Observe is the preferred strategy, as presumptive treatment would be expected to produce excessive harm and increased costs. Where Lyme disease is rare, clinicians and public health officials should consider observing patients with EM-like lesions who lack travel to Lyme disease-endemic areas.

  3. Ecotoxicological effects extrapolation models

    Energy Technology Data Exchange (ETDEWEB)

    Suter, G.W. II

    1996-09-01

    One of the central problems of ecological risk assessment is modeling the relationship between test endpoints (numerical summaries of the results of toxicity tests) and assessment endpoints (formal expressions of the properties of the environment that are to be protected). For example, one may wish to estimate the reduction in species richness of fishes in a stream reach exposed to an effluent and have only a fathead minnow 96 hr LC50 as an effects metric. The problem is to extrapolate from what is known (the fathead minnow LC50) to what matters to the decision maker, the loss of fish species. Models used for this purpose may be termed Effects Extrapolation Models (EEMs) or Activity-Activity Relationships (AARs), by analogy to Structure-Activity Relationships (SARs). These models have been previously reviewed in Ch. 7 and 9 of and by an OECD workshop. This paper updates those reviews and attempts to further clarify the issues involved in the development and use of EEMs. Although there is some overlap, this paper does not repeat those reviews and the reader is referred to the previous reviews for a more complete historical perspective, and for treatment of additional extrapolation issues.

  4. A marginal structural model to estimate the causal effect of antidepressant medication treatment on viral suppression among homeless and marginally housed persons with HIV.

    Science.gov (United States)

    Tsai, Alexander C; Weiser, Sheri D; Petersen, Maya L; Ragland, Kathleen; Kushel, Margot B; Bangsberg, David R

    2010-12-01

    Depression strongly predicts nonadherence to human immunodeficiency virus (HIV) antiretroviral therapy, and adherence is essential to maintaining viral suppression. This suggests that pharmacologic treatment of depression may improve virologic outcomes. However, previous longitudinal observational analyses have inadequately adjusted for time-varying confounding by depression severity, which could yield biased estimates of treatment effect. Application of marginal structural modeling to longitudinal observation data can, under certain assumptions, approximate the findings of a randomized controlled trial. To determine whether antidepressant medication treatment increases the probability of HIV viral suppression. Community-based prospective cohort study with assessments conducted every 3 months. Community-based research field site in San Francisco, California. One hundred fifty-eight homeless and marginally housed persons with HIV who met baseline immunologic (CD4+ T-lymphocyte count, 13) inclusion criteria, observed from April 2002 through August 2007. Probability of achieving viral suppression to less than 50 copies/mL. Secondary outcomes of interest were probability of being on an antiretroviral therapy regimen, 7-day self-reported percentage adherence to antiretroviral therapy, and probability of reporting complete (100%) adherence. Marginal structural models estimated a 2.03 greater odds of achieving viral suppression (95% confidence interval [CI], 1.15-3.58; P = .02) resulting from antidepressant medication treatment. In addition, antidepressant medication use increased the probability of antiretroviral uptake (weighted odds ratio, 3.87; 95% CI, 1.98-7.58; P effect is likely attributable to improved adherence to a continuum of HIV care, including increased uptake and adherence to antiretroviral therapy.

  5. Effects of early and late-onset treatment with carvedilol in an experimental model of aortic regurgitation

    DEFF Research Database (Denmark)

    Eskesen, Kristian; Olsen, Niels Thue; Dimaano, Veronica L

    2015-01-01

    measurements. RESULTS: AR resulted in eccentric hypertrophy and left ventricular (LV) dysfunction. LV remodeling and function as measured by echocardiography was unaffected by treatment. LV dimensions were similar between treated and untreated groups and measures of LV performance (including strain and strain...... rate) were also unaltered. This result was confirmed by invasive measurements showing maximal and minimal pressure-time development, LV volumes, and LV pressures, to be unaltered by treatment. On the contrary, despite relative bradycardia carvedilol did not reflect any negative impact on the heart...

  6. Migraine treatment and placebo effect.

    Science.gov (United States)

    Speciali, José G; Peres, Mário; Bigal, Marcelo E

    2010-03-01

    Placebos are typically defined as physiologically inactive substances that elicit a therapeutic response. The antipode of the placebo effect is the nocebo effect, or the negative effects of placebo, where unpleasant symptoms (e.g., adverse events) emerge after the administration of placebo. Placebo analgesia is one of the most striking examples of the cognitive modulation of pain perception. Herein we focus on the importance of placebo in headache research. We first review the mechanisms of the placebo effect. We then focus on the importance of placebo in the acute treatment of migraine. We follow by discussing the importance of placebo on the preventive treatment of migraine and our perspectives for the 5 years to come regarding the study of the placebos.

  7. Fertility effects of cancer treatment.

    Science.gov (United States)

    Marsden, Donald E; Hacker, Neville

    2003-01-01

    Cancer sufferers are a subfertile group, and most treatments have the potential to adversely affect gonadal function. As cancer treatment becomes more effective and survival rates improve there are more cancer survivors in the reproductive age group for whom parenting is an important consideration. This article outlines the effects on fertility of cancer treatments and techniques to minimise the risk of infertility. The overall prospects for younger cancer sufferers to either retain their fertility or have genetic offspring is now better than ever before, due to advances in assisted reproductive technology, the appropriate use of fertility sparing surgery and other techniques to reduce the toxicity of therapy on the reproductive organs. These advances raise new moral and ethical concerns that must be considered before advising cancer sufferers of the options for preserving reproductive capacity.

  8. Cost effectiveness of primary care referral to a commercial provider for weight loss treatment, relative to standard care: a modelled lifetime analysis.

    Science.gov (United States)

    Fuller, N R; Carter, H; Schofield, D; Hauner, H; Jebb, S A; Colagiuri, S; Caterson, I D

    2014-08-01

    Because of the high prevalence of overweight and obesity, there is a need to identify cost-effective approaches for weight loss in primary care and community settings. To evaluate the long-term cost effectiveness of a commercial weight loss programme (Weight Watchers) (CP) compared with standard care (SC), as defined by national guidelines. A Markov model was developed to calculate the incremental cost-effectiveness ratio (ICER), expressed as the cost per quality-adjusted life year (QALY) over the lifetime. The probabilities and quality-of-life utilities of outcomes were extrapolated from trial data using estimates from the published literature. A health sector perspective was adopted. Over a patient's lifetime, the CP resulted in an incremental cost saving of AUD 70 per patient, and an incremental 0.03 QALYs gained per patient. As such, the CP was found to be the dominant treatment, being more effective and less costly than SC (95% confidence interval: dominant to 6225 per QALY). Despite the CP delaying the onset of diabetes by ∼10 months, there was no significant difference in the incidence of type 2 diabetes, with the CP achieving <0.1% fewer cases than SC over the lifetime. The modelled results suggest that referral to community-based interventions may provide a highly cost-effective approach for those at high risk of weight-related comorbidities.

  9. Anti-fibrotic effects of chronic treatment with the selective FXR agonist obeticholic acid in the bleomycin-induced rat model of pulmonary fibrosis.

    Science.gov (United States)

    Comeglio, Paolo; Filippi, Sandra; Sarchielli, Erica; Morelli, Annamaria; Cellai, Ilaria; Corcetto, Francesca; Corno, Chiara; Maneschi, Elena; Pini, Alessandro; Adorini, Luciano; Vannelli, Gabriella Barbara; Maggi, Mario; Vignozzi, Linda

    2017-04-01

    Farnesoid X receptor (FXR) activation by obeticholic acid (OCA) has been demonstrated to inhibit inflammation and fibrosis development in liver, kidney and intestine in multiple disease models. FXR activation has also been demonstrated to suppress the inflammatory response and to promote lung repair after lung injury. This study investigated the protective effects of OCA treatment (3 or 10mg/kg/day) on inflammation, tissue remodeling and fibrosis in the bleomycin-induced pulmonary fibrosis rat model. Effects of OCA treatment on morphological and molecular alterations of the lung, as well as remodeling of the alveoli and the right ventricle were also evaluated. Lung function was assessed by measuring airway resistance to inflation. In the acute phase (7days), bleomycin promoted an initial thickening and fibrosis of the lung interstitium, with upregulation of genes related to epithelial proliferation, tissue remodeling and hypoxia. At 28days, an evident increase in the deposition of collagen in the lungs was observed. This excessive deposition was accompanied by an upregulation of transcripts related to the extracellular matrix (TGFβ1, SNAI1 and SNAI2), indicating lung fibrosis. Administration of OCA protected against bleomycin-induced lung damage by suppressing molecular mechanisms related to epithelial-to-mesenchymal transition (EMT), inflammation and collagen deposition, with a dose-dependent reduction of proinflammatory cytokines such as IL-1β and IL-6, as well as TGF-β1 and SNAI1 expression. Pirfenidone, a recently approved treatment for idiopathic pulmonary fibrosis (IPF), significantly counteracted bleomycin-induced pro-fibrotic genes expression, but did not exert significant effects on IL-1β and IL-6. OCA treatment in bleomycin-challenged rats also improved pulmonary function, by effectively normalizing airway resistance to inflation and lung stiffness in vivo. Results with OCA were similar, or even superior, to those obtained with pirfenidone. In

  10. Wildfires effects on soils: water repellency, NIR models and post-fire treatments. My personal view (SSS Division Outstanding ECS Award Lecture)

    Science.gov (United States)

    Arcenegui, Victoria

    2017-04-01

    I first was intrigued by fire, because all summers we had some of them in our location, and then I was involve in fire effects on soils. We had, and also have, a lot of question to answer. I am absolutely sure that soil science was my best choice. Soils are amazing, a lot of things are happening in soils. Soils and fire, are my main research topics. I studied the immediately effect of fire on soils, focus on the effect of fire in soil water repellency and aggregate stability. Two physical properties that are crucial to post-fire soil response. I also construct NIR models to know the maximum temperature reached in soils. It is well known that temperature is a key factor affecting soils properties. Then, it is a really important tool to predict the temperature reached in a soil after a wildfire. Currently, I am involve in a project to investigate what are the best post-fire treatments in our soils and how this treatments affects soil properties.

  11. Methodologies in the modeling of combined chemo-radiation treatments

    Science.gov (United States)

    Grassberger, C.; Paganetti, H.

    2016-11-01

    The variety of treatment options for cancer patients has increased significantly in recent years. Not only do we combine radiation with surgery and chemotherapy, new therapeutic approaches such as immunotherapy and targeted therapies are starting to play a bigger role. Physics has made significant contributions to radiation therapy treatment planning and delivery. In particular, treatment plan optimization using inverse planning techniques has improved dose conformity considerably. Furthermore, medical physics is often the driving force behind tumor control and normal tissue complication modeling. While treatment optimization and outcome modeling does focus mainly on the effects of radiation, treatment modalities such as chemotherapy are treated independently or are even neglected entirely. This review summarizes the published efforts to model combined modality treatments combining radiation and chemotherapy. These models will play an increasing role in optimizing cancer therapy not only from a radiation and drug dosage standpoint, but also in terms of spatial and temporal optimization of treatment schedules.

  12. Sequential modelling of the effects of mass drug treatments on anopheline-mediated lymphatic filariasis infection in Papua New Guinea.

    Directory of Open Access Journals (Sweden)

    Brajendra K Singh

    Full Text Available Lymphatic filariasis (LF has been targeted by the WHO for global eradication leading to the implementation of large scale intervention programs based on annual mass drug administrations (MDA worldwide. Recent work has indicated that locality-specific bio-ecological complexities affecting parasite transmission may complicate the prediction of LF extinction endpoints, casting uncertainty on the achievement of this initiative. One source of difficulty is the limited quantity and quality of data used to parameterize models of parasite transmission, implying the important need to update initially-derived parameter values. Sequential analysis of longitudinal data following annual MDAs will also be important to gaining new understanding of the persistence dynamics of LF. Here, we apply a Bayesian statistical-dynamical modelling framework that enables assimilation of information in human infection data recorded from communities in Papua New Guinea that underwent annual MDAs, into our previously developed model of parasite transmission, in order to examine these questions in LF ecology and control.Biological parameters underlying transmission obtained by fitting the model to longitudinal data remained stable throughout the study period. This enabled us to reliably reconstruct the observed baseline data in each community. Endpoint estimates also showed little variation. However, the updating procedure showed a shift towards higher and less variable values for worm kill but not for any other drug-related parameters. An intriguing finding is that the stability in key biological parameters could be disrupted by a significant reduction in the vector biting rate prevailing in a locality.Temporal invariance of biological parameters in the face of intervention perturbations indicates a robust adaptation of LF transmission to local ecological conditions. The results imply that understanding the mechanisms that underlie locally adapted transmission dynamics will

  13. Domestic Violence and Its Effects on Children: Fundamental Concepts, Safety Planning and Examples of Alternative Treatment Models

    Directory of Open Access Journals (Sweden)

    Melis Sedef Kahraman

    2016-12-01

    Full Text Available Domestic violence is defined as coercive and controlling behaviors that family members show toward each other. These behaviors are frequently seen as repetitive behavior patterns. Research indicates that many domestic violence incidents happen in the presence of children. Being exposed to domestic violence or witnessing domestic violence has similar emotional-behavioral problems in children. In this article, we emphasized different reactions of children to domestic violence within different age groups. Safety planning is a commonly used method in Western cultures for professionals either working with adult victims or child victims of domestic violence. Unfortunately, the importance of safety planning is not yet utilized in Turkey. In this article, the phases of safety planning and three different alternative treatment methods that have been proven successful for working with children who were exposed to domestic violence are explained. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2016; 8(4.000: 321-336

  14. Using a Hydrodynamic and Biogeochemical Model to Investigate the Effects of Nutrient Loading from a Wastewater Treatment Plant into Lake Michigan

    Science.gov (United States)

    Khazaei, B.; Bravo, H.; Bootsma, H.

    2017-12-01

    There is clear evidence that excessive nutrient, in particular phosphorus (P), loading into Lake Michigan has produced significant problems, such as algal blooms, hypoxia, and reduced water quality. Addressing those problems requires understanding the transport and fate of P in the lake. The dominance of mixing and dispersion processes on the P transport has been demonstrated, yet recent research has shown the remarkable influence of dreissenid mussels and Cladophora on water clarity and the P budget. Since mussels and Cladophora tend to concentrate near the coastlines, nearshore-offshore P exchange is of a big importance. In this research, a computer model was developed to simulate the P cycle by incorporating the biogeochemical processes relevant to the transport of P into a 3D high-resolution hydrodynamic model. The near-bottom biogeochemical model consists of three linked modules: Cladophora, mussel, and sediment storage modules. The model was applied to the Milwaukee Metropolitan Sewerage District South Shore Wastewater Treatment Plant, between June and October of 2013 and 2015, as a case study. The plant outfall introduces a point source of P into the study domain—the nearshore zone of Lake Michigan adjacent to Milwaukee County. The model was validated against field observations of water temperature, dissolved phosphorus (DP), particulate phosphorus (PP), Cladophora biomass, and P content. The model simulations showed reasonably good agreement with field measurements. Model results showed a) different temporal patterns in 2013 and 2015, b) a larger range of fluctuations in DP than that in PP, and c) that the effects of mussels and Cladophora could explain the differences in patterns and ranges. PP concentrations showed more frequent spikes of concentration in 2013 due to resuspension events during that year because of stronger winds. The model is being applied as a management tool to test scenarios of nutrient loading to determine effluent P limits for the

  15. The potential effects of changing HIV treatment policy on tuberculosis outcomes in South Africa: results from three tuberculosis-HIV transmission models.

    Science.gov (United States)

    Pretorius, Carel; Menzies, Nicolas A; Chindelevitch, Leonid; Cohen, Ted; Cori, Anne; Eaton, Jeffrey W; Fraser, Christophe; Gopalappa, Chaitra; Hallett, Timothy B; Salomon, Joshua A; Stover, John; White, Richard G; Dodd, Peter J

    2014-01-01

    Many countries are considering expanding HIV treatment following recent findings emphasizing the effects of antiretroviral therapy (ART) on reducing HIV transmission in addition to already established survival benefits. Given the close interaction of tuberculosis (TB) and HIV epidemics, ART expansion could have important ramifications for TB burden. Previous studies suggest a wide range of possible TB impacts following ART expansion. We used three independently developed TB-HIV models to estimate the TB-related impact of expanding ART in South Africa. We considered two dimensions of ART expansion--improving coverage of pre-ART and ART services, and expanding CD4-based ART eligibility criteria (from CD4 South African HIV-TB epidemic, and used to assess standardized ART policy changes. Key TB impact indicators were projected from 2014 to 2033. Compared with current eligibility and coverage, cumulative TB incidence was projected to decline by 6-30% over the period 2014-2033 if ART eligibility were expanded to all HIV positive individuals, and by 28-37% if effective ART coverage were additionally increased to 80%. Overall, expanding ART was estimated to avert one TB case for each 10-13 additional person-years of ART. All models showed that TB incidence and mortality reductions would grow over time, but would stabilize towards the end of the projection period. ART expansion could substantially reduce TB incidence and mortality in South Africa and could provide a platform for collaborative HIV-TB programs to effectively halt HIV-associated TB.

  16. Very long-chain acyl-CoA dehydrogenase (VLCAD-) deficiency-studies on treatment effects and long-term outcomes in mouse models.

    Science.gov (United States)

    Tucci, Sara

    2017-05-01

    Very-long-chain-acyl-CoA-dehydrogenase deficiency is the most common disorder of mitochondrial long-chain fatty acid (LCFA) oxidation, with an incidence of 1:50,000-1:100,000 in newborns. Catabolic situations contribute to the aggravation of symptoms and induce severe metabolic derangement. Treatment for VLCAD-deficiency includes avoidance of fasting and a long-chain fat-restricted and fat-modified diet in which LCFAs are fully or partially replaced by medium-chain triglycerides (MCT). The aim of this work was to investigate the outcome and the effects of long-term treatment in a mouse model of VLCAD-deficiency. The application of a single MCT bolus in a mouse model of VLCAD-deficiency (VLCAD -/- mice) immediately prior to exercise protected the muscles from the accumulation of acylcarnitines providing the required energy and it did not affect hepatic lipid metabolism. However, when MCT was applied over the course of a year as a regular part of the diet, female VLCAD -/- mice developed a severe clinical phenotype comparable to the human metabolic syndrome. Indeed, they were characterized by massive visceral fat infiltration, hepatosteatosis, disturbed fatty acid composition, hyperlipidemia, and systemic oxidative stress. In contrast, male VLCAD -/- mice seemed to be protected and displayed only signs of insulin resistance. Besides the sex-specific response to MCT supplementation with regard to the lipid metabolism, all VLCAD -/- mice developed progressive cardiac dysfunction over time which worsened when they were treated with regular MCT resulting in severe dilated cardiomyopathy. While long term use of MCT oil in mice has adverse effects, no such effects have been demonstrated in humans, likely reflecting the differences in long chain fatty acid oxidation between the two species.

  17. The Effects of Sub-Chronic Treatment with Pioglitazone on the Septic Mice Mortality in the Model of Cecal Ligation and Puncture: Involvement of Nitric Oxide Pathway

    Directory of Open Access Journals (Sweden)

    Hamed Shafaroodi

    2015-10-01

    Full Text Available Sepsis is a systemic inflammatory response syndrome caused by an infection and remains as a major challenge in health care. Many studies have reported that pioglitazone may display anti-inflammatory effects. This study was designed to evaluate the effect of subchronic treatment with pioglitazone on high-grade septic mice survival and nitrergic system involvement. Diffused sepsis was induced by cecal ligation and puncture (CLP surgery in male NMRI mice (20-30 g. Pioglitazone (5,10 and 20 mg/kg was administered by gavage daily for 5 days prior to surgery. Nitric oxide involvement was assessed by sub-chronic administration of a non-selective nitric oxide synthase inhibitor, L-NAME and a selective inducible nitric oxide synthase inhibitor, aminoguanidine. TNF-α  and IL-1β plasma levels were measured by ELISA. Pioglitazone (10 and 20 mg/kg significantly improved survival rate in septic mice. The chronic intraperitoneally co-administration of L-NAME (0.5 mg/kg, daily or aminoguanidine (1 mg/kg, daily with a daily dose of pioglitazone, 5 mg/kg, significantly increased the survival rate. This survival improving effect was accompanied by a significant reduction in pro-inflammatory cytokines TNF-α and IL-1β plasma levels. In conclusion, sub-chronic pioglitazone treatment can improve survival in mouse sepsis model by CLP. Inhibition of nitric oxide release, probably through inducible nitric oxide synthase at least in part is responsible for this effect. Suppression of TNF-α and IL-1β could be another mechanism in pioglitazone-induced survival improving effect in septic mice.

  18. A predictive model for the effect of temperature and predrying treatments in reducing Listeria monocytogenes populations during drying of beef jerky.

    Science.gov (United States)

    Yoon, Yohan; Skandamis, Panagiotis N; Kendall, Patricia A; Smith, Gary C; Sofos, John N

    2006-01-01

    The objective of this study was to model the effect of drying temperatures (52, 57, and 63 degrees C) and predrying treatments on the inactivation of Listeria monocytogenes on beef jerky. Before drying, beef slices were inoculated with a 10-strain composite of L. monocytogenes and then treated with the following: (i) nothing (C), (ii) traditional marinade (M), or (iii) dipping in 5% acetic acid solution for 10 min, followed by M (AM). In addition, sequential stresses (exposure to 10% NaCl, followed by an adjustment of the pH to 5.0 and, subsequently, a water bath at 45 degrees C) were applied to the inocula before beef contamination and drying at 63 degrees C. Surviving L. monocytogenes were determined on tryptic soy agar plus 0.6% yeast extract (TSAYE) and on PALCAM agar at 0, 2, 4, 6, 8, and 10 h during drying. Data were modeled by a linear regression (treatment AM) and a logistic-based equation capable of fitting biphasic inactivation curves without initial shoulder (treatments C and M). The total log reductions expressed as the CFU per square centimeter of L. monocytogenes (3.9 to 5.1) for the samples treated with M (3.5 to 5.4) when compared with C were similar, whereas AM-treated samples had higher (6.1 to 6.8) reductions. All survival curves were characterized by an initial rapid decrease in populations within the first 2 h, which was followed by a secondary death phase at a lower rate. No significant (P > or = 0.05) differences in inactivation were observed due to drying temperatures in the range (52 to 63 degrees C) tested. Inactivation differences between recovered counts of stressed and unstressed cells were significant (P beef jerky.

  19. Comparison between alkali heat treatment and sprayed hydroxyapatite coating on thermally-sprayed rough Ti surface in rabbit model: Effects on bone-bonding ability and osteoconductivity.

    Science.gov (United States)

    Kawai, Toshiyuki; Takemoto, Mitsuru; Fujibayashi, Shunsuke; Tanaka, Masashi; Akiyama, Haruhiko; Nakamura, Takashi; Matsuda, Shuichi

    2015-07-01

    In this study, we investigated the effect of different surface treatments (hydroxyapatite (HA) coating, alkali heat treatment, and no treatment) on the ability of bone to bond to a rough arc-sprayed Ti metal surface, using rabbit models. The bone-to-implant contacts for untreated, HA-coated, and alkali heat-treated implants were 21.2%, 72.1%, and 33.8% at 4 weeks, 21.8%, 70.9%, and 30.0% at 8 weeks, and 16.3%, 70.2%, and 29.9% at 16 weeks, respectively (n = 8). HA -coated implants showed significantly higher bone-to-implant contacts than the untreated and alkali heat-treated implants at all the time point, whereas alkali heat-treated implants showed significantly higher bone-to-implant contacts than untreated implants at 4 and 16 weeks. The failure loads in a mechanical test for untreated, HA coated, alkali heat-treated plates were 65.4 N, 70.7 N, and 90.8 N at 4 weeks, 76.1 N, 64.7 N, and 104.8 N at 8 weeks and 88.7 N, 92.6 N, and 118.5 N at 16 weeks, respectively (n = 8). The alkali heat-treated plates showed significantly higher failure loads than HA-coated plates at 8 and 16 weeks. The difference between HA-coated plates and untreated plates were not statistically significant at any time point. Thus HA coating, although it enables high bone-to-implant contact, may not enhance the bone-bonding properties of thermally-sprayed rough Ti metal surfaces. In contrast, alkali heat treatment can be successfully applied to thermally-sprayed Ti metal to enhance both bone-to-implant contact and bone-bonding strength. © 2014 Wiley Periodicals, Inc.

  20. The effects of gestational stress and SSRI antidepressant treatment on structural plasticity in the postpartum brain - a translational model for postpartum depression

    Science.gov (United States)

    Haim, Achikam; Albin-Brooks, Christopher; Sherer, Morgan; Mills, Emily; Leuner, Benedetta

    2015-01-01

    Postpartum depression (PPD) is a common complication following childbirth experienced by one in every five new mothers. Although the neural basis of PPD remains unknown previous research in rats has shown that gestational stress, a risk factor for PPD, induces depressive-like behavior during the postpartum period. Moreover, the effect of gestational stress on postpartum mood is accompanied by structural modifications within the nucleus accumbens (NAc) and the medial prefrontal cortex (mPFC) – limbic regions that have been linked to PPD. Mothers diagnosed with PPD are often prescribed selective serotonin reuptake inhibitor (SSRI) antidepressant medications and yet little is known about their effects in models of PPD. Thus, here we investigated whether postpartum administration of Citalopram, an SSRI commonly used to treat PPD, would ameliorate the behavioral and morphological consequences of gestational stress. In addition, we examined the effects of gestational stress and postpartum administration of Citalopram on structural plasticity within the basolateral amygdala (BLA) which together with the mPFC and NAc forms a circuit that is sensitive to stress and is involved in mood regulation. Our results show that postpartum rats treated with Citalopram do not exhibit gestational stress-induced depressive-like behavior in the forced swim test. In addition, Citalopram was effective in reversing gestational stress-induced structural alterations in the postpartum NAc shell and mPFC. We also found that gestational stress increased spine density within the postpartum BLA, an effect which was not reversed by Citalopram treatment. Overall, these data highlight the usefulness of gestational stress as a valid and informative translational model for PPD. Furthermore, they suggest that structural alterations in the mPFC-NAc pathway may underlie stress-induced depressive-like behavior during the postpartum period and provide much needed information on how SSRIs may act in the

  1. Endovascular treatment of diabetic foot in a selected population of patients with below-the-knee disease: is the angiosome model effective?

    Science.gov (United States)

    Fossaceca, Rita; Guzzardi, Giuseppe; Cerini, Paolo; Cusaro, Claudio; Stecco, Alessandro; Parziale, Giuseppe; Perchinunno, Marco; De Bonis, Marco; Carriero, Alessandro

    2013-06-01

    To evaluate the efficacy of percutaneous transluminal angioplasty (PTA) in a selected population of diabetic patients with below-the-knee (BTK) disease and to analyze the reliability of the angiosome model. We made a retrospective analysis of the results of PTA performed in 201 diabetic patients with BTK-only disease treated at our institute from January 2005 to December 2011. We evaluated the postoperative technical success, and at 1, 6, and 12 months' follow-up, we assessed the rates and values of partial and complete ulcer healing, restenosis, major and minor amputation, limb salvage, and percutaneous oximetry (TcPO2) (Student's t test). We used the angiosome model to compare different clinicolaboratory outcomes in patients treated by direct revascularization (DR) from patients treated with indirect revascularization (IR) technique by Student's t test and the χ(2) test. At a mean ± standard deviation follow-up of 17.5 ± 12 months, we observed a mortality rate of 3.5 %, a major amputation rate of 9.4 %, and a limb salvage rate of 87 % with a statistically significant increase of TcPO2 values at follow-up compared to baseline (p < 0.05). In 34 patients, treatment was performed with the IR technique and in 167 by DR; in both groups, there was a statistically significant increase of TcPO2 values at follow-up compared to baseline (p < 0.05), without statistically significant differences in therapeutic efficacy. PTA of the BTK-only disease is a safe and effective option. The DR technique is the first treatment option; we believe, however, that IR is similarly effective, with good results over time.

  2. Endovascular Treatment of Diabetic Foot in a Selected Population of Patients with Below-the-Knee Disease: Is the Angiosome Model Effective?

    Energy Technology Data Exchange (ETDEWEB)

    Fossaceca, Rita, E-mail: rfossaceca@hotmail.com; Guzzardi, Giuseppe, E-mail: guz@libero.it; Cerini, Paolo, E-mail: cerini84@hotmail.it [' Maggiore della Carita' Hospital, University of Eastern Piedmont ' Amedeo Avogadro' , Department of Diagnostic and Interventional Radiology (Italy); Cusaro, Claudio, E-mail: claudio.cusaro@libero.it [' Maggiore della Carita' Hospital, Department of Diabetic Complications (Italy); Stecco, Alessandro, E-mail: a.stecco@libero.it; Parziale, Giuseppe, E-mail: giuseppeparziale@gmail.com; Perchinunno, Marco, E-mail: marcoperchinunno@gmail.com; Bonis, Marco De, E-mail: marco_deb@hotmail.it; Carriero, Alessandro, E-mail: profcarriero@virgilio.it [' Maggiore della Carita' Hospital, University of Eastern Piedmont ' Amedeo Avogadro' , Department of Diagnostic and Interventional Radiology (Italy)

    2013-06-15

    Purpose. To evaluate the efficacy of percutaneous transluminal angioplasty (PTA) in a selected population of diabetic patients with below-the-knee (BTK) disease and to analyze the reliability of the angiosome model. Methods. We made a retrospective analysis of the results of PTA performed in 201 diabetic patients with BTK-only disease treated at our institute from January 2005 to December 2011. We evaluated the postoperative technical success, and at 1, 6, and 12 months' follow-up, we assessed the rates and values of partial and complete ulcer healing, restenosis, major and minor amputation, limb salvage, and percutaneous oximetry (TcPO{sub 2}) (Student's t test). We used the angiosome model to compare different clinicolaboratory outcomes in patients treated by direct revascularization (DR) from patients treated with indirect revascularization (IR) technique by Student's t test and the {chi}{sup 2} test. Results. At a mean {+-} standard deviation follow-up of 17.5 {+-} 12 months, we observed a mortality rate of 3.5 %, a major amputation rate of 9.4 %, and a limb salvage rate of 87 % with a statistically significant increase of TcPO{sub 2} values at follow-up compared to baseline (p < 0.05). In 34 patients, treatment was performed with the IR technique and in 167 by DR; in both groups, there was a statistically significant increase of TcPO{sub 2} values at follow-up compared to baseline (p < 0.05), without statistically significant differences in therapeutic efficacy. Conclusion. PTA of the BTK-only disease is a safe and effective option. The DR technique is the first treatment option; we believe, however, that IR is similarly effective, with good results over time.

  3. Wastewater treatment modelling: dealing with uncertainties

    DEFF Research Database (Denmark)

    Belia, E.; Amerlinck, Y.; Benedetti, L.

    2009-01-01

    This paper serves as a problem statement of the issues surrounding uncertainty in wastewater treatment modelling. The paper proposes a structure for identifying the sources of uncertainty introduced during each step of an engineering project concerned with model-based design or optimisation...... of a wastewater treatment system. It briefly references the methods currently used to evaluate prediction accuracy and uncertainty and discusses the relevance of uncertainty evaluations in model applications. The paper aims to raise awareness and initiate a comprehensive discussion among professionals on model...

  4. The Effectiveness of the Controlled Release of Gentamicin from Polyelectrolyte Multilayers in the Treatment of Staphylococcus aureus Infection in a Rabbit Bone Model

    Science.gov (United States)

    Moskowitz, Joshua; Blaisse, Michael; Samuel, Raymond; Hsu, Hu-Ping; Harris, Mitchel; Martin, Scott; Lee, Jean; Spector, Myron; Hammond, Paula

    2010-01-01

    While the infection rate of orthopedic implants is low, the required treatment, which can involve six weeks of antibiotic therapy and two additional surgical operations, is life threatening and expensive, and thus motivates the development of a one-stage re-implantation procedure. Polyelectrolyte multilayers incorporating gentamicin were fabricated using the layer-by-layer deposition process for use as a device coating to deal with an existing bone infection in a direct implant exchange operation. The films eluted about 70% of their payload in vitro during the first three days and subsequently continued to release drug for more than four additional weeks, reaching a total average release of over 550 μg/cm2. The coatings were demonstrated to be bactericidal against Staphylococcus aureus, and degradation products were generally nontoxic towards MC3T3-E1 murine preosteoblasts. Film-coated titanium implants were compared to uncoated implants in an in vivo S. aureus bone infection model. After a direct exchange procedure, the antimicrobial-coated devices yielded bone homogenates with a significantly lower degree of infection than uncoated devices at both day four (p < 0.004) and day seven (p < 0.03). This study has demonstrated that a self-assembled ultrathin film coating is capable of effectively treating an experimental bone infection in vivo and lays the foundation for development of a multi-therapeutic film for optimized, synergistic treatment of pain, infection, and osteomyelitis. PMID:20488534

  5. Modeling the Effect of Onsite Wastewater Treatment Systems on Nitrate Load Using SWAT in an Urban Watershed of Metropolitan Atlanta, Georgia

    Science.gov (United States)

    Hoghooghi, N.; Radcliffe, D. E.; Habteselassie, M.; Jeong, J.

    2016-12-01

    Onsite wastewater treatment systems (OWTSs) can be a source of nitrogen (N) pollution in both surface and ground waters. In Metropolitan Atlanta, GA more than 26% of homes are on OWTSs. The objective of this study was to estimate the effect of OWTS, including failing systems, on NO3- load in an urban watershed in Metropolitan Atlanta using the Soil Water Assessment Tool (SWAT) model. Big Haynes Creek watershed has a drainage area of 44-km2 with mainly urban land use (67%) and most of the homes use OWTS. A USGS gage station where stream flow was measured daily and nitrate (NO3-) concentrations were measured approximately monthly was selected as the outlet. The model was simulated from 1 January 2003 to 31 December 2014. Overall, the model showed satisfactory daily stream flow and NO3- loads with Nash-Sutcliffe coefficients of 0.62 and 0.58 for the calibration period, and 0.67 and 0.33 for the validation period, respectively at the outlet of the Big Haynes watershed. OWTS caused an average increase in NO3- load of about 23% at the watershed scale and 29% at the sub-basin outlet with the highest density of OWTS. Failing OWTS were estimated to be 1% of the total systems and did not have a large impact on stream flow or NO3- load. The NO3- load was 74% of the total N load in the watershed, suggesting the important effect of OWTS on stream loads in urban watersheds.

  6. Synergistic effects of fresh frozen plasma and valproic acid treatment in a combined model of traumatic brain injury and hemorrhagic shock.

    Science.gov (United States)

    Imam, Ayesha M; Jin, Guang; Duggan, Michael; Sillesen, Martin; Hwabejire, John O; Jepsen, Cecilie H; DePeralta, Danielle; Liu, Baoling; Lu, Jennifer; deMoya, Marc A; Socrate, Simona; Alam, Hasan B

    2013-08-01

    Traumatic brain injury (TBI) and hemorrhagic shock (HS) are major causes of trauma-related deaths and are especially lethal as a combined insult. Previously, we showed that early administration of fresh frozen plasma (FFP) decreased the size of the brain lesion and associated swelling in a swine model of combined TBI+HS. We have also shown separately that addition of valproic acid (VPA) to the resuscitation protocol attenuates inflammatory markers in the brain as well as the degree of TBI. The current study was performed to determine whether a combined FFP+VPA treatment strategy would exert a synergistic effect. Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters, intracranial pressure, and brain tissue oxygenation. TBI was created through a 20-mm craniotomy using a computer-controlled cortical impactor: 15-mm cylindrical tip impactor at 4 m/s velocity, 100 ms dwell time, and 12-mm penetration depth. The TBI was synchronized with the initiation of volume-controlled hemorrhage (40 ± 5% of total blood volume). After a 2-hour period of shock, animals were randomized to 1 of 3 resuscitation groups (n = 5 per group): (1) 0.9% saline (NS); (2) FFP; and (3) FFP and VPA 300 mg/kg (FFP+VPA). The resuscitative volume for FFP was equivalent to the shed blood, whereas NS was 3 times this volume. VPA treatment was started 1 hour after hemorrhage. Animals were monitored for 6 hours post-resuscitation. At this time the brains were harvested, sectioned into 5-mm slices, and stained with 2,3,5-triphenyltetrazolium chloride to quantify the lesion size (mm(3)) and brain swelling (percent change compared with the uninjured side). The combined TBI+HS model resulted in a highly reproducible brain injury. Lesion size and brain swelling (mean value ± standard error of the mean) in the FFP+VPA group (1,459 ± 218 mm(3) and 13 ± 1%, respectively) were less than the NS group (3,285 ± 131 mm(3) [P < .001] and 37 ± 2% [P < .001], respectively), and the FFP alone

  7. Modeling of combined effects of citral, linalool and beta-pinene used against Saccharomyces cerevisiae in citrus-based beverages subjected to a mild heat treatment.

    Science.gov (United States)

    Belletti, Nicoletta; Kamdem, Sylvain Sado; Tabanelli, Giulia; Lanciotti, Rosalba; Gardini, Fausto

    2010-01-01

    The aim of this work was to evaluate the antimicrobial activity of three terpenes (citral, linalool and beta-pinene), in combination with a mild heat treatment (55 degrees C, 15 min). The study has been carried out on an orange based soft drink inoculated using a wild strain of Saccharomyces cerevisiae. The results, expressed as growth/no-growth data, were analyzed with the logistic regression. A model comprising only of significant individual parameters (p < or = 0.05) and describing the relationships between terpene concentrations and the probability of having stable beverages was obtained. When citral and beta-pinene were combined, the citral concentration required to achieve a 50% probability of having stable bottles (P=0.5) dropped from 100.9 microL/L in the absence of beta-pinene to 49.3 microL/L in the presence of 20 microL/L of beta-pinene. The mixture of citral and linalool was less effective, in fact, the same probability (P=0.5) was obtained combining 60 microL/L of linalool with 35.1 microL/L of citral. The addition of 20 microL/L of linalool and beta-pinene reinforced citral bioactivity and the concentration of citral needed to reach P=0.5 fell from 100.9 microL/L in the presence of citral alone to 42.0 microL/L. The presence of both linalool and beta-pinene at a concentration of 40 or 60 microL/L in the absence of citral led to a lower spoilage probability (P=0.58 and P=0.93, respectively). It can be concluded that the antimicrobial potential of the three terpenes alone can be strengthened combining appropriate concentrations of each of them. This study confirmed also the potentiating effect of a mild temperature treatment on the antimicrobial efficacy of the molecules. Neither the thermal treatment alone nor the presence of the terpenes at their maximum concentrations (without thermal treatment) were able to guarantee the microbial stability of the beverages. 2009 Elsevier B.V. All rights reserved.

  8. Effect of Preventive and Curative Fingolimod Treatment Regimens on Microglia Activation and Disease Progression in a Rat Model of Multiple Sclerosis

    NARCIS (Netherlands)

    Vállez García, David; Doorduin, Janine; de Paula Faria, Daniele; Dierckx, Rudi A J O; de Vries, Erik F J

    Fingolimod was the first oral drug approved for multiple sclerosis treatment. Its principal mechanism of action is blocking of lymphocyte trafficking. In addition, recent studies have shown its capability to diminish microglia activation. The effect of preventive and curative fingolimod treatment on

  9. Mixed waste treatment model: Basis and analysis

    International Nuclear Information System (INIS)

    Palmer, B.A.

    1995-09-01

    The Department of Energy's Programmatic Environmental Impact Statement (PEIS) required treatment system capacities for risk and cost calculation. Los Alamos was tasked with providing these capacities to the PEIS team. This involved understanding the Department of Energy (DOE) Complex waste, making the necessary changes to correct for problems, categorizing the waste for treatment, and determining the treatment system requirements. The treatment system requirements depended on the incoming waste, which varied for each PEIS case. The treatment system requirements also depended on the type of treatment that was desired. Because different groups contributing to the PEIS needed specific types of results, we provided the treatment system requirements in a variety of forms. In total, some 40 data files were created for the TRU cases, and for the MLLW case, there were 105 separate data files. Each data file represents one treatment case consisting of the selected waste from various sites, a selected treatment system, and the reporting requirements for such a case. The treatment system requirements in their most basic form are the treatment process rates for unit operations in the desired treatment system, based on a 10-year working life and 20-year accumulation of the waste. These results were reported in cubic meters and for the MLLW case, in kilograms as well. The treatment system model consisted of unit operations that are linked together. Each unit operation's function depended on the input waste streams, waste matrix, and contaminants. Each unit operation outputs one or more waste streams whose matrix, contaminants, and volume/mass may have changed as a result of the treatment. These output streams are then routed to the appropriate unit operation for additional treatment until the output waste stream meets the treatment requirements for disposal. The total waste for each unit operation was calculated as well as the waste for each matrix treated by the unit

  10. Assessment of thermal effects in a model of the human head implanted with a wireless active microvalve for the treatment of glaucoma creating a filtering bleb

    Science.gov (United States)

    Schaumburg, F.; Guarnieri, F. A.

    2017-05-01

    A 3D anatomical computational model is developed to assess thermal effects due to exposure to the electromagnetic field required to power a new investigational active implantable microvalve for the treatment of glaucoma. Such a device, located in the temporal superior eye quadrant, produces a filtering bleb, which is included in the geometry of the model, together with the relevant ocular structures. The electromagnetic field source—a planar coil—as well as the microvalve antenna and casing are also included. Exposure to the electromagnetic field source of an implanted and a non-implanted subject are simulated by solving a magnetic potential formulation, using the finite element method. The maximum SAR10 is reached in the eyebrow and remains within the limits suggested by the IEEE and ICNIRP standards. The anterior chamber, filtering bleb, iris and ciliary body are the ocular structures where more absorption occurs. The temperature rise distribution is also obtained by solving the bioheat equation with the finite element method. The numerical results are compared with the in vivo measurements obtained from four rabbits implanted with the microvalve and exposed to the electromagnetic field source.

  11. The effects of exendin-4 treatment on graft failure: an animal study using a novel re-vascularized minimal human islet transplant model.

    Directory of Open Access Journals (Sweden)

    Afaf Sahraoui

    Full Text Available Islet transplantation has become a viable clinical treatment, but is still compromised by long-term graft failure. Exendin-4, a glucagon-like peptide 1 receptor agonist, has in clinical studies been shown to improve insulin secretion in islet transplanted patients. However, little is known about the effect of exendin-4 on other metabolic parameters. We therefore aimed to determine what influence exendin-4 would have on revascularized minimal human islet grafts in a state of graft failure in terms of glucose metabolism, body weight, lipid levels and graft survival. Introducing the bilateral, subcapsular islet transplantation model, we first transplanted diabetic mice with a murine graft under the left kidney capsule sufficient to restore normoglycemia. After a convalescent period, we performed a second transplantation under the right kidney capsule with a minimal human islet graft and allowed for a second recovery. We then performed a left-sided nephrectomy, and immediately started treatment with exendin-4 with a low (20μg/kg/day or high (200μg/kg/day dose, or saline subcutaneously twice daily for 15 days. Blood was sampled, blood glucose and body weight monitored. The transplanted human islet grafts were collected at study end point and analyzed. We found that exendin-4 exerts its effect on failing human islet grafts in a bell-shaped dose-response curve. Both doses of exendin-4 equally and significantly reduced blood glucose. Glucagon-like peptide 1 (GLP-1, C-peptide and pro-insulin were conversely increased. In the course of the treatment, body weight and cholesterol levels were not affected. However, immunohistochemistry revealed an increase in beta cell nuclei count and reduced TUNEL staining only in the group treated with a low dose of exendin-4 compared to the high dose and control. Collectively, these results suggest that exendin-4 has a potential rescue effect on failing, revascularized human islets in terms of lowering blood glucose

  12. Effects of combined treatment of tadalafil and tamsulosin on bladder dysfunction via the inhibition of afferent nerve activities in a rat model of bladder outlet obstruction.

    Science.gov (United States)

    Furuta, Akira; Suzuki, Yasuyuki; Igarashi, Taro; Koike, Yusuke; Egawa, Shin; Yoshimura, Naoki

    2018-03-08

    To investigate the effects of combined treatment of tadalafil (a phosphodiesterase-5 inhibitor) and tamsulosin (an α 1 -adrenoceptor antagonist) on bladder dysfunction in a rat model of bladder outlet obstruction (BOO). Cystometry was performed in conscious female BOO rats 6 weeks after partially ligation of the urethra. Either tadalafil (0.03, 0.1 and 0.3 mg/kg) or tamsulosin (0.001, 0.003 and 0.01 mg/kg) was cumulatively applied intravenously at 30-min intervals to examine changes in cystometric parameters and blood pressures. Changes in cystometric parameters and blood pressures were also checked when tadalafil (0.3 mg/kg), tamsulosin (0.003 mg/kg) or both were intravenously applied. In BOO rats, application of either tadalafil (0.3 mg/kg) or tamsulosin (0.003, 0.01 mg/kg) alone significantly increased threshold pressures and intercontraction intervals whereas there were no significant changes in other cystometric parameters. In addition, because a significant reduction in blood pressures was detected after the administration of tamsulosin (0.01 mg/kg), tamsulosin at a lower dose (0.003 mg/kg) was used for the combined treatment. The combination therapy of tadalafil and tamsulosin induced a significantly larger rate of increase in intercontraction intervals (1.7 times) compared with monotherapy of either drug (1.3 times each) although the combined therapy did not affect blood pressures. These results suggest that the combination therapy of tadalafil and tamsulosin can induce the additive inhibitory effects on urinary frequency compared with monotherapy, more likely via inhibition of the afferent limb of micturition reflex rather than the efferent function as evidenced by the increases in threshold pressures and intercontraction intervals without affecting bladder contractile function.

  13. Effect of pulsed electromagnetic field therapy on prostate volume and vascularity in the treatment of benign prostatic hyperplasia: a pilot study in a canine model.

    Science.gov (United States)

    Leoci, Raffaella; Aiudi, Giulio; Silvestre, Fabio; Lissner, Elaine; Lacalandra, Giovanni Michele

    2014-08-01

    Benign prostatic hyperplasia (BPH) is a result of urogenital aging. Recent studies suggest that an age-related impairment of the blood supply to the lower urinary tract plays a role in the development of BPH and thus may be a contributing factor in the pathogenesis of BPH. The canine prostate is a model for understanding abnormal growth of the human prostate gland. We studied the efficacy of pulsed electromagnetic field therapy (PEMF) in dogs to modify prostate blood flow and evaluated its effect on BPH. PEMF (5 min, twice a day for 3 weeks) was performed on 20 dogs affected by BPH. Prostatic volume, Doppler assessment by ultrasonography, libido, semen quality, testosterone levels, and seminal plasma volume, composition and pH were evaluated before and after treatment. The 3 weeks of PEMF produced a significant reduction in prostatic volume (average 57%) without any interference with semen quality, testosterone levels or libido. Doppler parameters showed a reduction of peripheral resistances and a progressive reduction throughout the trial of the systolic peak velocity, end-diastolic velocity, mean velocity, mean, and peak gradient of the blood flow in the dorsal branch of the prostatic artery. The pulsatility index and the resistance index did not vary significantly over time. The efficacy of PEMF on BPH in dogs, with no side effects, suggests the suitability of this treatment in humans and supports the hypothesis that impairment of blood supply to the lower urinary tract may be a causative factor in the development of BPH. © 2014 The Authors. The Prostate published by Wiley Periodicals, Inc.

  14. Fuel treatment guidebook: illustrating treatment effects on fire hazard

    Science.gov (United States)

    Morris Johnson; David L. Peterson; Crystal Raymond

    2009-01-01

    The Guide to Fuel Treatments (Johnson and others 2007) analyzes potential fuel treatments and the potential effects of those treatments for dry forest lands in the Western United States. The guide examines low- to mid-elevation dry forest stands with high stem densities and heavy ladder fuels, which are currently common due to fire exclusion and various land management...

  15. The effectiveness of stuttering treatments in Germany.

    Science.gov (United States)

    Euler, Harald A; Lange, Benjamin P; Schroeder, Sascha; Neumann, Katrin

    2014-03-01

    Persons who stutter (PWS) should be referred to the most effective treatments available, locally or regionally. A prospective comparison of the effects of the most common stuttering treatments in Germany is not available. Therefore, a retrospective evaluation by clients of stuttering treatments was carried out. The five most common German stuttering treatments (231 single treatment cases) were rated as to their perceived effectiveness, using a structured questionnaire, by 88 PWS recruited through various sources. The participants had received between 1 and 7 treatments for stuttering. Two stuttering treatments (stuttering modification, fluency shaping) showed favorable and three treatments (breathing therapy, hypnosis, unspecified logopedic treatment) showed unsatisfactory effectiveness ratings. The effectiveness ratings of stuttering modification and fluency shaping did not differ significantly. The three other treatments were equally ineffective. The differences between the effective and ineffective treatments were of large effect sizes. The typical therapy biography begins in childhood with an unspecified logopedic treatment administered extensively in single and individual sessions. Available comparisons showed intensive or interval treatments to be superior to extensive treatments, and group treatments to be superior to single client treatments. The stuttering treatment most often prescribed in Germany, namely a weekly session of individual treatment by a speech-language pathologist, usually with an assorted package of mostly unknown components, is of limited effectiveness. Better effectiveness can be expected from fluency shaping or stuttering modification approaches, preferably with an intensive time schedule and with group sessions. Readers will be able to: (a) discuss the five most prevalent stuttering treatments in Germany; (b) summarize the effectiveness of these treatments; and (c) describe structural treatment components that seem to be preferable

  16. Modelling the cost-effectiveness of pregabalin versus usual care in daily practice in the treatment of refractory generalised anxiety disorder in Spain.

    Science.gov (United States)

    De Salas-Cansado, Marina; Álvarez, Enrique; Olivares, José M; Carrasco, Jose L; Ferro, M Belén; Rejas, Javier

    2013-06-01

    To model the cost-effectiveness (CEA) of the use of pregabalin versus usual care (UC) in outpatients with refractory generalised anxiety disorder (GAD) treated in daily practice in mental health settings in Spain. This CEA model used data extracted from a 6-month prospective non-interventional trial: the Amplification of Definition of ANxiety (ADAN) study, which was conducted to determine the cost-of-illness in GAD subjects. Refractory subjects were those who reported persistent symptoms of anxiety and showed suboptimal response in the Hamilton-anxiety scale (HAM-A ≥ 16) after a standard dose regimen of anxiolytics other than pregabalin, alone or in combination, over 6 months. The pregabalin arm was documented with data extracted from patients who received pregabalin in the study for the first time, added or replacing the existing therapy. In the UC arm, treatment might include one or more of the following: a serotonin selective reuptake inhibitor, a serotonin-norepinephrine reuptake inhibitor, other anti-depressants, a benzodiazepine or an anti-epileptic drug other than pregabalin. The time horizon of the modelling was 6 months in the base-case scenario, and the National Health System perspective was chosen to calculate costs. Effectiveness was expressed as quality-adjusted life years (QALYs) gained, which were derived using the EQ-5D questionnaire, at baseline and end-of-trial visits. Results of the CEA model was expressed as an incremental cost-effectiveness ratio (ICER) per QALY gained. Probabilistic sensitivity analysis using bootstrapping techniques was also carried out to obtain the cost-effectiveness plane and the corresponding acceptability curve. Data from a total of 429 subjects per arm (mean HAM-A score 25.7) meeting eligible criteria for inclusion in CEA modelling were extracted from the original trial. Compared with UC, pregabalin (average dose 218 mg/day) was associated with significantly higher QALY gain; 0.1209 ± 0.1030 versus 0.0994

  17. Effects of uncertainties in the thermodynamic properties of aerosol components in an air quality model - Part 1: Treatment of inorganic electrolytes and organic compounds in the condensed phase

    Science.gov (United States)

    Clegg, S. L.; Kleeman, M. J.; Griffin, R. J.; Seinfeld, J. H.

    2008-02-01

    Air quality models that generate the concentrations of semi-volatile and other condensable organic compounds using an explicit reaction mechanism require estimates of the physical and thermodynamic properties of the compounds that affect gas/aerosol partitioning: vapour pressure (as a subcooled liquid), and activity coefficients in the aerosol phase. The model of Griffin, Kleeman and co-workers (e.g., Griffin et al., 2003; Kleeman et al., 1999) assumes that aerosol particles consist of an aqueous phase, containing inorganic electrolytes and soluble organic compounds, and a hydrophobic phase containing mainly primary hydrocarbon material. Thirty eight semi-volatile reaction products are grouped into ten surrogate species which partition between the gas phase and both phases in the aerosol. Activity coefficients of the organic compounds are calculated using UNIFAC. In a companion paper (Clegg et al., 2008) we examine the likely uncertainties in the vapour pressures of the semi-volatile compounds and their effects on partitioning over a range of atmospheric relative humidities. In this work a simulation for the South Coast Air Basin surrounding Los Angeles, using lower vapour pressures of the semi-volatile surrogate compounds consistent with estimated uncertainties in the boiling points on which they are based, yields a doubling of the predicted 24-h average secondary organic aerosol concentrations. The dependency of organic compound partitioning on the treatment of inorganic electrolytes in the air quality model, and the performance of this component of the model, are determined by analysing the results of a trajectory calculation using an extended version of the Aerosol Inorganics Model of Wexler and Clegg (2002). Simplifications are identified where substantial efficiency gains can be made, principally: the omission of dissociation of the organic acid surrogates; restriction of aerosol organic compounds to one of the two phases (aqueous or hydrophobic) where

  18. Effects of uncertainties in the thermodynamic properties of aerosol components in an air quality model - Part I: Treatment of inorganic electrolytes and organic compounds in the condensed phase

    Science.gov (United States)

    Clegg, S. L.; Kleeman, M. J.; Griffin, R. J.; Seinfeld, J. H.

    2007-07-01

    Air quality models that generate the concentrations of semi-volatile and other condensable organic compounds using an explicit reaction mechanism require estimates of the physical and thermodynamic properties of the compounds that affect gas/aerosol partitioning: vapour pressure (as a subcooled liquid), and activity coefficients in the aerosol phase. The model of Griffin, Kleeman and co-workers (e.g., Griffin et al., 1999; Kleeman et al., 1999) assumes that aerosol particles consist of an aqueous phase, containing inorganic electrolytes and soluble organic compounds, and a hydrophobic phase containing mainly primary hydrocarbon material. Thirty eight semi-volatile reaction products are grouped into ten surrogate species which partition between the gas phase and both phases in the aerosol. Activity coefficients of the organic compounds are calculated using UNIFAC. In a companion paper (Clegg et al., 2007) we examine the likely uncertainties in the vapour pressures of the semi-volatile compounds and their effects on partitioning over a range of atmospheric relative humidities. In this work a simulation for the South Coast Air Basin surrounding Los Angeles, using lower vapour pressures of the semi-volatile surrogate compounds consistent with estimated uncertainties in the boiling points on which they are based, yields a doubling of the predicted 24-h average secondary organic aerosol concentrations. The dependency of organic compound partitioning on the treatment of inorganic electrolytes in the air quality model, and the performance of this component of the model, are determined by analysing the results of a trajectory calculation using an extended version of the Aerosol Inorganics Model of Wexler and Clegg (2002). Simplifications are identified where substantial efficiency gains can be made, principally: the omission of dissociation of the organic acid surrogates; restriction of aerosol organic compounds to one of the two phases (aqueous or hydrophobic) where

  19. The Treatment Effectiveness Assessment (TEA

    Directory of Open Access Journals (Sweden)

    Ling W

    2013-09-01

    Full Text Available Walter Ling,1 David Farabee,1 Dagmar Liepa,2 Li-Tzy Wu3 1Integrated Substance Abuse Programs, University of California, Los Angeles, CA, 2Valley Care Medical Center, Panorama City, CA, 3Department of Psychiatry and Behavioral Sciences, School of Medicine, Duke University Medical Center, Durham, NC, USA We have been surprised and gratified by the readers’ responses to our article, The Treatment Effectiveness Assessment (TEA: an efficient, patient-centered instrument for evaluating progress in recovery from addiction, which was published in December 2012.1 In the six months since that time, we have received numerous questions and observations about the article, and about the TEA instrument. Respondents were clinicians: physicians, counselors, therapists, nurses; as well as administrators and policy makers.  View original paper by Ling W, Farabee D, Liepa D, Wu LT. 

  20. Adolescent D-amphetamine treatment in a rodent model of ADHD: Pro-cognitive effects in adolescence without an impact on cocaine cue reactivity in adulthood.

    Science.gov (United States)

    Jordan, Chloe J; Taylor, Danielle M; Dwoskin, Linda P; Kantak, Kathleen M

    2016-01-15

    Attention-deficit/hyperactivity disorder (ADHD) is comorbid with cocaine abuse. Whereas initiating ADHD medication in childhood does not alter later cocaine abuse risk, initiating medication during adolescence may increase risk. Preclinical work in the Spontaneously Hypertensive Rat (SHR) model of ADHD found that adolescent methylphenidate increased cocaine self-administration in adulthood, suggesting a need to identify alternatively efficacious medications for teens with ADHD. We examined effects of adolescent d-amphetamine treatment on strategy set shifting performance during adolescence and on cocaine self-administration and reinstatement of cocaine-seeking behavior (cue reactivity) during adulthood in male SHR, Wistar-Kyoto (inbred control), and Wistar (outbred control) rats. During the set shift phase, adolescent SHR needed more trials and had a longer latency to reach criterion, made more regressive errors and trial omissions, and exhibited slower and more variable lever press reaction times. d-Amphetamine improved performance only in SHR by increasing choice accuracy and decreasing errors and latency to criterion. In adulthood, SHR self-administered more cocaine, made more cocaine-seeking responses, and took longer to extinguish lever responding than control strains. Adolescent d-amphetamine did not alter cocaine self-administration in adult rats of any strain, but reduced cocaine seeking during the first of seven reinstatement test sessions in adult SHR. These findings highlight utility of SHR in modeling cognitive dysfunction and comorbid cocaine abuse in ADHD. Unlike methylphenidate, d-amphetamine improved several aspects of flexible learning in adolescent SHR and did not increase cocaine intake or cue reactivity in adult SHR. Thus, adolescent d-amphetamine was superior to methylphenidate in this ADHD model. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Comparison of treatment effects of teriparatide and the bisphosphonate risedronate in an aged, osteopenic, ovariectomized rat model under various clinical conditions.

    Science.gov (United States)

    Sugie-Oya, Ayano; Takakura, Aya; Takao-Kawabata, Ryoko; Sano, Hiroko; Shimazu, Yukari; Isogai, Yukihiro; Yamaguchi, Akira; Ishizuya, Toshinori

    2016-05-01

    Teriparatide and bisphosphonates are osteoporosis medications that increase bone mineral density (BMD) and prevent fracture, but each has a different mechanism of action. Teriparatide promotes bone formation, while bisphosphonates suppress bone resorption. In the clinical setting, however, drug selection is not always tailored to the particular clinical condition of the patient or mechanism of action of the drug. We compared the effects of teriparatide and the bisphosphonate risedronate on bone metabolism using two ovariectomized rat models to elucidate the optimal use of these two drugs in the clinical setting. We first performed dose-finding experiments to determine the equivalent effective doses of each drug (5.6 and 3.0 µg/kg for teriparatide and risedronate, respectively). We then compared the effects of these doses on bone metabolism after subcutaneous administration three times weekly for 4 months starting either the day after ovariectomy (preventive study) or 12 months after ovariectomy (therapeutic study). The increase in proximal tibial BMD under the physical conditions that increased bone turnover at 1 to 2 months after ovariectomy was greater in the risedronate group than in the teriparatide group. In contrast, the increases in lumbar vertebral BMD and bone strength under the physical conditions that significantly decreased BMD and bone strength at 12 months after ovariectomy were greater in the teriparatide group than in the risedronate group. The present study provides important information on the selection of antiosteoporotic drugs, including teriparatide and risedronate, in treatment protocols tailored to the clinical conditions of patients and drug mechanisms.

  2. Cost-Effectiveness Analysis of the Gonadotropin Treatments HP-hMG and rFSH for Assisted Reproductive Technology in France: A Markov Model Analysis.

    Science.gov (United States)

    Barriere, Paul; Porcu-Buisson, Géraldine; Hamamah, Samir

    2018-02-01

    The objectives of this study were to assess (1) the expected cost of a live birth (LB) after in vitro fertilization with two different gonadotropin treatments [high purified human menopausal gonadotropin (HP-hMG) and recombinant follicle-stimulating hormone (rFSH)] as the single cost variable, and (2) the cost effectiveness of HP-hMG relative to rFSH in the context of the routine practice of assisted reproductive technology (ART) in France. A Markov model was developed to simulate the therapeutic management, the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) courses, and the effects of complications in hypothetical cohorts of 30,000 patients undergoing IVF/ICSI with fresh embryo transfer (up to four attempts) using data from the MERIT and MEGASET clinical trials or from French routine ART practice. The cost per LB was estimated at €12,145 and at €14,247 with HP-hMG and rFSH, respectively, using efficacy data from published clinical trials. The resulting incremental cost-effectiveness ratio (ICER) was - €11,616 per LB. HP-hMG was less expensive by around €15.0 million and more effective by 1289 additional LBs. Using French clinical data, the cost per LB was €16,415 and €18,7531 with HP-hMG and rFSH, respectively. The ICER for HP-hMG versus rFSH was estimated at - €7,719 per LB with a saving of about €8.54 million and 1097 additional LBs. Deterministic sensitivity analyses showed that the main ICER drivers were the LB rate, followed by the total gonadotropin doses. The probabilistic sensitivity analysis indicated that HP-hMG was the dominant strategy in 71.2% of cases using the clinical trial data and in 50.2% of cases using the French data. This analysis indicates that compared with rFSH, HP-hMG is less costly for IVF/ICSI management from the French healthcare payer's viewpoint. The results of the present Markov model analysis are consistent with previous findings in other European countries.

  3. Evaluation of 5536 patients treated in an integrative outpatient tinnitus treatment center-immediate effects and a modeling approach for sustainability.

    Science.gov (United States)

    Ostermann, Thomas; Boehm, Katja; Kusatz, Martin

    2016-08-11

    Tinnitus is an increasingly serious problem for health care systems. According to epidemiological data, 7-14 % of outpatients have asked their physician about tinnitus and management strategies. Integrative outpatient treatments are currently regarded as promising therapeutic approaches for managing tinnitus. In this article we report on the treatment success of an outpatient tinnitus treatment center in Germany. This cohort study included pre-post data of 5536 outpatients which were treated between 2003 and 2010 in the tinnitus-therapy center, Krefeld-Düsseldorf (TTZ). The intervention consisted of psychological immunization training as well as an auditory stimulation therapy component. The main outcome parameter was the score of the Tinnitus Questionnaire (TQ) which was assessed before and after a 9 days treatment and (in a small subsample) at a 6 months follow-up. Missing data were multiply imputed. Pre-post effect sizes were calculated and adjusted for regression to the mean (RTM). RTM-adjusted treatment effects at the end of treatment were estimated as -18.6 (CI: -18.9 to 18.2, p < 0.001) score points which corresponds to a standardized effect of d = -1.03 (CI: -1.05 to -1.01). These effects can be corroborated in various subgroups and all subscales of the TQ (d ranging from -0.31 to -0.97). The study suggests the effectiveness of this outpatient tinnitus therapy concept. Multiple imputations techniques and RTM analysis were helpful in carving out true treatment effects.

  4. Effects of tailored neck-shoulder pain treatment based on a decision model guided by clinical assessments and standardized functional tests. A study protocol of a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Björklund Martin

    2012-05-01

    Full Text Available Abstract Background A major problem with rehabilitation interventions for neck pain is that the condition may have multiple causes, thus a single treatment approach is seldom efficient. The present study protocol outlines a single blinded randomised controlled trial evaluating the effect of tailored treatment for neck-shoulder pain. The treatment is based on a decision model guided by standardized clinical assessment and functional tests with cut-off values. Our main hypothesis is that the tailored treatment has better short, intermediate and long-term effects than either non-tailored treatment or treatment-as-usual (TAU on pain and function. We sub-sequentially hypothesize that tailored and non-tailored treatment both have better effect than TAU. Methods/Design 120 working women with minimum six weeks of nonspecific neck-shoulder pain aged 20–65, are allocated by minimisation with the factors age, duration of pain, pain intensity and disability in to the groups tailored treatment (T, non-tailored treatment (NT or treatment-as-usual (TAU. Treatment is given to the groups T and NT for 11 weeks (27 sessions evenly distributed. An extensive presentation of the tests and treatment decision model is provided. The main treatment components are manual therapy, cranio-cervical flexion exercise and strength training, EMG-biofeedback training, treatment for cervicogenic headache, neck motor control training. A decision algorithm based on the baseline assessment determines the treatment components given to each participant of T- and NT-groups. Primary outcome measures are physical functioning (Neck Disability Index and average pain intensity last week (Numeric Rating Scale. Secondary outcomes are general improvement (Patient Global Impression of Change scale, symptoms (Profile Fitness Mapping neck questionnaire, capacity to work in the last 6 weeks (quality and quantity and pressure pain threshold of m. trapezius. Primary and secondary outcomes will

  5. Methodology for the treatment of model uncertainty

    Science.gov (United States)

    Droguett, Enrique Lopez

    The development of a conceptual, unified, framework and methodology for treating model and parameter uncertainties is the subject of this work. Firstly, a discussion on the philosophical grounds of notions such as reality, modeling, models, and their relation is presented. On this, a characterization of the modeling process is presented. The concept of uncertainty, addressing controversial topics such as type and sources of uncertainty, are investigated arguing that uncertainty is fundamentally a characterization of lack of knowledge and as such all uncertainty are of the same type. A discussion about the roles of a model structure and model parameters is presented, in which it is argued that a distinction is for convenience and a function of the stage in the modeling process. From the foregoing discussion, a Bayesian framework for an integrated assessment of model and parameter uncertainties is developed. The methodology has as its central point the treatment of model as source of information regarding the unknown of interest. It allows for the assessment of the model characteristics affecting its performance, such as bias and precision. It also permits the assessment of possible dependencies among multiple models. Furthermore, the proposed framework makes possible the use of not only information from models (e.g., point estimates, qualitative assessments), but also evidence about the models themselves (performance data, confidence in the model, applicability of the model). The methodology is then applied in the context of fire risk models where several examples with real data are studied. These examples demonstrate how the framework and specific techniques developed in this study can address cases involving multiple models, use of performance data to update the predictive capabilities of a model, and the case where a model is applied in a context other than one for which it is designed.

  6. Anti-CD45 radioimmunotherapy with 90Y but not 177Lu is effective treatment in a syngeneic murine leukemia model.

    Directory of Open Access Journals (Sweden)

    Johnnie J Orozco

    Full Text Available Radioimmunotherapy (RIT for treatment of hematologic malignancies has primarily employed monoclonal antibodies (Ab labeled with 131I or 90Y which have limitations, and alternative radionuclides are needed to facilitate wider adoption of RIT. We therefore compared the relative therapeutic efficacy and toxicity of anti-CD45 RIT employing 90Y and 177Lu in a syngeneic, disseminated murine myeloid leukemia (B6SJLF1/J model. Biodistribution studies showed that both 90Y- and 177Lu-anti-murine CD45 Ab conjugates (DOTA-30F11 targeted hematologic tissues, as at 24 hours 48.8 ± 21.2 and 156 ± 14.6% injected dose per gram of tissue (% ID/g of 90Y-DOTA-30F11 and 54.2 ± 9.5 and 199 ± 11.7% ID/g of 177Lu-DOTA-30F11 accumulated in bone marrow (BM and spleen, respectively. However, 90Y-DOTA-30F11 RIT demonstrated a dose-dependent survival benefit: 60% of mice treated with 300 µCi 90Y-DOTA-30F11 lived over 180 days after therapy, and mice treated with 100 µCi 90Y-DOTA-30F11 had a median survival 66 days. 90Y-anti-CD45 RIT was associated with transient, mild myelotoxicity without hepatic or renal toxicity. Conversely, 177Lu- anti-CD45 RIT yielded no long-term survivors. Thus, 90Y was more effective than 177Lu for anti-CD45 RIT of AML in this murine leukemia model.

  7. Adverse effects of breast cancer treatment.

    Science.gov (United States)

    Odle, Teresa G

    2014-01-01

    As breast cancer outcomes improve and more people with breast cancer survive longer following diagnosis, many survivors must deal with the effects of treatment. Some adverse effects last a short time and have little influence on breast cancer patients' quality of life, yet others can cause long-term complications and add to increased morbidity and mortality among survivors. This article reviews the adverse effects of breast cancer treatments and how they affect the health and quality of life of those receiving treatment. The article also explains how adverse effects can interrupt treatment and how physicians and survivors can manage adverse effects of breast cancer treatment.

  8. Barthel Index-Enhanced Feedback for Effective Cardiac Treatment (BI-EFFECT) Study: contribution of the Barthel Index to the Heart Failure Risk Scoring System model in elderly adults with acute heart failure in the emergency department.

    Science.gov (United States)

    Martín-Sánchez, F Javier; Gil, Víctor; Llorens, Pere; Herrero, Pablo; Jacob, Javier; Fernández, Cristina; Miró, Òscar

    2012-03-01

    To evaluate whether the Enhanced Feedback for Effective Cardiac Treatment (EFFECT) scale for 30-day prediction of mortality is applicable to elderly adults with acute heart failure (AHF) in emergency departments (EDs) and whether discriminatory power is added with the inclusion of the Barthel Index (BI) to this scale (BI-EFFECT scale). BI-EFFECT is a multipurpose, nonintervention, multicenter cohort study. Twenty EDs. Individuals aged 65 and older with AHF. Information on baseline and episode characteristics and 30-day mortality was collected, and participants were categorized according to the EFFECT scale. Baseline degree of functional dependence was measured using the BI. Receiver operating characteristic (ROC) curves were made of the EFFECT and BI-EFFECT scales to predict mortality. One thousand sixty-eight participants were included. Thirty-day mortality was 5.1% and was directly and independently associated with high and very high risk categories of the EFFECT scale and with severe dependence. These two variables remained significant after adjustment of the model for both (OR = 4.5, 95% CI = 1.8-11.1 and OR = 2.9, 95% CI = 1.6-5.4, respectively). The EFFECT and the BI-EFFECT scales had significant ROC curves (area under the ROC curve (AUC) = 0.69, 95% CI = from 0.62 to 0.76; and AUC = 0.75, 95% CI = 0.69-0.81, respectively), and the difference in discriminatory power between the second and the first was also statistically significant (P = .02). The EFFECT scale may be applied in the elderly population, and inclusion of functional status according to the BI in the new BI-EFFECT scale significantly improves the model for the prediction of 30-day mortality. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

  9. Multistrain models predict sequential multidrug treatment strategies to result in less antimicrobial resistance than combination treatment

    DEFF Research Database (Denmark)

    Ahmad, Amais; Zachariasen, Camilla; Christiansen, Lasse Engbo

    2016-01-01

    generated by a mathematical model of the competitive growth of multiple strains of Escherichia coli.Results: Simulation studies showed that sequential use of tetracycline and ampicillin reduced the level of double resistance, when compared to the combination treatment. The effect of the cycling frequency...... (how frequently antibiotics are alternated in a sequential treatment) of the two drugs was dependent upon the order in which the two drugs were used.Conclusion: Sequential treatment was more effective in preventing the growth of resistant strains when compared to the combination treatment. The cycling...... frequency did not play a role in suppressing the growth of resistant strains, but the specific order of the two antimicrobials did. Predictions made from the study could be used to redesign multidrug treatment strategies not only for intramuscular treatment in pigs, but also for other dosing routes....

  10. Cost-effectiveness of preventive treatment of intracranial aneurysms New data and uncertainties

    NARCIS (Netherlands)

    Greving, Jacoba P.; Rinkel, Gabriel J. E.; Buskens, Erik; Algra, Ale

    2009-01-01

    Background: Previous modeling studies on treatment of unruptured intracranial aneurysms largely disregarded detailed data on treatment risks and omitted several factors that could influence cost-effectiveness. We performed a cost-effectiveness analysis of surgical and endovascular treatment of

  11. Hydraulic modelling of drinking water treatment plant operations

    Directory of Open Access Journals (Sweden)

    L. C. Rietveld

    2009-06-01

    Full Text Available The flow through a unit of a drinking water treatment plant is one of the most important parameters in terms of a unit's effectiveness. In the present paper, a new EPAnet library is presented with the typical hydraulic elements for drinking water treatment processes well abstraction, rapid sand filtration and cascade and tower aeration. Using this treatment step library, a hydraulic model was set up, calibrated and validated for the drinking water treatment plant Harderbroek. With the actual valve position and pump speeds, the flows were calculated through the several treatment steps. A case shows the use of the model to calculate the new setpoints for the current frequency converters of the effluent pumps during a filter backwash.

  12. Treatment of severe chronic hypotonic hyponatremia: a new treatment model

    Directory of Open Access Journals (Sweden)

    Antonio Burgio

    2013-03-01

    Full Text Available Recommended treatment of severe hypotonic hyponatremia is based on the infusion of 3% sodium chloride solution, with a daily correction rate below 10 mEq/L of sodium concentration, according to the Adrogué and Madias formula that includes the current desired change in sodium concentrations. However, such treatment needs close monitoring of the rate of infusion and does not take into account the body weight or age of the patient. This may result in hypercorrection and neurological damage. We made an inverse calculation using the same algorithms of the Adrogué and Madias formula to estimate the number of vials of sodium chloride needed to reach a correction rate of the serum sodium concentration below 0.4 mEq/h, taking into account the body weight and age of the patient. Three tables have been produced, each containing the number of vials to be infused, according to the patient’s age and body weight, the serum sodium concentration, and the rate of correction over 24 h to avoid the risk of brain damage. We propose a new practical model to calculate the need of sodium chloride infusate to safely correct the hyponatremia. The tables make treatment easier to manage in daily clinical practice in a wide range of patient ages and body weights.

  13. Development and assessment of an integrated ecological modelling framework to assess the effect of investments in wastewater treatment on water quality.

    Science.gov (United States)

    Holguin-Gonzalez, Javier E; Boets, Pieter; Everaert, Gert; Pauwels, Ine S; Lock, Koen; Gobeyn, Sacha; Benedetti, Lorenzo; Amerlinck, Youri; Nopens, Ingmar; Goethals, Peter L M

    2014-01-01

    Worldwide, large investments in wastewater treatment are made to improve water quality. However, the impacts of these investments on river water quality are often not quantified. To assess water quality, the European Water Framework Directive (WFD) requires an integrated approach. The aim of this study was to develop an integrated ecological modelling framework for the River Drava (Croatia) that includes physical-chemical and hydromorphological characteristics as well as the ecological river water quality status. The developed submodels and the integrated model showed accurate predictions when comparing the modelled results to the observations. Dissolved oxygen and nitrogen concentrations (ammonium and organic nitrogen) were the most important variables in determining the ecological water quality (EWQ). The result of three potential investment scenarios of the wastewater treatment infrastructure in the city of Varaždin on the EWQ of the River Drava was assessed. From this scenario-based analysis, it was concluded that upgrading the existing wastewater treatment plant with nitrogen and phosphorus removal will be insufficient to reach a good EWQ. Therefore, other point and diffuse pollution sources in the area should also be monitored and remediated to meet the European WFD standards.

  14. Thrombolytic and anticoagulation treatment in a rat embolic stroke model

    DEFF Research Database (Denmark)

    Rasmussen, Rune Skovgaard; Overgaard, K; Meden, P

    2003-01-01

    OBJECTIVES: The effects of pentasaccharide (PENTA), given alone or combined with thrombolysis using recombinant tissue plasminogen activator (rt-PA), on infarct size and clinical outcome were evaluated in a rat embolic stroke model. MATERIALS AND METHODS: Ninety-two rats were embolized unilaterally...... group, 4% (P treatment. Compared with rt-PA treatment alone, 0.5 mg/kg PENTA...... alone or combined with rt-PA did not significantly increase mortality or tendency for hemorrhage....

  15. Effectiveness and cost-effectiveness of potential responses to future high levels of transmitted HIV drug resistance in antiretroviral drug-naive populations beginning treatment: modelling study and economic analysis.

    Science.gov (United States)

    Phillips, Andrew N; Cambiano, Valentina; Miners, Alec; Revill, Paul; Pillay, Deenan; Lundgren, Jens D; Bennett, Diane; Raizes, Elliott; Nakagawa, Fumiyo; De Luca, Andrea; Vitoria, Marco; Barcarolo, Jhoney; Perriens, Joseph; Jordan, Michael R; Bertagnolio, Silvia

    2014-11-01

    With continued roll-out of antiretroviral therapy (ART) in resource-limited settings, evidence is emerging of increasing levels of transmitted drug-resistant HIV. We aimed to compare the effectiveness and cost-effectiveness of different potential public health responses to substantial levels of transmitted drug resistance. We created a model of HIV transmission, progression, and the effects of ART, which accounted for resistance generation, transmission, and disappearance of resistance from majority virus in the absence of drug pressure. We simulated 5000 ART programmatic scenarios with different prevalence levels of detectable resistance in people starting ART in 2017 (t0) who had not previously been exposed to antiretroviral drugs. We used the model to predict cost-effectiveness of various potential changes in policy triggered by different prevalence levels of resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) measured in the population starting ART. Individual-level resistance testing before ART initiation was not generally a cost-effective option, irrespective of the cost-effectiveness threshold. At a cost-effectiveness threshold of US$500 per quality-adjusted life-year (QALY), no change in policy was cost effective (ie, no change in policy would involve paying less than $500 per QALY gained), irrespective of the prevalence of pretreatment NNRTI resistance, because of the increased cost of the policy alternatives. At thresholds of $1000 or higher, and with the prevalence of pretreatment NNRTI resistance greater than 10%, a policy to measure viral load 6 months after ART initiation became cost effective. The policy option to change the standard first-line treatment to a boosted protease inhibitor regimen became cost effective at a prevalence of NNRTI resistance higher than 15%, for cost-effectiveness thresholds greater than $2000. Cost-effectiveness of potential policies to adopt in response to different levels of pretreatment HIV drug

  16. The effectiveness of neuro-music therapy according to the Heidelberg model compared to a single session of educational counseling as treatment for tinnitus: a controlled trial.

    Science.gov (United States)

    Argstatter, Heike; Grapp, Miriam; Hutter, Elisabeth; Plinkert, Peter K; Bolay, Hans-Volker

    2015-03-01

    Tinnitus is a very common symptom, yet the quest for an effective treatment is challenging. Results from several clinical trials support the notion that neuro-music therapy is an effective means to reduce tinnitus distress with short duration and long lasting effect. However, until now, the effectiveness has not been tested in a controlled trial against an active comparator. The trial was designed as two-center, parallel intervention group controlled study with two intervention groups: Counseling (50minute individualized personal instruction) or neuro-music therapy (counseling plus eight 50-minute sessions of individualized music therapy). Data of n=290 patients suffering from chronic tinnitus were analyzed. Outcome measure was the change in Tinnitus Questionnaire Total Scores (TQ) from baseline (admission) to end of treatment. Both treatment groups achieved a statistically relevant reduction in TQ scores, though 66% of patients in the music therapy group attained a clinically meaningful improvement compared to 33% in the counseling group. A binary logistic regression revealed two variables significantly influencing therapy outcome: initial tinnitus score and type of therapy with an OR for the music therapy compared to the counseling of 4.34 (CI 2.33-8.09). Counseling is an appropriate treatment option with well above chance of improvement. The neuro-music therapy outperformed the counseling. This treatment targets the tinnitus sound itself, is short in duration, intrinsically motivating and easy to operate and thus presents a possible complement to the therapeutic spectrum in chronic tinnitus. The trial was registered at the ClinicalTrials.gov registry (ID: NCT01845155). Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Incorporating model parameter uncertainty into inverse treatment planning

    International Nuclear Information System (INIS)

    Lian Jun; Xing Lei

    2004-01-01

    Radiobiological treatment planning depends not only on the accuracy of the models describing the dose-response relation of different tumors and normal tissues but also on the accuracy of tissue specific radiobiological parameters in these models. Whereas the general formalism remains the same, different sets of model parameters lead to different solutions and thus critically determine the final plan. Here we describe an inverse planning formalism with inclusion of model parameter uncertainties. This is made possible by using a statistical analysis-based frameset developed by our group. In this formalism, the uncertainties of model parameters, such as the parameter a that describes tissue-specific effect in the equivalent uniform dose (EUD) model, are expressed by probability density function and are included in the dose optimization process. We found that the final solution strongly depends on distribution functions of the model parameters. Considering that currently available models for computing biological effects of radiation are simplistic, and the clinical data used to derive the models are sparse and of questionable quality, the proposed technique provides us with an effective tool to minimize the effect caused by the uncertainties in a statistical sense. With the incorporation of the uncertainties, the technique has potential for us to maximally utilize the available radiobiology knowledge for better IMRT treatment

  18. New treatment models for compulsive disorders

    NARCIS (Netherlands)

    Grant, Jon E; Fineberg, Naomi; van Ameringen, Michael; Cath, Danielle; Visser, Henny; Carmi, Lior; Pallanti, Stefano; Hollander, Eric; van Balkom, Anton J L M

    Obsessive compulsive disorder (OCD) as well as related disorders such as body dysmorphic disorder, tic disorder, and trichotillomania are all common and often debilitating. Although treatments are available, more effective approaches to these problems are needed. Thus this review article presents

  19. Modeling information technology effectiveness

    OpenAIRE

    Aleksander Lotko

    2005-01-01

    Numerous cases of systems not bringing expected results cause that investments in information technology are treated more and more carefully and are not privileged amongst others. This gives rise to the need for applying costs–effect calculations. Modeling IT effectiveness is a procedure which helps to bring system complexity under control. By using proper measures it is possible to perform an objective investment appraisal for projects under consideration. In the paper, a framework of method...

  20. Inositol-deficient food augments a behavioral effect of long-term lithium treatment mediated by inositol monophosphatase inhibition: an animal model with relevance for bipolar disorder.

    Science.gov (United States)

    Shtein, Liza; Agam, Galila; Belmaker, R H; Bersudsky, Yuly

    2015-04-01

    Lithium treatment in rodents markedly enhances cholinergic agonists such as pilocarpine. This effect can be reversed in a stereospecific manner by administration of inositol, suggesting that the effect of lithium is caused by inositol monophosphatase inhibition and consequent inositol depletion. If so, inositol-deficient food would be expected to enhance lithium effects. Inositol-deficient food was prepared from inositol-free ingredients. Mice with a homozygote knockout of the inositol monophosphatase 1 gene unable to synthesize inositol endogenously and mimicking lithium-treated animals were fed this diet or a control diet. Lithium-treated wild-type animals were also treated with the inositol-deficient diet or control diet. Pilocarpine was administered after 1 week of treatment, and behavior including seizures was assessed using rating scale. Inositol-deficient food-treated animals, both lithium treated and with inositol monophosphatase 1 knockout, had significantly elevated cholinergic behavior rating and significantly increased or earlier seizures compared with the controls. The effect of inositol-deficient food supports the role of inositol depletion in the effects of lithium on pilocarpine-induced behavior. However, the relevance of this behavior to other more mood-related effects of lithium is not clear.

  1. Modeling of the laser and lamp treatment of telangiectasia

    Science.gov (United States)

    Al'Tshuler, G. B.; Smirnov, M. Z.; Pushkareva, A. E.

    2004-07-01

    The effects of monochromatic and polychromatic radiation on human skin and veins are modeled on the basis of the theory of radiation transfer and the theory of heat conduction. Using the criteria of safety and efficiency of treatment, conclusions regarding the optimal parameters of sources of radiation are drawn.

  2. Modelling of Activated Sludge Wastewater Treatment

    Directory of Open Access Journals (Sweden)

    Kurtanjeka, Ž.

    2008-02-01

    Full Text Available Activated sludge wastewater treatment is a highly complex physical, chemical and biological process, and variations in wastewater flow rate and its composition, combined with time-varying reactions in a mixed culture of microorganisms, make this process non-linear and unsteady. The efficiency of the process is established by measuring the quantities that indicate quality of the treated wastewater, but they can only be determined at the end of the process, which is when the water has already been processed and is at the outlet of the plant and released into the environment.If the water quality is not acceptable, it is already too late for its improvement, which indicates the need for a feed forward process control based on a mathematical model. Since there is no possibility of retracing the process steps back, all the mistakes in the control of the process could induce an ecological disaster of a smaller or bigger extent. Therefore, models that describe this process well may be used as a basis for monitoring and optimal control of the process development. This work analyzes the process of biological treatment of wastewater in the Velika Gorica plant. Two empirical models for the description of the process were established, multiple linear regression model (MLR with 16 predictor variables and piecewise linear regression model (PLR with 17 predictor variables. These models were developed with the aim to predict COD value of the effluent wastewater at the outlet, after treatment. The development of the models is based on the statistical analysis of experimental data, which are used to determine the relations among individual variables. In this work are applied linear models based on multiple linear regression (MLR and partial least squares (PLR methods. The used data were obtained by everyday measurements of the quantities that indicate the quality of the input and output water, working conditions of the plant and the quality of the activated sludge

  3. Stability of additive treatment effects in multiple treatment comparison meta-analysis: a simulation study

    Directory of Open Access Journals (Sweden)

    Mills E

    2012-04-01

    Full Text Available Kristian Thorlund1, Edward Mills1,21Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, 2Faculty of Health Sciences, University of Ottawa, Ottawa, ON, CanadaBackground: Many medical interventions are administered in the form of treatment combinations involving two or more individual drugs (eg, drug A + drug B. When the individual drugs and drug combinations have been compared in a number of randomized clinical trials, it is possible to quantify the comparative effectiveness of all drugs simultaneously in a multiple treatment comparison (MTC meta-analysis. However, current MTC models ignore the dependence between drug combinations (eg, A + B and the individual drugs that are part of the combination. In particular, current models ignore the possibility that drug effects may be additive, ie, the property that the effect of A and B combined is equal to the sum of the individual effects of A and B. Current MTC models may thus be suboptimal for analyzing data including drug combinations when their effects are additive or approximately additive. However, the extent to which the additivity assumption can be violated before the conventional model becomes the more optimal approach is unknown. The objective of this study was to evaluate the comparative statistical performance of the conventional MTC model and the additive effects MTC model in MTC scenarios where additivity holds true, is mildly violated, or is strongly violated.Methods: We simulated MTC scenarios in which additivity held true, was mildly violated, or was strongly violated. For each scenario we simulated 500 MTC data sets and applied the conventional and additive effects MTC models in a Bayesian framework. Under each scenario we estimated the proportion of treatment effect estimates that were 20% larger than ‘the truth' (ie, % overestimates, the proportion that were 20% smaller than ‘the truth' (ie, % underestimates,The coverage of the 95% credible

  4. Treatment model of dengue hemorrhagic fever infection in human body

    Science.gov (United States)

    Handayani, D.; Nuraini, N.; Primasari, N.; Wijaya, K. P.

    2014-03-01

    The treatment model of DHF presented in this paper involves the dynamic of five time-dependent compartments, i.e. susceptible, infected, free virus particle, immune cell, and haematocrit level. The treatment model is investigated based on normalization of haematocrit level, which is expressed as intravenous fluid infusion control. We analyze the stability of the disease free equilibrium and the endemic equilibrium. The numerical simulations will explain the dynamic of each compartment in human body. These results show particularly that infected compartment and free virus particle compartment are tend to be vanished in two weeks after the onset of dengue virus. However, these simulation results also show that without the treatment, the haematocrit level will decrease even though not up to the normal level. Therefore the effective haematocrit normalization should be done with the treatment control.

  5. Synergistic effects of fresh frozen plasma and valproic acid treatment in a combined model of traumatic brain injury and hemorrhagic shock

    DEFF Research Database (Denmark)

    Imam, Ayesha M; Jin, Guang; Duggan, Michael

    2013-01-01

    Traumatic brain injury (TBI) and hemorrhagic shock (HS) are major causes of trauma-related deaths and are especially lethal as a combined insult. Previously, we showed that early administration of fresh frozen plasma (FFP) decreased the size of the brain lesion and associated swelling in a swine...... model of combined TBI+HS. We have also shown separately that addition of valproic acid (VPA) to the resuscitation protocol attenuates inflammatory markers in the brain as well as the degree of TBI. The current study was performed to determine whether a combined FFP+VPA treatment strategy would exert...

  6. Short-term simvastatin treatment has no effect on plasma cytokine response in a human in vivo model of low-grade inflammation

    DEFF Research Database (Denmark)

    Erikstrup, C; Ullum, H; Pedersen, Bente Klarlund

    2006-01-01

    Statins reduce plasma cholesterol, but clinical trials and in vitro studies indicate that they might also possess anti-inflammatory properties. The effect of simvastatin on circulating cytokines and leucocytes was evaluated in a human in vivo model of low-grade inflammation. Thirty young healthy...

  7. A Computational Modeling Mystery Involving Airfoil Trailing Edge Treatments

    Science.gov (United States)

    Choo, Yeunun; Epps, Brenden

    2015-11-01

    In a curious result, Fairman (2002) observed that steady RANS calculations predicted larger lift than the experimentally-measured data for six different airfoils with non-traditional trailing edge treatments, whereas the time average of unsteady RANS calculations matched the experiments almost exactly. Are these results reproducible? If so, is the difference between steady and unsteady RANS calculations a numerical artifact, or is there a physical explanation? The goals of this project are to solve this thirteen year old mystery and further to model viscous/load coupling for airfoils with non-traditional trailing edges. These include cupped, beveled, and blunt trailing edges, which are common anti-singing treatments for marine propeller sections. In this talk, we present steady and unsteady RANS calculations (ANSYS Fluent) with careful attention paid to the possible effects of asymmetric unsteady vortex shedding and the modeling of turbulence anisotropy. The effects of non-traditional trailing edge treatments are visualized and explained.

  8. [AIT (Adolescent Identity Treatment) - an Integrative Treatment Model for the Treatment of Personality Disorders].

    Science.gov (United States)

    Schlüter-Müller, Susanne

    2017-07-01

    AIT (Adolescent Identity Treatment) - an Integrative Treatment Model for the Treatment of Personality Disorders Personality disorders are patterns of maladaptive personality traits that have an impact on the individual throughout the life span. Borderline Personality Disorder (BPD) is a very severe, but treatable mental disorder. Identity disturbance is seen as the central construct for detecting severe personality pathology - and, most notably, borderline personality disorder - in adults and adolescents. Crises in the development of identity usually resolve into a normal and consolidated identity with flexible and adaptive functioning whereas identity diffusion is viewed as a lack of integration of the concept of the self and significant others. It is seen as the basis for subsequent personality pathology, including that of borderline personality disorder. Although BPD has its onset in adolescence and emerging adulthood the diagnosis is often delayed. In most cases, specific treatment is only offered late in the course of the disorder and to relatively few individuals. Adolescent Identity Treatment (AIT) is a treatment model that focuses on identity pathology as the core characteristic of personality disorders. This model integrates specific techniques for the treatment of adolescent personality pathology on the background of object-relation theories and modified elements of Transference-Focused Psychotherapy. Moreover, psychoeducation, a behavior-oriented homeplan and intensive family work is part of AIT.

  9. Evaluation model of the effect of Rofecoxib on the co-prescription of gastroprotective agents observed during the treatment of ostheoarthritis

    Directory of Open Access Journals (Sweden)

    E. Degli Esposti

    2011-09-01

    Full Text Available Objective: This study was conducted to define an evaluation model to estimate changes in the co-prescription of gastroprotective agents (GPAs induced by rofecoxib in the treatment of osteoarthritis (OA. Methods: On the basis of a cross-linking information, which were stored in different administrative and clinical databases, a multivariate regression analysis was used to develop the model. Data were collected by 30 general practitioners of the Local Health Unit of Ravenna (middle-north of Italy. Results: The study population consisted of 2,944 patients treated with non-steroidal anti-inflammatory drugs (NSAIDs and 487 treated with rofecoxib. Patients treated with rofecoxib generally presented a higher number of gastrointestinal damage risk factors and also a lower level of GPAs co-prescription compared to those treated with NSAIDs. Including in the model variables such as type of anti-inflammatory treatment (NSAIDs or rofecoxib, gender, age by class, previous hospital admissions due to gastrointestinal complications, number of different NSAIDs used, and prescription of corticosteroids, the regression equation and its coefficients were identified. A non-linear relationship between the percentage of patients treated with rofecoxib and the relative reduction of GPAs co-prescription was found. It has been estimated the basis of the registered percentage of patients treated with rofecoxib (17,6% adjusting for gastrointestinal demage risk factors, and on a 63% (IC95%: 55%-70% relative reduction of GPA use with rofecoxib with respect to NSAIDs was estimated. Conclusions: Based on data collected in the clinical practice after the introduction of rofecoxib, a model evaluating the relationship between the frequency of its use in the OA population and the expected reduction of GPAs, has been developed.

  10. Effects of the Treatment with ‍Nigella sativa Oil on Brain Injury and Edema in Experimental Model of Stroke in Rats

    Directory of Open Access Journals (Sweden)

    H Panahpour

    2015-09-01

    Full Text Available Background & objectives: Stroke is third leading cause of death and disability in the most of human communities. The use of herbs and medicinal plants in different countries is increasing. Today, herbal medicine is used as alternative or complementary therapies with a fewer side effects. Nigella sativa has a rich medical and religious history. Oxidative stress has important role in the pathophysiology of stroke. As Nigella sativa has antioxidant effects, its administration may produce a protective effect against complications of this disease. We examined the effects of the treatment with Nigella sativa oil on the cerebral infarction and edema. Methods: 48 Male Sprague-Dawley rats were divided into three groups, sham, control ischemic and Nigella sativa oil treated (2 ml/kg ischemic groups. Transient focal cerebral ischemia was induced by 90-min-long occlusion of the left middle cerebral artery followed by 24-h-long reperfusion. Neurological deficit score was evaluated at the end of the reperfusion period. Thereafter, the animals were randomly selected and used for two projects: (i Measurement of the infarct volumes and neurological outcome (ii investigation of ischemic brain edema formation using a wet/dry method. Results: Induction of cerebral ischemia in the control group produced considerable brain infarction in conjunction with impaired motor functions and severely brain edema. Treatment with Nigella sativa oil significantly reduced the infarct volume and improved the motor functions. The water content in the left (lesioned hemisphere was considerably elevated in the control ischemic group. Administration of the Nigella sativa oil significantly lowered the water content in the ischemic lesioned hemisphere. Conclusion: Treatment with Nigella sativa oil can noticeably decrease the ischemic brain injury, attenuate edema formation and improve motor disabilities.

  11. Costs and water quality effects of wastewater treatment plant centralization

    Energy Technology Data Exchange (ETDEWEB)

    Macal, C.M.; Broomfield, B.J.

    1980-01-01

    The costs and water quality impacts of two regional configurations of municipal wastewater treatment plants in Northeastern Illinois are compared. In one configuration, several small treatment plants are consolidated into a smaller number of regional facilities. In the other, the smaller plants continue to operate. Costs for modifying the plants to obtain various levels of pollutant removal are estimated using a simulation model that considers the type of equipment existing at the plants and the costs of modifying that equipment to obtain a range of effluent levels for various pollutants. A dynamic water-quality/hydrology simulation model is used to determine the water quality effects of the various treatment technologies and pollutant levels. Cost and water quality data are combined and the cost-effectiveness of the two treatment configurations is compared. The regionalized treatment-plant configuration is found to be the more cost-effective.

  12. Relaxing monotonicity in the identification of local average treatment effects

    DEFF Research Database (Denmark)

    Huber, Martin; Mellace, Giovanni

    In heterogeneous treatment effect models with endogeneity, the identification of the local average treatment effect (LATE) typically relies on an instrument that satisfies two conditions: (i) joint independence of the potential post-instrument variables and the instrument and (ii) monotonicity...... of the treatment in the instrument, see Imbens and Angrist (1994). We show that identification is still feasible when replacing monotonicity by a strictly weaker local monotonicity condition. We demonstrate that the latter allows identifying the LATEs on the (i) compliers (whose treatment reacts to the instrument...

  13. Training effectiveness evaluation model

    International Nuclear Information System (INIS)

    Penrose, J.B.

    1993-01-01

    NAESCO's Training Effectiveness Evaluation Model (TEEM) integrates existing evaluation procedures with new procedures. The new procedures are designed to measure training impact on organizational productivity. TEEM seeks to enhance organizational productivity through proactive training focused on operation results. These results can be identified and measured by establishing and tracking performance indicators. Relating training to organizational productivity is not easy. TEEM is a team process. It offers strategies to assess more effectively organizational costs and benefits of training. TEEM is one organization's attempt to refine, manage and extend its training evaluation program

  14. Drosophila melanogaster as a model to explore the effects of methicillin-resistant Staphylococcus aureus strain type on virulence and response to linezolid treatment.

    Science.gov (United States)

    Ben-Ami, Ronen; Watson, Clay C; Lewis, Russell E; Albert, Nathaniel D; Arias, Cesar A; Raad, Issam I; Kontoyiannis, Dimitrios P

    2013-02-01

    USA300 is a uniquely successful methicillin-resistant Staphylococcus aureus (MRSA) clone that has been associated with Panton-Valentine leukocidin (PVL) production and severe infections. However, conflicting experimental and epidemiological data exist regarding the virulence of USA300 relative to other MRSA clones. We aimed to address this issue using Drosophila melanogaster as a model host to study strain and PVL-dependent variations in virulence among MRSA clinical isolates. We studied the relative virulence of 39 MRSA isolates: 17 (43%) were PFGE type USA300. Lethal MRSA infection was reproducibly induced both in wild-type (WT) and Toll-deficient D. melanogaster. USA300 strains had significantly lower lethality than non-USA300 strains in a WT background but not in Toll-deficient flies. PFGE type (USA300 versus non-USA300) and PVL status did not affect the response to treatment with linezolid. Virulence was similar in strains with high vancomycin MIC (≥2 μg/mL) versus those with vancomycin MIC<2 μg/mL. D. melanogaster is a potentially useful model host to study pathogenicity and response to antibiotic treatment in S. aureus. Our results imply that the attenuated virulence of PVL(+)/USA300 requires intact host innate immunity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. COSYMA: Health effects models

    International Nuclear Information System (INIS)

    Ehrhardt, J.

    1995-02-01

    As one of the main objectives of the MARIA project (''Methods for Assessing the Radiological Impact of Accidents'') initiated by the Commission of the European Communities the program package COSYMA (''COde SYstem from MARIA'') for assessing the radiological and economic off-site consequences of accidental releases of radioactive material to the atmosphere has been jointly developed by the Kernforschungszentrum Karlsruhe (KfK), FRG, and the National Radiological Protection Board (NRPB), UK. COSYMA includes models and data for assessing a broad spectrum of accident consequences, and they are implemented in independent modules. The subject of this report are those modules, which incorporate models and data for assessing individual and collective risks for deterministic and stochastic health effects. It describes the models implemented, the mathematical algorithms and the required data. Examples are given and explained for the input and output part of the modules. (orig.)

  16. Multi-factorial causative model for back pain management; relating causative factors and mechanisms to injury presentations and designing time- and cost effective treatment thereof.

    Science.gov (United States)

    Richmond, Jeremy

    2012-08-01

    Back pain resolution has not statistically improved over many years with some literature suggesting chronic back pain to be increasing. From a search of literature on causes, events, mechanisms, factors and treatment for back pain, a model is developed that relates causes of back injury to factors that result in pain through two primary mechanisms; muscle fatigue and muscle/tendon/connective tissue strain or sprain with other main mechanisms being diminished reactivity and strength, changes in tendon/tissue mechanical properties and fear of back pain recurrence/fear of movement following a back pain episode. The model highlights the fact that back pain/injury is multi-factorial with numerous circular relationships. Therefore treatment should also be multi-factorial; a combination of physical and psychological therapy with attention to mechanisms at work or in daily living that exacerbate the injury and delay recovery thereof. Exercise is one method that can reduce muscle imbalance, improve resilience to muscle fatigue, and address reactivity and strength. More importantly, eccentric exercise can rectify musculotendinous or connective tissue injury which plays a role in prolonging the back injury cycle. Posture is identified as a causative factor for back pain with the time exposure for posture representing the largest portion of daily activities. From literature and from clinical observation, treatment methods can be improved and incorporated into integrated multi-modal programs. An integrated exercise program that commences with motor control exercise and progresses into functional movement is suggested. Furthermore a modification of the McKenzie extension movement may benefit back injury rehabilitation for a majority of lower back pain patients. Otherwise the sit-to-stand movement is a regular and frequent exacerbating mechanism of back pain and likely continuously tears connective tissue during the movement thus prolonging the cycle of back pain and can be

  17. Recovery among Adolescents: Models for Post-Treatment Gains in Drug Abuse Treatments

    Science.gov (United States)

    Joe, George W.; Knight, Danica Kalling; Becan, Jennifer E.; Flynn, Patrick M.

    2013-01-01

    Recovery among adolescents undergoing substance abuse treatment was modeled in terms of pre-treatment motivation, therapeutic relationships, psychological functioning, treatment retention, legal pressures, DSM diagnoses, and client demographics. To address between program differences, a within-covariance matrix, based on 547 youth, was used. Applicability of the results across treatment modalities was also examined. The data were from the NIDA-sponsored DATOS Adolescent study. Results from structural equation models (estimated using Mplus) indicated that higher pre-treatment motivation predicted stronger counselor and in-treatment peer relationships, better counselor relationships and retention predicted less illegal drug use at follow-up, and DSM diagnosis was important in the treatment process. Overall, illegal drug use at follow-up was associated with post-treatment alcohol consumption, cigarette use, condom nonuse, psychological distress, criminality, and school non-attendance. The results document the importance of motivation and therapeutic relationships on recovery, even when taking into account the relative effects of legal pressures, DSM diagnoses, and demographics. PMID:24238715

  18. Costs and effectiveness of treatment alternatives for proximal caries lesions.

    Directory of Open Access Journals (Sweden)

    Falk Schwendicke

    Full Text Available OBJECTIVES: Invasive therapy of proximal caries lesions initiates a cascade of re-treatment cycles with increasing loss of dental hard tissue. Non- and micro-invasive treatment aim at delaying this cascade and may thus reduce both the health and economic burden of such lesions. This study compared the costs and effectiveness of alternative treatments of proximal caries lesions. METHODS: A Markov-process model was used to simulate the events following the treatment of a proximal posterior lesion (E2/D1 in a 20-year-old patient in Germany. We compared three interventions (non-invasive; micro-invasive using resin infiltration; invasive using composite restoration. We calculated the risk of complications of initial and possible follow-up treatments and modelled time-dependent non-linear transition probabilities. Costs were calculated based on item-fee catalogues in Germany. Monte-Carlo-microsimulations were performed to compare cost-effectiveness of non- versus micro-invasive treatment and to analyse lifetime costs of all three treatments. RESULTS: Micro-invasive treatment was both more costly and more effective than non-invasive therapy, with ceiling-value-thresholds for willingness-to-pay between 16.73 € for E2 and 1.57 € for D1 lesions. Invasive treatment was the most costly strategy. Calculated costs and effectiveness were sensitive to lesion stage, patient's age, discounting rate and assumed initial treatment costs. CONCLUSIONS: Non- and micro-invasive treatments have lower long-term costs than invasive therapy of proximal lesions. Micro-invasive therapy had the highest cost-effectiveness for treating D1 lesions in young patients. Decision makers with a willingness-to-pay over 16.73 € and 1.57 € for E2 and D1 lesions, respectively, will find micro-invasive treatment more cost-effective than non-invasive therapy.

  19. Costs and effectiveness of treatment alternatives for proximal caries lesions.

    Science.gov (United States)

    Schwendicke, Falk; Meyer-Lueckel, Hendrik; Stolpe, Michael; Dörfer, Christof Edmund; Paris, Sebastian

    2014-01-01

    Invasive therapy of proximal caries lesions initiates a cascade of re-treatment cycles with increasing loss of dental hard tissue. Non- and micro-invasive treatment aim at delaying this cascade and may thus reduce both the health and economic burden of such lesions. This study compared the costs and effectiveness of alternative treatments of proximal caries lesions. A Markov-process model was used to simulate the events following the treatment of a proximal posterior lesion (E2/D1) in a 20-year-old patient in Germany. We compared three interventions (non-invasive; micro-invasive using resin infiltration; invasive using composite restoration). We calculated the risk of complications of initial and possible follow-up treatments and modelled time-dependent non-linear transition probabilities. Costs were calculated based on item-fee catalogues in Germany. Monte-Carlo-microsimulations were performed to compare cost-effectiveness of non- versus micro-invasive treatment and to analyse lifetime costs of all three treatments. Micro-invasive treatment was both more costly and more effective than non-invasive therapy, with ceiling-value-thresholds for willingness-to-pay between 16.73 € for E2 and 1.57 € for D1 lesions. Invasive treatment was the most costly strategy. Calculated costs and effectiveness were sensitive to lesion stage, patient's age, discounting rate and assumed initial treatment costs. Non- and micro-invasive treatments have lower long-term costs than invasive therapy of proximal lesions. Micro-invasive therapy had the highest cost-effectiveness for treating D1 lesions in young patients. Decision makers with a willingness-to-pay over 16.73 € and 1.57 € for E2 and D1 lesions, respectively, will find micro-invasive treatment more cost-effective than non-invasive therapy.

  20. Effect of Bumble Bee Venom in the Treatment of Polycystic Ovary Syndrome, the Relationship Between Tissue Factor Affecting the Level of TNFα in the Wistar Rat Model

    Directory of Open Access Journals (Sweden)

    M Nabiuni

    2013-04-01

    Full Text Available Abstract Background & aim: Polycystic ovary syndrome (PCOS is an endocrine failure leading to anovulation. TNFα is an effective factor in the regulation of normal functioning of the ovaries. High levels of TNFα causes PCOS is further. In this study, the effects of bumble bee venom (HBV on TNFα and other symptoms of ovarian PCOS were studied. Methods: In this experimental study, 60 female Wistar rats were divided into three groups: control, sham and experimental groups. The experimental group was injected with estradiol valerate-induced PCOS direction. Induced rats (PCOS were divided into two groups and treated with HBV. The treatment Group received 0.2mg of HBV for 10 consecutive days. Serum and ovarian tissue was collected from each of the four groups to compare the histological and changes in blood sugar levels. Results: A significant increase in ovarian PCOS weight was observed in the control group , whereas in the treated group with HBV rate fell (15.5 mg Glucose levels in PCOS was 256.5, the control group138, and the treatment group 158. Thickness of the theca layer of antral follicles in the treated group compared with PCOS showed a significant decrease (110 μm and 150 μm respectively. Immunohistochemical results showed increased TNFα factor in PCOS group than in the control group, whereas these levels in samples treated with HBV Reduced. Conclusion: The results of this study revealed that the beneficial effects of HBV in PCOS may be due to the inhibitory effect on factor TNFα. Key words: Polycystic ovary syndrome, Bumble bee venom, Tumor necrosis factor, Immunohistochemistry

  1. Perspectives on modelling micropollutants in wastewater treatment plants

    DEFF Research Database (Denmark)

    Clouzot, Ludiwine; Cloutier, Frédéric; Vanrolleghem, Peter A.

    2013-01-01

    Models for predicting the fate of micropollutants (MPs) in wastewater treatment plants (WWTPs) have been developed to provide engineers and decision-makers with tools that they can use to improve their understanding of, and evaluate how to optimize, the removal of MPs and determine their impact o......) addressing advancements in WWTP treatment technologies, (iii) making use of common approaches to data acquisition for model calibration and (iv) integrating ecotoxicological effects of MPs in receiving waters.......Models for predicting the fate of micropollutants (MPs) in wastewater treatment plants (WWTPs) have been developed to provide engineers and decision-makers with tools that they can use to improve their understanding of, and evaluate how to optimize, the removal of MPs and determine their impact...... on the receiving waters. This paper provides an overview of such models, and discusses the impact of regulation, engineering practice and research on model development. A review of the current status of MP models reveals that a single model cannot represent the wide range of MPs that are present in wastewaters...

  2. Treatment with anti-C5aR mAb leads to early-onset clinical and mechanistic effects in the murine delayed-type hypersensitivity arthritis model

    DEFF Research Database (Denmark)

    Atkinson, Sara Marie; Nansen, Anneline; Usher, Pernille A.

    2015-01-01

    Blockade of the complement cascade at the C5a/C5a receptor (C5aR)-axis is believed to be an attractive treatment avenue in rheumatoid arthritis (RA). However, the effects of such interventions during the early phases of arthritis remain to be clarified. In this study we use the murine delayed...... development in a DTHA model strengthening the rationale of C5aR-blockade as a treatment strategy for RA, especially during the early stages of arthritis flare....

  3. Mesothelioma Treatment: Recovery, Side Effects, What to Expect

    Science.gov (United States)

    ... Treatment > Mesothelioma Treatment > Mesothelioma Treatment Recovery Side Effects Mesothelioma Treatment and Recovery Scenarios: e-News Signup Click ... questions. (877) END-MESO (877) 363-6376 Testimonials Mesothelioma Treatment: Recovery, Side Effects, What to Expect Mesothelioma ...

  4. Modeling antimicrobial tolerance and treatment of heterogeneous biofilms.

    Science.gov (United States)

    Zhao, Jia; Seeluangsawat, Paisa; Wang, Qi

    2016-12-01

    A multiphasic, hydrodynamic model for spatially heterogeneous biofilms based on the phase field formulation is developed and applied to analyze antimicrobial tolerance of biofilms by acknowledging the existence of persistent and susceptible cells in the total population of bacteria. The model implements a new conversion rate between persistent and susceptible cells and its homogeneous dynamics is bench-marked against a known experiment quantitatively. It is then discretized and solved on graphic processing units (GPUs) in 3-D space and time. With the model, biofilm development and antimicrobial treatment of biofilms in a flow cell are investigated numerically. Model predictions agree qualitatively well with available experimental observations. Specifically, numerical results demonstrate that: (i) in a flow cell, nutrient, diffused in solvent and transported by hydrodynamics, has an apparent impact on persister formation, thereby antimicrobial persistence of biofilms; (ii) dosing antimicrobial agents inside biofilms is more effective than dosing through diffusion in solvent; (iii) periodic dosing is less effective in antimicrobial treatment of biofilms in a nutrient deficient environment than in a nutrient sufficient environment. This model provides us with a simulation tool to analyze mechanisms of biofilm tolerance to antimicrobial agents and to derive potentially optimal dosing strategies for biofilm control and treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Impact of Treatment Integrity on Intervention Effectiveness

    Science.gov (United States)

    Fryling, Mitch J.; Wallace, Michele D.; Yassine, Jordan N.

    2012-01-01

    Treatment integrity has cogent implications for intervention effectiveness. Understanding these implications is an important, but often neglected, undertaking in behavior analysis. This paper reviews current research on treatment integrity in applied behavior analysis. Specifically, we review research evaluating the relation between integrity…

  6. Steroid Treatments Equally Effective Against Sudden Deafness

    Science.gov (United States)

    ... 6, 2011 Steroid Treatments Equally Effective Against Sudden Deafness Injecting steroids into the middle ear works just ... when it comes to restoring hearing for sudden deafness patients. This finding, the result of a large ...

  7. Pantethine treatment is effective in recovering the disease phenotype induced by ketogenic diet in a pantothenate kinase-associated neurodegeneration mouse model

    Science.gov (United States)

    Brunetti, Dario; Dusi, Sabrina; Giordano, Carla; Lamperti, Costanza; Morbin, Michela; Fugnanesi, Valeria; Marchet, Silvia; Fagiolari, Gigliola; Sibon, Ody; Moggio, Maurizio; d’Amati, Giulia

    2014-01-01

    Pantothenate kinase-associated neurodegeneration, caused by mutations in the PANK2 gene, is an autosomal recessive disorder characterized by dystonia, dysarthria, rigidity, pigmentary retinal degeneration and brain iron accumulation. PANK2 encodes the mitochondrial enzyme pantothenate kinase type 2, responsible for the phosphorylation of pantothenate or vitamin B5 in the biosynthesis of co-enzyme A. A Pank2 knockout (Pank2−/−) mouse model did not recapitulate the human disease but showed azoospermia and mitochondrial dysfunctions. We challenged this mouse model with a low glucose and high lipid content diet (ketogenic diet) to stimulate lipid use by mitochondrial beta-oxidation. In the presence of a shortage of co-enzyme A, this diet could evoke a general impairment of bioenergetic metabolism. Only Pank2−/− mice fed with a ketogenic diet developed a pantothenate kinase-associated neurodegeneration-like syndrome characterized by severe motor dysfunction, neurodegeneration and severely altered mitochondria in the central and peripheral nervous systems. These mice also showed structural alteration of muscle morphology, which was comparable with that observed in a patient with pantothenate kinase-associated neurodegeneration. We here demonstrate that pantethine administration can prevent the onset of the neuromuscular phenotype in mice suggesting the possibility of experimental treatment in patients with pantothenate kinase-associated neurodegeneration. PMID:24316510

  8. A sheep model for fracture treatment in osteoporosis: benefits of the model versus animal welfare.

    Science.gov (United States)

    Egermann, M; Goldhahn, J; Holz, R; Schneider, E; Lill, C A

    2008-10-01

    Animal models are necessary to evaluate new options for the treatment of fractures in osteoporotic bone. They permit both the biological response of a living system and the influence of the pathological processes to be taken into account. A sheep model for osteoporosis was established by combining oestrogen deficiency, calcium and vitamin D-deficient diet with steroid medication. Bone mineral density (BMD) was reduced by >30% after 12 weeks of combined treatment. Osteoporosis similar to the human situation with corresponding changes in the micro-architecture and mechanical properties of bone was observed. This publication focuses on the impressive results obtained with the model and contrasts them with considerations of animal welfare. Considerable side-effects associated with steroid medication became manifest. Animals in the treatment groups showed signs of infection of various degrees due to the immunosuppressive effect of the medication. The infections were mostly caused by Corynebacterium pseudotuberculosis. Antibody testing revealed a 100% prevalence of infection in this breed of sheep. A modification of the steroid treatment, i.e. less-frequent injections, reduced the incidence of side-effects. This sheep model shows a significant and reproducible reduction in cancellous BMD of >30%, including relevant changes in biomechanical properties and increased fracture risk. However, the severity of the side-effects cannot be overlooked. The model must be improved if it is to be used in the future. Options to reduce the side-effects are discussed.

  9. 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

  10. Effect of a short- and long-term treatment with Ginkgo biloba extract on amyloid precursor protein levels in a transgenic mouse model relevant to Alzheimer's disease.

    Science.gov (United States)

    Augustin, Sabine; Rimbach, Gerald; Augustin, Kay; Schliebs, Reinhard; Wolffram, Siegfried; Cermak, Rainer

    2009-01-15

    Several clinical trials have reported beneficial effects of the Ginkgo biloba extract EGb761 in the prevention and therapy of cognitive disorders including Alzheimer's disease (AD). The aim of the present long-term feeding trial was to study the impact of dietary EGb761 on Amyloid precursor protein (APP) metabolism in mice transgenic for human APP (Tg2576). Tg2576 mice were fed diets with and without EGb761 (300 mg/kg diet) for 1 and 16 months, respectively. Long-term treatment (16 months) with EGb761 significantly lowered human APP protein levels by approximately 50% as compared to controls in the cortex but not in the hippocampus. However, APP levels were not affected by EGb761 in young mice. Current data indicate that APP seems to be an important molecular target of EGb761 in relation to the duration of the Ginkgo biloba treatment and/or the age of the animals. Potential neuroprotective properties of EGb761 may be, at least partly, related to its APP lowering activity.

  11. Beneficial Effect of Chronic Treatment with Extracts from Rhodiola Rosea L. and Curcuma Longa L. on the Immunoreactivity of Animals Subjected to a Chronic Mild Stress Model

    Directory of Open Access Journals (Sweden)

    Vasileva Liliya V.

    2017-12-01

    Full Text Available Background: Recent studies have suggested increased levels of pro-inflammatory cytokines in depression. Aim: The present study aimed to evaluate the effect of extracts from Rhodiola and Curcuma on immunoreactivity of animals subjected to a chronic mild stress (CMS model followed by lipopolysaccharide-induced inflammation. Materials and methods: Male Wistar rats (n=56 divided in 7 groups were treated orally with: distilled water 10 ml/kg (control and CMS model groups; Rhodiola 250 mg/kg; Rhodiola 500 mg/kg; Curcuma 250 mg/kg; Curcuma 500 mg/kg, Rhodiola 250 mg/kg and Curcuma 250 mg/kg. All groups except the control were stressed daily according to a CMS protocol. Changes in glucose preference, weight gain and locomotor activity were recorded. In the sixth week the animals were challenged with LPS and rats’ sera were obtained for ELISA evaluation of TNF-α and IL-6 levels. Results: The animals from the model group decreased their weight gain, glucose preference and locomotor activity compared to controls. The groups exposed to stress and treated with Rhodiola 500 mg/kg, Curcuma 500 mg/kg and their combination increased their locomotor activity compared to the model group. High expression of the pro-inflammatory cytokines TNF-α and IL-6 were found in all groups exposed to CMS and challenged by LPS. Conclusions: The groups exposed to the stress procedure showed a variety of depression-like behavioral changes. In addition, ELISA tests showed that CMS is affecting rats’ immunity by increasing the cytokines’ levels. These changes could be reversed by administration of Rhodiola and Curcuma in combination suggesting synergic interaction regarding their anti-inflammatory and anti-stress effects.

  12. Monitoring and modeling treatment of atypical hemolytic uremic syndrome.

    Science.gov (United States)

    Heinen, Stefan; Pluthero, Fred G; van Eimeren, Viola F; Quaggin, Susan E; Licht, Christoph

    2013-05-01

    Atypical hemolytic uremic syndrome (aHUS), is mainly present in children, who have high risks of end-stage kidney disease (ESKD), post-transplant recurrence and death. aHUS is linked to defective regulation of the complement alternative pathway (AP), with a prominent cause being mutation/inhibition of the negative regulator complement factor H (CFH). CFH function can be restored via infusion of fresh frozen plasma (FFP), a treatment that was effective for several years in a patient heterozygous for a cfh mutation, before the patient progressed to ESKD. While on dialysis, FFP was replaced with eculizumab, which blocks C5 cleavage and thus halts progression of the terminal complement pathway. Patient plasma samples collected during FFP and eculizumab treatment phases were assessed for AP activity (via erythrocyte lysis assays) and for overall complement activity (via ELISA-based screen). Assay results indicated that FFP partially restored AP regulation, an observation supported by in vitro modeling of FFP treatment using purified CFH, while eculizumab completely blocked complement activity. The same approach was used to model in vitro a potential aHUS treatment approach based on blocking the AP effector properdin (complement factor P; CFP) with an anti-properdin antibody. These results provide insights into the efficacy of aHUS treatment and highlight the usefulness of in vitro assays in monitoring and predicting therapeutic responses and testing new treatment possibilities. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Modelling malaria treatment practices in Bangladesh using spatial statistics

    Directory of Open Access Journals (Sweden)

    Haque Ubydul

    2012-03-01

    Full Text Available Abstract Background Malaria treatment-seeking practices vary worldwide and Bangladesh is no exception. Individuals from 88 villages in Rajasthali were asked about their treatment-seeking practices. A portion of these households preferred malaria treatment from the National Control Programme, but still a large number of households continued to use drug vendors and approximately one fourth of the individuals surveyed relied exclusively on non-control programme treatments. The risks of low-control programme usage include incomplete malaria treatment, possible misuse of anti-malarial drugs, and an increased potential for drug resistance. Methods The spatial patterns of treatment-seeking practices were first examined using hot-spot analysis (Local Getis-Ord Gi statistic and then modelled using regression. Ordinary least squares (OLS regression identified key factors explaining more than 80% of the variation in control programme and vendor treatment preferences. Geographically weighted regression (GWR was then used to assess where each factor was a strong predictor of treatment-seeking preferences. Results Several factors including tribal affiliation, housing materials, household densities, education levels, and proximity to the regional urban centre, were found to be effective predictors of malaria treatment-seeking preferences. The predictive strength of each of these factors, however, varied across the study area. While education, for example, was a strong predictor in some villages, it was less important for predicting treatment-seeking outcomes in other villages. Conclusion Understanding where each factor is a strong predictor of treatment-seeking outcomes may help in planning targeted interventions aimed at increasing control programme usage. Suggested strategies include providing additional training for the Building Resources across Communities (BRAC health workers, implementing educational programmes, and addressing economic factors.

  14. Preventative treatment in an animal model of ADHD: Behavioral and biochemical effects of methylphenidate and its interactions with ovarian hormones in female rats.

    Science.gov (United States)

    Lukkes, Jodi L; Freund, Nadja; Thompson, Britta S; Meda, Shirisha; Andersen, Susan L

    2016-09-01

    Clinical and preclinical studies on attention deficit hyperactivity disorder (ADHD) show that juvenile males that are exposed to methylphenidate (MPH) show reduced risk for substance use later in life. In contrast, little is known about whether females have the same enduring treatment response to stimulants and how gonadal hormones influence their behavior later in life. Females received either a sham or 6-hydroxydopamine (6-OHDA) microinjection in the prefrontal cortex (PFC) at postnatal day (P)10. Subjects were then treated with Vehicle or MPH (2mg/kg, p.o.) between P20-35 and tested during late adolescence/young adulthood (P60); half of these subjects underwent ovariectomy at P55 to determine hormonal influences. Females with 6-OHDA were depleted of PFC dopamine by 61% and demonstrated increased impulsive choice (delayed discounting) and preferences for cocaine-associated environments relative to control females. Both MPH and ovariectomy reduced impulsive choice and cocaine preferences in 6-OHDA females, but had no enduring effect in Sham females. Ovariectomy itself did not significantly affect impulsivity. Juvenile MPH interacted strongly with 6-OHDA to increase D4, D5, Alpha-1A, Alpha-2A, and 5-HT-1A mRNA receptor expression in the PFC. MPH alone effected D1 mRNA, while 6-OHDA increased BDNF; all markers were decreased by ovariectomy. Together, these data suggest that 6-OHDA changes in dopamine are not only relevant for ADHD-like behaviors, but their long-term modulation by treatment and the influence of cyclical differences in menstrual cycle. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  15. Quantification of antiangiogenic treatment effects on tissue heterogeneity in glioma tumour xenograft model using a combination of DCE-MRI and 3D-ultramicroscopy.

    Science.gov (United States)

    Dominietto, Marco; Dobosz, Michael; Bürgi, Sandra; Renner, Anja; Zahlmann, Gudrun; Scheuer, Werner; Rudin, Markus

    2017-07-01

    This study aimed at assessing the effects of an anti-angiogenic treatment, which neutralises vascular endothelial growth factor (VEGF), on tumour heterogeneity. Murine glioma cells have been inoculated into the right brain frontal lobe of 16 mice. Anti-VEGF antibody was administered to a first group (n = 8), while a second group (n = 8) received a placebo. Magnetic resonance acquisitions, performed at days 10, 12, 15 and 23 following the implantation, allowed the derivation of a three-dimensional features dataset characterising tumour heterogeneity. Three-dimensional ultramicroscopy and standard histochemistry analysis have been performed to verify in vivo results. Placebo-treated mice displayed a highly-vascularised area at the tumour periphery, a monolithic necrotic core and a chaotic dense vasculature across the entire tumour. In contrast, the B20-treated group did not show any highly vascularised regions and presents a fragmented necrotic core. A significant reduction of the number of vessel segments smaller than 17 μm has been observed. There was no difference in overall tumour volume and growth rate between the two groups. Region-specific analysis revealed that VEGF inhibition affects only: (1) highly angiogenic compartments expressing high levels of VEGF and characterised by small capillaries, and also (2) the formation and structure of necrotic regions. These effects appear to be transient and limited in time. • VEGF inhibition affects only the highly angiogenic region and small capillaries network • VEGF inhibition is transient in time • Tumour volume is not affected by anti-angiogenic treatment • VEGF inhibition also influences the architecture of necrotic regions.

  16. Electrokinetic Treatment for Model Caissons with Increasing Dimensions

    Directory of Open Access Journals (Sweden)

    Eltayeb Mohamedelhassan

    2012-01-01

    Full Text Available Electrokinetic treatment has been known in geotechnical engineering for over six decades, yet, the technique is rarely used. This stems from the absence of design guidelines and specifications for electrokinetic treatment systems. An important issue that need to be investigated and understood in order to devise guidelines from experimental results is the effect of the foundation element size on the outcome of the treatment. Also important is determining the optimum distance between the electrodes and estimating the energy consumption prior to treatment. This experimental study is a preliminary step in understanding some of the issues critical for the guidelines and specifications. Four model caissons with surface areas between 16000 and 128000 mm2 were embedded in soft clayey soil under water and treated for 168 hr with a dc voltage of 6 V. From the results, a distance between the anode (model caisson and the cathode equal 0.25 times the outside diameter of the model caisson was identified as optimum. Relationships between the surface area and axial capacity of the model caisson and the surface area and energy consumption were presented. The equations can be used to preliminary estimate the load capacity and the energy consumption for full-scale applications.

  17. Neuroprotective effect of non-viral gene therapy treatment based on tetanus toxin C-fragment in a severe mouse model of Spinal Muscular Atrophy.

    Directory of Open Access Journals (Sweden)

    Sara Olivan Garcia

    2016-08-01

    Full Text Available Spinal muscular atrophy (SMA is a hereditary childhood disease that causes paralysis and progressive degeneration of skeletal muscles and spinal motor neurons. SMA is associated with reduced levels of full-length Survival of Motor Neuron (SMN protein, due to mutations in the Survival of Motor Neuron 1 gene. Nowadays there are no effective therapies available to treat patients with SMA, so our aim was to test whether the non-toxic carboxy-terminal fragment of tetanus toxin heavy chain (TTC, which exhibits neurotrophic properties, might have a therapeutic role or benefit in SMA. In this manuscript, we have demonstrated that TTC enhance the SMN expression in motor neurons in vitro and evaluated the effect of intramuscular injection of TTC-encoding plasmid in the spinal cord and the skeletal muscle of SMNdelta7 mice. For this purpose, we studied the weight and the survival time, as well as, the survival and cell death pathways and muscular atrophy. Our results showed that TTC treatment reduced the expression of autophagy markers (Becn1, Atg5, Lc3 and p62 and pro-apoptotic genes such as Bax and Casp3 in spinal cord. In skeletal muscle, TTC was able to downregulate the expression of the main marker of autophagy, Lc3, to wild type levels and the expression of the apoptosis effector protein, Casp3. Regarding the genes related to muscular atrophy (Ankrd1, Calm1, Col19a1, Fbox32, Mt2, Myod1, NogoA, Pax7, Rrad, and Sln, TTC suggest a compensatory effect for muscle damage response, diminished oxidative stress and modulated calcium homeostasis. These preliminary findings suggest the need for further experiments to depth study the effect of TTC in SMA disease.

  18. Long-Term Treatment with Liraglutide, a Glucagon-Like Peptide-1 (GLP-1 Receptor Agonist, Has No Effect on β-Amyloid Plaque Load in Two Transgenic APP/PS1 Mouse Models of Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Henrik H Hansen

    Full Text Available One of the major histopathological hallmarks of Alzheimer's disease (AD is cerebral deposits of extracellular β-amyloid peptides. Preclinical studies have pointed to glucagon-like peptide 1 (GLP-1 receptors as a potential novel target in the treatment of AD. GLP-1 receptor agonists, including exendin-4 and liraglutide, have been shown to promote plaque-lowering and mnemonic effects of in a number of experimental models of AD. Transgenic mouse models carrying genetic mutations of amyloid protein precursor (APP and presenilin-1 (PS1 are commonly used to assess the pharmacodynamics of potential amyloidosis-lowering and pro-cognitive compounds. In this study, effects of long-term liraglutide treatment were therefore determined in two double APP/PS1 transgenic mouse models of Alzheimer's disease carrying different clinical APP/PS1 mutations, i.e. the 'London' (hAPPLon/PS1A246E and 'Swedish' mutation variant (hAPPSwe/PS1ΔE9 of APP, with co-expression of distinct PS1 variants. Liraglutide was administered in 5 month-old hAPPLon/PS1A246E mice for 3 months (100 or 500 ng/kg/day, s.c., or 7 month-old hAPPSwe/PS1ΔE9 mice for 5 months (500 ng/kg/day, s.c.. In both models, regional plaque load was quantified throughout the brain using stereological methods. Vehicle-dosed hAPPSwe/PS1ΔE9 mice exhibited considerably higher cerebral plaque load than hAPPLon/PS1A246E control mice. Compared to vehicle-dosed transgenic controls, liraglutide treatment had no effect on the plaque levels in hAPPLon/PS1A246E and hAPPSwe/PS1ΔE9 mice. In conclusion, long-term liraglutide treatment exhibited no effect on cerebral plaque load in two transgenic mouse models of low- and high-grade amyloidosis, which suggests differential sensitivity to long-term liraglutide treatment in various transgenic mouse models mimicking distinct pathological hallmarks of AD.

  19. Long-Term Treatment with Liraglutide, a Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist, Has No Effect on β-Amyloid Plaque Load in Two Transgenic APP/PS1 Mouse Models of Alzheimer's Disease.

    Science.gov (United States)

    Hansen, Henrik H; Fabricius, Katrine; Barkholt, Pernille; Kongsbak-Wismann, Pernille; Schlumberger, Chantal; Jelsing, Jacob; Terwel, Dick; Termont, Annelies; Pyke, Charles; Knudsen, Lotte Bjerre; Vrang, Niels

    2016-01-01

    One of the major histopathological hallmarks of Alzheimer's disease (AD) is cerebral deposits of extracellular β-amyloid peptides. Preclinical studies have pointed to glucagon-like peptide 1 (GLP-1) receptors as a potential novel target in the treatment of AD. GLP-1 receptor agonists, including exendin-4 and liraglutide, have been shown to promote plaque-lowering and mnemonic effects of in a number of experimental models of AD. Transgenic mouse models carrying genetic mutations of amyloid protein precursor (APP) and presenilin-1 (PS1) are commonly used to assess the pharmacodynamics of potential amyloidosis-lowering and pro-cognitive compounds. In this study, effects of long-term liraglutide treatment were therefore determined in two double APP/PS1 transgenic mouse models of Alzheimer's disease carrying different clinical APP/PS1 mutations, i.e. the 'London' (hAPPLon/PS1A246E) and 'Swedish' mutation variant (hAPPSwe/PS1ΔE9) of APP, with co-expression of distinct PS1 variants. Liraglutide was administered in 5 month-old hAPPLon/PS1A246E mice for 3 months (100 or 500 ng/kg/day, s.c.), or 7 month-old hAPPSwe/PS1ΔE9 mice for 5 months (500 ng/kg/day, s.c.). In both models, regional plaque load was quantified throughout the brain using stereological methods. Vehicle-dosed hAPPSwe/PS1ΔE9 mice exhibited considerably higher cerebral plaque load than hAPPLon/PS1A246E control mice. Compared to vehicle-dosed transgenic controls, liraglutide treatment had no effect on the plaque levels in hAPPLon/PS1A246E and hAPPSwe/PS1ΔE9 mice. In conclusion, long-term liraglutide treatment exhibited no effect on cerebral plaque load in two transgenic mouse models of low- and high-grade amyloidosis, which suggests differential sensitivity to long-term liraglutide treatment in various transgenic mouse models mimicking distinct pathological hallmarks of AD.

  20. An automation model of Effluent Treatment Plant

    Directory of Open Access Journals (Sweden)

    Luiz Alberto Oliveira Lima Roque

    2012-07-01

    on the conservation of water resources, this paper aims to propose an automation model of an Effluent Treatment Plant, using Ladder programming language and supervisory systems.

  1. Statistical analysis of Amenamevir (ASP2151) between pharmacokinetics and clinical efficacies with non-linear effect model for the treatment of genital herpes.

    Science.gov (United States)

    Takada, Akitsugu; Katashima, Masataka; Kaibara, Atsunori; Sawamoto, Taiji; Zhang, Wenhui; Keirns, James

    2014-09-01

    Amenamevir is the international non-proprietary name for ASP2151 synthesized by Astellas Pharma, Inc. It is a structurally novel class of helicase-primase inhibitor and demonstrated more potency in vitro anti-viral activity with low cytotoxicity against varicella-zoster virus (VZV), herpes simplex virus type 1 (HSV-1), and herpes simplex virus type 2 (HSV-2) than acyclovir (ACV). Phase II randomized trial assessed the safety and efficacy of ASP2151 for episodic therapy of recurrent genital herpes was conducted. Participants self-initiated with ASP2151 (100, 200, or 400 mg daily for 3 days), ASP2151 (1,200 mg as a single dose), placebo for 3 days, or Valacyclovir (500 mg twice daily for 3 days). We present a first population pharmacokinetic (PPK) modeling analysis of Amenamevir for genital herpes patients. The final model retained the effect of Weight and Albumin on CL. Statistical analysis between pharmacokinetics and clinical efficacies was done by using the time above 200 ng/mL (T200 ). T200 derived from the final PPK model to consider the correlation with Time to lesion healing and viral shedding. This finding suggested that it could be necessary to maintain the Amenamevir concentration above the threshold level to prevent the virus replication. © 2014, The American College of Clinical Pharmacology.

  2. Quantification of antiangiogenic treatment effects on tissue heterogeneity in glioma tumour xenograft model using a combination of DCE-MRI and 3D-ultramicroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Dominietto, Marco [University and ETH Zurich, Institute for Biomedical Engineering, Zurich (Switzerland); University of Basel, Biomaterials Science Center, Allschwil (Switzerland); Dobosz, Michael; Renner, Anja; Scheuer, Werner [Roche Innovation Center Penzberg, Discovery Oncology, Pharmaceutical Research and Early Development (pRED), Penzberg (Germany); Buergi, Sandra; Rudin, Markus [University and ETH Zurich, Institute for Biomedical Engineering, Zurich (Switzerland); Zahlmann, Gudrun [pRED, Oncology DTA, Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel (Switzerland)

    2017-07-15

    This study aimed at assessing the effects of an anti-angiogenic treatment, which neutralises vascular endothelial growth factor (VEGF), on tumour heterogeneity. Murine glioma cells have been inoculated into the right brain frontal lobe of 16 mice. Anti-VEGF antibody was administered to a first group (n = 8), while a second group (n = 8) received a placebo. Magnetic resonance acquisitions, performed at days 10, 12, 15 and 23 following the implantation, allowed the derivation of a three-dimensional features dataset characterising tumour heterogeneity. Three-dimensional ultramicroscopy and standard histochemistry analysis have been performed to verify in vivo results. Placebo-treated mice displayed a highly-vascularised area at the tumour periphery, a monolithic necrotic core and a chaotic dense vasculature across the entire tumour. In contrast, the B20-treated group did not show any highly vascularised regions and presents a fragmented necrotic core. A significant reduction of the number of vessel segments smaller than 17 μm has been observed. There was no difference in overall tumour volume and growth rate between the two groups. Region-specific analysis revealed that VEGF inhibition affects only: (1) highly angiogenic compartments expressing high levels of VEGF and characterised by small capillaries, and also (2) the formation and structure of necrotic regions. These effects appear to be transient and limited in time. (orig.)

  3. The effect of alternative biological modelling parameters (α/β and half time of repair T ½ ) on reported EQD2 values in the treatment of advanced cervical cancer.

    Science.gov (United States)

    De Leeuw, Astrid A C; Van de Kamer, Jeroen B; Moerland, Marinus A; Philippens, Marielle E P; Jürgenliemk-Schulz, Ina-M

    2011-11-01

    To evaluate the effect of different α/β and half-time of repair T(½) on the assessment of clinical treatment plans for patients with cervical cancer. We used EBRT and BT treatment plans of five patients, planned with MRI guided BT. We computed 3D EQD2 dose distributions of combined EBRT and BT treatments and calculated D90 of high-risk clinical target volume (HR-CTV) and D(2cc) for bladder and rectum, and the ratio D(2cc)(bladder)/D90(HR-CTV). BT was modelled as PDR (two applications of 32×60cGy) and HDR (two applications of 2×7Gy). We assumed a low, standard and high value for the biological parameters: HR-CTV α/β=5/10/15Gy and T(½)=0.5/1.5/2.5h; OAR α/β=2/3/4Gy; T(½)=0.5/1.5/4.5h. The chosen variation in modelling parameters had a much larger effect on PDR treatments than on HDR treatments, especially for OAR, thus creating larger uncertainties. The relative mean range of the ratio D(2cc)(bladder)/D90(HR-CTV) is 72% for PDR and 25% for HDR. Out of the 125 modelled combinations 48 PDR plans and 23 HDR plans comply with clinical objectives. For HDR brachytherapy, only α/β has a significant impact on reported EQD2 values, whereas for PDR both α/β and T(½) are important. Generally, the ratio D(2cc)(bladder)/D90(HR-CTV) is more favourable for PDR, even considering the larger uncertainties in EQD2. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  4. Bioeconomic modeling of lactational antimicrobial treatment of new bovine subclinical intramammary infections caused by contagious pathogens

    NARCIS (Netherlands)

    Borne, van den B.H.P.; Halasa, T.; Schaik, van G.; Hogeveen, H.; Nielen, M.

    2010-01-01

    This study determined the direct and indirect epidemiologic and economic effects of lactational treatment of new bovine subclinical intramammary infections (IMI) caused by contagious pathogens using an existing bioeconomic model. The dynamic and stochastic model simulated the dynamics of

  5. Combined aliskiren and L-arginine treatment has antihypertensive effects and prevents vascular endothelial dysfunction in a model of renovascular hypertension

    Directory of Open Access Journals (Sweden)

    C.H. Santuzzi

    2015-01-01

    Full Text Available Angiotensin II is a key player in the pathogenesis of renovascular hypertension, a condition associated with endothelial dysfunction. We investigated aliskiren (ALSK and L-arginine treatment both alone and in combination on blood pressure (BP, and vascular reactivity in aortic rings. Hypertension was induced in 40 male Wistar rats by clipping the left renal artery. Animals were divided into Sham, 2-kidney, 1-clip (2K1C hypertension, 2K1C+ALSK (ALSK, 2K1C+L-arginine (L-arg, and 2K1C+ALSK+L-arginine (ALSK+L-arg treatment groups. For 4 weeks, BP was monitored and endothelium-dependent and independent vasoconstriction and relaxation were assessed in aortic rings. ALSK+L-arg reduced BP and the contractile response to phenylephrine and improved acetylcholine relaxation. Endothelium removal and incubation with N-nitro-L-arginine methyl ester (L-NAME increased the response to phenylephrine in all groups, but the effect was greater in the ALSK+L-arg group. Losartan reduced the contractile response in all groups, apocynin reduced the contractile response in the 2K1C, ALSK and ALSK+L-arg groups, and incubation with superoxide dismutase reduced the phenylephrine response in the 2K1C and ALSK groups. eNOS expression increased in the 2K1C and L-arg groups, and iNOS was increased significantly only in the 2K1C group compared with other groups. AT1 expression increased in the 2K1C compared with the Sham, ALSK and ALSK+L-arg groups, AT2 expression increased in the ALSK+L-arg group compared with the Sham and L-arg groups, and gp91phox decreased in the ALSK+L-arg group compared with the 2K1C and ALSK groups. In conclusion, combined ALSK+L-arg was effective in reducing BP and preventing endothelial dysfunction in aortic rings of 2K1C hypertensive rats. The responsible mechanisms appear to be related to the modulation of the local renin-angiotensin system, which is associated with a reduction in endothelial oxidative stress.

  6. Thermocatalytic treatment of biomass tar model compounds via radio frequency.

    Science.gov (United States)

    Anis, Samsudin; Zainal, Z A; Bakar, M Z A

    2013-05-01

    A new effective RF tar thermocatalytic treatment process with low energy intensive has been proposed to remove tar from biomass gasification. Toluene and naphthalene as biomass tar model compounds were removed via both thermal and catalytic treatment over a wide temperature range from 850 °C to 1200 °C and 450 °C to 900 °C, respectively at residence time of 0-0.7 s. Thermal characteristics of the new technique are also described in this paper. This study clearly clarified that toluene was much easier to be removed than naphthalene. Soot was found as the final product of thermal treatment of the tar model and completely removed during catalytic treatment. Radical reactions generated by RF non-thermal effect improve the tar removal. The study showed that Y-zeolite has better catalytic activity compared to dolomite on toluene and naphthalene removal due to its acidic nature and large surface area, even at lower reaction temperature of about 550 °C. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. A pilot study to examine the effect of chronic treatment with immunosuppressive drugs on mucociliary clearance in a vagotomized murine model.

    Directory of Open Access Journals (Sweden)

    Abhiram R Bhashyam

    Full Text Available Previously, we have demonstrated that mucociliary clearance (MCC is diminished within the first months after surgery in lung transplant patients and the explanation for the reduction in MCC is unknown. We hypothesized that chronic treatment with a commonly prescribed regimen of immunosuppressive drugs significantly impairs MCC. We tested this hypothesis in a murine model of lung transplantation.Fifteen C57BL/6 mice underwent vagotomy on the right side to simulate denervation associated with lung transplantation in humans. For 6 days, seven mice (controls were intraperitoneally injected with three 100 µL doses of phosphate buffered saline and eight mice (immunosuppressed were injected with three 100 µL injections of tacrolimus (1 mg/kg, mycophenolate mofetil (30 mg/kg, and prednisone (2 mg/kg once daily. Then, mice inhaled the radioisotope (99mtechnetium and underwent gamma camera imaging of their lungs for 6.5 hrs. Counts in the right lung at 1-1.5 hrs and at 6-6.5 hrs were first background-corrected and then decay-corrected to time 0 counts. Decay-corrected counts were then divided by time 0 counts. Retention at each time point was subtracted from 1.00 and multiplied by 100% to obtain percent removed by mucociliary clearance.Although there was a slowing of MCC at 1-1.5 hrs for the immunosuppressed mice, there was no statistical difference in MCC measured at 1-1.5 hrs for the two groups of mice. At 6-6.5 hrs, MCC was significantly slower in the immunosuppressed mice, compared to controls, with 7.78±5.9% cleared versus 23.01±11.7% cleared, respectively (p = 0.006.These preliminary results suggest that chronic treatment with immunosuppressive medications significantly slows MCC in vagotomized C57BL/6 mice. These findings could shed light on why MCC is reduced in lung transplant patients whose lungs are denervated during surgery and who are chronically treated with immunosuppressive drugs post surgery.

  8. The effect of prenatal pravastatin treatment on altered fetal programming of postnatal growth and metabolic function in a preeclampsia-like murine model.

    Science.gov (United States)

    McDonnold, Mollie; Tamayo, Esther; Kechichian, Talar; Gamble, Phyllis; Longo, Monica; Hankins, Gary D V; Saade, George R; Costantine, Maged M

    2014-06-01

    Preeclampsia alters fetal programming and results in long-term metabolic consequences in the offspring. Pravastatin has been shown to prevent preeclampsia in animal models. Our aim was to characterize the effects of preeclampsia on fetal programming of adult growth and metabolic function, and evaluate the role of preventive pravastatin therapy, using a well characterized murine model. CD-1 mice were injected through the tail vein with adenovirus carrying soluble fms-like tyrosine kinase 1 (sFlt-1) and randomly allocated to pravastatin (5 mg/kg/day; sFlt-1/prav, n = 7) or water (sFlt-1, n = 6) until weaning. A control group was injected with adenovirus carrying the murine immunoglobulin G2α Fc fragment (mFc, n = 8). Male and female offspring (6-8/group) were weighed every month until 6 months of age. Intraperitoneal glucose tolerance testing was performed after 16 hours of fasting at 3 and 6 months of age; glucose and insulin responses were measured. sFlt-1 offspring weight was lower than mFc control (P < .001) until 2 months of age for females and 5 months of age for males (P < .001). There were no differences in postnatal growth between mFc and sFlt-1/prav offspring. At 3 and 6 months, female sFlt-1 offspring had higher glucose response compared with mFc and sFlt-1/prav. Three-month-old male sFlt-1 had lower insulin response compared with mFc offspring. Preeclampsia alters postnatal growth and metabolic function in the adult offspring in this animal model. Maternal therapy with prav prevents some of these alterations in the offspring. Copyright © 2014 Mosby, Inc. All rights reserved.

  9. Analysis of a Heroin Epidemic Model with Saturated Treatment Function

    Directory of Open Access Journals (Sweden)

    Isaac Mwangi Wangari

    2017-01-01

    Full Text Available A mathematical model is developed that examines how heroin addiction spreads in society. The model is formulated to take into account the treatment of heroin users by incorporating a realistic functional form that “saturates” representing the limited availability of treatment. Bifurcation analysis reveals that the model has an intrinsic backward bifurcation whenever the saturation parameter is larger than a fixed threshold. We are particularly interested in studying the model’s global stability. In the absence of backward bifurcations, Lyapunov functions can often be found and used to prove global stability. However, in the presence of backward bifurcations, such Lyapunov functions may not exist or may be difficult to construct. We make use of the geometric approach to global stability to derive a condition that ensures that the system is globally asymptotically stable. Numerical simulations are also presented to give a more complete representation of the model dynamics. Sensitivity analysis performed by Latin hypercube sampling (LHS suggests that the effective contact rate in the population, the relapse rate of heroin users undergoing treatment, and the extent of saturation of heroin users are mechanisms fuelling heroin epidemic proliferation.

  10. SARS: systematic review of treatment effects.

    Directory of Open Access Journals (Sweden)

    Lauren J Stockman

    2006-09-01

    Full Text Available BACKGROUND: The SARS outbreak of 2002-2003 presented clinicians with a new, life-threatening disease for which they had no experience in treating and no research on the effectiveness of treatment options. The World Health Organization (WHO expert panel on SARS treatment requested a systematic review and comprehensive summary of treatments used for SARS-infected patients in order to guide future treatment and identify priorities for research. METHODS AND FINDINGS: In response to the WHO request we conducted a systematic review of the published literature on ribavirin, corticosteroids, lopinavir and ritonavir (LPV/r, type I interferon (IFN, intravenous immunoglobulin (IVIG, and SARS convalescent plasma from both in vitro studies and in SARS patients. We also searched for clinical trial evidence of treatment for acute respiratory distress syndrome. Sources of data were the literature databases MEDLINE, EMBASE, BIOSIS, and the Cochrane Central Register of Controlled Trials (CENTRAL up to February 2005. Data from publications were extracted and evidence within studies was classified using predefined criteria. In total, 54 SARS treatment studies, 15 in vitro studies, and three acute respiratory distress syndrome studies met our inclusion criteria. Within in vitro studies, ribavirin, lopinavir, and type I IFN showed inhibition of SARS-CoV in tissue culture. In SARS-infected patient reports on ribavirin, 26 studies were classified as inconclusive, and four showed possible harm. Seven studies of convalescent plasma or IVIG, three of IFN type I, and two of LPV/r were inconclusive. In 29 studies of steroid use, 25 were inconclusive and four were classified as causing possible harm. CONCLUSIONS: Despite an extensive literature reporting on SARS treatments, it was not possible to determine whether treatments benefited patients during the SARS outbreak. Some may have been harmful. Clinical trials should be designed to validate a standard protocol for dosage

  11. The effectiveness of evidence-based treatments for personality disorders when comparing treatment-as-usual and bona fide treatments.

    Science.gov (United States)

    Budge, Stephanie L; Moore, Jonathan T; Del Re, A C; Wampold, Bruce E; Baardseth, Timothy P; Nienhuis, Jacob B

    2013-12-01

    The purpose of Study 1 was to examine the relative efficacy of evidence-based treatments (EBTs) when compared to treatment-as-usual (TAU) for adults diagnosed with a personality disorder (PD). The purpose of Study 2 was to investigate the strength of the differences between bona fide psychotherapeutic treatments for PDs. Two separate computerized searches were conducted of: (a) studies that directly compared an EBT with a TAU for treatment of PDs, or (b) studies that compared at least two bona fide treatments for PDs. Meta-analytic methods were used to estimate the effectiveness of the treatments when compared to one another and to model how various confounding variables impacted the results of this comparative research. A total of 30 studies (Study 1; N=1662) were included in the meta-analysis comparing EBTs to TAU. A total of 12 studies (Study 2; N=723) were included in the meta-analysis comparing bona fide treatments. Study 1 found that EBTs were superior to TAU, although the TAU conditions were not comparable in many respects (e.g., not psychotherapy, lacking supervision, lacking training, etc.) to the EBT and there was significant heterogeneity in the effects. Study 2 found that some bona fide treatments were superior to others. © 2013.

  12. Photon iso-effective dose for cancer treatment with mixed field radiation based on dose-response assessment from human and an animal model: clinical application to boron neutron capture therapy for head and neck cancer

    Science.gov (United States)

    González, S. J.; Pozzi, E. C. C.; Monti Hughes, A.; Provenzano, L.; Koivunoro, H.; Carando, D. G.; Thorp, S. I.; Casal, M. R.; Bortolussi, S.; Trivillin, V. A.; Garabalino, M. A.; Curotto, P.; Heber, E. M.; Santa Cruz, G. A.; Kankaanranta, L.; Joensuu, H.; Schwint, A. E.

    2017-10-01

    Boron neutron capture therapy (BNCT) is a treatment modality that combines different radiation qualities. Since the severity of biological damage following irradiation depends on the radiation type, a quantity different from absorbed dose is required to explain the effects observed in the clinical BNCT in terms of outcome compared with conventional photon radiation therapy. A new approach for calculating photon iso-effective doses in BNCT was introduced previously. The present work extends this model to include information from dose-response assessments in animal models and humans. Parameters of the model were determined for tumour and precancerous tissue using dose-response curves obtained from BNCT and photon studies performed in the hamster cheek pouch in vivo models of oral cancer and/or pre-cancer, and from head and neck cancer radiotherapy data with photons. To this end, suitable expressions of the dose-limiting Normal Tissue Complication and Tumour Control Probabilities for the reference radiation and for the mixed field BNCT radiation were developed. Pearson’s correlation coefficients and p-values showed that TCP and NTCP models agreed with experimental data (with r  >  0.87 and p-values  >0.57). The photon iso-effective dose model was applied retrospectively to evaluate the dosimetry in tumours and mucosa for head and neck cancer patients treated with BNCT in Finland. Photon iso-effective doses in tumour were lower than those obtained with the standard RBE-weighted model (between 10% to 45%). The results also suggested that the probabilities of tumour control derived from photon iso-effective doses are more adequate to explain the clinical responses than those obtained with the RBE-weighted values. The dosimetry in the mucosa revealed that the photon iso-effective doses were about 30% to 50% higher than the corresponding RBE-weighted values. While the RBE-weighted doses are unable to predict mucosa toxicity, predictions based on the proposed

  13. Effective treatment of liver metastases with photodynamic therapy, using the second-generation photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC), in a rat model

    NARCIS (Netherlands)

    Rovers, J. P.; Saarnak, A. E.; Molina, A.; Schuitmaker, J. J.; Sterenborg, H. J.; Terpstra, O. T.

    1999-01-01

    The only curative treatment for patients with liver metastases to date is surgery, but few patients are suitable candidates for hepatic resection. The majority of patients will have to rely on other treatment modalities for palliation. Photodynamic therapy (PDT) could be a selective, minimally

  14. The Effects of Verbal, Vocally Modeled, Kinesthetic, and Audio-Visual Treatment Conditions on Male and Female Middle-School Vocal Music Students' Abilities to Expressively Sing Melodies

    Science.gov (United States)

    Ebie, Brian D.

    2004-01-01

    The purpose of this research was to determine whether there were significant differences in male or female middle-school students' ability to appropriately convey the emotions of happiness, sadness, anger, and fear while singing musical passages within the context of four treatment situations. Four treatment methodologies were designed to identify…

  15. Applicability of [11C]PIB micro-PET imaging for in vivo follow-up of anti-amyloid treatment effects in APP23 mouse model.

    Science.gov (United States)

    Snellman, Anniina; Rokka, Johanna; López-Picón, Francisco R; Helin, Semi; Re, Francesca; Löyttyniemi, Eliisa; Pihlaja, Rea; Forloni, Gianluigi; Salmona, Mario; Masserini, Massimo; Solin, Olof; Rinne, Juha O; Haaparanta-Solin, Merja

    2017-09-01

    In this study, we evaluated the anti-amyloid effect of functionalized nanoliposomes (mApoE-PA-LIP) in a mouse model of Alzheimer's disease with use of positron emission tomography and β-amyloid (Aβ)-targeted tracer [ 11 C]Pittsburgh compound B ([ 11 C]PIB). APP23 mice were injected with mApoE-PA-LIP or saline (3 times per week for 3 weeks) and [ 11 C]PIB imaging was performed at baseline, after the treatment and after 3 months follow-up period, accompanied by Aβ immunohistochemistry and ELISA. After the treatment, [ 11 C]PIB binding ratios between mApoE-PA-LIP and saline groups were equivalent in all analyzed brain regions; however, in the saline group, binding ratios increased from the baseline, whereas no increase was detected in the mApoE-PA-LIP group. During the additional follow-up, [ 11 C]PIB binding increased significantly from baseline in both groups, and binding ratios correlated with the immunohistochemically defined Aβ load. This study further supports the use of [ 11 C]PIB positron emission tomography imaging as a biomarker of Aβ deposition in APP23 mice and highlights the benefits of noninvasive follow-up, that is, using baseline data for animal stratification and normalization of treatment effects to baseline values, for future anti-amyloid treatment studies. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Effectiveness of psychopharmacology in Anorexia Nervosa treatment

    Directory of Open Access Journals (Sweden)

    Zadka Lukasz

    2015-06-01

    Full Text Available The eating disorder that generates the highest death rate is that of anorexia nervosa, and current treatment is a combination of equalization of somatic state and patient education. Moreover, psychical symptoms occurring in the course of anorexia nervosa are thought to have a crucial influence on the course of the disease. Hence, in medical literature, the effectiveness of psychotherapeutic interventions is also widely described. Still, the implementation of appropriate psychopharmacology is now considered an additional method of treatment, rather than a therapy of choice. Yet, in spite of many years of research, there are no absolute recommendations given, nor are instructions within the scope of psychopharmacological treatment proffered, although the selection of psychopharmacological items must respect both the patient’s psychic and somatic states. In recent years, the popularity of psychopharmacological treatment has increased; therefore, we feel that it is justified to present the latest scientific information in this respect.

  17. An Integer Linear Programming Model for the Radiotherapy Treatment Scheduling Problem

    OpenAIRE

    Burke, Edmund K.; Leite-Rocha, Pedro; Petrovic, Sanja

    2011-01-01

    Radiotherapy represents an important phase of treatment for a large number of cancer patients. It is essential that resources used to deliver this treatment are employed effectively. This paper presents a new integer linear programming model for real-world radiotherapy treatment scheduling and analyses the effectiveness of using this model on a daily basis in a hospital. Experiments are conducted varying the days on which schedules can be created. Results obtained using real-world data from t...

  18. Models for effective prevention.

    Science.gov (United States)

    Perry, C L; Kelder, S H

    1992-07-01

    The social influence models do provide some optimism for primary prevention efforts. Prevention programs appear most effective when 1) the target behavior of the intervention has received increasing societal disapproval (such as cigarette smoking), 2) multiple years of behavioral health education are planned, and 3) community-wide involvement or mass media complement a school-based peer-led program (45,46). Short-term programs and those involving alcohol use have had less favorable outcomes. Future research in primary prevention should address concerns of high-risk groups and high-risk countries, such as lower income populations in the United States or countries that have large adolescent homeless populations. The utilization of adolescent leaders for program dissemination might be particularly critical in these settings. A second major and global concern should focus upon alcohol use and alcohol-related problems. In many communities adolescent alcohol use is normative and even adult supported. Thus, young people are getting quite inconsistent messages on alcohol from their schools, from TV, from peers, and from parents. This inconsistency may translate into many tragic and avoidable deaths for young people. Clearly, in the area of alcohol-related problems, community-wide involvement may be necessary. A third direction for prevention research should involve issues of norms, access, and enforcement including policy interventions, such as involve the availability of cigarette vending machines or the ease of under-age buying or levels of taxation. These methods affect adolescents more acutely since their financial resources, for the most part, are more limited. These policy level methods also signify to adolescents what adults consider appropriate.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. The effects of surface treatments on rapid chloride permeability tests

    KAUST Repository

    Yoon, Seyoon

    2012-08-01

    Surface treatments are commonly applied to improve the chloride resistance of concrete structures exposed to saline environments. Information on chloride ingress to surface-treated concrete is mostly provided by application of the rapid chloride permeability test (RCPT); this test is short in duration and provides rapid results. This study presents a numerical formulation, based on the extended Nernst-Plank/Poisson (NPP) equation, to model the effect of the surface treatment on a sample tested by RCPT. Predictions of the model are compared to experimental measurements. The simulations show that the results from RCPT, in terms of ionic profiles and measurement of the electric field, are dependent on the effectiveness of surface treatments. During RCPT, highly effective surface treatments cause both cations and anions to flocculate at the interface between the surface treatment and the concrete, creating a local electric field. Our numerical model includes these phenomena and presents a methodology to obtain more accurate diffusivities of the surface-treated- concrete from RCPT. © 2012 Elsevier B.V. All rights reserved.

  20. Modelling the Ozone-Based Treatments for Inactivation of Microorganisms.

    Science.gov (United States)

    Brodowska, Agnieszka Joanna; Nowak, Agnieszka; Kondratiuk-Janyska, Alina; Piątkowski, Marcin; Śmigielski, Krzysztof

    2017-10-09

    The paper presents the development of a model for ozone treatment in a dynamic bed of different microorganisms ( Bacillus subtilis , B. cereus , B. pumilus , Escherichia coli , Pseudomonas fluorescens , Aspergillus niger , Eupenicillium cinnamopurpureum ) on a heterogeneous matrix (juniper berries, cardamom seeds) initially treated with numerous ozone doses during various contact times was studied. Taking into account various microorganism susceptibility to ozone, it was of great importance to develop a sufficiently effective ozone dose to preserve food products using different strains based on the microbial model. For this purpose, we have chosen the Weibull model to describe the survival curves of different microorganisms. Based on the results of microorganism survival modelling after ozone treatment and considering the least susceptible strains to ozone, we selected the critical ones. Among tested strains, those from genus Bacillus were recognized as the most critical strains. In particular, B. subtilis and B. pumilus possessed the highest resistance to ozone treatment because the time needed to achieve the lowest level of its survival was the longest (up to 17.04 min and 16.89 min for B. pumilus reduction on juniper berry and cardamom seed matrix, respectively). Ozone treatment allow inactivate microorganisms to achieving lower survival rates by ozone dose (20.0 g O₃/m³ O₂, with a flow rate of 0.4 L/min) and contact time (up to 20 min). The results demonstrated that a linear correlation between parameters p and k in Weibull distribution, providing an opportunity to calculate a fitted equation of the process.

  1. Toxic Stress: Effects, Prevention and Treatment.

    Science.gov (United States)

    Franke, Hillary A

    2014-11-03

    Children who experience early life toxic stress are at risk of long-term adverse health effects that may not manifest until adulthood. This article briefly summarizes the findings in recent studies on toxic stress and childhood adversity following the publication of the American Academy of Pediatrics (AAP) Policy Report on the effects of toxic stress. A review of toxic stress and its effects is described, including factors of vulnerability, resilience, and the relaxation response. An integrative approach to the prevention and treatment of toxic stress necessitates individual, community and national focus.

  2. Modelling of biological nitrogen removal during treatment of piggery wastewater.

    Science.gov (United States)

    Béline, F; Boursier, H; Guiziou, F; Paul, E

    2007-01-01

    During this study, a mathematical model simulating piggery wastewater treatment was developed, with the objective of process optimisation. To achieve this, the effect of temperature and free ammonia concentration on the nitrification rate were experimentally studied using respirometry. The maximum growth rates obtained were higher for ammonium-oxidising biomass than for nitrite-oxidising biomass for the temperatures above 20 degrees C; values at 35 degrees C were equal to 1.9 and 1.35 day(-1), respectively. No inhibition of nitrification was observed for free ammonia concentrations up to 50 mgN/L. Using these data with others experimental data obtained from a pilot-scale reactor to treat piggery wastewater, a model based on a modified version of the ASM1 was developed and calibrated. In order to model the nitrite accumulation observed, the ASM1 model was extended with a two-step nitrification and denitrification including nitrite as intermediate. Finally, the produced model called PiWaT1 demonstrated a good fit with the experimental data. In addition to the temperature, oxygen concentration was identified as an important factor influencing the nitrite accumulation during nitrification. Even if some improvements of the model are still necessary, this model can already be used for process improvement.

  3. Stochastic modelling to evaluate the economic efficiency of treatment of chronic subclinical mastitis

    NARCIS (Netherlands)

    Steeneveld, W.; Hogeveen, H.; Borne, van den B.H.P.; Swinkels, J.M.

    2006-01-01

    Treatment of subclinical mastitis is traditionally no common practice. However, some veterinarians regard treatment of some types of subclinical mastitis to be effective. The goal of this research was to develop a stochastic Monte Carlo simulation model to support decisions around treatment of

  4. An Integrated, Multidimensional Treatment Model for Individuals Living with HIV, Mental Illness, and Substance Abuse

    Science.gov (United States)

    Bouis, Stephanie; Reif, Susan; Whetten, Kathryn; Scovil, Janet; Murray, Andrea; Swartz, Marvin

    2007-01-01

    The challenge of providing effective treatment services for the growing population of HIV-positive individuals who are also dually diagnosed with substance use and mental disorders has only recently been recognized as an important public health concern affecting both HIV treatment and prevention. This article describes a treatment model that was…

  5. Lectins from Synadenium carinatum (ScLL and Artocarpus heterophyllus (ArtinM are able to induce beneficial immunomodulatory effects in a murine model for treatment of Toxoplasma gondii infection

    Directory of Open Access Journals (Sweden)

    Leandro Peixoto Ferreira Souza

    2016-11-01

    M treatment induced production of pro-inflammatory and anti-inflammatory cytokines, showing differential but complementary profiles. Moreover, when compared with non treated mice, the parasite burden was significantly lower and survival rates higher in mice treated with ScLL or ScLL plus ArtinM, similarly with sulfadiazine treatment. In conclusion, the results demonstrated the suitable potential immunotherapeutic effect of ScLL and ArtinM lectins to control acute toxoplasmosis in this experimental murine model.

  6. Models Predicting Success of Infertility Treatment: A Systematic Review

    Science.gov (United States)

    Zarinara, Alireza; Zeraati, Hojjat; Kamali, Koorosh; Mohammad, Kazem; Shahnazari, Parisa; Akhondi, Mohammad Mehdi

    2016-01-01

    Background: Infertile couples are faced with problems that affect their marital life. Infertility treatment is expensive and time consuming and occasionally isn’t simply possible. Prediction models for infertility treatment have been proposed and prediction of treatment success is a new field in infertility treatment. Because prediction of treatment success is a new need for infertile couples, this paper reviewed previous studies for catching a general concept in applicability of the models. Methods: This study was conducted as a systematic review at Avicenna Research Institute in 2015. Six data bases were searched based on WHO definitions and MESH key words. Papers about prediction models in infertility were evaluated. Results: Eighty one papers were eligible for the study. Papers covered years after 1986 and studies were designed retrospectively and prospectively. IVF prediction models have more shares in papers. Most common predictors were age, duration of infertility, ovarian and tubal problems. Conclusion: Prediction model can be clinically applied if the model can be statistically evaluated and has a good validation for treatment success. To achieve better results, the physician and the couples’ needs estimation for treatment success rate were based on history, the examination and clinical tests. Models must be checked for theoretical approach and appropriate validation. The privileges for applying the prediction models are the decrease in the cost and time, avoiding painful treatment of patients, assessment of treatment approach for physicians and decision making for health managers. The selection of the approach for designing and using these models is inevitable. PMID:27141461

  7. Using a GIS-based spot growth model and visual simulator to evaluate the effects of silvicultural treatments on southern pine beetle-infested stands

    Science.gov (United States)

    Chiao-Ying Chou; Roy L. Hedden; Bo Song; Thomas M. Williams

    2013-01-01

    Many models are available for simulating the probability of southern pine beetle (Dendroctonus frontalis Zimmermann) (SPB) infestation and outbreak dynamics. However, only a few models focused on the potential spatial SPB growth. Although the integrated pest management systems are currently adopted, SPB management is still challenging because of...

  8. Modeling the effect of heat fluxes on ammonia and nitrous oxide emissions from an anaerobic swine waste treatment lagoon using artificial neural network

    Science.gov (United States)

    Understanding factors that affect ammonia and nitrous emissions from anaerobic swine waste treatment lagoons or any animal waste receptacles is a necessary first step in deploying potential remediation options. In this study, we examined the various meteorological factors (i.e., air temperatures, s...

  9. Modeling the Effect of Onsite Wastewater Treatment Systems on Nitrate Load Using SWAT in an Urban Watershed of Metropolitan Atlanta, GA

    Science.gov (United States)

    Onsite Wastewater Treatment Systems (OWTSs) can be a source of nitrate (NO3-) contamination in both surface and ground waters as a result of failing or high density systems. In metropolitan Atlanta, more than 26% of homes are on OWTS and this percentage is expected to increase wi...

  10. Safeguards system effectiveness modeling

    International Nuclear Information System (INIS)

    Bennett, H.A.; Boozer, D.D.; Chapman, L.D.; Daniel, S.L.; Engi, D.; Hulme, B.L.; Varnado, G.B.

    1976-01-01

    A general methodology for the comparative evaluation of physical protection system effectiveness at nuclear facilities is presently under development. The approach is applicable to problems of sabotage or theft at fuel cycle facilities. The overall methodology and the primary analytic techniques used to assess system effectiveness are briefly outlined

  11. Safeguards system effectiveness modeling

    International Nuclear Information System (INIS)

    Bennett, H.A.; Boozer, D.D.; Chapman, L.D.; Daniel, S.L.; Engi, D.; Hulme, B.L.; Varnado, G.B.

    1976-01-01

    A general methodology for the comparative evaluation of physical protection system effectiveness at nuclear facilities is presently under development. The approach is applicable to problems of sabotage or theft at fuel cycle facilities. In this paper, the overall methodology and the primary analytic techniques used to assess system effectiveness are briefly outlined

  12. The use of mathematical models in teaching wastewater treatment engineering

    DEFF Research Database (Denmark)

    Morgenroth, Eberhard Friedrich; Arvin, Erik; Vanrolleghem, P.

    2002-01-01

    Mathematical modeling of wastewater treatment processes has become increasingly popular in recent years. To prepare students for their future careers, environmental engineering education should provide students with sufficient background and experiences to understand and apply mathematical models...

  13. Effectiveness of virtual reality simulation software in radiotherapy treatment planning involving non-coplanar beams with partial breast irradiation as a model.

    Science.gov (United States)

    Glaser, S; Warfel, B; Price, J; Sinacore, J; Albuquerque, K

    2012-10-01

    Virtual reality simulation software (VRS - FocalSim Version 4.40 with VRS prototype, Computerized Medical Systems, St. Louis, MO) is a new radiation dose planning tool that allows for 3D visualization of the patient and the machine couch (treatment table) in relationship to the linear accelerator. This allows the radiation treatment planner to have a "room's-eye-view" and enhances the process of virtual simulation. The aim of this study was to compare VRS to a standard planning program (XiO - Version 4.50, Computerized Medical Systems, St. Louis, MO) in regards to the time it took to use each program, the angles chosen in each, and to determine if there was a dosimetric benefit to using VRS. Ten patients who had undergone left-sided lumpectomies were chosen to have treatment plans generated. A partial breast irradiation (PBI) treatment plan by external beam radiation therapy (EBRT) was generated for each patient using two different methods. In the first method the full plan was generated using XiO software. In the second method beam angles were chosen using the VRS software, those angles were transferred to XiO, and the remaining part of the plan was completed using XiO (since VRS does not allow dose calculations). On average, using VRS to choose angles took about 10 minutes longer than XiO. None of the five gantry angles differed significantly between the two programs, but four of the five couch angles did. Dose-volume histogram (DVH) data showed a significantly better conformality index, and trends toward decreased hot spots and increased coverage of the planed treatment volume (PTV) when using VRS. However, when angels were chosen in VRS a greater volume of the ipsilateral breast received a low dose of radiation (between 3% and 50% of the prescribed dose) (VRS = 23.06%, XiO = 19.57%, p < 0.0005). A significant advantage that VRS provided over XiO was the ability to detect potential collisions prior to actual treatment of the patient in three of the ten patients

  14. Psychiatrist effects in the psychopharmacological treatment of depression.

    Science.gov (United States)

    McKay, Kevin M; Imel, Zac E; Wampold, Bruce E

    2006-06-01

    The National Institutes of Mental Health's (NIMH) 1985 Treatment of Depression Collaborative Research Program (TDCRP) reported that imipramine hydrochloride with clinical management (IMI-CM) was significantly more beneficial than placebo with clinical management (PLA-CM) for individuals undergoing treatment for depression. Unfortunately, in analyzing the NIMH TDCRP data, researchers ignored the potential effect that psychiatrists have on patient outcomes, thereby assuming that psychiatrists are equally effective. However, this assumption has yet to be supported empirically. Therefore, the purpose of the current study is to examine psychiatrist effects in the NIMH TDCRP study and to compare the variation among psychiatrists to the variation between treatments. Data from 112 patients [IMI-CM (n = 57, 9 psychiatrists); PLA-CM (n = 55, 9 psychiatrists)] from the NIMH TDCRP study were reanalyzed using a multi-level model. The proportion of variance in the BDI scores due to medication was 3.4% (p < .05), while the proportion of variance in BDI scores due to psychiatrists was 9.1% (p < .05). The proportion of variance in the HAM-D scores due to medication was 5.9% (p < .05), while the proportion of variance in HAM-D scores due to psychiatrist was 6.7% (p = .053). Therefore, the psychiatrist effects were greater than the treatment effects. In this study, both psychiatrists and treatments contributed to outcomes in the treatment of depression. However, given that psychiatrists were responsible for more of the variance in outcomes it can be concluded that effective treatment psychiatrists can, in fact, augment the effects of the active ingredients of anti-depressant medication as well as placebo.

  15. Effectiveness of Acupuncture Treatment in Cervical Pain.

    Directory of Open Access Journals (Sweden)

    Norma Ríos García

    2012-09-01

    Full Text Available A study is performed, longitudinal, prospective, descriptive in patients who attended the consultation of The Health Center With Beds (CSCC of Torbeck, in the Southern Department of Haiti, in order to determine the effectiveness of acupuncture treatment in patients with cervical pain, in the period between January and June 2011. We studied a universe of 73 patients and a sample of 60 patients, from these persons 30 used drug therapy (Group B and 30 patients which used acupuncture (Group A. We note that in both groups, the females were the most affected, with a prevalence between 31 and 60. The main symptom for both groups was pain (100%. Patients who were administered the acupuncture successfully evolved between the second and fourth days of starting treatment and patients in group B between 5 and 6 days. Acupuncture is an effective therapy in the management of neck pain, with few adverse reactions of the patient and drug zero cost.

  16. Anti-RANKL treatment inhibits erosive joint destruction and lowers inflammation but has no effect on bone formation in the delayed-type hypersensitivity arthritis (DTHA) model

    DEFF Research Database (Denmark)

    Atkinson, Sara Marie; Bleil, Janine; Maier, Rene

    2016-01-01

    . Periarticular bone formation was observed from day 10. Induction of new bone formation indicated by enhanced Runx2, collagen X, osteocalcin, MMP2, MMP9, and MMP13 mRNA expression was observed only between days 8 and 11. Anti-RANKL treatment resulted in a modest reduction in paw and ankle swelling...... and bone formation were analyzed by mRNA deep sequencing. Serum concentrations of tartrate-resistant acid phosphatase 5b, carboxy-terminal telopeptide I (CTX-I), matrix metalloproteinase 3 (MMP3), and serum amyloid P component (SAP) were determined by enzyme-linked immunosorbent assay. Anti......-RANKL monoclonal antibody treatment was initiated at the time of immunization. Results: Bone destruction (MMP3 serum levels, cathepsin B activity, and RANKL mRNA) peaked at day 3 after arthritis induction, followed by a peak in cartilage destruction and bone erosion on day 5 after arthritis induction...

  17. Evaluating Treatment Effects Using Data Envelopment Analysis on Matched Samples

    DEFF Research Database (Denmark)

    Bogetoft, Peter; Kromann, Lene

    2018-01-01

    An intuitively obvious approach to evaluating the effects of a new business model is to compare the performance of firms using the business model (the treatment group) with the performance of a simi- lar group of firms that do not use the business model (the control group). Data Envelopment...... Analysis (DEA) can be a powerful tool in such comparisons because it allows us to estimate changes in average performance as well as in frontier performance. In this paper, we suggest using matching together with DEA as a way to ensure sub-sample homogeneity. The advantages of using a matched sample...

  18. A Stochastic Programming Model for Fuel Treatment Management

    Directory of Open Access Journals (Sweden)

    Mohannad Kabli

    2015-06-01

    Full Text Available This work considers a two-stage stochastic integer programming (SIP approach for optimizing fuel treatment planning under uncertainty in weather and fire occurrence for rural forests. Given a set of areas for potentially performing fuel treatment, the problem is to decide the best treatment option for each area under uncertainty in future weather and fire occurrence. A two-stage SIP model is devised whose objective is to minimize the here-and-now cost of fuel treatment in the first-stage, plus the expected future costs due to uncertain impact from potential fires in the second-stage calculated as ecosystem services losses. The model considers four fuel treatment options: no treatment, mechanical thinning, prescribed fire, and grazing. Several constraints such as budgetary and labor constraints are included in the model and a standard fire behavior model is used to estimate some of the parameters of the model such as fuel levels at the beginning of the fire season. The SIP model was applied to data for a study area in East Texas with 15 treatment areas under different weather scenarios. The results of the study show, for example, that unless the expected ecosystem services values for an area outweigh fuel treatment costs, no treatment is the best choice for the area. Thus the valuation of the area together with the probability of fire occurrence and behavior strongly drive fuel treatment choices.

  19. A Structured Protocol Model of Depression Care versus Clinical Acumen: A Cluster Randomized Trial of the Effects on Depression Screening, Diagnostic Evaluation, and Treatment Uptake in Ugandan HIV Clinics.

    Science.gov (United States)

    Wagner, Glenn J; Ngo, Victoria; Goutam, Prodyumna; Glick, Peter; Musisi, Seggane; Akena, Dickens

    2016-01-01

    Depression is common among people living with HIV, and it has consequences for both HIV prevention and treatment response, yet depression treatment is rarely integrated into HIV care in sub-Saharan Africa, partly due to the paucity of mental health professionals. We conducted a cluster randomized controlled trial of two task-shifting models to facilitating depression care delivered by medical providers: one that utilized a structured protocol, and one that relied on clinical acumen, in 10 HIV clinics in Uganda. Both models started with routine depression screening of all clients at triage using the 2-item Patient Health Questionnaire (PHQ-2), from which we enrolled 1252 clients (640 at structured protocol clinics, 612 at clinical acumen clinics) who had screened positive over 12 months. We compared the two models on (1) proportion of all client participants, and those clinically depressed (based on survey-administered 9-item PHQ-9>9), who received post-screening evaluation for depression using the PHQ-9; and (2) proportion of clinically depressed who were prescribed antidepressant therapy. Linear probability regression analyses were conducted using a wild cluster bootstrap to control for clustering; patient characteristics, clinic size and time fixed effects were included as covariates. Among all client participants, those in the structured protocol arm were far more likely to have received further evaluation by a medical provider using the PHQ-9 (84% vs. 49%; beta = .33; p = .01). Among the clinically depressed clients (n = 369), the advantage of the structured protocol model over clinical acumen was not statistically significant with regard to PHQ-9 depression evaluation (93% vs. 68%; beta = .21; p = .14) or prescription of antidepressants (69% vs. 58%; beta = .10; p = .50), in part because only 30% of clients who screened positive were clinically depressed. These findings reveal that in both models depression care practices were widely adopted by providers, and

  20. Water quality modelling and optimisation of wastewater treatment ...

    African Journals Online (AJOL)

    2016-10-04

    Oct 4, 2016 ... Using this model, it was demonstrated that water quality standards can be met at all monitoring points at a minimum cost by simultaneously optimising treatment levels at each treatment plant. Keywords: instream water quality, mixed integer optimisation, wastewater treatment levels, Streeter-Phelps.

  1. Psoriasis: characteristics, psychosocial effects and treatment options.

    LENUS (Irish Health Repository)

    Ryan, Sheila

    2012-02-01

    Psoriasis is a complex chronic non-infectious inflammatory skin disease with a variety of different presentations. The classic presentation is of well-defined red plaques with silver scale. The characteristic scale makes the disorder highly visible and intrusive on the patient\\'s lifestyle. The visible nature of the disease ensures that psoriasis has both physical and psychosocial effects. In normal skin, epidermal cell reproduction and proliferation takes 28 days. In psoriasis this process is considerably accelerated to approximately 4 days, resulting in the deposit of immature cells on the skin. While the exact cause of this process is unknown, certain environmental and genetic factors are known to be triggers. Disease management depends on disease severity, psychosocial effects and the patient\\'s lifestyle. To effectively treat this disease the nurse must be skilled in psoriasis management, and in patient education and motivation. This article reviews the characteristics, aetiology, psychosocial effects and treatment strategies of psoriasis.

  2. Dual-energy computed tomography for the assessment of early treatment effects of regorafenib in a preclinical tumor model: comparison with dynamic contrast-enhanced CT and conventional contrast-enhanced single-energy CT

    International Nuclear Information System (INIS)

    Knobloch, Gesine; Hamm, Bernd; Jost, Gregor; Pietsch, Hubertus; Huppertz, Alexander

    2014-01-01

    The potential diagnostic value of dual-energy computed tomography (DE-CT) compared to dynamic contrast-enhanced CT (DCE-CT) and conventional contrast-enhanced CT (CE-CT) in the assessment of early regorafenib treatment effects was evaluated in a preclinical setting. A rat GS9L glioma model was examined with contrast-enhanced dynamic DE-CT measurements (80 kV/140 kV) for 4 min before and on days 1 and 4 after the start of daily regorafenib or placebo treatment. Tumour time-density curves (0-240 s, 80 kV), DE-CT (60 s) derived iodine maps and the DCE-CT (0-30 s, 80 kV) based parameters blood flow (BF), blood volume (BV) and permeability (PMB) were calculated and compared to conventional CE-CT (60 s, 80 kV). The regorafenib group showed a marked decrease in the tumour time-density curve, a significantly lower iodine concentration and a significantly lower PMB on day 1 and 4 compared to baseline, which was not observed for the placebo group. CE-CT showed a significant decrease in tumour density on day 4 but not on day 1. The DE-CT-derived iodine concentrations correlated with PMB and BV but not with BF. DE-CT allows early treatment monitoring, which correlates with DCE-CT. Superior performance was observed compared to single-energy CE-CT. circle Regorafenib treatment response was evaluated by CT in a rat tumour model. (orig.)

  3. Dual-energy computed tomography for the assessment of early treatment effects of regorafenib in a preclinical tumor model: comparison with dynamic contrast-enhanced CT and conventional contrast-enhanced single-energy CT

    Energy Technology Data Exchange (ETDEWEB)

    Knobloch, Gesine; Hamm, Bernd [Charite - Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany); Jost, Gregor; Pietsch, Hubertus [Bayer Healthcare, MR and CT Contrast Media Research, Berlin (Germany); Huppertz, Alexander [Imaging Science Institute Charite - Siemens, Berlin (Germany)

    2014-08-15

    The potential diagnostic value of dual-energy computed tomography (DE-CT) compared to dynamic contrast-enhanced CT (DCE-CT) and conventional contrast-enhanced CT (CE-CT) in the assessment of early regorafenib treatment effects was evaluated in a preclinical setting. A rat GS9L glioma model was examined with contrast-enhanced dynamic DE-CT measurements (80 kV/140 kV) for 4 min before and on days 1 and 4 after the start of daily regorafenib or placebo treatment. Tumour time-density curves (0-240 s, 80 kV), DE-CT (60 s) derived iodine maps and the DCE-CT (0-30 s, 80 kV) based parameters blood flow (BF), blood volume (BV) and permeability (PMB) were calculated and compared to conventional CE-CT (60 s, 80 kV). The regorafenib group showed a marked decrease in the tumour time-density curve, a significantly lower iodine concentration and a significantly lower PMB on day 1 and 4 compared to baseline, which was not observed for the placebo group. CE-CT showed a significant decrease in tumour density on day 4 but not on day 1. The DE-CT-derived iodine concentrations correlated with PMB and BV but not with BF. DE-CT allows early treatment monitoring, which correlates with DCE-CT. Superior performance was observed compared to single-energy CE-CT. circle Regorafenib treatment response was evaluated by CT in a rat tumour model. (orig.)

  4. Optimal treatment interruptions control of TB transmission model

    Science.gov (United States)

    Nainggolan, Jonner; Suparwati, Titik; Kawuwung, Westy B.

    2018-03-01

    A tuberculosis model which incorporates treatment interruptions of infectives is established. Optimal control of individuals infected with active TB is given in the model. It is obtained that the control reproduction numbers is smaller than the reproduction number, this means treatment controls could optimize the decrease in the spread of active TB. For this model, controls on treatment of infection individuals to reduce the actively infected individual populations, by application the Pontryagins Maximum Principle for optimal control. The result further emphasized the importance of controlling disease relapse in reducing the number of actively infected and treatment interruptions individuals with tuberculosis.

  5. Stability analysis of an HIV/AIDS epidemic model with treatment

    Science.gov (United States)

    Cai, Liming; Li, Xuezhi; Ghosh, Mini; Guo, Baozhu

    2009-07-01

    An HIV/AIDS epidemic model with treatment is investigated. The model allows for some infected individuals to move from the symptomatic phase to the asymptomatic phase by all sorts of treatment methods. We first establish the ODE treatment model with two infective stages. Mathematical analyses establish that the global dynamics of the spread of the HIV infectious disease are completely determined by the basic reproduction number [real]0. If [real]01. Then, we introduce a discrete time delay to the model to describe the time from the start of treatment in the symptomatic stage until treatment effects become visible. The effect of the time delay on the stability of the endemically infected equilibrium is investigated. Moreover, the delay model exhibits Hopf bifurcations by using the delay as a bifurcation parameter. Finally, numerical simulations are presented to illustrate the results.

  6. Vasoactive side effects of intravenous immunoglobulin preparations in a rat model and their treatment with recombinant platelet-activating factor acetylhydrolase

    NARCIS (Netherlands)

    Bleeker, W. K.; Teeling, J. L.; Verhoeven, A. J.; Rigter, G. M.; Agterberg, J.; Tool, A. T.; Koenderman, A. H.; Kuijpers, T. W.; Hack, C. E.

    2000-01-01

    Previously, we observed in a rat model that intravenous administration of intramuscular immunoglobulin preparations induced a long-lasting hypotension, which appeared to be associated with the presence of IgG polymers and dimers in the preparations, but unrelated to complement activation. We found

  7. Process modeling for the Integrated Nonthermal Treatment System (INTS) study

    Energy Technology Data Exchange (ETDEWEB)

    Brown, B.W.

    1997-04-01

    This report describes the process modeling done in support of the Integrated Nonthermal Treatment System (INTS) study. This study was performed to supplement the Integrated Thermal Treatment System (ITTS) study and comprises five conceptual treatment systems that treat DOE contract-handled mixed low-level wastes (MLLW) at temperatures of less than 350{degrees}F. ASPEN PLUS, a chemical process simulator, was used to model the systems. Nonthermal treatment systems were developed as part of the INTS study and include sufficient processing steps to treat the entire inventory of MLLW. The final result of the modeling is a process flowsheet with a detailed mass and energy balance. In contrast to the ITTS study, which modeled only the main treatment system, the INTS study modeled each of the various processing steps with ASPEN PLUS, release 9.1-1. Trace constituents, such as radionuclides and minor pollutant species, were not included in the calculations.

  8. Modeling pathogenesis and treatment response in childhood absence epilepsy.

    Science.gov (United States)

    Knox, Andrew T; Glauser, Tracy; Tenney, Jeffrey; Lytton, William W; Holland, Katherine

    2018-01-01

    Childhood absence epilepsy (CAE) is a genetic generalized epilepsy syndrome with polygenic inheritance, with genes for γ-aminobutyric acid (GABA) receptors and T-type calcium channels implicated in the disorder. Previous studies of T-type calcium channel electrophysiology have shown genetic changes and medications have multiple effects. The aim of this study was to use an established thalamocortical computer model to determine how T-type calcium channels work in concert with cortical excitability to contribute to pathogenesis and treatment response in CAE. The model is comprised of cortical pyramidal, cortical inhibitory, thalamocortical relay, and thalamic reticular single-compartment neurons, implemented with Hodgkin-Huxley model ion channels and connected by AMPA, GABA A , and GABA B synapses. Network behavior was simulated for different combinations of T-type calcium channel conductance, inactivation time, steady state activation/inactivation shift, and cortical GABA A conductance. Decreasing cortical GABA A conductance and increasing T-type calcium channel conductance converted spindle to spike and wave oscillations; smaller changes were required if both were changed in concert. In contrast, left shift of steady state voltage activation/inactivation did not lead to spike and wave oscillations, whereas right shift reduced network propensity for oscillations of any type. These results provide a window into mechanisms underlying polygenic inheritance in CAE, as well as a mechanism for treatment effects and failures mediated by these channels. Although the model is a simplification of the human thalamocortical network, it serves as a useful starting point for predicting the implications of ion channel electrophysiology in polygenic epilepsy such as CAE. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  9. Effects of fuels, engine load and exhaust after-treatment on diesel engine SVOC emissions and development of SVOC profiles for receptor modeling

    Science.gov (United States)

    Huang, Lei; Bohac, Stanislav V.; Chernyak, Sergei M.; Batterman, Stuart A.

    2015-01-01

    Diesel exhaust emissions contain numerous semivolatile organic compounds (SVOCs) for which emission information is limited, especially for idling conditions, new fuels and the new after-treatment systems. This study investigates exhaust emissions of particulate matter (PM), polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs (NPAHs), and sterane and hopane petroleum biomarkers from a heavy-duty (6.4 L) diesel engine at various loads (idle, 600 and 900 kPa BMEP), with three types of fuel (ultra-low sulfur diesel or ULSD, Swedish low aromatic diesel, and neat soybean biodiesel), and with and without a diesel oxidation catalyst (DOC) and diesel particulate filter (DPF). Swedish diesel and biodiesel reduced emissions of PM2.5, Σ15PAHs, Σ11NPAHs, Σ5Hopanes and Σ6Steranes, and biodiesel resulted in the larger reductions. However, idling emissions increased for benzo[k]fluoranthene (Swedish diesel), 5-nitroacenaphthene (biodiesel) and PM2.5 (biodiesel), a significant result given the attention to exposures from idling vehicles and the toxicity of high-molecular-weight PAHs and NPAHs. The DOC + DPF combination reduced PM2.5 and SVOC emissions during DPF loading (>99% reduction) and DPF regeneration (83–99%). The toxicity of diesel exhaust, in terms of the estimated carcinogenic risk, was greatly reduced using Swedish diesel, biodiesel fuels and the DOC + DPF. PAH profiles showed high abundances of three and four ring compounds as well as naphthalene; NPAH profiles were dominated by nitro-naphthalenes, 1-nitropyrene and 9-nitroanthracene. Both the emission rate and the composition of diesel exhaust depended strongly on fuel type, engine load and after-treatment system. The emissions data and chemical profiles presented are relevant to the development of emission inventories and exposure and risk assessments. PMID:25709535

  10. Effects of fuels, engine load and exhaust after-treatment on diesel engine SVOC emissions and development of SVOC profiles for receptor modeling.

    Science.gov (United States)

    Huang, Lei; Bohac, Stanislav V; Chernyak, Sergei M; Batterman, Stuart A

    2015-02-01

    Diesel exhaust emissions contain numerous semivolatile organic compounds (SVOCs) for which emission information is limited, especially for idling conditions, new fuels and the new after-treatment systems. This study investigates exhaust emissions of particulate matter (PM), polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs (NPAHs), and sterane and hopane petroleum biomarkers from a heavy-duty (6.4 L) diesel engine at various loads (idle, 600 and 900 kPa BMEP), with three types of fuel (ultra-low sulfur diesel or ULSD, Swedish low aromatic diesel, and neat soybean biodiesel), and with and without a diesel oxidation catalyst (DOC) and diesel particulate filter (DPF). Swedish diesel and biodiesel reduced emissions of PM 2.5 , Σ 15 PAHs, Σ 11 NPAHs, Σ 5 Hopanes and Σ 6 Steranes, and biodiesel resulted in the larger reductions. However, idling emissions increased for benzo[k]fluoranthene (Swedish diesel), 5-nitroacenaphthene (biodiesel) and PM 2.5 (biodiesel), a significant result given the attention to exposures from idling vehicles and the toxicity of high-molecular-weight PAHs and NPAHs. The DOC + DPF combination reduced PM 2.5 and SVOC emissions during DPF loading (>99% reduction) and DPF regeneration (83-99%). The toxicity of diesel exhaust, in terms of the estimated carcinogenic risk, was greatly reduced using Swedish diesel, biodiesel fuels and the DOC + DPF. PAH profiles showed high abundances of three and four ring compounds as well as naphthalene; NPAH profiles were dominated by nitro-naphthalenes, 1-nitropyrene and 9-nitroanthracene. Both the emission rate and the composition of diesel exhaust depended strongly on fuel type, engine load and after-treatment system. The emissions data and chemical profiles presented are relevant to the development of emission inventories and exposure and risk assessments.

  11. The enduring effects of psychodynamic treatments vis-à-vis alternative treatments: A multilevel longitudinal meta-analysis.

    Science.gov (United States)

    Kivlighan, D Martin; Goldberg, Simon B; Abbas, Maleeha; Pace, Brian T; Yulish, Noah E; Thomas, Joel G; Cullen, Megan M; Flückiger, Christoph; Wampold, Bruce E

    2015-08-01

    Although evidence suggests that the benefits of psychodynamic treatments are sustained over time, presently it is unclear whether these sustained benefits are superior to non-psychodynamic treatments. Additionally, the extant literature comparing the sustained benefits of psychodynamic treatments compared to alternative treatments is limited with methodological shortcomings. The purpose of the current study was to conduct a rigorous test of the growth of the benefits of psychodynamic treatments relative to alternative treatments across distinct domains of change (i.e., all outcome measures, targeted outcome measures, non-targeted outcome measures, and personality outcome measures). To do so, the study employed strict inclusion criteria to identify randomized clinical trials that directly compared at least one bona fide psychodynamic treatment and one bona fide non-psychodynamic treatment. Hierarchical linear modeling (Raudenbush, Bryk, Cheong, Congdon, & du Toit, 2011) was used to longitudinally model the impact of psychodynamic treatments compared to non-psychodynamic treatments at post-treatment and to compare the growth (i.e., slope) of effects beyond treatment completion. Findings from the present meta-analysis indicated that psychodynamic treatments and non-psychodynamic treatments were equally efficacious at post-treatment and at follow-up for combined outcomes (k=20), targeted outcomes (k=19), non-targeted outcomes (k=17), and personality outcomes (k=6). Clinical implications, directions for future research, and limitations are discussed. Published by Elsevier Ltd.

  12. Parameter trajectory analysis to identify treatment effects of pharmacological interventions.

    Directory of Open Access Journals (Sweden)

    Christian A Tiemann

    Full Text Available The field of medical systems biology aims to advance understanding of molecular mechanisms that drive disease progression and to translate this knowledge into therapies to effectively treat diseases. A challenging task is the investigation of long-term effects of a (pharmacological treatment, to establish its applicability and to identify potential side effects. We present a new modeling approach, called Analysis of Dynamic Adaptations in Parameter Trajectories (ADAPT, to analyze the long-term effects of a pharmacological intervention. A concept of time-dependent evolution of model parameters is introduced to study the dynamics of molecular adaptations. The progression of these adaptations is predicted by identifying necessary dynamic changes in the model parameters to describe the transition between experimental data obtained during different stages of the treatment. The trajectories provide insight in the affected underlying biological systems and identify the molecular events that should be studied in more detail to unravel the mechanistic basis of treatment outcome. Modulating effects caused by interactions with the proteome and transcriptome levels, which are often less well understood, can be captured by the time-dependent descriptions of the parameters. ADAPT was employed to identify metabolic adaptations induced upon pharmacological activation of the liver X receptor (LXR, a potential drug target to treat or prevent atherosclerosis. The trajectories were investigated to study the cascade of adaptations. This provided a counter-intuitive insight concerning the function of scavenger receptor class B1 (SR-B1, a receptor that facilitates the hepatic uptake of cholesterol. Although activation of LXR promotes cholesterol efflux and -excretion, our computational analysis showed that the hepatic capacity to clear cholesterol was reduced upon prolonged treatment. This prediction was confirmed experimentally by immunoblotting measurements of SR-B1

  13. Continuum treatment of electronic polarization effect.

    Science.gov (United States)

    Tan, Yu-Hong; Luo, Ray

    2007-03-07

    A continuum treatment of electronic polarization has been explored for in molecular mechanics simulations in implicit solvents. The dielectric constant for molecule interior is the only parameter in the continuum polarizable model. A value of 4 is found to yield optimal agreement with high-level ab initio quantum mechanical calculations for the tested molecular systems. Interestingly, its performance is not sensitive to the definition of molecular volume, in which the continuum electronic polarization is defined. In this model, quantum mechanical electrostatic field in different dielectric environments from vacuum, low-dielectric organic solvent, and water can be used simultaneously in atomic charge fitting to achieve consistent treatment of electrostatic interactions. The tests show that a single set of atomic charges can be used consistently in different dielectric environments and different molecular conformations, and the atomic charges transfer well from training monomers to tested dimers. The preliminary study gives us the hope of developing a continuum polarizable force field for more consistent simulations of proteins and nucleic acids in implicit solvents.

  14. Continuum treatment of electronic polarization effect

    Science.gov (United States)

    Tan, Yu-Hong; Luo, Ray

    2007-03-01

    A continuum treatment of electronic polarization has been explored for in molecular mechanics simulations in implicit solvents. The dielectric constant for molecule interior is the only parameter in the continuum polarizable model. A value of 4 is found to yield optimal agreement with high-level ab initio quantum mechanical calculations for the tested molecular systems. Interestingly, its performance is not sensitive to the definition of molecular volume, in which the continuum electronic polarization is defined. In this model, quantum mechanical electrostatic field in different dielectric environments from vacuum, low-dielectric organic solvent, and water can be used simultaneously in atomic charge fitting to achieve consistent treatment of electrostatic interactions. The tests show that a single set of atomic charges can be used consistently in different dielectric environments and different molecular conformations, and the atomic charges transfer well from training monomers to tested dimers. The preliminary study gives us the hope of developing a continuum polarizable force field for more consistent simulations of proteins and nucleic acids in implicit solvents.

  15. Effective modelling of acoustofluidic devices

    DEFF Research Database (Denmark)

    Ley, Mikkel Wennemoes Hvitfeld

    , and 3) acoustic streaming patterns in the devices considered in model 2). 1) We derive an effective model for numerical studies of hydrodynamic particle-particle interactions in microfluidic high-concentration suspensions. A suspension of microparticles placed in a microfluidic channel and influenced...... and travelling waves as well as absorption. We model the connective tubing at the outlets, either as being free reflecting surfaces or perfect absorbers of outgoing acoustic waves, and we make an effective description of the mechanical actuation of the attached piezoelectric transducer. 3) Using the model...

  16. The use of mathematical models in teaching wastewater treatment engineering

    DEFF Research Database (Denmark)

    Morgenroth, Eberhard Friedrich; Arvin, Erik; Vanrolleghem, P.

    2002-01-01

    Mathematical modeling of wastewater treatment processes has become increasingly popular in recent years. To prepare students for their future careers, environmental engineering education should provide students with sufficient background and experiences to understand and apply mathematical models...... efficiently and responsibly. Approaches for introducing mathematical modeling into courses on wastewater treatment engineering are discussed depending on the learning objectives, level of the course and the time available....

  17. Modelling of heat treatment of soy

    NARCIS (Netherlands)

    Hout, van den R.

    1997-01-01


    Soybeans are used as raw material for human nutrition and animal feed because of their high nutritional value. Consumption of raw beans has negative effects on the growth and health of human beings and animals. These effects are caused by antinutritional. factors (ANFs). Trypsin

  18. Prevention, screening and treatment of colorectal cancer: a global and regional generalized cost effectiveness analysis

    Directory of Open Access Journals (Sweden)

    Johns Benjamin P

    2010-03-01

    Full Text Available Abstract Background Regional generalized cost-effectiveness estimates of prevention, screening and treatment interventions for colorectal cancer are presented. Methods Standardised WHO-CHOICE methodology was used. A colorectal cancer model was employed to provide estimates of screening and treatment effectiveness. Intervention effectiveness was determined via a population state-transition model (PopMod that simulates the evolution of a sub-regional population accounting for births, deaths and disease epidemiology. Economic costs of procedures and treatment were estimated, including programme overhead and training costs. Results In regions characterised by high income, low mortality and high existing treatment coverage, the addition of screening to the current high treatment levels is very cost-effective, although no particular intervention stands out in cost-effectiveness terms relative to the others. In regions characterised by low income, low mortality with existing treatment coverage around 50%, expanding treatment with or without screening is cost-effective or very cost-effective. Abandoning treatment in favour of screening (no treatment scenario would not be cost effective. In regions characterised by low income, high mortality and low treatment levels, the most cost-effective intervention is expanding treatment. Conclusions From a cost-effectiveness standpoint, screening programmes should be expanded in developed regions and treatment programmes should be established for colorectal cancer in regions with low treatment coverage.

  19. Rasagiline treatment effects on parkinsonian tremor.

    Science.gov (United States)

    Lew, Mark F

    2013-12-01

    Tremor is a common symptom of Parkinson's disease (PD). The underlying pathophysiology of parkinsonian rest tremor is not well understood. Rest tremor is less responsive to dopaminergic therapy than are symptoms of bradykinesia and rigidity. This paper reviews the effects of 1 mg daily oral rasagiline, as monotherapy and as adjunct therapy, on parkinsonian tremor. A literature search of the EMBASE database was conducted to identify relevant articles in English published between 2000 and October, 2012 using the search terms "rasagiline," or "Azilect®," or "Agilect®," and refined using the terms "Parkinson's disease" and "clinical trial." Of 22 identified publications, two large placebo-controlled trials of rasagiline monotherapy (TEMPO and ADAGIO) and two large placebo-controlled trials of rasagiline as adjunctive therapy with levodopa (PRESTO and LARGO) specifically evaluated the effect of rasagiline on tremor using the Unified Parkinson's Disease Rating Scale (UPDRS) motor examination. Prospective and post-hoc analyses from these phase III studies show rasagiline monotherapy significantly improved tremor symptoms in early PD, independent of disease duration, compared with placebo. In levodopa-treated patients with motor fluctuations who were already receiving optimized dopaminergic treatment, the addition of rasagiline adjunct therapy significantly improved tremor symptoms. Significant improvement was evident as early as 10 weeks from treatment initiation. Tremor symptoms also improved in a subset of patients with severe tremor when rasagiline was added to their existing PD treatment regimen. These data suggest that rasagiline used as monotherapy and as adjunctive therapy is effective for reducing tremor severity in patients with PD.

  20. Development of a model to assess acoustic treatments to reduce railway noise

    OpenAIRE

    Jeong, Hongseok; Squicciarini, Giacomo; Thompson, David; Ryue, Jungsoo

    2016-01-01

    Porous materials have recently been used in absorptive treatments around railway tracks to reduce noise emissions. To investigate the effect of porous materials, a finite element model has been developed. 2D models for porous materials have been considered either as an equivalent fluid or as a poroelastic material based on the Biot theory. The two models have been validated and compared with each other to check the effect of the skeleton vibration. The poroelastic FE model has been coupled wi...

  1. Effects of the combined treatment of bone marrow stromal cells with mild exercise and thyroid hormone on brain damage and apoptosis in a mouse focal cerebral ischemia model.

    Science.gov (United States)

    Akhoundzadeh, Kobar; Vakili, Abedin; Sameni, Hamid Reza; Vafaei, Abbas Ali; Rashidy-Pour, Ali; Safari, Manouchehr; Mohammadkhani, Razieh

    2017-08-01

    This study examined whether post-stroke bone marrow stromal cells (BMSCs) therapy combined with exercise (EX) and/or thyroid hormone (TH) could reduce brain damage in an experimental ischemic stroke in mice. Focal cerebral ischemia was induced under Laser Doppler Flowmetry (LDF) guide by 45 min of middle cerebral artery occlusion (MCAO), followed by 7 days of reperfusion in albino mice. BMSCs were injected into the right cerebral ventricle 24 h after MCAO, followed by daily injection of T3 (20 μg/100 g weight S.C) and 6 days of running on a treadmill. Infarct size, neurobehavioral test, TUNEL and BrdU positive cells were evaluated at 7 days after MCAO. Treatment with BMSCs and mild EX alone significantly reduced the infarct volume by 23% and 44%, respectively (both, p cells (a marker of apoptosis) was significantly reduced in the EX, BMSCs, BMSCs + EX, BMSCs + TH, and BMSCs + EX + TH groups (all, p cells in the subventricular zone (SVZ) (p cells and the attenuation of apoptosis in ischemia stroke in young mice.

  2. Variability over time-since- diagnosis in the protective effect of psychological resilience against depression in Australian prostate cancer patients: implications for patient treatment models.

    Science.gov (United States)

    Sharpley, Christopher F; Wootten, Addie C; Bitsika, Vicki; Christie, David R H

    2013-09-01

    Although there is some evidence that psychological resilience may "buffer" against depression following major stressors, no data have been reported on the nature and variability of this buffering effect among prostate cancer patients during the 5 years following their initial diagnosis. Patients from two sites in Australia and who had received their initial diagnosis within 5 years (n = 255) were surveyed, and the results indicated that there was a significant inverse relationship between resilience and depression in the overall data, but that was mostly accounted for by a single factor of the resilience scale ("Confidence to cope with change"). Variability in that buffering effect was noted over time since diagnosis, with peaks during the first 6 months, at 24 and 60 months. These findings support the argument to develop focused psychiatric interventions at various periods following a diagnosis of prostate cancer.

  3. 3D Image Modelling and Specific Treatments in Orthodontics Domain

    Directory of Open Access Journals (Sweden)

    Dionysis Goularas

    2007-01-01

    Full Text Available In this article, we present a 3D specific dental plaster treatment system for orthodontics. From computer tomography scanner images, we propose first a 3D image modelling and reconstruction method of the Mandible and Maxillary based on an adaptive triangulation allowing management of contours meant for the complex topologies. Secondly, we present two specific treatment methods directly achieved on obtained 3D model allowing the automatic correction for the setting in occlusion of the Mandible and the Maxillary, and the teeth segmentation allowing more specific dental examinations. Finally, these specific treatments are presented via a client/server application with the aim of allowing a telediagnosis and treatment.

  4. Transport of Pathogen Surrogates in Soil Treatment Units: Numerical Modeling

    Directory of Open Access Journals (Sweden)

    Ivan Morales

    2014-04-01

    Full Text Available Segmented mesocosms (n = 3 packed with sand, sandy loam or clay loam soil were used to determine the effect of soil texture and depth on transport of two septic tank effluent (STE-borne microbial pathogen surrogates—green fluorescent protein-labeled E. coli (GFPE and MS-2 coliphage—in soil treatment units. HYDRUS 2D/3D software was used to model the transport of these microbes from the infiltrative surface. Mesocosms were spiked with GFPE and MS-2 coliphage at 105 cfu/mL STE and 105–106 pfu/mL STE, respectively. In all soils, removal rates were >99.99% at 25 cm. The transport simulation compared (1 optimization; and (2 trial-and-error modeling approaches. Only slight differences between the transport parameters were observed between these approaches. Treating both the die-off rates and attachment/detachment rates as variables resulted in an overall better model fit, particularly for the tailing phase of the experiments. Independent of the fitting procedure, attachment rates computed by the model were higher in sandy and sandy loam soils than clay, which was attributed to unsaturated flow conditions at lower water content in the coarser-textured soils. Early breakthrough of the bacteria and virus indicated the presence of preferential flow in the system in the structured clay loam soil, resulting in faster movement of water and microbes through the soil relative to a conservative tracer (bromide.

  5. Cancer treatment model with the Caputo-Fabrizio fractional derivative

    Science.gov (United States)

    Ali Dokuyucu, Mustafa; Celik, Ercan; Bulut, Hasan; Mehmet Baskonus, Haci

    2018-03-01

    In this article, a model for cancer treatment is examined. The model is integrated into the Caputo-Fabrizio fractional derivative first, to examine the existence of the solution. Then, the uniqueness of the solution is investigated and we identified under which conditions the model provides a unique solution.

  6. Immunologic Effects Of Peritoneal Photodynamic Treatment

    Science.gov (United States)

    Lynch, David H.; Haddad, Sandra; Jolles, Christopher J.; King, Vernon J.; Ott, Mark J.; Robertson, Bekkie; Straight, Richard C.

    1989-06-01

    One of the side effects of peritoneal photodynamic treatment (PDT) of mice is a systemic suppression of contact hypersensitivity (CH) responses. Treatment with either laser alone or the photosensitizer, Photofrin II (PFII), alone does not cause suppression of CH responses. Immunosuppression of CH responses is an active process that is adoptively transferable using viable cells, but not serum, from PDT-treated mice. The induction of adoptively transferable suppressor cells in PDT-treated mice requires exposure to an antigenic stimulus, yet the suppressor cells are antigen non-specific in their function. T cell function in PDT-treated mice, as measured by the ability of splenic lymphoid cells to generate allogeneic cytotoxic T lymphocyte responses, is comparable to that detected in normal mice. However, the ability of spleen cells from PDT-treated mice to act as stimulators in a mixed lymhocyte reaction is dramatically impaired, suggesting that the major cell type affected by peritoneal PDT is of the macrophage lineage. Support for this concept is provided by experiments in which spleen cells from PDT-treated mice were chromatographically separated into populations of T cells, B cells and macrophages prior to adoptive transfer into naive recipients. The results indicate that the cell type mediating adoptively transferable suppression of CH responsiveness is of the macrophage lineage. Analysis of hematologic parameters revealed that induction of suppression by PDT-treatment was associated with a marked neutrophilia and lymphocytosis, and was also accompanied by a 5-fold increase in concentration of the acute phase protein, Serum Amyloid P. Finally, attempts to ameliorate PDT-induced immunosuppression by pharmacologic intervention have proved successful using implants of pellets that release indomethacin at a rate of 1.25µg/day. Thus, the data suggest that PDT-treatment induces macrophages to produce factors (e.g., prostaglandins) that are known to be potently

  7. Undesirable effects after treatment with dermal fillers.

    Science.gov (United States)

    Rodrigues-Barata, Ana Rita; Camacho-Martínez, Francisco M

    2013-04-01

    Soft tissue augmentation is one of the most frequent techniques in cosmetic dermatology. Nowadays, there are a high number of available materials. Nonanimal hyaluronic acid (HA) is one of most useful fillers for lip augmentation and for treating nasolabial folds, marionette lines, and the dynamic wrinkles of the upper face. To evaluate the type and management of undesirable effects of nonanimal reticulated or stabilized HA observed in our cosmetic unit in the past 3 years. The consecutive patients using HA attending to our clinic in the past 3 years were divided into 3 categories, according to the time of presentation of the adverse reactions: immediate, early, and late-onset complications. All patients were treated. Twenty-three patients presented to our clinic complaining of complications after soft tissue augmentation with HA. Ten patients presented immediate-onset complications, 8 showed early-onset complications, and 5 cases complaint of late-onset complications. Treatment of the first group consisted of hyaluronidase injection, massage, and topical antibiotics. Early- and late-onset complications were treated with intralesional triamcinolone acetonide. All patients improved, with the exception of a woman with recurrent granulomas. Generally, undesirable effects of HA (immediate, early, or late onset) are not frequent, and when present, they improve if treated properly. Physicians need to be aware of these possible adverse events in order to establish proper treatment and prevent scarring or other sequelae.

  8. MATHEMATICAL MODELING OF HEATING RATE PRODUCT AT HIGH HEAT TREATMENT

    Directory of Open Access Journals (Sweden)

    M. M. Akhmedova

    2014-01-01

    Full Text Available Methods of computing and mathematical modeling are all widely used in the study of various heat exchange processes that provide the ability to study the dynamics of the processes, as well as to conduct a reasonable search for the optimal technological parameters of heat treatment.This work is devoted to the identification of correlations among the factors that have the greatest effect on the rate of heating of the product at hightemperature heat sterilization in a stream of hot air, which are chosen as the temperature difference (between the most and least warming up points and speed cans during heat sterilization.As a result of the experimental data warming of the central and peripheral layers compote of apples in a 3 liter pot at high-temperature heat treatment in a stream of hot air obtained by the regression equation in the form of a seconddegree polynomial, taking into account the effects of pair interaction of these parameters. 

  9. New framework for standardized notation in wastewater treatment modelling

    DEFF Research Database (Denmark)

    Corominas, L.; Rieger, L.; Takacs, I.

    2010-01-01

    Many unit process models are available in the field of wastewater treatment. All of these models use their own notation, causing problems for documentation, implementation and connection of different models (using different sets of state variables). The main goal of this paper is to propose a new...... is a framework that can be used in whole plant modelling, which consists of different fields such as activated sludge, anaerobic digestion, sidestream treatment, membrane bioreactors, metabolic approaches, fate of micropollutants and biofilm processes. The main objective of this consensus building paper...... is to establish a consistent set of rules that can be applied to existing and most importantly, future models. Applying the proposed notation should make it easier for everyone active in the wastewater treatment field to read, write and review documents describing modelling projects....

  10. Modelling of an oil refinery wastewater treatment plant.

    Science.gov (United States)

    Pinzón Pardo, A L; Brdjanovic, D; Moussa, M S; López-Vázquez, C M; Meijer, S C F; Van Straten, H H A; Janssen, A J H; Amy, G; Van Loosdrecht, M C M

    2007-11-01

    The Activated Sludge Model No. 3 (ASM3) and Dutch calibration guidelines (STOWA) were evaluated in the modelling of an activated sludge system treating effluents from a large oil refinery. The plant was designed to remove suspended solids, organic matter and nitrogen from wastewater at an average water temperature of 34 degrees C. The plant consists of three tanks in series; the first two tanks operate in on-off aeration mode with pure oxygen for N-removal, whilst extra methanol is added for the denitrification, and the third tank is maintained as constantly aerobic. Calibration was performed based on a simplified influent characterisation and extra batch experiments (nitrification and denitrification). With the adjustment of only four parameters the model proved capable of describing the performance of the plant concerning both the liquid phase and the biomass. The model was further used to analyse possible modifications in the plant layout and optimize operational conditions in order to reduce operating costs. Modelling results indicated reduction in methanol dosage by implementing an idle time between aerobic and anoxic phases. In this way, surplus methanol was prevented from entering during the aerobic period. Moreover, simulations showed that the most cost-effective option regarding the denitrification process was a combined pre-post-denitrification scheme, without the need for enlarging existing basins. It can be concluded that although ASM3 and STOWA guidelines were originally developed for domestic wastewater application at a temperature range of 10 to 20 degrees C, they proved well capable of describing the performance of an oil refinery wastewater treatment plant operating at 34 degrees C. Moreover, the plant model proved useful for optimization of the plant performance regarding operational costs.

  11. Mathematical model for HIV spreads control program with ART treatment

    Science.gov (United States)

    Maimunah; Aldila, Dipo

    2018-03-01

    In this article, using a deterministic approach in a seven-dimensional nonlinear ordinary differential equation, we establish a mathematical model for the spread of HIV with an ART treatment intervention. In a simplified model, when no ART treatment is implemented, disease-free and the endemic equilibrium points were established analytically along with the basic reproduction number. The local stability criteria of disease-free equilibrium and the existing criteria of endemic equilibrium were analyzed. We find that endemic equilibrium exists when the basic reproduction number is larger than one. From the sensitivity analysis of the basic reproduction number of the complete model (with ART treatment), we find that the increased number of infected humans who follow the ART treatment program will reduce the basic reproduction number. We simulate this result also in the numerical experiment of the autonomous system to show how treatment intervention impacts the reduction of the infected population during the intervention time period.

  12. 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.

  13. Multistrain models predict sequential multidrug treatment strategies to result in less antimicrobial resistance than combination treatment

    DEFF Research Database (Denmark)

    Ahmad, Amais; Zachariasen, Camilla; Christiansen, Lasse Engbo

    2016-01-01

    frequency did not play a role in suppressing the growth of resistant strains, but the specific order of the two antimicrobials did. Predictions made from the study could be used to redesign multidrug treatment strategies not only for intramuscular treatment in pigs, but also for other dosing routes.......Background: Combination treatment is increasingly used to fight infections caused by bacteria resistant to two or more antimicrobials. While multiple studies have evaluated treatment strategies to minimize the emergence of resistant strains for single antimicrobial treatment, fewer studies have...... considered combination treatments. The current study modeled bacterial growth in the intestine of pigs after intramuscular combination treatment (i.e. using two antibiotics simultaneously) and sequential treatments (i.e. alternating between two antibiotics) in order to identify the factors that favor...

  14. Computer modeling of lung cancer diagnosis-to-treatment process.

    Science.gov (United States)

    Ju, Feng; Lee, Hyo Kyung; Osarogiagbon, Raymond U; Yu, Xinhua; Faris, Nick; Li, Jingshan

    2015-08-01

    We introduce an example of a rigorous, quantitative method for quality improvement in lung cancer care-delivery. Computer process modeling methods are introduced for lung cancer diagnosis, staging and treatment selection process. Two types of process modeling techniques, discrete event simulation (DES) and analytical models, are briefly reviewed. Recent developments in DES are outlined and the necessary data and procedures to develop a DES model for lung cancer diagnosis, leading up to surgical treatment process are summarized. The analytical models include both Markov chain model and closed formulas. The Markov chain models with its application in healthcare are introduced and the approach to derive a lung cancer diagnosis process model is presented. Similarly, the procedure to derive closed formulas evaluating the diagnosis process performance is outlined. Finally, the pros and cons of these methods are discussed.

  15. HIV models for treatment interruption: Adaptation and comparison

    Science.gov (United States)

    Hillmann, Andreas; Crane, Martin; Ruskin, Heather J.

    2017-10-01

    In recent years, Antiretroviral Therapy (ART) has become commonplace for treating HIV infections, although a cure remains elusive, given reservoirs of replicating latently-infected cells, which are resistant to normal treatment regimes. Treatment interruptions, whether ad hoc or structured, are known to cause a rapid increase in viral production to detectable levels, but numerous clinical trials remain inconclusive on the dangers inherent in this resurgence. In consequence, interest in examining interruption strategies has recently been rekindled. This overview considers modelling approaches, which have been used to explore the issue of treatment interruption. We highlight their purpose and the formalisms employed and examine ways in which clinical data have been used. Implementation of selected models is demonstrated, illustrative examples provided and model performance compared for these cases. Possible extensions to bottom-up modelling techniques for treatment interruptions are briefly discussed.

  16. MO-FG-CAMPUS-TeP3-02: Benchmarks of a Proton Relative Biological Effectiveness (RBE) Model for DNA Double Strand Break (DSB) Induction in the FLUKA, MCNP, TOPAS, and RayStation™ Treatment Planning System

    Energy Technology Data Exchange (ETDEWEB)

    Stewart, R [University of Washington, Seattle, WA (United States); Streitmatter, S [University of Utah Hospitals, Salt Lake City, UT (United States); Traneus, E [RAYSEARCH LABORATORIES AB, Stockholm (Sweden); Moskvin, V [St. Jude Children’s Hospital, Memphis, TN (United States); Schuemann, J [Massachusetts General Hospital, Boston, MA (United States)

    2016-06-15

    Purpose: Validate implementation of a published RBE model for DSB induction (RBEDSB) in several general purpose Monte Carlo (MC) code systems and the RayStation™ treatment planning system (TPS). For protons and other light ions, DSB induction is a critical initiating molecular event that correlates well with the RBE for cell survival. Methods: An efficient algorithm to incorporate information on proton and light ion RBEDSB from the independently tested Monte Carlo Damage Simulation (MCDS) has now been integrated into MCNP (Stewart et al. PMB 60, 8249–8274, 2015), FLUKA, TOPAS and a research build of the RayStation™ TPS. To cross-validate the RBEDSB model implementation LET distributions, depth-dose and lateral (dose and RBEDSB) profiles for monodirectional monoenergetic (100 to 200 MeV) protons incident on a water phantom are compared. The effects of recoil and secondary ion production ({sub 2}H{sub +}, {sub 3}H{sub +}, {sub 3}He{sub 2+}, {sub 4}He{sub 2+}), spot size (3 and 10 mm), and transport physics on beam profiles and RBEDSB are examined. Results: Depth-dose and RBEDSB profiles among all of the MC models are in excellent agreement using a 1 mm distance criterion (width of a voxel). For a 100 MeV proton beam (10 mm spot), RBEDSB = 1.2 ± 0.03 (− 2–3%) at the tip of the Bragg peak and increases to 1.59 ± 0.3 two mm distal to the Bragg peak. RBEDSB tends to decrease as the kinetic energy of the incident proton increases. Conclusion: The model for proton RBEDSB has been accurately implemented into FLUKA, MCNP, TOPAS and the RayStation™TPS. The transport of secondary light ions (Z > 1) has a significant impact on RBEDSB, especially distal to the Bragg peak, although light ions have a small effect on (dosexRBEDSB) profiles. The ability to incorporate spatial variations in proton RBE within a TPS creates new opportunities to individualize treatment plans and increase the therapeutic ratio. Dr. Erik Traneus is employed full-time as a Research Scientist

  17. Global stability of two models with incomplete treatment for tuberculosis

    International Nuclear Information System (INIS)

    Yang Yali; Li Jianquan; Ma Zhien; Liu Luju

    2010-01-01

    Research highlights: → Two tuberculosis models with incomplete treatment. → Intuitive epidemiological interpretations for the basic reproduction numbers. → Global dynamics of the two models. → Strategies to control the spread of tuberculosis. - Abstract: Two tuberculosis (TB) models with incomplete treatment are investigated. It is assumed that the treated individuals may enter either the latent compartment due to the remainder of Mycobacterium tuberculosis or the infectious compartment due to the treatment failure. The first model is a simple one with treatment failure reflecting the current TB treatment fact in most countries with high tuberculosis incidence. The second model refines the simple one by dividing the latent compartment into slow and fast two kinds of progresses. This improvement can be used to describe the case that the latent TB individuals have been infected with some other chronic diseases (such as HIV and diabetes) which may weaken the immunity of infected individuals and shorten the latent period of TB. Both of the two models assume mass action incidence and exponential distributions of transfers between different compartments. The basic reproduction numbers of the two models are derived and their intuitive epidemiological interpretations are given. The global dynamics of two models are all proved by using Liapunov functions. At last, some strategies to control the spread of tuberculosis are discussed.

  18. Global stability of two models with incomplete treatment for tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Yang Yali, E-mail: yylhgr@126.co [Department of Applied Mathematics, Xi' an Jiaotong University, Xi' an 710049 (China) and Department of Applied Mathematics and Physics, Air Force Engineering University, Xi' an 710051 (China); Li Jianquan, E-mail: jianq_li@263.ne [Department of Applied Mathematics and Physics, Air Force Engineering University, Xi' an 710051 (China); Ma Zhien, E-mail: zhma@mail.xjtu.edu.c [Department of Applied Mathematics, Xi' an Jiaotong University, Xi' an 710049 (China); Liu Luju, E-mail: dahai20401095@yahoo.com.c [Department of Mathematics, Henan University of Science and Technology, Luoyang 471003 (China)

    2010-12-15

    Research highlights: Two tuberculosis models with incomplete treatment. Intuitive epidemiological interpretations for the basic reproduction numbers. Global dynamics of the two models. Strategies to control the spread of tuberculosis. - Abstract: Two tuberculosis (TB) models with incomplete treatment are investigated. It is assumed that the treated individuals may enter either the latent compartment due to the remainder of Mycobacterium tuberculosis or the infectious compartment due to the treatment failure. The first model is a simple one with treatment failure reflecting the current TB treatment fact in most countries with high tuberculosis incidence. The second model refines the simple one by dividing the latent compartment into slow and fast two kinds of progresses. This improvement can be used to describe the case that the latent TB individuals have been infected with some other chronic diseases (such as HIV and diabetes) which may weaken the immunity of infected individuals and shorten the latent period of TB. Both of the two models assume mass action incidence and exponential distributions of transfers between different compartments. The basic reproduction numbers of the two models are derived and their intuitive epidemiological interpretations are given. The global dynamics of two models are all proved by using Liapunov functions. At last, some strategies to control the spread of tuberculosis are discussed.

  19. Improving treatment outcome assessment in a mouse tuberculosis model.

    Science.gov (United States)

    Mourik, Bas C; Svensson, Robin J; de Knegt, Gerjo J; Bax, Hannelore I; Verbon, Annelies; Simonsson, Ulrika S H; de Steenwinkel, Jurriaan E M

    2018-04-09

    Preclinical treatment outcome evaluation of tuberculosis (TB) occurs primarily in mice. Current designs compare relapse rates of different regimens at selected time points, but lack information about the correlation between treatment length and treatment outcome, which is required to efficiently estimate a regimens' treatment-shortening potential. Therefore we developed a new approach. BALB/c mice were infected with a Mycobacterium tuberculosis Beijing genotype strain and were treated with rifapentine-pyrazinamide-isoniazid-ethambutol (R p ZHE), rifampicin-pyrazinamide-moxifloxacin-ethambutol (RZME) or rifampicin-pyrazinamide-moxifloxacin-isoniazid (RZMH). Treatment outcome was assessed in n = 3 mice after 9 different treatment lengths between 2-6 months. Next, we created a mathematical model that best fitted the observational data and used this for inter-regimen comparison. The observed data were best described by a sigmoidal E max model in favor over linear or conventional E max models. Estimating regimen-specific parameters showed significantly higher curative potentials for RZME and R p ZHE compared to RZMH. In conclusion, we provide a new design for treatment outcome evaluation in a mouse TB model, which (i) provides accurate tools for assessment of the relationship between treatment length and predicted cure, (ii) allows for efficient comparison between regimens and (iii) adheres to the reduction and refinement principles of laboratory animal use.

  20. 3D Image Modelling and Specific Treatments in Orthodontics Domain

    OpenAIRE

    Goularas, Dionysis; Djemal, Khalifa; Mannoussakis, Yannis

    2007-01-01

    In this article, we present a 3D specific dental plaster treatment system for orthodontics. From computer tomography scanner images, we propose first a 3D image modelling and reconstruction method of the Mandible and Maxillary based on an adaptive triangulation allowing management of contours meant for the complex topologies. Secondly, we present two specific treatment methods directly achieved on obtained 3D model allowing the automatic correction for the setting in occlusion of the Mandible...

  1. Botulinum toxin type-A effect as a preemptive treatment in a model of acute trigeminal pain: a pre-clinical double-blind and placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Elcio Juliato Piovesan

    2011-02-01

    Full Text Available The purpose of this study was to investigate if botulinum neurotoxin type-A (BoNT/A had a preemptive antinociceptive effect in a formalin-induced orofacial pain model (FT. To test this hypothesis, male Rattus norvegicus were injected with isotonic saline solution 0.9% or BoNT/A administered as a 40 μl bolus, lateral to their nose, at 24 hours, 8, 15, 22, 29 or 36 days pre-FT. The procedures were repeated 42 days later. Influence on motor activity was assessed through the open-field test. Pain scores corresponded to the time spent rubbing and flicking the injected area. Animals pre-treated with BoNT/A at the first protocol (8 days subgroup showed reduced inflammatory scores (p=0.011. For the other groups no significant results were observed at any phase. Motor activity was similar in both groups. BoNT/A showed to be effective preventing inflammatory pain up to eight days after the first treatment, an effect not reproduced on the second dose administration.

  2. Randomized Controlled Trial of Video Self-Modeling Following Speech Restructuring Treatment for Stuttering

    Science.gov (United States)

    Cream, Angela; O'Brian, Sue; Jones, Mark; Block, Susan; Harrison, Elisabeth; Lincoln, Michelle; Hewat, Sally; Packman, Ann; Menzies, Ross; Onslow, Mark

    2010-01-01

    Purpose: In this study, the authors investigated the efficacy of video self-modeling (VSM) following speech restructuring treatment to improve the maintenance of treatment effects. Method: The design was an open-plan, parallel-group, randomized controlled trial. Participants were 89 adults and adolescents who undertook intensive speech…

  3. Analytical modelling for ultrasonic surface mechanical attrition treatment

    Directory of Open Access Journals (Sweden)

    Guan-Rong Huang

    2015-07-01

    Full Text Available The grain refinement, gradient structure, fatigue limit, hardness, and tensile strength of metallic materials can be effectively enhanced by ultrasonic surface mechanical attrition treatment (SMAT, however, never before has SMAT been treated with rigorous analytical modelling such as the connection among the input energy and power and resultant temperature of metallic materials subjected to SMAT. Therefore, a systematic SMAT model is actually needed. In this article, we have calculated the averaged speed, duration time of a cycle, kinetic energy and kinetic energy loss of flying balls in SMAT for structural metallic materials. The connection among the quantities such as the frequency and amplitude of attrition ultrasonic vibration motor, the diameter, mass and density of balls, the sample mass, and the height of chamber have been considered and modelled in details. And we have introduced the one-dimensional heat equation with heat source within uniform-distributed depth in estimating the temperature distribution and heat energy of sample. In this approach, there exists a condition for the frequency of flying balls reaching a steady speed. With these known quantities, we can estimate the strain rate, hardness, and grain size of sample.

  4. Neuroinflammatory targets and treatments for epilepsy validated in experimental models.

    Science.gov (United States)

    Aronica, Eleonora; Bauer, Sebastian; Bozzi, Yuri; Caleo, Matteo; Dingledine, Raymond; Gorter, Jan A; Henshall, David C; Kaufer, Daniela; Koh, Sookyong; Löscher, Wolfgang; Louboutin, Jean-Pierre; Mishto, Michele; Norwood, Braxton A; Palma, Eleonora; Poulter, Michael O; Terrone, Gaetano; Vezzani, Annamaria; Kaminski, Rafal M

    2017-07-01

    A large body of evidence that has accumulated over the past decade strongly supports the role of inflammation in the pathophysiology of human epilepsy. Specific inflammatory molecules and pathways have been identified that influence various pathologic outcomes in different experimental models of epilepsy. Most importantly, the same inflammatory pathways have also been found in surgically resected brain tissue from patients with treatment-resistant epilepsy. New antiseizure therapies may be derived from these novel potential targets. An essential and crucial question is whether targeting these molecules and pathways may result in anti-ictogenesis, antiepileptogenesis, and/or disease-modification effects. Therefore, preclinical testing in models mimicking relevant aspects of epileptogenesis is needed to guide integrated experimental and clinical trial designs. We discuss the most recent preclinical proof-of-concept studies validating a number of therapeutic approaches against inflammatory mechanisms in animal models that could represent novel avenues for drug development in epilepsy. Finally, we suggest future directions to accelerate preclinical to clinical translation of these recent discoveries. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  5. New Gravity Wave Treatments for GISS Climate Models

    Science.gov (United States)

    Geller, Marvin A.; Zhou, Tiehan; Ruedy, Reto; Aleinov, Igor; Nazarenko, Larissa; Tausnev, Nikolai L.; Sun, Shan; Kelley, Maxwell; Cheng, Ye

    2011-01-01

    Previous versions of GISS climate models have either used formulations of Rayleigh drag to represent unresolved gravity wave interactions with the model-resolved flow or have included a rather complicated treatment of unresolved gravity waves that, while being climate interactive, involved the specification of a relatively large number of parameters that were not well constrained by observations and also was computationally very expensive. Here, the authors introduce a relatively simple and computationally efficient specification of unresolved orographic and nonorographic gravity waves and their interaction with the resolved flow. Comparisons of the GISS model winds and temperatures with no gravity wave parameterization; with only orographic gravity wave parameterization; and with both orographic and nonorographic gravity wave parameterizations are shown to illustrate how the zonal mean winds and temperatures converge toward observations. The authors also show that the specifications of orographic and nonorographic gravity waves must be different in the Northern and Southern Hemispheres. Then results are presented where the nonorographic gravity wave sources are specified to represent sources from convection in the intertropical convergence zone and spontaneous emission from jet imbalances. Finally, a strategy to include these effects in a climate-dependent manner is suggested.

  6. Personalized neuromusculoskeletal modeling to improve treatment of mobility impairments: a perspective from European research sites

    Directory of Open Access Journals (Sweden)

    Fregly Benjamin J

    2012-03-01

    Full Text Available Abstract Mobility impairments due to injury or disease have a significant impact on quality of life. Consequently, development of effective treatments to restore or replace lost function is an important societal challenge. In current clinical practice, a treatment plan is often selected from a standard menu of options rather than customized to the unique characteristics of the patient. Furthermore, the treatment selection process is normally based on subjective clinical experience rather than objective prediction of post-treatment function. The net result is treatment methods that are less effective than desired at restoring lost function. This paper discusses the possible use of personalized neuromusculoskeletal computer models to improve customization, objectivity, and ultimately effectiveness of treatments for mobility impairments. The discussion is based on information gathered from academic and industrial research sites throughout Europe, and both clinical and technical aspects of personalized neuromusculoskeletal modeling are explored. On the clinical front, we discuss the purpose and process of personalized neuromusculoskeletal modeling, the application of personalized models to clinical problems, and gaps in clinical application. On the technical front, we discuss current capabilities of personalized neuromusculoskeletal models along with technical gaps that limit future clinical application. We conclude by summarizing recommendations for future research efforts that would allow personalized neuromusculoskeletal models to make the greatest impact possible on treatment design for mobility impairments.

  7. Analytical treatment of the runaway-effect

    International Nuclear Information System (INIS)

    Kaeppeler, H.J.

    1980-09-01

    In the analytical treatment of the runaway-effect there appear the integrals Isub(m)(α). For m = 1, 2 and 3, series expansions for these integrals can be found in the literature. Furthermore, asymptotic solutions for Isub(m)(α) are known. It is shown here that the solutions for Isub(m)(α) can be approximated by the modified Bessel Function Ksub(n)(αsup(ν)) in such a way that for α → 0 the exact limiting value for Isub(m)(α) follows and that for α → infinite essentially the known asymptotic solutions for Isub(m)(α) follow. The maximum error for this approximation in the order of percent is considered justifiable for the application considered. (orig.)

  8. Effects of IFN-β1a and IFN-β1b treatment on the expression of cytokines, inducible NOS (NOS type II), and myelin proteins in animal model of multiple sclerosis.

    Science.gov (United States)

    Lubina-Dąbrowska, Natalia; Stepień, Adam; Sulkowski, Grzegorz; Dąbrowska-Bouta, Beata; Langfort, Józef; Chalimoniuk, Małgorzata

    2017-08-01

    The aim of this study was to investigate the effects of interferon (IFN)-β1a and IFN-β1b treatment on inflammatory factors and myelin protein levels in the brain cortex of the Lewis rat experimental autoimmune encephalomyelitis (EAE), animal model of multiple sclerosis. To induce EAE, rat were immunized with inoculums containing spinal cord guinea pig homogenized in phosphate-buffered saline and emulsified in Freund's complete adjuvant containing 110 µg of the appropriate antigen in 100 µl of an emulsion and additionally 4-mg/ml Mycobacterium tuberculosis (H37Ra). The rats were treated three times per week with subcutaneous applications of 300,000 units IFN-β1a or IFN-β1b. The treatments were started 8 days prior to immunization and continued until day 14 after immunization. The rats were killed on the 14th day of the experiment. EAE induced dramatic increase in interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-concentrations and inducible nitric oxide synthase (iNOS) expression in the brain, which closely corresponded to the course of neurological symptoms and the loss of weight. Both IFN-β1b and IFN-β1a treatments inhibited the pro-inflammatory cytokines (IL-6, IL-1β, TNF-α and IFN-γ), decreased the activation of astrocytes, increased the myelin protein level in the brain cortex, and improved the neurological status of EAE rats by different mechanisms; IFN-β1a reduced iNOS expression, at least in part, by the enhancement of IL-10, while IFN-β1b diminished IL-10 concentration and did not decrease EAE-induced iNOS expression.

  9. Endocrine system on chip for a diabetes treatment model.

    Science.gov (United States)

    Nguyen, Dao Thi Thuy; van Noort, Danny; Jeong, In-Kyung; Park, Sungsu

    2017-02-21

    The endocrine system is a collection of glands producing hormones which, among others, regulates metabolism, growth and development. One important group of endocrine diseases is diabetes, which is caused by a deficiency or diminished effectiveness of endogenous insulin. By using a microfluidic perfused 3D cell-culture chip, we developed an 'endocrine system on chip' to potentially be able to screen drugs for the treatment of diabetes by measuring insulin release over time. Insulin-secreting β-cells are located in the pancreas, while L-cells, located in the small intestines, stimulate insulin secretion. Thus, we constructed a co-culture of intestinal-pancreatic cells to measure the effect of glucose on the production of glucagon-like peptide-1 (GLP-1) from the L-cell line (GLUTag) and insulin from the pancreatic β-cell line (INS-1). After three days of culture, both cell lines formed aggregates, exhibited 3D cell morphology, and showed good viability (>95%). We separately measured the dynamic profile of GLP-1 and insulin release at glucose concentrations of 0.5 and 20 mM, as well as the combined effect of GLP-1 on insulin production at these glucose concentrations. In response to glucose stimuli, GLUTag and INS-1 cells produced higher amounts of GLP-1 and insulin, respectively, compared to a static 2D cell culture. INS-1 combined with GLUTag cells exhibited an even higher insulin production in response to glucose stimulation. At higher glucose concentrations, the diabetes model on chip showed faster saturation of the insulin level. Our results suggest that the endocrine system developed in this study is a useful tool for observing dynamical changes in endocrine hormones (GLP-1 and insulin) in a glucose-dependent environment. Moreover, it can potentially be used to screen GLP-1 analogues and natural insulin and GLP-1 stimulants for diabetes treatment.

  10. The effects of periodontal treatment on diabetes.

    Science.gov (United States)

    Taylor, George W

    2003-10-01

    Diabetes mellitus and periodontal diseases are common chronic diseases in the United States. Periodontal infection may adversely affect glycemic control in people with diabetes. This article reviews the evidence regarding how treatment of periodontal diseases affects glycemic control. The review consisted of a MEDLINE literature search to identify primary research reports on the relationship between periodontal therapy and changes in glycemic control. The review identified three randomized clinical trials and nine nonrandomized clinical follow-up studies. The strength, quantity and breadth of evidence are varied, precluding clear-cut guidance for determining whether treating periodontal infection has a beneficial effect on glycemic control. Despite the variation and limitations in the literature, evidence supports the concept that periodontal diseases can contribute to poorer glycemic control in people with diabetes. Although the evidence is not unequivocal, it provides sufficient support for additional investigations of the effect of preventing and treating periodontal infections on managing glycemic control. Sufficient evidence exists to incorporate oral examinations and periodontal care in management regimens for people with diabetes. It is prudent to assess patients' glycemic control status and communicate the importance of referring patients with diabetes for thorough oral health evaluations and necessary care.

  11. Modeling of water treatment plant using timed continuous Petri nets

    Science.gov (United States)

    Nurul Fuady Adhalia, H.; Subiono, Adzkiya, Dieky

    2017-08-01

    Petri nets represent graphically certain conditions and rules. In this paper, we construct a model of the Water Treatment Plant (WTP) using timed continuous Petri nets. Specifically, we consider that (1) the water pump always active and (2) the water source is always available. After obtaining the model, the flow through the transitions and token conservation laws are calculated.

  12. TAPWAT: Definition structure and applications for modelling drinking water treatment

    NARCIS (Netherlands)

    Versteegh JFM; Gaalen FW van; Rietveld LC; Evers EG; Aldenberg TA; Cleij P; Technische Universiteit Delft; LWD

    2001-01-01

    The 'Tool for the Analysis of the Production of drinking WATer' (TAPWAT) model has been developed for describing drinking-water quality in integral studies in the context of the Environmental Policy Assessment of the RIVM. The model consists of modules that represent individual steps in a treatment

  13. Water quality modelling and optimisation of wastewater treatment ...

    African Journals Online (AJOL)

    Instream water quality management encompasses field monitoring and utilisation of mathematical models. These models can be coupled with optimisation techniques to determine more efficient water quality management alternatives. Among these activities, wastewater treatment plays a crucial role. In this work, a ...

  14. Modeling quantization effects in field effect transistors

    CERN Document Server

    Troger, C

    2001-01-01

    Numerical simulation in the field of semiconductor device development advanced to a valuable, cost-effective and flexible facility. The most widely used simulators are based on classical models, as they need to satisfy time and memory constraints. To improve the performance of field effect transistors such as MOSFETs and HEMTs these devices are continuously scaled down in their dimensions. Consequently the characteristics of such devices are getting more and more determined by quantum mechanical effects arising from strong transversal fields in the channel. In this work an approach based on a two-dimensional electron gas is used to describe the confinement of the carriers. Quantization is considered in one direction only. For the derivation of a one-dimensional Schroedinger equation in the effective mass framework a non-parabolic correction for the energy dispersion due to Kane is included. For each subband a non-parabolic dispersion relation characterized by subband masses and subband non-parabolicity coeffi...

  15. Late effects after treatment for Hodgkin lymphoma

    NARCIS (Netherlands)

    Daniëls, Laurien Aletta

    2014-01-01

    Although modern treatment strategies have made Hodgkin Lymphoma (HL) a highly curable disease, there is a life-long increased risk of morbidity and mortality due to treatment. Over time it has become increasingly evident that the historically used extensive treatment fields can potentially lead to

  16. Modeling of the water uptake process for cowpea seeds (vigna unguiculata l.) under common treatment and microwave treatment

    International Nuclear Information System (INIS)

    Demirhan, E.

    2015-01-01

    The water uptake kinetics of cowpea seeds were carried out at two different water absorption treatments - common treatment and microwave treatment - to evaluate the effects of rehydration temperatures and microwave output powers on rehydration. Water uptake of cowpea seeds during soaking in water was studied at various temperatures of 20 - 45 degree C, and at various microwave output powers of 180 - 900 W. As the rehydration temperature and microwave output power increased, the water uptake of cowpea seeds increased and the rehydration time decreased. The Peleg and Richards Models were capable of predicting water uptake of cowpea seeds undergoing common treatment and microwave treatment, respectively. The effective diffusivity values were evaluated by fitting experimental absorption data to Fick second law of diffusion. The effective diffusivity coefficients for cowpea seeds varied from 7.75*10-11 to 1.99*10-10 m2/s and from 2.23*10-9 to 9.78*10-9 m2/s for common treatment and microwave treatment, respectively. (author)

  17. Accounting for treatment use when validating a prognostic model: a simulation study.

    Science.gov (United States)

    Pajouheshnia, Romin; Peelen, Linda M; Moons, Karel G M; Reitsma, Johannes B; Groenwold, Rolf H H

    2017-07-14

    Prognostic models often show poor performance when applied to independent validation data sets. We illustrate how treatment use in a validation set can affect measures of model performance and present the uses and limitations of available analytical methods to account for this using simulated data. We outline how the use of risk-lowering treatments in a validation set can lead to an apparent overestimation of risk by a prognostic model that was developed in a treatment-naïve cohort to make predictions of risk without treatment. Potential methods to correct for the effects of treatment use when testing or validating a prognostic model are discussed from a theoretical perspective.. Subsequently, we assess, in simulated data sets, the impact of excluding treated individuals and the use of inverse probability weighting (IPW) on the estimated model discrimination (c-index) and calibration (observed:expected ratio and calibration plots) in scenarios with different patterns and effects of treatment use. Ignoring the use of effective treatments in a validation data set leads to poorer model discrimination and calibration than would be observed in the untreated target population for the model. Excluding treated individuals provided correct estimates of model performance only when treatment was randomly allocated, although this reduced the precision of the estimates. IPW followed by exclusion of the treated individuals provided correct estimates of model performance in data sets where treatment use was either random or moderately associated with an individual's risk when the assumptions of IPW were met, but yielded incorrect estimates in the presence of non-positivity or an unobserved confounder. When validating a prognostic model developed to make predictions of risk without treatment, treatment use in the validation set can bias estimates of the performance of the model in future targeted individuals, and should not be ignored. When treatment use is random, treated

  18. Accounting for treatment use when validating a prognostic model: a simulation study

    Directory of Open Access Journals (Sweden)

    Romin Pajouheshnia

    2017-07-01

    Full Text Available Abstract Background Prognostic models often show poor performance when applied to independent validation data sets. We illustrate how treatment use in a validation set can affect measures of model performance and present the uses and limitations of available analytical methods to account for this using simulated data. Methods We outline how the use of risk-lowering treatments in a validation set can lead to an apparent overestimation of risk by a prognostic model that was developed in a treatment-naïve cohort to make predictions of risk without treatment. Potential methods to correct for the effects of treatment use when testing or validating a prognostic model are discussed from a theoretical perspective.. Subsequently, we assess, in simulated data sets, the impact of excluding treated individuals and the use of inverse probability weighting (IPW on the estimated model discrimination (c-index and calibration (observed:expected ratio and calibration plots in scenarios with different patterns and effects of treatment use. Results Ignoring the use of effective treatments in a validation data set leads to poorer model discrimination and calibration than would be observed in the untreated target population for the model. Excluding treated individuals provided correct estimates of model performance only when treatment was randomly allocated, although this reduced the precision of the estimates. IPW followed by exclusion of the treated individuals provided correct estimates of model performance in data sets where treatment use was either random or moderately associated with an individual's risk when the assumptions of IPW were met, but yielded incorrect estimates in the presence of non-positivity or an unobserved confounder. Conclusions When validating a prognostic model developed to make predictions of risk without treatment, treatment use in the validation set can bias estimates of the performance of the model in future targeted individuals, and

  19. ANTIPSYCHOTIC TREATMENT - SIDE-EFFECT AND/OR METABOLIC SYNDROME

    OpenAIRE

    Dadić-Hero, Elizabeta; Ružić, Klementina; Grahovac, Tanja; Žarković Palijan, Tija; Petranović, Duška; Šepić-Grahovac, Dubravka

    2011-01-01

    According to current medical opinion chronic mental diseases such as schizophrenia require life-long treatment. The choice of antipsychotics is an important treatment factor, since their side-effects often influence patients' compliance with treatment. Severe side-effects may cause the patients to reject such treatment, the latter being their right. In case a psychiatrist does not agree with the patient's decision to interrupt his antipsychotic treatment regardless its serious side-e...

  20. Hydraulic modelling of drinking water treatment plant operations

    NARCIS (Netherlands)

    Worm, G.I.M.; Mesman, G.A.M.; Van Schagen, K.M.; Borger, K.J.; Rietveld, L.C.

    2009-01-01

    The flow through a unit of a drinking water treatment plant is one of the most important parameters in terms of a unit's effectiveness. In the present paper, a new EPAnet library is presented with the typical hydraulic elements for drinking water treatment processes well abstraction, rapid sand

  1. Effective post-exposure treatment of Ebola infection.

    Directory of Open Access Journals (Sweden)

    Heinz Feldmann

    2007-01-01

    Full Text Available Ebola viruses are highly lethal human pathogens that have received considerable attention in recent years due to an increasing re-emergence in Central Africa and a potential for use as a biological weapon. There is no vaccine or treatment licensed for human use. In the past, however, important advances have been made in developing preventive vaccines that are protective in animal models. In this regard, we showed that a single injection of a live-attenuated recombinant vesicular stomatitis virus vector expressing the Ebola virus glycoprotein completely protected rodents and nonhuman primates from lethal Ebola challenge. In contrast, progress in developing therapeutic interventions against Ebola virus infections has been much slower and there is clearly an urgent need to develop effective post-exposure strategies to respond to future outbreaks and acts of bioterrorism, as well as to treat laboratory exposures. Here we tested the efficacy of the vesicular stomatitis virus-based Ebola vaccine vector in post-exposure treatment in three relevant animal models. In the guinea pig and mouse models it was possible to protect 50% and 100% of the animals, respectively, following treatment as late as 24 h after lethal challenge. More important, four out of eight rhesus macaques were protected if treated 20 to 30 min following an otherwise uniformly lethal infection. Currently, this approach provides the most effective post-exposure treatment strategy for Ebola infections and is particularly suited for use in accidentally exposed individuals and in the control of secondary transmission during naturally occurring outbreaks or deliberate release.

  2. Effects of uncertainties in the thermodynamic properties of aerosol components in an air quality model ─ Part 1: Treatment of inorganic electrolytes and organic compounds in the condensed phase

    Directory of Open Access Journals (Sweden)

    J. H. Seinfeld

    2008-02-01

    Full Text Available Air quality models that generate the concentrations of semi-volatile and other condensable organic compounds using an explicit reaction mechanism require estimates of the physical and thermodynamic properties of the compounds that affect gas/aerosol partitioning: vapour pressure (as a subcooled liquid, and activity coefficients in the aerosol phase. The model of Griffin, Kleeman and co-workers (e.g., Griffin et al., 2003; Kleeman et al., 1999 assumes that aerosol particles consist of an aqueous phase, containing inorganic electrolytes and soluble organic compounds, and a hydrophobic phase containing mainly primary hydrocarbon material. Thirty eight semi-volatile reaction products are grouped into ten surrogate species which partition between the gas phase and both phases in the aerosol. Activity coefficients of the organic compounds are calculated using UNIFAC. In a companion paper (Clegg et al., 2008 we examine the likely uncertainties in the vapour pressures of the semi-volatile compounds and their effects on partitioning over a range of atmospheric relative humidities. In this work a simulation for the South Coast Air Basin surrounding Los Angeles, using lower vapour pressures of the semi-volatile surrogate compounds consistent with estimated uncertainties in the boiling points on which they are based, yields a doubling of the predicted 24-h average secondary organic aerosol concentrations. The dependency of organic compound partitioning on the treatment of inorganic electrolytes in the air quality model, and the performance of this component of the model, are determined by analysing the results of a trajectory calculation using an extended version of the Aerosol Inorganics Model of Wexler and Clegg (2002. Simplifications are identified where substantial efficiency gains can be made, principally: the omission of dissociation of the organic acid surrogates; restriction of aerosol organic compounds to one of the two phases (aqueous or

  3. Using Peer Modeling and Differential Reinforcement in the Treatment of Food Selectivity

    Science.gov (United States)

    Sira, Bipon K.; Fryling, Mitch J.

    2012-01-01

    Behavior analysts have evaluated a wide range of assessment and treatment strategies in the area of feeding disorders. However, little is known about the effects of interventions employing peer modeling. This study extends upon the existing research on peer modeling and differential reinforcement with a 9-year-old boy diagnosed with autism who…

  4. Modelling of environmental impacts from biological treatment of organic municipal waste in EASEWASTE

    DEFF Research Database (Denmark)

    Boldrin, Alessio; Neidel, Trine Lund; Damgaard, Anders

    2011-01-01

    The waste-LCA model EASEWASTE quantifies potential environmental effects from biological treatment of organic waste, based on mass and energy flows, emissions to air, water, soil and groundwater as well as effects from upstream and downstream processes. Default technologies for composting, anaero...... the environmental performance of alternative biological treatment technologies in relation to their mass flows, energy consumption, gaseous emissions, biogas recovery and compost/digestate utilization....

  5. Treatment effectiveness for dysfunctions of sexual desire.

    Science.gov (United States)

    Schover, L R; LoPiccolo, J

    1982-01-01

    Archival data from the Sex Therapy Center at Stony Brook were analyzed to determine the prevalence of desire phase sexual dysfunctions and the effectiveness of treating them with behavioral sex therapy. When cases were rediagnosed with a multi-axial problem-oriented system, increases from 1974-1981 in both the prevalence of desire phase problems and of male low sexual desire were observed. Data suggested that wives display more extreme patterns of sexual avoidance than do husbands in couples seeking sex therapy. Outcome statistics on marital adjustment, overall sexual satisfaction, the frequency of intercourse and masturbation, and patterns of initiation of sexual activity reveal significant positive changes after treatment. These changes are not due to nonspecific factors and are maintained at follow-up. Sex therapy was equally successful for male-centered vs. female-centered problems, for low sexual desire vs. aversion to sex, and for global or lifelong dysfunctions vs. the more recent or situational ones. Posttreatment gains reflect a minimally adequate sexual relationship, however, rather than an optimal degree of intimacy and pleasure.

  6. Effects of radiation treatment on foodstuffs

    International Nuclear Information System (INIS)

    Dehne, L.; Boegl, W.

    1980-01-01

    The purpose of this study is to discuss and compile methods and results of irradiation experiments carried out on 54 plant and animal foodstuffs in order to obtain a survey on chemical changes, in particular as regards the reduction of nutritional value and savoriness of irradiated foodstuffs. According to this task, microbiological aspects as well as an interpretation of the experimental results as to the physiology of nutrition and toxicology were not included. The results published by the authors of the original papers were compiled in a kind of dictionary which contains all relevant information such as radiation sources, irradiation conditions, investigation methods, results of chemical or organoleptical changes etc. The most important results were summarized in tables and can be found at the end of this study. Because of the abundance of existing literature the series 'Effects of radiation treatment on foodstuffs' will be continued in Part IV, and the final discussion of the results will be published separately after further data have been included. (orig.) [de

  7. Modeling Incoherent Electron Cloud Effects

    International Nuclear Information System (INIS)

    Vay, Jean-Luc; Benedetto, E.; Fischer, W.; Franchetti, G.; Ohmi, K.; Schulte, D.; Sonnad, K.; Tomas, R.; Vay, J.-L.; Zimmermann, F.; Rumolo, G.; Pivi, M.; Raubenheimer, T.

    2007-01-01

    Incoherent electron effects could seriously limit the beam lifetime in proton or ion storage rings, such as LHC, SPS, or RHIC, or blow up the vertical emittance of positron beams, e.g., at the B factories or in linear-collider damping rings. Different approaches to modeling these effects each have their own merits and drawbacks. We describe several simulation codes which simplify the descriptions of the beam-electron interaction and of the accelerator structure in various different ways, and present results for a toy model of the SPS. In addition, we present evidence that for positron beams the interplay of incoherent electron-cloud effects and synchrotron radiation can lead to a significant increase in vertical equilibrium emittance. The magnitude of a few incoherent e+e- scattering processes is also estimated. Options for future code development are reviewed

  8. Psychological mechanisms of effective cognitive-behavioral treatments for PTSD.

    Science.gov (United States)

    Zalta, Alyson K

    2015-04-01

    Several psychotherapies have been established as effective treatments for posttraumatic stress disorder (PTSD) including prolonged exposure, cognitive processing therapy, and cognitive therapy for PTSD. Understanding the key mechanisms of these treatments, i.e., how these treatments lead to therapeutic benefits, will enable us to maximize the efficacy, effectiveness, and efficiency of these therapies. This article provides an overview of the theorized mechanisms for each of these treatments, reviews the recent empirical evidence on psychological mechanisms of these treatments, discusses the ongoing debates in the field, and provides recommendations for future research. Few studies to date have examined whether changes in purported treatment mechanisms predict subsequent changes in treatment outcomes. Future clinical trials examining treatments for PTSD should use study designs that enable researchers to establish the temporal precedence of change in treatment mechanisms prior to symptom reduction. Moreover, further research is needed that explores the links between specific treatment components, underlying change mechanisms, and treatment outcomes.

  9. Evaluation of family treatment models for eating disorders.

    Science.gov (United States)

    Lock, James

    2011-07-01

    Interest in the effectiveness of family interventions for eating disorders has increased over the past 5 years. This review considers the theoretical justification and current evidence base for the use of family treatments for eating disorders in children and adolescents. Family-based treatment is the best studied treatment. It has the strongest evidence base for effectiveness for anorexia nervosa in adolescents. Family-based treatment can be delivered in several formats and doses, and preliminary data suggest it can be disseminated by training and manuals. There is a more limited evidence base demonstrating the usefulness of family interventions for bulimia nervosa in adolescents. The implications of the findings of this review are that family interventions are the current first-line treatment for adolescent anorexia nervosa and promising for adolescent bulimia nervosa. Pilot studies suggest that family interventions can be disseminated in diverse clinical settings.

  10. The right to refuse treatment: a model act.

    Science.gov (United States)

    1983-08-01

    Although the right to refuse medical treatment is universally recognized as a fundamental principle of liberty, this right is not always honored. A refusal can be thwarted either because a patient is unable to competently communicate or because providers insist on continuing treatment. To help enhance the patient's right to refuse treatment, many states have enacted so-called "living will" or "natural death" statutes. We believe the time has come to move beyond these current legislative models, and we therefore propose a Model Act that clearly enunciates an individual's right to refuse treatment, does not limit its exercise to the terminally ill or to heroic measures, and provides a mechanism by which individuals can set forth their wishes in advance and designate another person to enforce them.

  11. Cost Effectiveness of Pembrolizumab for Advanced Melanoma Treatment in Portugal.

    Science.gov (United States)

    Miguel, Luis Silva; Lopes, Francisca Vargas; Pinheiro, Bernardete; Wang, Jingshu; Xu, Ruifeng; Pellissier, James; Laires, Pedro Almeida

    2017-09-01

    The aim of this study was to assess the cost-effectiveness of pembrolizumab in treating patients with ipilimumab-naïve advanced melanoma in Portugal. A cost-effectiveness model was developed to analyze the costs and consequences of treatment with pembrolizumab compared to treatment with ipilimumab in patients with advanced melanoma not previously treated with ipilimumab. The model was parameterized by using data from a head-to-head phase III randomized clinical trial, KEYNOTE-006. Extrapolation of long-term outcomes was based on approaches previously applied, combining ipilimumab data and melanoma patients' registry data. The analysis was conducted from the perspective of the Portuguese National Health Service, and a lifetime horizon (40 years) was used. Portugal-specific disease management costs were estimated by convening a panel of six clinical experts to derive health state resource use and multiplying the results by national unit costs. To test for the robustness of the conclusions, we conducted deterministic and probabilistic sensitivity analyses. Pembrolizumab increases life expectancy in 1.57 undiscounted life-years (LYs) and is associated with an increase in costs versus that of ipilimumab. The estimated incremental cost-effectiveness ratio is €47,221 per quality-adjusted life-year (QALY) and €42,956 per LY. Deterministic sensitivity analysis showed that the results were robust to the change of most input values or assumptions and were sensitive to time on treatment scenarios. According to the probabilistic sensitivity analysis performed, pembrolizumab is associated with a cost per QALY gained inferior to €50,000 in 75% of the cases. Considering the usually accepted thresholds in oncology, pembrolizumab is a cost-effective alternative for treating patients with advanced melanoma in Portugal. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  12. The cost-effectiveness of changes to the care pathway used to identify depression and provide treatment amongst people with diabetes in England: a model-based economic evaluation.

    Science.gov (United States)

    Kearns, Ben; Rafia, R; Leaviss, J; Preston, L; Brazier, J E; Palmer, S; Ara, R

    2017-01-24

    Diabetes is associated with premature death and a number of serious complications. The presence of comorbid depression makes these outcomes more likely and results in increased healthcare costs. The aim of this work was to assess the health economic outcomes associated with having both diabetes and depression, and assess the cost-effectiveness of potential policy changes to improve the care pathway: improved opportunistic screening for depression, collaborative care for depression treatment, and the combination of both. A mathematical model of the care pathways experienced by people diagnosed with type-2 diabetes in England was developed. Both an NHS perspective and wider social benefits were considered. Evidence was taken from the published literature, identified via scoping and targeted searches. Compared with current practice, all three policies reduced both the time spent with depression and the number of diabetes-related complications experienced. The policies were associated with an improvement in quality of life, but with an increase in health care costs. In an incremental analysis, collaborative care dominated improved opportunistic screening. The incremental cost-effectiveness ratio (ICER) for collaborative care compared with current practice was £10,798 per QALY. Compared to collaborative care, the combined policy had an ICER of £68,017 per QALY. Policies targeted at identifying and treating depression early in patients with diabetes may lead to reductions in diabetes related complications and depression, which in turn increase life expectancy and improve health-related quality of life. Implementing collaborative care was cost-effective based on current national guidance in England.

  13. 21 CFR 1240.10 - Effective bactericidal treatment.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Effective bactericidal treatment. 1240.10 Section... DISEASES General Provisions § 1240.10 Effective bactericidal treatment. Whenever, under the provisions of this part, bactericidal treatment is required, it shall be accomplished by one or more of the following...

  14. Process modeling for the Integrated Thermal Treatment System (ITTS) study

    Energy Technology Data Exchange (ETDEWEB)

    Liebelt, K.H.; Brown, B.W.; Quapp, W.J.

    1995-09-01

    This report describes the process modeling done in support of the integrated thermal treatment system (ITTS) study, Phases 1 and 2. ITTS consists of an integrated systems engineering approach for uniform comparison of widely varying thermal treatment technologies proposed for treatment of the contact-handled mixed low-level wastes (MLLW) currently stored in the U.S. Department of Energy complex. In the overall study, 19 systems were evaluated. Preconceptual designs were developed that included all of the various subsystems necessary for a complete installation, from waste receiving through to primary and secondary stabilization and disposal of the processed wastes. Each system included the necessary auxiliary treatment subsystems so that all of the waste categories in the complex were fully processed. The objective of the modeling task was to perform mass and energy balances of the major material components in each system. Modeling of trace materials, such as pollutants and radioactive isotopes, were beyond the present scope. The modeling of the main and secondary thermal treatment, air pollution control, and metal melting subsystems was done using the ASPEN PLUS process simulation code, Version 9.1-3. These results were combined with calculations for the remainder of the subsystems to achieve the final results, which included offgas volumes, and mass and volume waste reduction ratios.

  15. Orlistat for the treatment of obesity: cost utility model.

    Science.gov (United States)

    Foxcroft, D R

    2005-11-01

    This study aimed to assess the cost utility of orlistat treatment based on (i) criteria from recent guidance from the National Institute for Clinical Excellence (NICE) for England and Wales (treatment discontinued if weight loss < 5% at 3 months; and < 10% at 6 months); and (ii) alternative criteria from the European Agency for the Evaluation of Medicinal Products (EMEA) licence for orlistat prescription in the European Community (treatment discontinued if weight loss < 5% at 3 months). Subjects were 1398 obese individuals who participated in three large European Phase III trials of orlistat treatment for adults (BMI: 28-47 kg m(-2)). Measures were: response to treatment in orlistat and placebo treatment groups; health benefit expressed as quality adjusted life years (QALYs) gained associated with weight loss; costs associated with orlistat treatment. In the cost utility model with multiway sensitivity analysis, the cost/QALY gained using the NICE criteria was estimated to be 24,431 pounds (sensitivity analysis range: 10,856 to 77,197 pounds). The cost/QALY gained using the alternative EMEA criteria was estimated to be 19,005 pounds (range: 8,840 to 57,798 pounds). In conclusion, NICE guidance for the continued use of orlistat was supported in this updated cost utility model, comparing favourably with a previously published estimate of 45,881 pounds per QALY gained. Moreover, the value for money of orlistat treatment is improved further if EMEA treatment criteria for continued orlistat treatment are applied. The EMEA criteria should be considered in any future changes to the NICE guidance or in guidance issued by similar agencies.

  16. An investigation of an open-access model for scaling up methadone maintenance treatment.

    Science.gov (United States)

    Madden, Lynn M; Farnum, Scott O; Eggert, Kathryn F; Quanbeck, Andrew R; Freeman, Robert M; Ball, Samuel A; Schottenfeld, Richard S; Shi, Julia M; Savage, Mary Ellen; Barry, Declan T

    2018-02-17

    To examine retrospectively patient and programmatic outcomes following the development and implementation of an 'open-access' model in which prospective patients were enrolled rapidly in methadone maintenance treatment, irrespective of ability to pay, and provided real-time access to multiple voluntary treatment options. Medical and administrative records were abstracted to compare data for 1 year before and 9 years after initiating the implementation of an open-access treatment model in May 2007. Methadone maintenance treatment center in Connecticut, USA. Individuals with opioid use disorder entering treatment between July 2006 and June 2015. In June 2015, 64% (n = 2594) of the sample were men and 80% (n = 3133) reported that they were white. The Network for the Improvement of Addiction Treatment-informed open-access treatment model uses process improvement strategies to improve treatment access and capacity. Census, waiting time, retention, non-medical opioid use, patient mortality and financial sustainability (net income and state-block grants as proportions of revenue). In the 9 years following the initial implementation of the open-access model, patient census increased by 183% from 1431 to 4051, and average waiting-time days decreased from 21 to 0.3 (same day) without apparent deleterious effects on rates of retention, non-medical opioid use or mortality. Between fiscal years (FY) 06 and FY 15, net operating margin rose from 2 to 10%, while state-block grant revenues declined 14% and the proportion of total revenue from state-block grant revenue decreased from 49 to 24%. An open-access model for rapid enrolment of people with opioid use disorder in methadone treatment appears to improve treatment access, capacity, and financial sustainability without evidence of deleterious effects on treatment outcomes. © 2018 Society for the Study of Addiction.

  17. Multiscale Modelling of Cancer Progression and Treatment Control: The Role of Intracellular Heterogeneities in Chemotherapy Treatment

    Science.gov (United States)

    Chaplain, Mark A. J.; Powathil, Gibin G.

    Cancer is a complex, multiscale process involving interactions at intracellular, intercellular and tissue scales that are in turn susceptible to microenvironmental changes. Each individual cancer cell within a cancer cell mass is unique, with its own internal cellular pathways and biochemical interactions. These interactions contribute to the functional changes at the cellular and tissue scale, creating a heterogenous cancer cell population. Anticancer drugs are effective in controlling cancer growth by inflicting damage to various target molecules and thereby triggering multiple cellular and intracellular pathways, leading to cell death or cell-cycle arrest. One of the major impediments in the chemotherapy treatment of cancer is drug resistance driven by multiple mechanisms, including multi-drug and cell-cycle mediated resistance to chemotherapy drugs. In this article, we discuss two hybrid multiscale modelling approaches, incorporating multiple interactions involved in the sub-cellular, cellular and microenvironmental levels to study the effects of cell-cycle, phase-specific chemotherapy on the growth and progression of cancer cells.

  18. Cost-effectiveness of ceftriaxone in the treatment of community ...

    African Journals Online (AJOL)

    effectiveness of four intravenous antibiotic treatment regimens in the treatment of severe community-acquired pneumonia (CAP) in adults in a private hospital setting. The study compared some third-generation cephalosporin regimens with a ...

  19. On the treatment of airline travelers in mathematical models.

    Directory of Open Access Journals (Sweden)

    Michael A Johansson

    Full Text Available The global spread of infectious diseases is facilitated by the ability of infected humans to travel thousands of miles in short time spans, rapidly transporting pathogens to distant locations. Mathematical models of the actual and potential spread of specific pathogens can assist public health planning in the case of such an event. Models should generally be parsimonious, but must consider all potentially important components of the system to the greatest extent possible. We demonstrate and discuss important assumptions relative to the parameterization and structural treatment of airline travel in mathematical models. Among other findings, we show that the most common structural treatment of travelers leads to underestimation of the speed of spread and that connecting travel is critical to a realistic spread pattern. Models involving travelers can be improved significantly by relatively simple structural changes but also may require further attention to details of parameterization.

  20. Modeling fuels and fire effects in 3D: Model description and applications

    Science.gov (United States)

    Francois Pimont; Russell Parsons; Eric Rigolot; Francois de Coligny; Jean-Luc Dupuy; Philippe Dreyfus; Rodman R. Linn

    2016-01-01

    Scientists and managers critically need ways to assess how fuel treatments alter fire behavior, yet few tools currently exist for this purpose.We present a spatially-explicit-fuel-modeling system, FuelManager, which models fuels, vegetation growth, fire behavior (using a physics-based model, FIRETEC), and fire effects. FuelManager's flexible approach facilitates...

  1. Cost-effectiveness of two versus three or more doses of intermittent preventive treatment for malaria during pregnancy in sub-Saharan Africa: a modelling study of meta-analysis and cost data.

    Science.gov (United States)

    Fernandes, Silke; Sicuri, Elisa; Kayentao, Kassoum; van Eijk, Anne Maria; Hill, Jenny; Webster, Jayne; Were, Vincent; Akazili, James; Madanitsa, Mwayi; ter Kuile, Feiko O; Hanson, Kara

    2015-03-01

    In 2012, WHO changed its recommendation for intermittent preventive treatment of malaria during pregnancy (IPTp) from two doses to monthly doses of sulfadoxine-pyrimethamine during the second and third trimesters, but noted the importance of a cost-effectiveness analysis to lend support to the decision of policy makers. We therefore estimated the incremental cost-effectiveness of IPTp with three or more (IPTp-SP3+) versus two doses of sulfadoxine-pyrimethamine (IPTp-SP2). For this analysis, we used data from a 2013 meta-analysis of seven studies in sub-Saharan Africa. We developed a decision tree model with a lifetime horizon. We analysed the base case from a societal perspective. We did deterministic and probabilistic sensitivity analyses with appropriate parameter ranges and distributions for settings with low, moderate, and high background risk of low birthweight, and did a separate analysis for HIV-negative women. Parameters in the model were obtained for all countries included in the original meta-analysis. We did simulations in hypothetical cohorts of 1000 pregnant women receiving either IPTp-SP3+ or IPTp-SP2. We calculated disability-adjusted life-years (DALYs) for low birthweight, severe to moderate anaemia, and clinical malaria. We calculated cost estimates from data obtained in observational studies, exit surveys, and from public procurement databases. We give financial and economic costs in constant 2012 US$. The main outcome measure was the incremental cost per DALY averted. The delivery of IPTp-SP3+ to 1000 pregnant women averted 113·4 DALYs at an incremental cost of $825·67 producing an incremental cost-effectiveness ratio (ICER) of $7·28 per DALY averted. The results remained robust in the deterministic sensitivity analysis. In the probabilistic sensitivity analyses, the ICER was $7·7 per DALY averted for moderate risk of low birthweight, $19·4 per DALY averted for low risk, and $4·0 per DALY averted for high risk. The ICER for HIV

  2. Effects of phase vector and history extension on prediction power of adaptive-network based fuzzy inference system (ANFIS) model for a real scale anaerobic wastewater treatment plant operating under unsteady state.

    Science.gov (United States)

    Perendeci, Altinay; Arslan, Sever; Tanyolaç, Abdurrahman; Celebi, Serdar S

    2009-10-01

    A conceptual neural fuzzy model based on adaptive-network based fuzzy inference system, ANFIS, was proposed using available input on-line and off-line operational variables for a sugar factory anaerobic wastewater treatment plant operating under unsteady state to estimate the effluent chemical oxygen demand, COD. The predictive power of the developed model was improved as a new approach by adding the phase vector and the recent values of COD up to 5-10 days, longer than overall retention time of wastewater in the system. History of last 10 days for COD effluent with two-valued phase vector in the input variable matrix including all parameters had more predictive power. History of 7 days with two-valued phase vector in the matrix comprised of only on-line variables yielded fairly well estimations. The developed ANFIS model with phase vector and history extension has been able to adequately represent the behavior of the treatment system.

  3. Herbal Treatment for Anxiety: Is It Effective?

    Science.gov (United States)

    ... from Brent A. Bauer, M.D. Several herbal remedies have been studied as a treatment for anxiety, ... is preliminary and limited. Oral lavender can cause constipation and headaches. It can also increase appetite, increase ...

  4. Mindfulness-based treatment to prevent addictive behavior relapse: theoretical models and hypothesized mechanisms of change.

    Science.gov (United States)

    Witkiewitz, Katie; Bowen, Sarah; Harrop, Erin N; Douglas, Haley; Enkema, Matthew; Sedgwick, Carly

    2014-04-01

    Mindfulness-based treatments are growing in popularity among addiction treatment providers, and several studies suggest the efficacy of incorporating mindfulness practices into the treatment of addiction, including the treatment of substance use disorders and behavioral addictions (i.e., gambling). The current paper provides a review of theoretical models of mindfulness in the treatment of addiction and several hypothesized mechanisms of change. We provide an overview of mindfulness-based relapse prevention (MBRP), including session content, treatment targets, and client feedback from participants who have received MBRP in the context of empirical studies. Future research directions regarding operationalization and measurement, identifying factors that moderate treatment effects, and protocol adaptations for specific populations are discussed.

  5. A rationale and model for addressing tobacco dependence in substance abuse treatment

    Directory of Open Access Journals (Sweden)

    Richter Kimber P

    2006-08-01

    Full Text Available Abstract Most persons in drug treatment smoke cigarettes. Until drug treatment facilities systematically treat their patients' tobacco use, millions will flow through the drug treatment system, overcome their primary drug of abuse, but die prematurely from tobacco-related illnesses. This paper reviews the literature on the health benefits of quitting smoking for drug treatment patients, whether smoking causes relapse to other drug or alcohol abuse, the treatment of tobacco dependence, and good and bad times for quitting smoking among drug treatment patients. It also presents a conceptual model and recommendations for treating tobacco in substance abuse treatment, and provides references to internet and paper-copy tools and information for treating tobacco dependence. At present, research on tobacco treatment in drug treatment is in its infancy. Although few drug treatment programs currently offer formal services, many more will likely begin to treat nicotine dependence as external forces and patient demand for these services increases. In the absence of clear guidelines and attention to quality of care, drug treatment programs may adopt smoking cessation services based on cost, convenience, or selection criteria other than efficacy. Because research in this field is relatively new, substance abuse treatment professionals should adhere to the standards of care for the general population, but be prepared to update their practices with emerging interventions that have proven to be effective for patients in drug treatment.

  6. Better models are more effectively connected models

    Science.gov (United States)

    Nunes, João Pedro; Bielders, Charles; Darboux, Frederic; Fiener, Peter; Finger, David; Turnbull-Lloyd, Laura; Wainwright, John

    2016-04-01

    The concept of hydrologic and geomorphologic connectivity describes the processes and pathways which link sources (e.g. rainfall, snow and ice melt, springs, eroded areas and barren lands) to accumulation areas (e.g. foot slopes, streams, aquifers, reservoirs), and the spatial variations thereof. There are many examples of hydrological and sediment connectivity on a watershed scale; in consequence, a process-based understanding of connectivity is crucial to help managers understand their systems and adopt adequate measures for flood prevention, pollution mitigation and soil protection, among others. Modelling is often used as a tool to understand and predict fluxes within a catchment by complementing observations with model results. Catchment models should therefore be able to reproduce the linkages, and thus the connectivity of water and sediment fluxes within the systems under simulation. In modelling, a high level of spatial and temporal detail is desirable to ensure taking into account a maximum number of components, which then enables connectivity to emerge from the simulated structures and functions. However, computational constraints and, in many cases, lack of data prevent the representation of all relevant processes and spatial/temporal variability in most models. In most cases, therefore, the level of detail selected for modelling is too coarse to represent the system in a way in which connectivity can emerge; a problem which can be circumvented by representing fine-scale structures and processes within coarser scale models using a variety of approaches. This poster focuses on the results of ongoing discussions on modelling connectivity held during several workshops within COST Action Connecteur. It assesses the current state of the art of incorporating the concept of connectivity in hydrological and sediment models, as well as the attitudes of modellers towards this issue. The discussion will focus on the different approaches through which connectivity

  7. Uncertainties in model-based outcome predictions for treatment planning

    International Nuclear Information System (INIS)

    Deasy, Joseph O.; Chao, K.S. Clifford; Markman, Jerry

    2001-01-01

    Purpose: Model-based treatment-plan-specific outcome predictions (such as normal tissue complication probability [NTCP] or the relative reduction in salivary function) are typically presented without reference to underlying uncertainties. We provide a method to assess the reliability of treatment-plan-specific dose-volume outcome model predictions. Methods and Materials: A practical method is proposed for evaluating model prediction based on the original input data together with bootstrap-based estimates of parameter uncertainties. The general framework is applicable to continuous variable predictions (e.g., prediction of long-term salivary function) and dichotomous variable predictions (e.g., tumor control probability [TCP] or NTCP). Using bootstrap resampling, a histogram of the likelihood of alternative parameter values is generated. For a given patient and treatment plan we generate a histogram of alternative model results by computing the model predicted outcome for each parameter set in the bootstrap list. Residual uncertainty ('noise') is accounted for by adding a random component to the computed outcome values. The residual noise distribution is estimated from the original fit between model predictions and patient data. Results: The method is demonstrated using a continuous-endpoint model to predict long-term salivary function for head-and-neck cancer patients. Histograms represent the probabilities for the level of posttreatment salivary function based on the input clinical data, the salivary function model, and the three-dimensional dose distribution. For some patients there is significant uncertainty in the prediction of xerostomia, whereas for other patients the predictions are expected to be more reliable. In contrast, TCP and NTCP endpoints are dichotomous, and parameter uncertainties should be folded directly into the estimated probabilities, thereby improving the accuracy of the estimates. Using bootstrap parameter estimates, competing treatment

  8. Knowledge-Management-Based-Nursing Care Model Improves Patient Adherence to Tuberculosis Treatment

    Directory of Open Access Journals (Sweden)

    Ninuk Dian Kurniawati

    2016-04-01

    Full Text Available Introduction. Pulmonary tuberculosis remains prominent as one of public health problems in the world. Patients’ non-compliance to treatment is a significant contributor to drug resistance. This study aimed to develop and to test the efficacy of a nursing care model to prevent non-compliance. Method This study consisted of two phases: phase one, model development, used a descriptive analytic, and phase two, model testing, employed a quasi-experimental design. Participants, comprised both patients and nurses at two health care centres in Surabaya, were recruited by consecutive sampling. Data were collected by interview, self-administered-questionnaires, check-list and focused group discussion. Data analyses were performed using both partial least squares and Wilcoxon signed rank test. Results. The model was statistically effective to improve nearly all aspects of patients’ compliance to TB treatment (knowledge, discipline in taking medications regularity of controls, and abilities to monitor the results of treatment with p < 0.05, except for abilities to cope with drug adverse effects (p = 1.000. This is possible because seldom do patients aware of the medication side effects, so their experiences were probably limited. Conclusion. This study concludes that the KM nursing care model was proven effective to improve patients’ adherence to treatment. Future study is suggested to evaluate the impact of the KM nursing care model in bigger population.

  9. Modeling Jambo wastewater treatment system to predict water re ...

    African Journals Online (AJOL)

    user

    Full Length Research Paper. Modeling Jambo wastewater treatment system to predict water re-use options. Kyeyune Simonpeter and Mulamba Peter*. Department of Agricultural and Bio-Systems Engineering, Makerere University, P.O. Box 7062, Kampala, Uganda. Received 22 August, 2012; Accepted 29 December, 2014.

  10. Computational models as predictors of HIV treatment outcomes for ...

    African Journals Online (AJOL)

    Background: Selecting the optimal combination of HIV drugs for an individual in resourcelimited settings is challenging because of the limited availability of drugs and genotyping. Objective: The evaluation as a potential treatment support tool of computational models that predict response to therapy without a genotype, ...

  11. Animal models for arthritis: innovative tools for prevention and treatment

    NARCIS (Netherlands)

    Kollias, G.; Papadaki, P.; Apparailly, F.; Vervoordeldonk, M.J.; Holmdahl, R.; Baumans, V.; Desaintes, C.; Di Santo, J.; Distler, J.; Garside, P.; Hegen, M.; Huizinga, T.W.J.; Jüngel, A.; Klareskog, L.; McInnes, I.; Ragoussis, I.; Schett, G.; Hart, B.t.; Tak, P.P.; Toes, R.; van den Berg, W.; Wurst, W.; Gay, S.

    2011-01-01

    The development of novel treatments for rheumatoid arthritis (RA) requires the interplay between clinical observations and studies in animal models. Given the complex molecular pathogenesis and highly heterogeneous clinical picture of RA, there is an urgent need to dissect its multifactorial nature

  12. An Energy Savings Model for the Heat Treatment of Castings

    Energy Technology Data Exchange (ETDEWEB)

    Y. Rong; R. Sisson; J. Morral; H. Brody

    2006-12-31

    An integrated system of software, databases, and design rules have been developed, verified, and to be marketed to enable quantitative prediction and optimization of the heat treatment of aluminum castings to increase quality, increase productivity, reduce heat treatment cycle times and reduce energy consumption. The software predicts the thermal cycle in critical locations of individual components in a furnace, the evolution of microstructure, and the attainment of properties in heat treatable aluminum alloy castings. The model takes into account the prior casting process and the specific composition of the component. The heat treatment simulation modules can be used in conjunction with software packages for simulation of the casting process. The system is built upon a quantitative understanding of the kinetics of microstructure evolution in complex multicomponent alloys, on a quantitative understanding of the interdependence of microstructure and properties, on validated kinetic and thermodynamic databases, and validated quantitative models.

  13. intercritical heat treatments effects on low carbon steels quenched

    African Journals Online (AJOL)

    DR B. A. EZEKOYE

    hardening and precipitation effects [2]. Of all the metallic materials of engineering ... of this work was to investigate the effect of diverse intercritical heat treatments on the ... INTERCRITICAL HEAT TREATMENT EFFECTS ON LOW CARBON STEELS QUENCHED FROM INTERMEDIATE ... Series II- Intercritical quench with.

  14. Evaluation of the therapeutic community treatment model in Thailand: policy implications for compulsory and prison-based treatment.

    Science.gov (United States)

    Johnson, Knowlton W; Young, Linda; Shamblen, Stephen; Suresh, Geetha; Browne, Thom; Chookhare, Khun Warunee

    2012-01-01

    This study, conducted in 2005 to 2007, presents results that are based on a proscriptive cohort design. The sample consisted of 769 residents in 22 drug user treatment programs who stayed in treatment for at least 30 days to one year; 510 former residents (66%) from 21 programs (95%) were interviewed again at a 6-month post-treatment follow-up assessment. A majority of the participants were male, lived with family or relatives, had completed only primary school, and had a full-time or a part-time job prior to entering treatment. The participating therapeutic community (TC) programs were a mixture of volunteer, compulsory-probation, and prison-based programs. In-person interview data and urine testing showed that the self-reported drug use prevalence rates are reliable. The results show large positive treatment effects on 30-day and 6-month illegal drug use and small to medium effects on the severity of alcohol use and related problems. A multilevel regression analysis suggests that residents' reduced stigma, adaptation of the TC model, and frequency of alcohol and drug use-related consequences partially predict treatment success. Study limitations and policy implications are discussed.

  15. Mathematical model for gyroscope effects

    Science.gov (United States)

    Usubamatov, Ryspek

    2015-05-01

    Gyroscope effects are used in many engineering calculations of rotating parts, and a gyroscope is the basic unit of numerous devices and instruments used in aviation, space, marine and other industries. The primary attribute of a gyroscope is a spinning rotor that persists in maintaining its plane of rotation, creating gyroscope effects. Numerous publications represent the gyroscope theory using mathematical models based on the law of kinetic energy conservation and the rate of change in angular momentum of a spinning rotor. Gyroscope theory still attracts many researchers who continue to discover new properties of gyroscopic devices. In reality, gyroscope effects are more complex and known mathematical models do not accurately reflect the actual motions. Analysis of forces acting on a gyroscope shows that four dynamic components act simultaneously: the centrifugal, inertial and Coriolis forces and the rate of change in angular momentum of the spinning rotor. The spinning rotor generates a rotating plane of centrifugal and Coriols forces that resist the twisting of the spinning rotor with external torque applied. The forced inclination of the spinning rotor generates inertial forces, resulting in precession torque of a gyroscope. The rate of change of the angular momentum creates resisting and precession torques which are not primary one in gyroscope effects. The new mathematical model for the gyroscope motions under the action of the external torque applied can be as base for new gyroscope theory. At the request of the author of the paper, this corrigendum was issued on 24 May 2016 to correct an incomplete Table 1 and errors in Eq. (47) and Eq. (48).

  16. Effect of patient's life expectancy on the cost-effectiveness of treatment for ocular hypertension.

    Science.gov (United States)

    Kymes, Steven M; Plotzke, Michael R; Kass, Michael A; Boland, Michael V; Gordon, Mae O

    2010-05-01

    To assess the influence of expected life span on the cost-effectiveness of treating ocular hypertension to prevent primary open-angle glaucoma. We used a Markov simulation model to estimate the cost and benefit of ocular hypertension treatment over a person's remaining life. We examined the influence of age on the cost-effectiveness decision in 2 ways: (1) by evaluating specific age cohorts to assess the influence of age at the initiation of treatment; and (2) by evaluating the influence of a specific life span. At a willingness to pay $50,000/quality-adjusted life year to $100,000/quality-adjusted life year, treatment of people with a 2% or greater annual risk of developing glaucoma was cost-effective for people aged 45 years with a life expectancy of at least 18 remaining years. However, to be cost-effective, a person aged 55 years must have a life expectancy of 21 remaining years and someone aged 65 years must have a life expectancy of 23 remaining years. A person with ocular hypertension must have a life expectancy of at least 18 remaining years to justify treatment at a threshold of a 2% or greater annual risk of developing glaucoma. Persons at higher levels of risk require a life expectancy of 7 to 10 additional years to justify treatment.

  17. Effectiveness of Emdogain in the periodontal treatment.

    Science.gov (United States)

    Kurhańska-Flisykowska, Anna; Łojewski, Włodzimierz; Wyganowska-Swiatkowska, Marzena

    2012-01-01

    The study was designed to investigate how the periodontal disease treatment with Emdogain may influence the parameters of serum acute phase response and the total antioxidant status (TAS) of nonstimulated saliva. The wound healing process after periodontal treatment provided with EMD and regular open flap procedure was observed in 28 patients. TAS in saliva and acute phase proteins in blood was measured before and after treatment. The PD varied from 3,91 mm before treatment to 1,27 after it in EMD group and from 3,83 mm and 1,33 in the control group. CAL varied from 3,2 - 2,4 mm in EMD group and from 2,70 - 2,2 in the control group (p<0,01 and p<0,001). On the basis and after treatment of acute phase proteins analysis existence of chronic inflammatory state with slight decreased total concentration of AGP, ACP. Low TAS level found in the saliva of the subjects in our study may suggest that the antioxidant defence of saliva in patients with chronic periodontitis is poor.

  18. Effectiveness of propanolol for treatment of infantile haemangioma

    DEFF Research Database (Denmark)

    Andersen, Ida Gillberg; Rechnitzer, Catherine; Charabi, Birgitte

    2014-01-01

    was considered sufficient in most cases (71%). Children who started treatment before five months of age had a significantly better response than children who started treatment at a later age. No relation was found between location of IH and the effect of treatment. There were only few and mild side effects....... CONCLUSION: Propranolol is effective in the treatment of IH and it has only few and mild side effects. In most cases, a low dose of 1 mg/kg/day was sufficient. Early initiation of treatment is recommended as the response to treatment was better in younger children and because early initiation helps prevent......INTRODUCTION: Infantile haemangiomas (IH) are the most common benign tumours in children. They are characterised by rapid growth during the first year of life followed by spontaneous regression during childhood. Indications for treatment are functional impairment, bleeding/ulceration, rapid growth...

  19. Psychiatric side effects of interferon treatment.

    Science.gov (United States)

    Patten, Scott B

    2006-05-01

    Interferons are employed in the management of multiple sclerosis, hepatitis C and certain malignancies. Neuropsychiatric toxicity can interfere with the successful use of these drugs. This review was based on Medline literature searches, supplemented by bibliographical citations in identified papers. Information uncovered in the literature review was interpreted in light of related pharmacoepidemiological and psychiatric literature. Interferon-associated neurotoxicity does not adhere closely to standard psychiatric syndromal and diagnostic definitions. Delirium, depression, non-specific symptoms related to sickness behavior and, rarely, manic and psychotic syndromes are all potential adverse events during interferon treatment. For depression, the evidence of increased risk is stronger for interferon alpha than for interferon beta. The availability of preventive and treatment interventions suggest that neuropsychiatric toxicity can often be managed without needing to discontinue the treatment. Safety can be maximized by organization of health services in ways that enhance detection and management of neuropsychiatric problems, and which support access to basic and specialized mental health services.

  20. 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.

  1. Mathematical Modeling of Some Heating and Thermal Treatment Processes

    Directory of Open Access Journals (Sweden)

    N. P. Voronova

    2006-01-01

    Full Text Available The purpose of the paper-is to construct a mathematical model that makes it possible to investigate and modify design and heat technological models of units intended for heating and thermal treatment of products with due account of all parameters affecting the quality of the process proceeding. Orthogonal Bubnov-Galiorcin method has been used to solve boundary equation problems of heat conduction with corresponding initial and limiting conditions of the first, second and third origin. Maximum error of the results obtained with the help of the proposed model does not exceed 3,7 %, that testifies its adequacy and proves its possible usage with the purpose to optimize heating and thermal treatment processes of products.

  2. The experimental autoimmune encephalomyelitis (EAE) model of MS: utility for understanding disease pathophysiology and treatment

    Science.gov (United States)

    ROBINSON, ANDREW P.; HARP, CHRISTOPHER T.; NORONHA, AVERTANO; MILLER, STEPHEN D.

    2014-01-01

    While no single model can exactly recapitulate all aspects of multiple sclerosis (MS), animal models are essential in understanding the induction and pathogenesis of the disease and to develop therapeutic strategies that limit disease progression and eventually lead to effective treatments for the human disease. Several different models of MS exist, but by far the best understood and most commonly used is the rodent model of experimental autoimmune encephalomyelitis (EAE). This model is typically induced by either active immunization with myelin-derived proteins or peptides in adjuvant or by passive transfer of activated myelin-specific CD4+ T lymphocytes. Mouse models are most frequently used because of the inbred genotype of laboratory mice, their rapid breeding capacity, the ease of genetic manipulation, and availability of transgenic and knockout mice to facilitate mechanistic studies. Although not all therapeutic strategies for MS have been developed in EAE, all of the current US Food and Drug Administration (FDA)-approved immunomodulatory drugs are effective to some degree in treating EAE, a strong indicator that EAE is an extremely useful model to study potential treatments for MS. Several therapies, such as glatiramer acetate (GA: Copaxone), and natalizumab (Tysabri), were tested first in the mouse model of EAE and then went on to clinical trials. Here we discuss the usefulness of the EAE model in understanding basic disease pathophysiology and developing treatments for MS as well as the potential drawbacks of this model. PMID:24507518

  3. Optical fluence modelling for ultraviolet light emitting diode-based water treatment systems.

    Science.gov (United States)

    Simons, R; Gabbai, U E; Moram, M A

    2014-12-01

    This work presents a validated optical fluence rate model optimised for ultraviolet light-emitting diodes (UV-LEDs), which allow a very wide range of emission wavelengths and source geometries to be used in water treatment units. The model is based on a Monte Carlo approach, in which an incremental ray-tracing algorithm is used to calculate the local volumetric rate of energy absorption and subsequently convert it to the local fluence rate distribution for an UV-LED water treatment chamber of arbitrary design. The model includes contributions from optical reflections and scattering by treatment chamber walls and from scattering due to particulates and/or microorganisms. The model successfully predicts optical fluence rates in point-of-use water treatment units, as verified using biodosimetry with MS-2 bacteriophage at a UV-LED emission wavelength of 254 nm. The effects of chamber geometry are also modelled effectively and are consistent with the inactivation data for E. coli at 254 nm. The data indicate that this model is suitable for application in the design and optimisation of UV-LED-based water treatment systems. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Is aggressive treatment of traumatic brain injury cost-effective?

    Science.gov (United States)

    Whitmore, Robert G; Thawani, Jayesh P; Grady, M Sean; Levine, Joshua M; Sanborn, Matthew R; Stein, Sherman C

    2012-05-01

    The object of this study was to determine whether aggressive treatment of severe traumatic brain injury (TBI), including invasive intracranial monitoring and decompressive craniectomy, is cost-effective. A decision-analytical model was created to compare costs, outcomes, and cost-effectiveness of 3 strategies for treating a patient with severe TBI. The aggressive-care approach is compared with "routine care," in which Brain Trauma Foundation guidelines are not followed. A "comfort care" category, in which a single day in the ICU is followed by routine floor care, is included for comparison only. Probabilities of each treatment resulting in various Glasgow Outcome Scale (GOS) scores were obtained from the literature. The GOS scores were converted to quality-adjusted life years (QALYs), based on expected longevity and calculated quality of life associated with each GOS category. Estimated direct (acute and long-term medical care) and indirect (loss of productivity) costs were calculated from the perspective of society. Sensitivity analyses employed a 2D Monte Carlo simulation of 1000 trials, each with 1000 patients. The model was also used to estimate these values for patients 40, 60, and 80 years of age. For the average 20-year-old, aggressive care yields 11.7 (± 1.6 [SD]) QALYs, compared with routine care (10.0 ± 1.5 QALYs). This difference is highly significant (p care remains significantly better at all ages. When all costs are considered, aggressive care is also significantly less costly than routine care ($1,264,000 ± $118,000 vs $1,361,000 ± $107,000) for the average 20-year-old. Aggressive care remains significantly less costly until age 80, at which age it costs more than routine care. However, even in the 80-year-old, aggressive care is likely the more cost-effective approach. Comfort care is associated with poorer outcomes at all ages and with higher costs for all groups except 80-year-olds. When all the costs of severe TBI are considered, aggressive

  5. Pharmacokinetic modeling of gentamicin in treatment of infective endocarditis: Model development and validation of existing models.

    Directory of Open Access Journals (Sweden)

    Anna Gomes

    Full Text Available Gentamicin shows large variations in half-life and volume of distribution (Vd within and between individuals. Thus, monitoring and accurately predicting serum levels are required to optimize effectiveness and minimize toxicity. Currently, two population pharmacokinetic models are applied for predicting gentamicin doses in adults. For endocarditis patients the optimal model is unknown. We aimed at: 1 creating an optimal model for endocarditis patients; and 2 assessing whether the endocarditis and existing models can accurately predict serum levels. We performed a retrospective observational two-cohort study: one cohort to parameterize the endocarditis model by iterative two-stage Bayesian analysis, and a second cohort to validate and compare all three models. The Akaike Information Criterion and the weighted sum of squares of the residuals divided by the degrees of freedom were used to select the endocarditis model. Median Prediction Error (MDPE and Median Absolute Prediction Error (MDAPE were used to test all models with the validation dataset. We built the endocarditis model based on data from the modeling cohort (65 patients with a fixed 0.277 L/h/70kg metabolic clearance, 0.698 (±0.358 renal clearance as fraction of creatinine clearance, and Vd 0.312 (±0.076 L/kg corrected lean body mass. External validation with data from 14 validation cohort patients showed a similar predictive power of the endocarditis model (MDPE -1.77%, MDAPE 4.68% as compared to the intensive-care (MDPE -1.33%, MDAPE 4.37% and standard (MDPE -0.90%, MDAPE 4.82% models. All models acceptably predicted pharmacokinetic parameters for gentamicin in endocarditis patients. However, these patients appear to have an increased Vd, similar to intensive care patients. Vd mainly determines the height of peak serum levels, which in turn correlate with bactericidal activity. In order to maintain simplicity, we advise to use the existing intensive-care model in clinical practice to

  6. Effect of systemic insulin treatment on diabetic wound healing.

    Science.gov (United States)

    Vatankhah, Nasibeh; Jahangiri, Younes; Landry, Gregory J; Moneta, Gregory L; Azarbal, Amir F

    2017-04-01

    This study investigates if different diabetic treatment regimens affect diabetic foot ulcer healing. From January 2013 to December 2014, 107 diabetic foot ulcers in 85 patients were followed until wound healing, amputation or development of a nonhealing ulcer at the last follow-up visit. Demographic data, diabetic treatment regimens, presence of peripheral vascular disease, wound characteristics, and outcome were collected. Nonhealing wound was defined as major or minor amputation or those who did not have complete healing until the last observation. Median age was 60.0 years (range: 31.1-90.1 years) and 58 cases (68.2%) were males. Twenty-four cases reached a complete healing (healing rate: 22.4%). The median follow-up period in subjects with classified as having chronic wounds was 6.0 months (range: 0.7-21.8 months). Insulin treatment was a part of diabetes management in 52 (61.2%) cases. Insulin therapy significantly increased the wound healing rate (30.3% [20/66 ulcers] vs. 9.8% [4/41 ulcers]) (p = 0.013). In multivariate random-effect logistic regression model, adjusting for age, gender, smoking status, type of diabetes, hypertension, chronic kidney disease, peripheral arterial disease, oral hypoglycemic use, wound infection, involved side, presence of Charcot's deformity, gangrene, osteomyelitis on x-ray, and serum hemoglobin A1C levels, insulin treatment was associated with a higher chance of complete healing (beta ± SE: 15.2 ± 6.1, p = 0.013). Systemic insulin treatment can improve wound healing in diabetic ulcers after adjusting for multiple confounding covariates. © 2017 by the Wound Healing Society.

  7. Treatment Effects with Many Covariates and Heteroskedasticity

    DEFF Research Database (Denmark)

    Cattaneo, Matias D.; Jansson, Michael; Newey, Whitney K.

    The linear regression model is widely used in empirical work in Economics. Researchers often include many covariates in their linear model specification in an attempt to control for confounders. We give inference methods that allow for many covariates and heteroskedasticity. Our results...

  8. Simulation of wastewater treatment plant within integrated urban wastewater models.

    Science.gov (United States)

    Heusch, S; Kamradt, B; Ostrowski, M

    2010-01-01

    In the federal state of Hesse in Germany the application of an integrated software modelling framework is becoming part of the planning process to attain legal approval for the operation of combined sewer systems. The software allows for parallel simulation of flow and water quality routing in the sewer system and in receiving rivers. It combines existing pollution load model approaches with a simplified version of the River Water Quality Model No. 1 (RWQM1). Comprehensive simulation of the wastewater treatment plant (WWTP) is not considered yet. The paper analyses alternatives for the implementation of a WWTP module to model activated sludge plants. For both primary and secondary clarifiers as well as for the activated sludge process concepts for the integration into the existing software framework were developed. The activated sludge concept which uses a linearized version of the well known ASM1 model is presented in detail.

  9. Effects of Outpatient Treatment of Dyslexia.

    Science.gov (United States)

    van Daal, Victor H. P.; Reitsma, Pieter

    1999-01-01

    A Dutch intervention program proved to be successful with 109 10-year-old children with dyslexia and 29 children with reading problems and cognitive deficits or psychiatric symptoms. The children with pure dyslexia profited most. Differences in treatment outcomes were related to the absolute level of word reading and age at intake. (Author/CR)

  10. Effects of ecosystem-based management treatments

    Science.gov (United States)

    Michael G. Harrington; Carl E. Fiedler; Stephen F. Arno; Ward W. McCaughey; Leon J. Theroux; Clinton E. Carlson; Kristin L. Zouhar; Thomas H. DeLuca; Donald J. Bedunah; Dayna M. Ayers; Elizabeth A. Beringer; Sallie J. Hejl; Lynn Bacon; Robert E. Benson; Jane Kapler Smith; Rick Floch

    1999-01-01

    The prescribed burn treatments were applied to reduce pre-existing and new slash fuel loadings, reduce understory tree density to lower crown fire potential, stimulate vigor of decadent understory vegetation, produce mineral seedbeds for seral species establishment, and increase availability of mineral nutrients. To test the feasibility of prescribed burning under a...

  11. Nonparametric Bounds and Sensitivity Analysis of Treatment Effects

    Science.gov (United States)

    Richardson, Amy; Hudgens, Michael G.; Gilbert, Peter B.; Fine, Jason P.

    2015-01-01

    This paper considers conducting inference about the effect of a treatment (or exposure) on an outcome of interest. In the ideal setting where treatment is assigned randomly, under certain assumptions the treatment effect is identifiable from the observable data and inference is straightforward. However, in other settings such as observational studies or randomized trials with noncompliance, the treatment effect is no longer identifiable without relying on untestable assumptions. Nonetheless, the observable data often do provide some information about the effect of treatment, that is, the parameter of interest is partially identifiable. Two approaches are often employed in this setting: (i) bounds are derived for the treatment effect under minimal assumptions, or (ii) additional untestable assumptions are invoked that render the treatment effect identifiable and then sensitivity analysis is conducted to assess how inference about the treatment effect changes as the untestable assumptions are varied. Approaches (i) and (ii) are considered in various settings, including assessing principal strata effects, direct and indirect effects and effects of time-varying exposures. Methods for drawing formal inference about partially identified parameters are also discussed. PMID:25663743

  12. Long-Term Effects of a Psycholinguistic Treatment for Dyslexia.

    Science.gov (United States)

    Tijms, Jurgen; Hoeks, Jan J. W. M.; Paulussen-Hoogeboom, Marja C.; Smolenaars, Anton J.

    2003-01-01

    Evaluates short- and long-term effects of a treatment for dyslexia. Notes that the treatment focuses on learning to recognize and to make use of the phonological and morphological structure of Dutch words. Finds that the results of the treatment were clear improvements in reading words, reading text and spelling. (SG)

  13. Placebo effect in the treatment of duodenal ulcer

    Science.gov (United States)

    de Craen, Anton J M; Moerman, Daniel E; Heisterkamp, Simon H; Tytgat, Guido N J; Tijssen, Jan G P; Kleijnen, Jos

    1999-01-01

    Aims To assess whether frequency of placebo administration is associated with duodenal ulcer healing. Methods A systematic literature review of randomized clinical trials was undertaken. 79 of 80 trials that met the inclusion criteria. The pooled 4 week placebo healing rate of all duodenal ulcer trials that employed a four times a day regimen was compared with the rate obtained from trials with a twice a day regimen. Results The pooled 4 week healing rate of the 51 trials with a four times a day regimen was 44.2% (805 of 1821 patients) compared with 36.2% (545 of 1504 patients) in the 28 trials with a twice a day regimen (difference, 8.0% [equal effects model]; 95% confidence interval, 4.6% to 11.3%). Depending on the statistical analysis, the rate difference ranged from 6.0% (multivariable random effects model) to 8.0% (equal effects model). A number of sensitivity analyses showed comparable differences between the two regimens. Most of these sensitivity analyses were not significant, probably because a number of trials were excluded resulting in a loss of power. Conclusions We found a relation between frequency of placebo administration and healing of duodenal ulcer. We realize that the comparison was based on nonrandomized data. However, we speculate that the difference between regimens was induced by the difference in frequency of placebo administration. A better knowledge of various placebo effects is required in order to make clinically relevant assessments of treatment effects derived from placebo-controlled trials. PMID:10594490

  14. Treatment effects in prostate cancer following traditional and emerging therapies.

    Science.gov (United States)

    Mazzucchelli, R; Scarpelli, M; Lopez-Beltran, A; Cheng, L; Di Primio, R; Montironi, R

    2013-01-01

    Treatment options for prostate cancer consist of radical prostatectomy, hormonal therapy and radiation therapy. Hormonal and radiation therapy have well-known, often profound, effects on the histological appearance of benign and malignant prostate tissue. Novel therapies including focal ablative treatments, chemotherapies and targeted molecular therapies are beginning to emerge and pathologists will play a central role in documenting the effects of these treatments at the tissue level. As such, knowledge of treatment-related changes and access to clinical information are essential to ensure accurate interpretation and reporting of post-treatment prostate specimens by pathologists.

  15. Deformable object model and simulation. Application to lung cancer treatment

    International Nuclear Information System (INIS)

    Baudet, V.

    2006-06-01

    Ionising treatment against cancers such as conformal radiotherapy and hadron therapy are set with error margins that take into account statistics of tumour motions, for instance. We are looking for reducing these margins by searching deformable models that would simulate displacements occurring in lungs during a treatment. It must be personalized with the geometry obtained from CT scans of the patient and also it must be parameterized with physiological measures of the patient. In this Ph. D. thesis, we decided to use a mass-spring system to model lungs because of its fast and physically realist deformations obtained in animation. As a starting point, we chose the model proposed by Van Gelder in order to parameterize a mass-spring system with rheological characteristics of an homogeneous, linear elastic isotropic material in two dimensions (2D). However, we tested this model and proved it was false. Hence we did a Lagrangian study in order to obtain a parametric model with rectangular in 2D (cubic in 3D) elements. We also determined the robustness by testing with stretching, inflating, shearing and bending experiments and also by comparing results with other infinite element method. Thus, in this Ph.D. thesis, we explain how to obtain this parametric model, and how it will be linked to physiological data and how accurate it will be. (author)

  16. Greenhouse gases from wastewater treatment - A review of modelling tools.

    Science.gov (United States)

    Mannina, Giorgio; Ekama, George; Caniani, Donatella; Cosenza, Alida; Esposito, Giovanni; Gori, Riccardo; Garrido-Baserba, Manel; Rosso, Diego; Olsson, Gustaf

    2016-05-01

    Nitrous oxide, carbon dioxide and methane are greenhouse gases (GHG) emitted from wastewater treatment that contribute to its carbon footprint. As a result of the increasing awareness of GHG emissions from wastewater treatment plants (WWTPs), new modelling, design, and operational tools have been developed to address and reduce GHG emissions at the plant-wide scale and beyond. This paper reviews the state-of-the-art and the recently developed tools used to understand and manage GHG emissions from WWTPs, and discusses open problems and research gaps. The literature review reveals that knowledge on the processes related to N2O formation, especially due to autotrophic biomass, is still incomplete. The literature review shows also that a plant-wide modelling approach that includes GHG is the best option for the understanding how to reduce the carbon footprint of WWTPs. Indeed, several studies have confirmed that a wide vision of the WWPTs has to be considered in order to make them more sustainable as possible. Mechanistic dynamic models were demonstrated as the most comprehensive and reliable tools for GHG assessment. Very few plant-wide GHG modelling studies have been applied to real WWTPs due to the huge difficulties related to data availability and the model complexity. For further improvement in GHG plant-wide modelling and to favour its use at large real scale, knowledge of the mechanisms involved in GHG formation and release, and data acquisition must be enhanced. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Comparison of a Psychoanalytic and a Client-Centered Group Treatment Model on Measures of Anxiety and Self-Actualization.

    Science.gov (United States)

    Elizabeth, Pamela

    1983-01-01

    Compared the effects of a psychoanalytic or group treatment model in promoting self-actualization in 19 counselor trainees. Results showed significant differences between treatment models: psychoanalytic groups reported higher anxiety, and client-centered groups showed greater initial gains on the Personal Orientation Inventory and maintained…

  18. 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.

  19. Side effects as influencers of treatment outcome.

    Science.gov (United States)

    Sharif, Zafar

    2008-01-01

    Research relative to the efficacy of a therapeutic agent commands a clinician's greatest interest, but treatment decisions are made based on optimizing efficacy and tolerability/safety considerations. Second-generation atypical antipsychotic drugs are a study in the importance of taking a careful look at the full benefit-risk profile of each drug. The disorders that atypical antipsychotics are approved to treat--schizophrenia, schizoaffective disorder, and bipolar disorder--are associated with an increased rate of certain medical comorbidities compared to the general population. Between-drug differences in efficacy are relatively modest for the atypicals, or between atypicals and conventionals, while differences in safety and tolerability are larger and more clinically relevant. The current article will provide a brief summary of safety-related issues that influence treatment outcome and choice of drug.

  20. Sexually transmitted infections screening at HIV treatment centers for MSM can be cost-effective

    NARCIS (Netherlands)

    Vriend, Henrike J.; Lugnér, Anna K.; Xiridou, Maria; Schim van der Loeff, Maarten F.; Prins, Maria; de Vries, Henry J. C.; Geerlings, Suzanne E.; Prins, Jan M.; Rijnders, Bart J. A.; van Veen, Maaike G.; Fennema, Johannes S. A.; Postma, Maarten J.; van der Sande, Marianne A. B.

    2013-01-01

    To estimate the cost-effectiveness of anorectal chlamydia screening among men who have sex with men (MSM) in care at HIV treatment centers. Transmission model combined with economic analysis over a 20-year period. MSM in care at HIV treatment centers. Once-yearly or twice-yearly screening for

  1. Sexually transmitted infections screening at HIV treatment centers for MSM can be cost-effective

    NARCIS (Netherlands)

    Vriend, Henrike J.; Lugnér, Anna K.; Xiridou, Maria; Van Der Loeff, Maarten F. Schim; Prins, Maria; De Vries, Henry J.C.; Geerlings, Suzanne E.; Prins, Jan M.; Rijnders, Bart J.A.; Van Veen, Maaike G.; Fennema, Johannes S.A.; Postma, Maarten J.; Van Der Sande, Marianne A.B.

    2013-01-01

    Objective:To estimate the cost-effectiveness of anorectal chlamydia screening among men who have sex with men (MSM) in care at HIV treatment centers. Design:Transmission model combined with economic analysis over a 20-year period. Setting and participants:MSM in care at HIV treatment centers.

  2. Effects of Cancer Treatment on Fertility (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Effects of Cancer Treatment on Fertility KidsHealth / For Parents / ... infertile couple's embryo via in vitro fertilization. Emotional Effects As you explore the options, it's important to ...

  3. Evaluation of treatment effects by ranking

    DEFF Research Database (Denmark)

    Halekoh, U; Kristensen, K

    2008-01-01

    to account for the repeated measurements. The estimation was based on a Bayesian approach, which was analysed via Markov Chain Monte Carlo sampling. A simulation study showed that the approach was able to estimate the relative ordering of the treatments. The efficiency of the estimation increased....... This method seems to be less sensitive to the judge and also eliminates any possible drift over the judging process in the more traditional method...

  4. Toxic Stress: Effects, Prevention and Treatment

    OpenAIRE

    Franke, Hillary A.

    2014-01-01

    Children who experience early life toxic stress are at risk of long-term adverse health effects that may not manifest until adulthood. This article briefly summarizes the findings in recent studies on toxic stress and childhood adversity following the publication of the American Academy of Pediatrics (AAP) Policy Report on the effects of toxic stress. A review of toxic stress and its effects is described, including factors of vulnerability, resilience, and the relaxation response. An integrat...

  5. Prediction of effluent concentration in a wastewater treatment plant using machine learning models.

    Science.gov (United States)

    Guo, Hong; Jeong, Kwanho; Lim, Jiyeon; Jo, Jeongwon; Kim, Young Mo; Park, Jong-pyo; Kim, Joon Ha; Cho, Kyung Hwa

    2015-06-01

    Of growing amount of food waste, the integrated food waste and waste water treatment was regarded as one of the efficient modeling method. However, the load of food waste to the conventional waste treatment process might lead to the high concentration of total nitrogen (T-N) impact on the effluent water quality. The objective of this study is to establish two machine learning models-artificial neural networks (ANNs) and support vector machines (SVMs), in order to predict 1-day interval T-N concentration of effluent from a wastewater treatment plant in Ulsan, Korea. Daily water quality data and meteorological data were used and the performance of both models was evaluated in terms of the coefficient of determination (R2), Nash-Sutcliff efficiency (NSE), relative efficiency criteria (drel). Additionally, Latin-Hypercube one-factor-at-a-time (LH-OAT) and a pattern search algorithm were applied to sensitivity analysis and model parameter optimization, respectively. Results showed that both models could be effectively applied to the 1-day interval prediction of T-N concentration of effluent. SVM model showed a higher prediction accuracy in the training stage and similar result in the validation stage. However, the sensitivity analysis demonstrated that the ANN model was a superior model for 1-day interval T-N concentration prediction in terms of the cause-and-effect relationship between T-N concentration and modeling input values to integrated food waste and waste water treatment. This study suggested the efficient and robust nonlinear time-series modeling method for an early prediction of the water quality of integrated food waste and waste water treatment process. Copyright © 2015. Published by Elsevier B.V.

  6. The effects of heat treatment on physical and technological ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-10-19

    Oct 19, 2009 ... Heat treatment of wood is an effective method to improve the dimensional stability and durability against biodegradation. In this study, the effects of heat treatment on physical properties and surface roughness of European Hophornbeam (Ostrya carpinifolia Scop.) wood were examined. Samples obtained ...

  7. Effects of long-term treatment with corticosteroids in COPD

    NARCIS (Netherlands)

    Renkema, TEJ; Schouten, JP; Koeter, GH; Postma, DS

    Study objective: To determine the effectiveness of treatment with corticosteroids in patients with COPD. Methods: In this study, we investigated the effect of a 2-year treatment with corticosteroids on clinical symptoms and the decline of lung function in 58 nonallergic patients with COPD. Subjects

  8. BCG-mediated bladder cancer immunotherapy: identifying determinants of treatment response using a calibrated mathematical model.

    Directory of Open Access Journals (Sweden)

    Cyrill A Rentsch

    Full Text Available Intravesical Bacillus Calmette Guérin (BCG immunotherapy is considered the standard of care for treatment of non-muscle invasive bladder cancer; however the treatment parameters were established empirically. In order to evaluate potential optimization of clinical parameters of BCG induction therapy, we constructed and queried a new mathematical model. Specifically, we assessed the impact of (1 duration between resection and the first instillation; (2 BCG dose; (3 indwelling time; and (4 treatment interval of induction therapy - using cure rate as the primary endpoint. Based on available clinical and in vitro experimental data, we constructed and parameterized a stochastic mathematical model describing the interactions between BCG, the immune system, the bladder mucosa and tumor cells. The primary endpoint of the model was the probability of tumor extinction following BCG induction therapy in patients with high risk for tumor recurrence. We theoretically demonstrate that extending the duration between the resection and the first BCG instillation negatively influences treatment outcome. Simulations of higher BCG doses and longer indwelling times both improved the probability of tumor extinction. A remarkable finding was that an inter-instillation interval two times longer than the seven-day interval used in the current standard of care would substantially improve treatment outcome. We provide insight into relevant clinical questions using a novel mathematical model of BCG immunotherapy. Our model predicts an altered regimen that may decrease side effects of treatment while improving response to therapy.

  9. TU-G-210-00: Treatment Planning Strategies, Modeling, Control

    International Nuclear Information System (INIS)

    2015-01-01

    Modeling can play a vital role in predicting, optimizing and analyzing the results of therapeutic ultrasound treatments. Simulating the propagating acoustic beam in various targeted regions of the body allows for the prediction of the resulting power deposition and temperature profiles. In this session we will apply various modeling approaches to breast, abdominal organ and brain treatments. Of particular interest is the effectiveness of procedures for correcting for phase aberrations caused by intervening irregular tissues, such as the skull in transcranial applications or inhomogeneous breast tissues. Also described are methods to compensate for motion in targeted abdominal organs such as the liver or kidney. Douglas Christensen – Modeling for Breast and Brain HIFU Treatment Planning Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Learning Objectives: Understand the role of acoustic beam modeling for predicting the effectiveness of therapeutic ultrasound treatments. Apply acoustic modeling to specific breast, liver, kidney and transcranial anatomies. Determine how to obtain appropriate acoustic modeling parameters from clinical images. Understand the separate role of absorption and scattering in energy delivery to tissues. See how organ motion can be compensated for in ultrasound therapies. Compare simulated data with clinical temperature measurements in transcranial applications. Supported by NIH R01 HL172787 and R01 EB013433 (DC); EU Seventh Framework Programme (FP7/2007-2013) under 270186 (FUSIMO) and 611889 (TRANS-FUSIMO)(TP); and P01 CA159992, GE, FUSF and InSightec (UV)

  10. TU-G-210-01: Modeling for Breast and Brain HIFU Treatment Planning

    International Nuclear Information System (INIS)

    Christensen, D.

    2015-01-01

    Modeling can play a vital role in predicting, optimizing and analyzing the results of therapeutic ultrasound treatments. Simulating the propagating acoustic beam in various targeted regions of the body allows for the prediction of the resulting power deposition and temperature profiles. In this session we will apply various modeling approaches to breast, abdominal organ and brain treatments. Of particular interest is the effectiveness of procedures for correcting for phase aberrations caused by intervening irregular tissues, such as the skull in transcranial applications or inhomogeneous breast tissues. Also described are methods to compensate for motion in targeted abdominal organs such as the liver or kidney. Douglas Christensen – Modeling for Breast and Brain HIFU Treatment Planning Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Learning Objectives: Understand the role of acoustic beam modeling for predicting the effectiveness of therapeutic ultrasound treatments. Apply acoustic modeling to specific breast, liver, kidney and transcranial anatomies. Determine how to obtain appropriate acoustic modeling parameters from clinical images. Understand the separate role of absorption and scattering in energy delivery to tissues. See how organ motion can be compensated for in ultrasound therapies. Compare simulated data with clinical temperature measurements in transcranial applications. Supported by NIH R01 HL172787 and R01 EB013433 (DC); EU Seventh Framework Programme (FP7/2007-2013) under 270186 (FUSIMO) and 611889 (TRANS-FUSIMO)(TP); and P01 CA159992, GE, FUSF and InSightec (UV)

  11. TU-G-210-01: Modeling for Breast and Brain HIFU Treatment Planning

    Energy Technology Data Exchange (ETDEWEB)

    Christensen, D. [University of Utah (United States)

    2015-06-15

    Modeling can play a vital role in predicting, optimizing and analyzing the results of therapeutic ultrasound treatments. Simulating the propagating acoustic beam in various targeted regions of the body allows for the prediction of the resulting power deposition and temperature profiles. In this session we will apply various modeling approaches to breast, abdominal organ and brain treatments. Of particular interest is the effectiveness of procedures for correcting for phase aberrations caused by intervening irregular tissues, such as the skull in transcranial applications or inhomogeneous breast tissues. Also described are methods to compensate for motion in targeted abdominal organs such as the liver or kidney. Douglas Christensen – Modeling for Breast and Brain HIFU Treatment Planning Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Learning Objectives: Understand the role of acoustic beam modeling for predicting the effectiveness of therapeutic ultrasound treatments. Apply acoustic modeling to specific breast, liver, kidney and transcranial anatomies. Determine how to obtain appropriate acoustic modeling parameters from clinical images. Understand the separate role of absorption and scattering in energy delivery to tissues. See how organ motion can be compensated for in ultrasound therapies. Compare simulated data with clinical temperature measurements in transcranial applications. Supported by NIH R01 HL172787 and R01 EB013433 (DC); EU Seventh Framework Programme (FP7/2007-2013) under 270186 (FUSIMO) and 611889 (TRANS-FUSIMO)(TP); and P01 CA159992, GE, FUSF and InSightec (UV)

  12. TU-G-210-00: Treatment Planning Strategies, Modeling, Control

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2015-06-15

    Modeling can play a vital role in predicting, optimizing and analyzing the results of therapeutic ultrasound treatments. Simulating the propagating acoustic beam in various targeted regions of the body allows for the prediction of the resulting power deposition and temperature profiles. In this session we will apply various modeling approaches to breast, abdominal organ and brain treatments. Of particular interest is the effectiveness of procedures for correcting for phase aberrations caused by intervening irregular tissues, such as the skull in transcranial applications or inhomogeneous breast tissues. Also described are methods to compensate for motion in targeted abdominal organs such as the liver or kidney. Douglas Christensen – Modeling for Breast and Brain HIFU Treatment Planning Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Learning Objectives: Understand the role of acoustic beam modeling for predicting the effectiveness of therapeutic ultrasound treatments. Apply acoustic modeling to specific breast, liver, kidney and transcranial anatomies. Determine how to obtain appropriate acoustic modeling parameters from clinical images. Understand the separate role of absorption and scattering in energy delivery to tissues. See how organ motion can be compensated for in ultrasound therapies. Compare simulated data with clinical temperature measurements in transcranial applications. Supported by NIH R01 HL172787 and R01 EB013433 (DC); EU Seventh Framework Programme (FP7/2007-2013) under 270186 (FUSIMO) and 611889 (TRANS-FUSIMO)(TP); and P01 CA159992, GE, FUSF and InSightec (UV)

  13. Mathematical Model of Seasonal Influenza with Treatment in Constant Population

    Science.gov (United States)

    Kharis, M.; Arifudin, R.

    2017-04-01

    Seasonal Influenza is one of disease that outbreaks periodically at least once every year. This disease caused many people hospitalized. Many hospitalized people as employers would infect production quantities, distribution time, and some economic aspects. It will infect economic growth. Infected people need treatments to reduce infection period and cure the infection. In this paper, we discussed about a mathematical model of seasonal influenza with treatment. Factually, the disease was held in short period, less than one year. Hence, we can assume that the population is constant at the disease outbreak time. In this paper, we analyzed the existence of the equilibrium points of the model and their stability. We also give some simulation to give a geometric image about the results of the analysis process.

  14. Advances in Glioblastoma Multiforme Treatment: New Models for Nanoparticle Therapy

    Directory of Open Access Journals (Sweden)

    Elif Ozdemir-Kaynak

    2018-03-01

    Full Text Available The most lethal form of brain cancer, glioblastoma multiforme, is characterized by rapid growth and invasion facilitated by cell migration and degradation of the extracellular matrix. Despite technological advances in surgery and radio-chemotherapy, glioblastoma remains largely resistant to treatment. New approaches to study glioblastoma and to design optimized therapies are greatly needed. One such approach harnesses computational modeling to support the design and delivery of glioblastoma treatment. In this paper, we critically summarize current glioblastoma therapy, with a focus on emerging nanomedicine and therapies that capitalize on cell-specific signaling in glioblastoma. We follow this summary by discussing computational modeling approaches focused on optimizing these emerging nanotherapeutics for brain cancer. We conclude by illustrating how mathematical analysis can be used to compare the delivery of a high potential anticancer molecule, delphinidin, in both free and nanoparticle loaded forms across the blood-brain barrier for glioblastoma.

  15. Treatment Effect Estimation Using Nonlinear Two-Stage Instrumental Variable Estimators: Another Cautionary Note.

    Science.gov (United States)

    Chapman, Cole G; Brooks, John M

    2016-12-01

    To examine the settings of simulation evidence supporting use of nonlinear two-stage residual inclusion (2SRI) instrumental variable (IV) methods for estimating average treatment effects (ATE) using observational data and investigate potential bias of 2SRI across alternative scenarios of essential heterogeneity and uniqueness of marginal patients. Potential bias of linear and nonlinear IV methods for ATE and local average treatment effects (LATE) is assessed using simulation models with a binary outcome and binary endogenous treatment across settings varying by the relationship between treatment effectiveness and treatment choice. Results show that nonlinear 2SRI models produce estimates of ATE and LATE that are substantially biased when the relationships between treatment and outcome for marginal patients are unique from relationships for the full population. Bias of linear IV estimates for LATE was low across all scenarios. Researchers are increasingly opting for nonlinear 2SRI to estimate treatment effects in models with binary and otherwise inherently nonlinear dependent variables, believing that it produces generally unbiased and consistent estimates. This research shows that positive properties of nonlinear 2SRI rely on assumptions about the relationships between treatment effect heterogeneity and choice. © Health Research and Educational Trust.

  16. Clostridium Difficile Infection Due to Pneumonia Treatment: Mortality Risk Models.

    Science.gov (United States)

    Chmielewska, M; Zycinska, K; Lenartowicz, B; Hadzik-Błaszczyk, M; Cieplak, M; Kur, Z; Wardyn, K A

    2017-01-01

    One of the most common gastrointestinal infection after the antibiotic treatment of community or nosocomial pneumonia is caused by the anaerobic spore Clostridium difficile (C. difficile). The aim of this study was to retrospectively assess mortality due to C. difficile infection (CDI) in patients treated for pneumonia. We identified 94 cases of post-pneumonia CDI out of the 217 patients with CDI. The mortality issue was addressed by creating a mortality risk models using logistic regression and multivariate fractional polynomial analysis. The patients' demographics, clinical features, and laboratory results were taken into consideration. To estimate the influence of the preceding respiratory infection, a pneumonia severity scale was included in the analysis. The analysis showed two statistically significant and clinically relevant mortality models. The model with the highest prognostic strength entailed age, leukocyte count, serum creatinine and urea concentration, hematocrit, coexisting neoplasia or chronic obstructive pulmonary disease. In conclusion, we report on two prognostic models, based on clinically relevant factors, which can be of help in predicting mortality risk in C. difficile infection, secondary to the antibiotic treatment of pneumonia. These models could be useful in preventive tailoring of individual therapy.

  17. ASSISTED MODELLING OF MOBILE MEDICAL TREATMENT EQUIPMENT, UPPER RESPIRATORY AFFECTIONS

    Directory of Open Access Journals (Sweden)

    GOANTA Adrian Mihai

    2012-09-01

    Full Text Available The paper aims to present some aspects of parametric modelling application in medical engineering, specifically in the design of medical instruments for ENT diseases. The work also contains both stages, how to obtain all parts parametrically and related accessories that are part of a mobile aerosol -generating medical equipment intended for the treatment of the upper respiratory diseases. Also photorealistic visualization capabilities are highlighted with NX Software from Siemens as well as how to obtain the corresponding 2D documentation.

  18. Modeling the treatment table; Modelado de la mesa de tratamiento

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz Arrebola, S.; Vilches Pacheco, M.; Manchado de Sola, F.; Guirado Llorente, D.

    2011-07-01

    This paper presents an analytical model to characterize the attenuation caused by the treatment table of a linear accelerator recently established. The discrepancy for certain angles of the arm between the attenuation value indicated by the manufacturer and the actually observed is the origin of this work. Our goal was to obtain an analytical attenuation function can be implemented in a simple way, in any planning system SP, through the modulation of the incident flow matrix.

  19. Simulation of welding and heat treatment:modelling and validation

    OpenAIRE

    Alberg, Henrik

    2005-01-01

    Many aerospace components with complex geometry are fabricated from smaller parts using joining techniques such as welding. Welding and the heat treatment which usually follows, can result in unwanted deformation and stresses. Expensive materials, tight geometrical tolerances and the need to decrease product and manufacturing development time, cost and associated risks have motivated the development of models and methods for the simulation of manufacturing processes. The work presented concer...

  20. Deep heat muscle treatment: A mathematical model - I

    International Nuclear Information System (INIS)

    Ogulu, A.; Bestman, A.R.

    1992-03-01

    The flow of blood during deep heat muscle treatment is studied in this paper. We model the blood vessel as a long tube in circular section whose radius varied slowly. Under the Boussinesq approximation, we seek asymptotic series expansions for the velocity components, temperature and pressure about a small parameter, ε, characterizing the radius variation. The study reveals mathematically why physicians recommend a hot bath for cuts and physiotherapists use ice packs for bruises. (author). 5 refs, 3 figs

  1. Asymmetric inhibitory treatment effects in multilingual aphasia.

    Science.gov (United States)

    Goral, Mira; Naghibolhosseini, Maryam; Conner, Peggy S

    2013-01-01

    Findings from recent psycholinguistic studies of bilingual processing support the hypothesis that both languages of a bilingual are always active and that bilinguals continually engage in processes of language selection. This view aligns with the convergence hypothesis of bilingual language representation. Furthermore, it is hypothesized that when bilinguals perform a task in one language they need to inhibit their other, nontarget language(s) and that stronger inhibition is required when the task is performed in the weaker language than in the stronger one. The study of multilingual individuals who acquire aphasia resulting from a focal brain lesion offers a unique opportunity to test the convergence hypothesis and the inhibition asymmetry. We report on a trilingual person with chronic nonfluent aphasia who at the time of testing demonstrated greater impairment in her first acquired language (Persian) than in her third, later learned language (English). She received treatment in English followed by treatment in Persian. An examination of her connected language production revealed improvement in her grammatical skills in each language following intervention in that language, but decreased grammatical accuracy in English following treatment in Persian. The increased error rate was evident in structures that are used differently in the two languages (e.g., auxiliary verbs). The results support the prediction that greater inhibition is applied to the stronger language than to the weaker language, regardless of their age of acquisition. We interpret the findings as consistent with convergence theories that posit overlapping neuronal representation and simultaneous activation of multiple languages and with proficiency-dependent asymmetric inhibition in multilinguals.

  2. Treatment Effect on Recidivism for Juveniles Who Have Sexually Offended: a Multilevel Meta-Analysis.

    Science.gov (United States)

    Ter Beek, Ellis; Spruit, Anouk; Kuiper, Chris H Z; van der Rijken, Rachel E A; Hendriks, Jan; Stams, Geert Jan J M

    2018-04-01

    The current study investigated the effect on recidivism of treatment aimed at juveniles who have sexually offended. It also assessed the potential moderating effect of type of recidivism, and several treatment, participant and study characteristics. In total, 14 published and unpublished primary studies, making use of a comparison group and reporting on official recidivism rates, were included in a multilevel meta-analysis. This resulted in the use of 77 effect sizes, and 1726 participants. A three-level meta-analytic model was used to calculate the combined effect sizes (Cohens d) and to perform moderator analyses. Study quality was assessed with the EPHPP Quality Assessment Tool for Quantitative Studies. A moderate effect size was found (d = 0.37), indicating that the treatment groups achieved an estimated relative reduction in recidivism of 20.5% as compared to comparison groups. However, after controlling for publication bias, a significant treatment effect was no longer found. Type of recidivism did not moderate the effect of treatment, indicating that treatment groups were equally effective for all types of recidivism. Also, no moderating effects of participant or treatment characteristics were found. Regarding study characteristics, a shorter follow up time showed a trend for larger effect sizes, and the effect size calculation based on proportions yielded larger effect sizes than calculation via mean frequency of offending. Implications for future research and clinical practice are discussed.

  3. A Neutrophil Phenotype Model for Extracorporeal Treatment of Sepsis.

    Directory of Open Access Journals (Sweden)

    Alexander D Malkin

    2015-10-01

    Full Text Available Neutrophils play a central role in eliminating bacterial pathogens, but may also contribute to end-organ damage in sepsis. Interleukin-8 (IL-8, a key modulator of neutrophil function, signals through neutrophil specific surface receptors CXCR-1 and CXCR-2. In this study a mechanistic computational model was used to evaluate and deploy an extracorporeal sepsis treatment which modulates CXCR-1/2 levels. First, a simplified mechanistic computational model of IL-8 mediated activation of CXCR-1/2 receptors was developed, containing 16 ODEs and 43 parameters. Receptor level dynamics and systemic parameters were coupled with multiple neutrophil phenotypes to generate dynamic populations of activated neutrophils which reduce pathogen load, and/or primed neutrophils which cause adverse tissue damage when misdirected. The mathematical model was calibrated using experimental data from baboons administered a two-hour infusion of E coli and followed for a maximum of 28 days. Ensembles of parameters were generated using a Bayesian parallel tempering approach to produce model fits that could recreate experimental outcomes. Stepwise logistic regression identified seven model parameters as key determinants of mortality. Sensitivity analysis showed that parameters controlling the level of killer cell neutrophils affected the overall systemic damage of individuals. To evaluate rescue strategies and provide probabilistic predictions of their impact on mortality, time of onset, duration, and capture efficacy of an extracorporeal device that modulated neutrophil phenotype were explored. Our findings suggest that interventions aiming to modulate phenotypic composition are time sensitive. When introduced between 3-6 hours of infection for a 72 hour duration, the survivor population increased from 31% to 40-80%. Treatment efficacy quickly diminishes if not introduced within 15 hours of infection. Significant harm is possible with treatment durations ranging from 5

  4. Consequences of Misspecifying the Number of Latent Treatment Attendance Classes in Modeling Group Membership Turnover within Ecologically-Valid Behavioral Treatment Trials

    Science.gov (United States)

    Morgan-Lopez, Antonio A.; Fals-Stewart, William

    2015-01-01

    Historically, difficulties in analyzing treatment outcome data from open enrollment groups have led to their avoidance in use in federally-funded treatment trials, despite the fact that 79% of treatment programs use open enrollment groups. Recently, latent class pattern mixture models (LCPMM) have shown promise as a defensible approach for making overall (and attendance class-specific) inferences from open enrollment groups with membership turnover. We present a statistical simulation study comparing LCPMMs to longitudinal growth models (LGM) to understand when both frameworks are likely to produce conflicting inferences concerning overall treatment efficacy. LCPMMs performed well under all conditions examined; meanwhile LGMs produced problematic levels of bias and Type I errors under two joint conditions: moderate-to-high dropout (30–50%) and treatment by attendance class interactions exceeding Cohen's d ≈.2. This study highlights key concerns about using LGM for open enrollment data: treatment effect overestimation and advocacy for treatments that may be ineffective in reality. PMID:18513917

  5. Consequences of misspecifying the number of latent treatment attendance classes in modeling group membership turnover within ecologically valid behavioral treatment trials.

    Science.gov (United States)

    Morgan-Lopez, Antonio A; Fals-Stewart, William

    2008-12-01

    Historically, difficulties in analyzing treatment outcome data from open-enrollment groups have led to their avoidance in use in federally funded treatment trials despite the fact that 79% of treatment programs use open-enrollment groups. Recently, latent class pattern mixture models (LCPMM) have shown promise as a defensible approach for making overall (and attendance-class-specific) inferences from open-enrollment groups with membership turnover. We present a statistical simulation study comparing LCPMMs to longitudinal growth models (LGM) to understand when both frameworks are likely to produce conflicting inferences concerning overall treatment efficacy. LCPMMs performed well under all conditions examined; meanwhile, LGMs produced problematic levels of bias and Type I errors under two joint conditions: moderate to high dropout (30%-50%) and treatment by attendance class interactions exceeding Cohen's d approximately .2. This study highlights key concerns about using LGM for open-enrollment data: treatment effect overestimation and advocacy for treatments that may be ineffective in reality.

  6. An Alternative Animal Model for Comparison of Treatments for Cryptococcal Meningitis

    Science.gov (United States)

    Najvar, Laura K.; Bocanegra, Rosie; Graybill, John R.

    1999-01-01

    Weanling outbred rats were infected with Cryptococcus neoformans by direct percranial puncture and inoculation into the cranium. A lethal infection ensued. Treatment with LY295337, a depsipeptide with antifungal activity, was effective in prolonging survival and reducing fungal counts in brain tissue. Weanling rats are an acceptable model for the study of central nervous system infection with C. neoformans. PMID:9925548

  7. Treatment efficacy in a soman-poisoned guinea pig model: Added value of physostigmine?

    NARCIS (Netherlands)

    Joosen, M.J.A.; Smit, A.B.; Helden, H.P.M. van

    2011-01-01

    Current treatment of organophosphate poisoning is insufficient, and survivors may suffer from long-lasting adverse effects, such as cognitive deficits and sleep-wake disturbances. In the present study, we aimed at developing a guinea pig model to investigate the benefits of immediate and delayed

  8. Evaluation of treatment response in depression studies using a Bayesian parametric cure rate model.

    Science.gov (United States)

    Santen, Gijs; Danhof, Meindert; Della Pasqua, Oscar

    2008-10-01

    Efficacy trials with antidepressant drugs often fail to show significant treatment effect even though efficacious treatments are investigated. This failure can, amongst other factors, be attributed to the lack of sensitivity of the statistical method as well as of the endpoints to pharmacological activity. For regulatory purposes the most widely used efficacy endpoint is still the mean change in HAM-D score at the end of the study, despite evidence from literature showing that the HAM-D scale might not be a sensitive tool to assess drug effect and that changes from baseline at the end of treatment may not reflect the extent of response. In the current study, we evaluate the prospect of applying a Bayesian parametric cure rate model (CRM) to analyse antidepressant effect in efficacy trials with paroxetine. The model is based on a survival approach, which allows for a fraction of surviving patients indefinitely after completion of treatment. Data was extracted from GlaxoSmithKline's clinical databases. Response was defined as a 50% change from baseline HAM-D at any assessment time after start of therapy. Survival times were described by a log-normal distribution and drug effect was parameterised as a covariate on the fraction of non-responders. The model was able to fit the data from different studies accurately and results show that response to treatment does not lag for two weeks, as is mythically believed. In conclusion, we demonstrate how parameterisation of a survival model can be used to characterise treatment response in depression trials. The method contrasts with the long-established snapshot on changes from baseline, as it incorporates the time course of response throughout treatment.

  9. Network meta-analysis of disconnected networks: How dangerous are random baseline treatment effects?

    Science.gov (United States)

    Béliveau, Audrey; Goring, Sarah; Platt, Robert W; Gustafson, Paul

    2017-12-01

    In network meta-analysis, the use of fixed baseline treatment effects (a priori independent) in a contrast-based approach is regularly preferred to the use of random baseline treatment effects (a priori dependent). That is because, often, there is not a need to model baseline treatment effects, which carry the risk of model misspecification. However, in disconnected networks, fixed baseline treatment effects do not work (unless extra assumptions are made), as there is not enough information in the data to update the prior distribution on the contrasts between disconnected treatments. In this paper, we investigate to what extent the use of random baseline treatment effects is dangerous in disconnected networks. We take 2 publicly available datasets of connected networks and disconnect them in multiple ways. We then compare the results of treatment comparisons obtained from a Bayesian contrast-based analysis of each disconnected network using random normally distributed and exchangeable baseline treatment effects to those obtained from a Bayesian contrast-based analysis of their initial connected network using fixed baseline treatment effects. For the 2 datasets considered, we found that the use of random baseline treatment effects in disconnected networks was appropriate. Because those datasets were not cherry-picked, there should be other disconnected networks that would benefit from being analyzed using random baseline treatment effects. However, there is also a risk for the normality and exchangeability assumption to be inappropriate in other datasets even though we have not observed this situation in our case study. We provide code, so other datasets can be investigated. Copyright © 2017 John Wiley & Sons, Ltd.

  10. The oral adverse effects of isotretinoin treatment in acne vulgaris ...

    African Journals Online (AJOL)

    Background: Isotretinoin is the most effective therapy to treat severe acne vulgaris and its systemic adverse effects have been well documented, but little is known on dental side effects over the course of treatment. Objectives: This prospective case-control study aimed to evaluate the oral adverse effects of isotretinoin in ...

  11. Strategic Placement of Treatments (SPOTS): Maximizing the Effectiveness of Fuel and Vegetation Treatments on Problem Fire Behavior and Effects

    Science.gov (United States)

    Diane M. Gercke; Susan A. Stewart

    2006-01-01

    In 2005, eight U.S. Forest Service and Bureau of Land Management interdisciplinary teams participated in a test of strategic placement of treatments (SPOTS) techniques to maximize the effectiveness of fuel treatments in reducing problem fire behavior, adverse fire effects, and suppression costs. This interagency approach to standardizing the assessment of risks and...

  12. Effect of thermal treatment on Zn nanodisks

    Energy Technology Data Exchange (ETDEWEB)

    Acuña-Avila, Pedro E., E-mail: pacunaa004@alumno.uaemex.mx; López, Roberto; Vigueras-Santiago, Enrique; Hernández-López, Susana; Camacho-López, Marco [Laboratorio de Investigación y Desarrollo de Materiales Avanzados (LIDMA). Facultad de Química de la Universidad Autónoma del Estado de México. Paseo Colón esquina Paseo Tollocan C.P. 50120, Toluca, Estado de México, México (Mexico); Ornelas-Gutierrez, Carlos; Antunez, Wilber [Centro de investigación en Materiales Avanzados S. C. (CIMAV). Miguel de Cervantes N° 120. C.P. 31109. Chihuahua, Chihuahua, México (Mexico)

    2015-06-15

    Metallic Zn nanodisks with hexagonal morphology were obtained onto glass substrate under vacuum thermal evaporation. A thermal characterization of Zn nanodiks showed a lower oxidation temperature than source powder Zn. Different thermal treatment on Zn nanodisks played an important role on the morphology, crystal size and surface vibrational modes of ZnO. The growth of ZnO nanoneedles started at the edge of metallic zinc hexagonal structures according with SEM images, the higher temperature the longer needles were grown. XRD diffractogram confirmed the wurtzite structure of ZnO with metallic nuclei. A wide band between 530 and 580 cm{sup −1} of Raman scattering corresponded at surface vibrational modes not observed at higher temperature.

  13. Effect of thermal treatment on Zn nanodisks

    Directory of Open Access Journals (Sweden)

    Pedro E. Acuña-Avila

    2015-06-01

    Full Text Available Metallic Zn nanodisks with hexagonal morphology were obtained onto glass substrate under vacuum thermal evaporation. A thermal characterization of Zn nanodiks showed a lower oxidation temperature than source powder Zn. Different thermal treatment on Zn nanodisks played an important role on the morphology, crystal size and surface vibrational modes of ZnO. The growth of ZnO nanoneedles started at the edge of metallic zinc hexagonal structures according with SEM images, the higher temperature the longer needles were grown. XRD diffractogram confirmed the wurtzite structure of ZnO with metallic nuclei. A wide band between 530 and 580 cm−1 of Raman scattering corresponded at surface vibrational modes not observed at higher temperature.

  14. Fibromyalgia Syndrome in Need of Effective Treatments

    Science.gov (United States)

    Tsilioni, Irene; Arbetman, Lauren; Panagiotidou, Smaro; Stewart, Julia M.; Gleason, Rae M.; Russell, Irwin J.

    2015-01-01

    Fibromyalgia syndrome (FMS) is a chronic, idiopathic condition of widespread musculoskeletal pain, affecting primarily women. It is clinically characterized by chronic, nonarticular pain and a heightened response to pressure along with sleep disturbances, fatigue, bowel and bladder abnormalities, and cognitive dysfunction. The diagnostic criteria have changed repeatedly, and there is neither a definitive pathogenesis nor reliable diagnostic or prognostic biomarkers. Clinical and laboratory studies have provided evidence of altered central pain pathways. Recent evidence suggests the involvement of neuroinflammation with stress peptides triggering the release of neurosenzitizing mediators. The management of FMS requires a multidimensional approach including patient education, behavioral therapy, exercise, and pain management. Here we review recent data on the pathogenesis and propose new directions for research and treatment. PMID:26306765

  15. Variance-based sensitivity analysis for wastewater treatment plant modelling.

    Science.gov (United States)

    Cosenza, Alida; Mannina, Giorgio; Vanrolleghem, Peter A; Neumann, Marc B

    2014-02-01

    Global sensitivity analysis (GSA) is a valuable tool to support the use of mathematical models that characterise technical or natural systems. In the field of wastewater modelling, most of the recent applications of GSA use either regression-based methods, which require close to linear relationships between the model outputs and model factors, or screening methods, which only yield qualitative results. However, due to the characteristics of membrane bioreactors (MBR) (non-linear kinetics, complexity, etc.) there is an interest to adequately quantify the effects of non-linearity and interactions. This can be achieved with variance-based sensitivity analysis methods. In this paper, the Extended Fourier Amplitude Sensitivity Testing (Extended-FAST) method is applied to an integrated activated sludge model (ASM2d) for an MBR system including microbial product formation and physical separation processes. Twenty-one model outputs located throughout the different sections of the bioreactor and 79 model factors are considered. Significant interactions among the model factors are found. Contrary to previous GSA studies for ASM models, we find the relationship between variables and factors to be non-linear and non-additive. By analysing the pattern of the variance decomposition along the plant, the model factors having the highest variance contributions were identified. This study demonstrates the usefulness of variance-based methods in membrane bioreactor modelling where, due to the presence of membranes and different operating conditions than those typically found in conventional activated sludge systems, several highly non-linear effects are present. Further, the obtained results highlight the relevant role played by the modelling approach for MBR taking into account simultaneously biological and physical processes. © 2013.

  16. The effectiveness of compulsory drug treatment: A systematic review.

    Science.gov (United States)

    Werb, D; Kamarulzaman, A; Meacham, M C; Rafful, C; Fischer, B; Strathdee, S A; Wood, E

    2016-02-01

    Despite widespread implementation of compulsory treatment modalities for drug dependence, there has been no systematic evaluation of the scientific evidence on the effectiveness of compulsory drug treatment. We conducted a systematic review of studies assessing the outcomes of compulsory treatment. We conducted a search in duplicate of all relevant peer-reviewed scientific literature evaluating compulsory treatment modalities. The following academic databases were searched: PubMed, PAIS International, Proquest, PsycINFO, Web of Science, Soc Abstracts, JSTOR, EBSCO/Academic Search Complete, REDALYC, SciELO Brazil. We also searched the Internet, and article reference lists, from database inception to July 15th, 2015. Eligibility criteria are as follows: peer-reviewed scientific studies presenting original data. Primary outcome of interest was post-treatment drug use. Secondary outcome of interest was post-treatment criminal recidivism. Of an initial 430 potential studies identified, nine quantitative studies met the inclusion criteria. Studies evaluated compulsory treatment options including drug detention facilities, short (i.e., 21-day) and long-term (i.e., 6 months) inpatient treatment, community-based treatment, group-based outpatient treatment, and prison-based treatment. Three studies (33%) reported no significant impacts of compulsory treatment compared with control interventions. Two studies (22%) found equivocal results but did not compare against a control condition. Two studies (22%) observed negative impacts of compulsory treatment on criminal recidivism. Two studies (22%) observed positive impacts of compulsory inpatient treatment on criminal recidivism and drug use. There is limited scientific literature evaluating compulsory drug treatment. Evidence does not, on the whole, suggest improved outcomes related to compulsory treatment approaches, with some studies suggesting potential harms. Given the potential for human rights abuses within compulsory

  17. Validation and uncertainty analysis of a pre-treatment 2D dose prediction model

    Science.gov (United States)

    Baeza, Jose A.; Wolfs, Cecile J. A.; Nijsten, Sebastiaan M. J. J. G.; Verhaegen, Frank

    2018-02-01

    Independent verification of complex treatment delivery with megavolt photon beam radiotherapy (RT) has been effectively used to detect and prevent errors. This work presents the validation and uncertainty analysis of a model that predicts 2D portal dose images (PDIs) without a patient or phantom in the beam. The prediction model is based on an exponential point dose model with separable primary and secondary photon fluence components. The model includes a scatter kernel, off-axis ratio map, transmission values and penumbra kernels for beam-delimiting components. These parameters were derived through a model fitting procedure supplied with point dose and dose profile measurements of radiation fields. The model was validated against a treatment planning system (TPS; Eclipse) and radiochromic film measurements for complex clinical scenarios, including volumetric modulated arc therapy (VMAT). Confidence limits on fitted model parameters were calculated based on simulated measurements. A sensitivity analysis was performed to evaluate the effect of the parameter uncertainties on the model output. For the maximum uncertainty, the maximum deviating measurement sets were propagated through the fitting procedure and the model. The overall uncertainty was assessed using all simulated measurements. The validation of the prediction model against the TPS and the film showed a good agreement, with on average 90.8% and 90.5% of pixels passing a (2%,2 mm) global gamma analysis respectively, with a low dose threshold of 10%. The maximum and overall uncertainty of the model is dependent on the type of clinical plan used as input. The results can be used to study the robustness of the model. A model for predicting accurate 2D pre-treatment PDIs in complex RT scenarios can be used clinically and its uncertainties can be taken into account.

  18. Is cannabis an effective treatment for joint pain?

    Science.gov (United States)

    Miller, Richard J; Miller, Rachel E

    2017-01-01

    Cannabis has been used to treat pain for thousands of years. However, since the early part of the 20th century, laws restricting cannabis use have limited its evaluation using modern scientific criteria. Over the last decade, the situation has started to change because of the increased availability of cannabis in the United States for either medical or recreational purposes, making it important to provide the public with accurate information as to the effectiveness of the drug for joint pain among other indications. The major psychotropic component of cannabis is Δ9-tetrahydrocannabinol (THC), one of some 120 naturally occurring phytocannabinoids. Cannabidiol (CBD) is another molecule found in herbal cannabis in large amounts. Although CBD does not produce psychotropic effects, it has been shown to produce a variety of pharmacological effects. Hence, the overall effects of herbal cannabis represent the collective activity of THC, CBD and a number of minor components. The action of THC is mediated by two major G-protein coupled receptors, cannabinoid receptor type 1 (CB1) and CB2, and recent work has suggested that other targets may also exist. Arachidonic acid derived endocannabinoids are the normal physiological activators of the two cannabinoid receptors. Natural phytocannabinoids and synthetic derivatives have produced clear activity in a variety of models of joint pain in animals. These effects are the result of both inhibition of pain pathway signalling (mostly CB1) and anti-inflammatory effects (mostly CB2). There are also numerous anecdotal reports of the effectiveness of smoking cannabis for joint pain. Indeed, it is the largest medical request for the use of the drug. However, these reports generally do not extend to regulated clinical trials for rheumatic diseases. Nevertheless, the preclinical and human data that do exist indicate that the use of cannabis should be taken seriously as a potential treatment of joint pain.

  19. Psychotherapy: The Humanistic (and Effective) Treatment

    Science.gov (United States)

    Wampold, Bruce E.

    2007-01-01

    Although it is well established that psychotherapy is remarkably effective, the change process in psychotherapy is not well understood. Psychotherapy is compared with medicine and cultural healing practices to argue that critical aspects of psychotherapy involve human processes that are used in religious, spiritual, and cultural healing practices.…

  20. Key indexes of the effectiveness of mask surface treatments

    Science.gov (United States)

    Lin, Chen-Yang; Liu, Chung-Hsuan; Lin, Kuan-Wen; Lu, Chi-Lun; Hsu, Luke; Chin, Angus; Yen, Anthony

    2015-10-01

    A proper surface treatment, such as O2 plasma, helps to improve particle removal efficiency (PRE) because of the formation of hydrogen bonding between particles, water and the mask surface after treatment. The effectiveness of surface treatments cannot be determined only by the static wettability after processes. More key indexes should be considered. In this paper, we report our findings on the relationship between surface treatments on photomasks and the resulting wettability. In addition, added defects after the treatment and the cleaning process were inspected with a 193- nm KLA inspector on 193-nm immersion and EUV photomasks, which consist of SiO2, MoSi, Cr, Ta-based absorber and Ru. Based on our work, three indexes can be built for determining the effectiveness of surface treatments. The first is to check whether the surface becomes super-hydrophilic after treatment. The second is to determine the efficiency of surface treatments on enhancing wettability. The last is to quantify the added watermark count after the surface treatment and the cleaning process. With a proper surface treatment, watermarks can be greatly eased. These three indexes can quickly determine possible effective methods for treating the surfaces of different materials.

  1. Modeling Hydrogen Generation Rates in the Hanford Waste Treatment and Immobilization Plant

    Energy Technology Data Exchange (ETDEWEB)

    Camaioni, Donald M.; Bryan, Samuel A.; Hallen, Richard T.; Sherwood, David J.; Stock, Leon M.

    2004-03-29

    This presentation describes a project in which Hanford Site and Environmental Management Science Program investigators addressed issues concerning hydrogen generation rates in the Hanford waste treatment and immobilization plant. The hydrogen generation rates of radioactive wastes must be estimated to provide for safe operations. While an existing model satisfactorily predicts rates for quiescent wastes in Hanford underground storage tanks, pretreatment operations will alter the conditions and chemical composition of these wastes. Review of the treatment process flowsheet identified specific issues requiring study to ascertain whether the model would provide conservative values for waste streams in the plant. These include effects of adding hydroxide ion, alpha radiolysis, saturation with air (oxygen) from pulse-jet mixing, treatment with potassium permanganate, organic compounds from degraded ion exchange resins and addition of glass-former chemicals. The effects were systematically investigated through literature review, technical analyses and experimental work.

  2. Effective physical treatment for chronic low back pain.

    Science.gov (United States)

    Maher, C G

    2004-01-01

    It is now feasible to adopt an evidence-based approach when providing physical treatment for patients with chronic LBP. A summary of the efficacy of a range of physical treatments is provided in Table 1. The evidence-based primary care options are exercise, laser, massage, and spinal manipulation; however, the latter three have small or transient effects that limit their value as therapies for chronic LBP. In contrast, exercise produces large reductions in pain and disability, a feature that suggests that exercise should play a major role in the management of chronic LBP. Physical treatments, such as acupuncture, backschool, hydrotherapy, lumbar supports, magnets, TENS, traction, ultrasound, Pilates therapy, Feldenkrais therapy, Alexander technique, and craniosacral therapy are either of unknown value or ineffective and so should not be considered. Outside of primary care, multidisciplinary treatment or functional restoration is effective; however, the high cost probably means that these programs should be reserved for patients who do not respond to cheaper treatment options for chronic LBP. Although there are now effective treatment options for chronic LBP, it needs to be acknowledged that the problem of chronic LBP is far from solved. Though treatments can provide marked improvements in the patient's condition, the available evidence suggests that the typical chronic LBP patient is left with some residual pain and disability. Developing new, more powerful treatments and refining the current group of known effective treatments is the challenge for the future.

  3. [Study on relationship of dose-effect and time-effect of APA microencapsulated bovine chromaffin cells on pain treatment].

    Science.gov (United States)

    Hui, Jianfeng; Li, Tao; Du, Zhi; Song, Jichang

    2011-12-01

    This study was to investigate the relationship of dose-effect and time-effect of Alginate-Polylysine-Alginate (APA) microencapsulated bovine chromaffin cells on the treatment of pain model rats. Using a rat model of painful peripheral neuropathy, the antinociceptive effects of APA microencapsulated bovine cells transplanted into the subarachnoid space was evaluated by cold allodynia test and hot hyperalgesia test. Compared with control group, the withdrawal difference with cell number 50 thousands groups, 100 thousands groups and 200 thousands groups was reduced (P APA microencapsulated bovine chromaffin cells which were transplanted to treat pain model rats, and the effective antinociception remained longer than 12 weeks.

  4. Nanofibrous Mats for Effective Water Treatment

    Directory of Open Access Journals (Sweden)

    Parmiss Mojir Shaibani

    2013-01-01

    Full Text Available One-dimensional BiFeO3 (BFO nanofibers fabricated by electrospinning of a solution of Nylon6/BFO followed by calcination were used for photocatalytic degradation of contaminants in water. The BFO fibers were characterized using scanning electron microscopy (SEM, X-ray diffraction (XRD, and UV-Vis spectroscopy. The SEM images of the as-spun samples demonstrated the successful production of nanofibers and the SEM images of the samples after calcination confirmed the integrity of the continuous BFO nanofibers. XRD analysis indicated the dominant presence of BFO phase throughout the calcinated nanofibers. Photocatalytic activity of the nanofibers and their application in water purification were investigated against 4-chlorophenol (4CP as a model water contaminant. The results of the UV-Vis spectroscopy show the degradation of the 4CP by means of the photocatalytic activity of the BFO nanofibers. The kinetics of the photodegradation of 4CP is believed to be governed by a pseudo-first-order kinetics model.

  5. Effect of criminal justice mandate on drug treatment completion among women

    Science.gov (United States)

    2015-01-01

    Background Drug and alcohol abuse among women is a growing problem in the United States. Drug treatment is an effective way to manage the psychological, biological, financial, and social cost of drug abuse. Prior research has identified criminal justice referrals or coercion as a predictor of treatment completion among men but questions remain about the same effect in women. Objectives This study uses the Treatment Episodes Datasets Discharge 2006–2008 (TEDS-D) to explore the association between coercion and treatment completion among women. Methods Analysis compared primary treatment episodes of coerced women to those who entered treatment voluntarily. A logistic model of the odds of treatment success was performed controlling for race/ethnicity, age, education, employment, primary substance of abuse, number of substances reported at admission, referral source, treatment setting, and treatment duration. Results 582,671 primary treatment episodes were analyzed comparing women with coercion referrals (n=196,660) to those who entered treatment voluntarily (n=390,054). Results of multivariable logistic modeling showed that coerced women had better odds of completion or transfer than women who entered voluntarily. However, this association was modified by treatment setting with better odds in ambulatory (OR=1.49 (1.47, 1.51)) than in inpatient (OR=1.06 (1.03, 1.10)) and worst outcomes in detoxification (OR=0.89 (0.84, 0.96)). Conclusion These results dispute the broad effectiveness of legal mandates across all drug treatment settings among women. They show the need for further recognition of female specific characteristics that can affect motivation and treatment success to better inform healthcare and judicial policies on drug treatment services for women. PMID:24528184

  6. Neuroimaging in aphasia treatment research : Standards for establishing the effects of treatment

    NARCIS (Netherlands)

    Kiran, Swathi; Ansaldo, Ana; Bastiaanse, Roelien; Cherney, Leora R.; Howard, David; Faroqi-Shah, Yasmeen; Meinzer, Marcus; Thompson, Cynthia K.

    2013-01-01

    The goal of this paper is to discuss experimental design options available for establishing the effects of treatment in studies that aim to examine the neural mechanisms associated with treatment-induced language recovery in aphasia, using functional magnetic resonance imaging (fMRI). We present

  7. Recidivism after treatment in a forensic youth-psychiatric setting: the effect of treatment characteristics

    NARCIS (Netherlands)

    van der Put, C.E.; Asscher, J.J.; Stams, G.J.J.M.; van der Laan, P.H.; Breuk, R.; Jongman, E.; Doreleijers, T.A.H.

    2013-01-01

    The aim of this study was to examine the effect of treatment characteristics on recidivism in a forensic youth-psychiatric outpatient clinic. The treatment offered comprised functional family therapy (FFT), individual cognitive behavioural therapy (CBT), or CBT in combination with parent training.

  8. Mathematical modeling identifies optimum lapatinib dosing schedules for the treatment of glioblastoma patients.

    Directory of Open Access Journals (Sweden)

    Shayna Stein

    2018-01-01

    Full Text Available Human primary glioblastomas (GBM often harbor mutations within the epidermal growth factor receptor (EGFR. Treatment of EGFR-mutant GBM cell lines with the EGFR/HER2 tyrosine kinase inhibitor lapatinib can effectively induce cell death in these models. However, EGFR inhibitors have shown little efficacy in the clinic, partly because of inappropriate dosing. Here, we developed a computational approach to model the in vitro cellular dynamics of the EGFR-mutant cell line SF268 in response to different lapatinib concentrations and dosing schedules. We then used this approach to identify an effective treatment strategy within the clinical toxicity limits of lapatinib, and developed a partial differential equation modeling approach to study the in vivo GBM treatment response by taking into account the heterogeneous and diffusive nature of the disease. Despite the inability of lapatinib to induce tumor regressions with a continuous daily schedule, our modeling approach consistently predicts that continuous dosing remains the best clinically feasible strategy for slowing down tumor growth and lowering overall tumor burden, compared to pulsatile schedules currently known to be tolerated, even when considering drug resistance, reduced lapatinib tumor concentrations due to the blood brain barrier, and the phenotypic switch from proliferative to migratory cell phenotypes that occurs in hypoxic microenvironments. Our mathematical modeling and statistical analysis platform provides a rational method for comparing treatment schedules in search for optimal dosing strategies for glioblastoma and other cancer types.

  9. Adsorption of natural organic matter and disinfection byproduct precursors from surface water onto TiO2nanoparticles: pH effects, isotherm modelling and implications for using TiO2for drinking water treatment.

    Science.gov (United States)

    Gora, Stephanie L; Andrews, Susan A

    2017-05-01

    Titanium dioxide is a photocatalyst that can remove organic contaminants of interest to the drinking water treatment industry, including natural organic matter (NOM) and disinfection byproduct (DBP) precursors. The photocatalytic reaction occurs in two steps: adsorption of the contaminant followed by degradation of the adsorbed contaminant upon irradiation with UV light. The second part of this process can lead to the formation of reactive intermediates and negative impacts on treated water quality, such as increased DBP formation potential (DBPfp). Adsorption alone does not result in the formation of reactive intermediates and thus may prove to be a safe way to incorporate TiO 2 into drinking water treatment processes. The goal of this study was to expand on the current understanding of NOM adsorption on TiO 2 and examine it in a drinking water context by observing NOM adsorption from real water sources and evaluating the effects of the resulting reductions on the DBPfp of the treated water. Bottle point isotherm tests were conducted with raw water from two Canadian water treatment plants adjusted to pH 4, pH 6 and pH 8 and dosed with TiO 2 nanoparticles. The DOC results were a good fit to a modified Freundlich isotherm. DBP precursors and liquid chromatography with organic carbon detection NOM fractions associated with DBP formation were removed to some extent at all pHs, but most effectively at pH 4. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. The Effects of Spiral Taping Treatment on Low Back Pain

    Directory of Open Access Journals (Sweden)

    Hwang Jae-Ok

    2006-02-01

    Full Text Available Objective : The purpose of this study is to estimate the effects of spiral taping treatment on low back pain. Methods : 420 low back pain patients were treated with spiral taping or spiral taping plus herbal medicine, and no other treatments such as acupuncture, herbal acupuncture, and chiropractic therapy were added. We evaluated the improvement by physical examination and pain. Results : 364 patients felt no pain or inconvenience of daily life and 43 patients showed improvement of pain or symptom after 1 month of treatment. 13 patients showed same pain with before treatment. Conclusions : These results suggest spiral taping treatments contribute to the improvement of low back pain. Further study is needed for the confirmation of this effect of spiral taping treatments on low back pain.

  11. The Effects of Cryogenic Treatment on Cutting Tools

    Science.gov (United States)

    Kumar, Satish; Khedkar, Nitin K.; Jagtap, Bhushan; Singh, T. P.

    2017-08-01

    Enhancing the cutting tool life is important and economic factor to reduce the tooling as well as manufacturing cost. The tool life is improved considerably by 92 % after cryogenic treatment. The cryogenic treatment is a one-time permanent, sub-zero heat treatment that entirely changes cross-section of cutting tool. The cryogenic treatment is carried out with deep freezing of cutting tool materials to enhance physical and mechanical properties. The cryogenic treatment improves mechanical such as hardness, toughness and tribological properties such as wear resistance, coefficient of friction, surface finish, dimensional stability and stress relief. The deep cryogenic treatment is the most beneficial treatment applied on cutting tools. The cryogenic treatment is the most advanced heat treatment and popular to improve performance of the cutting tool. The optimization of cryogenic treatment variables is necessary to improve tool life. This study reviews the effects of cryogenic treatment on microstructure, tribological properties of tool steels and machining applications of cutting tool by investigating the surface and performing the surface characterization test like SEM. The economy of cutting tool can be achieved by deep cryogenic treatment.

  12. The treatment effects of Invisalign orthodontic aligners: a systematic review.

    Science.gov (United States)

    Lagravère, Manuel O; Flores-Mir, Carlos

    2005-12-01

    The authors conducted a systematic review of the literature to determine the treatment effects of the Invisalign orthodontic system (Align Technology), Santa Clara, Calif.). The authors reviewed clinical trials that assessed Invisalign's treatment effects in nongrowing patients. They did not consider trials involving surgical or other simultaneous fixed or removable orthodontic treatment interventions. The authors searched electronic databases (PubMed, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, Evidence Based Medicine Reviews, EMBASE Excerpta Medica, Thomsen's ISI Web of Science and LILACS) with the help of a senior health sciences librarian. They used "Invisalign" as the sole search term, and 22 documents appeared in the combined search. Thereafter, they used "clinical trials," "humans" and "Invisalign treatment effects" as abstract selection criteria. Only two published articles met these inclusion criteria, though after reading the actual articles, the authors determined that they did not adequately evaluate Invisalign treatment effects. Both articles identified methodological issues. The inadequately designed studies the authors found represented only a lower level of evidence (level II). Therefore, the authors found that no strong conclusions could be made regarding the treatment effects of Invisalign appliances. Future prospective randomized clinical trials are required to support, with sound scientific evidence, the claims about Invisalign's treatment effects. Clinicians will have to rely on their Invisalign clinical experience, the opinions of experts and the limited published evidence when using Invisalign appliances.

  13. The Holistic Effects of Acupuncture Treatment

    Directory of Open Access Journals (Sweden)

    Jing-Wen Yang

    2014-01-01

    Full Text Available Traditional Chinese Medicine (TCM, as a complex medical science which reflects philosophical principles and embodies large dialectical thought, is used to place the human body into a large system for observation. Acupuncture as a vital part of TCM, has been practiced to treat various diseases and symptoms. However, acupuncture is also facing severe challenges resulted from insufficient modern scientific research. Nowadays, the holistic effects of acupuncture can be researched by some modern approaches, such as the systems biology and fMRI technique. It is believed that having a better understand will greatly promote acupuncture research and be beneficial to scientization and modernization of acupuncture.

  14. Quality of Life and Cost Effectiveness of Prostate Cancer Treatment

    Science.gov (United States)

    2008-03-01

    measurement of satisfaction with treatment . AM J Man Care. 1997;3:579-594. 38. Borras JM, Sancez-Hernandez A, Navarro M, et al. Compliance...of Prostate Cancer Treatment PRINCIPAL INVESTIGATOR: Ravishankar Jayadevappa, Ph.D. CONTRACTING ORGANIZATION: University of...and Cost Effectiveness of Prostate Cancer Treatment 5b. GRANT NUMBER W81XWH-04-1-0257 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Ravishankar

  15. Model for Quantitative Evaluation of Enzyme Replacement Treatment

    Directory of Open Access Journals (Sweden)

    Radeva B.

    2009-12-01

    Full Text Available Gaucher disease is the most frequent lysosomal disorder. Its enzyme replacement treatment was the new progress of modern biotechnology, successfully used in the last years. The evaluation of optimal dose of each patient is important due to health and economical reasons. The enzyme replacement is the most expensive treatment. It must be held continuously and without interruption. Since 2001, the enzyme replacement therapy with Cerezyme*Genzyme was formally introduced in Bulgaria, but after some time it was interrupted for 1-2 months. The dose of the patients was not optimal. The aim of our work is to find a mathematical model for quantitative evaluation of ERT of Gaucher disease. The model applies a kind of software called "Statistika 6" via the input of the individual data of 5-year-old children having the Gaucher disease treated with Cerezyme. The output results of the model gave possibilities for quantitative evaluation of the individual trends in the development of the disease of each child and its correlation. On the basis of this results, we might recommend suitable changes in ERT.

  16. A new model for 'accept or reject' strategies in off-line and on-line megavoltage treatment evaluation

    International Nuclear Information System (INIS)

    Yan Di; Wong, John W.; Gustafson, Gary; Martinez, Alvaro

    1995-01-01

    Purpose: With megavoltage on-line imaging, a temporal record of the treatment setup variation is made available during the course of radiotherapy. This work describes the theoretical framework where the imaging data is incorporated as feedback for deriving off-line and on-line 'accept or reject' decisions to improve the quality of radiotherapy on an individual patient basis. Methods and Materials: A dynamic model of treatment setup variation is developed to describe: (a) the variations of multifraction treatment position and (b) the variation of measurement. Based on this model, a confidence region of subsequent treatment position is estimated from measurements of previous treatment position. The confidence region is compared with an allowance region of the treatment position, representing the acceptable margin of setup variation. The difference of the two regions are then evaluated to derive off-line and on-line 'accept or reject' treatment decisions. Results: The model was simulated retrospectively using sequential daily images from different treatment sites. 'Accept or reject' decisions were produced for on-line and off-line applications. The results also demonstrate the ability of the model to include the effects of setup variation that drifted during the course of treatment. Conclusion: The preliminary result demonstrates that 'accept or reject' treatment decisions can be derived quantitatively from on-line imaging data. The model shows potential to guide the physician and therapist in implementing efficient and accurate treatment adjustments. Further work is required to test the model in the clinical setting

  17. Mode-Specific Effects among Three Treatments for Depression.

    Science.gov (United States)

    Imber, Stanley D.; And Others

    1990-01-01

    Randomly assigned 250 depressed outpatients to interpersonal psychotherapy, cognitive-behavioral therapy, imipramine plus clinical management, or pill placebo plus clinical management treatments. All treatments demonstrated significant symptom reduction with few differences in general outcomes. None of the therapies produced consistent effects on…

  18. Effect of heat treatment on structure and magnetic properties of ...

    Indian Academy of Sciences (India)

    Wintec

    Abstract. Fe46Co35Ni19/CNTs nanocomposites have been prepared by an easy two-step route including adsorp- tion and heat treatment processes. We investigated the effect of heat treatment conditions on structure, mor- phology, nanoparticle sizes and magnetic properties of the Fe46Co35Ni19 alloy nanoparticles ...

  19. Clinical effects of sirolimus treatment in patients with increased ...

    African Journals Online (AJOL)

    In addition, liver function, blood glucose, blood lipid levels, rejection reaction incidence, and mortality were recorded to evaluate the effects of SRL. Results: Scr .... and after treatment (p > 0.05). Blood glucose levels were normalized after treatment, and this difference was significant (p < 0.05) (Table 1). Adverse reactions.

  20. Effect of fibre content and alkali treatment on mechanical properties ...

    Indian Academy of Sciences (India)

    Roystonea regia fibre; epoxy resin; alkali treatment; mechanical properties. Abstract. The present paper investigates the effect of fibre content and alkali treatment on tensile, flexural and impact properties of unidirectional Roystonea regia natural-fibre-reinforced epoxy composites which are partially biodegradable.

  1. Effects of source, water conditioning and thermal treatment on ...

    African Journals Online (AJOL)

    Effects of source, water conditioning and thermal treatment on germination of Ricinodendron heudelotii (baill.) seeds. ... Journal of Applied Science and Technology ... R. heudelotii seeds soaked in water for 15 days at moisture content of 24 % over dry weight followed by thermal treatment improved germination by 22 %.

  2. Moringa extracts used in sugarcane juice treatment and effects on ...

    African Journals Online (AJOL)

    The objective of this study was to evaluate the effects of sugarcane juice treatment using Moringa oleifera leaf and seeds extracts on ethanolic fermentation. The experiment was arranged in a split plot statistical design, with four replications. Main treatments were three sedimentation agents (synthetic polyelectrolyte, ...

  3. The Clinical effectiveness of sequential treatment of skeletal class III ...

    African Journals Online (AJOL)

    Aim: To assess the dentofacial changes induced by the sequential treatment in the skeletal class III malocclusion with maxillary retrognathism. Study design: Controlled clinical trial assessing the effectiveness of sequential treatment of skeletal class III malocclusion. Materials and Methods: The treated group consisted of 30 ...

  4. Effect of polyaluminium chloride water treatment sludge on effluent ...

    African Journals Online (AJOL)

    Effect of polyaluminium chloride water treatment sludge on effluent quality of domestic wastewater treatment. ... The results obtained showed a decrease in total suspended solids (TSS), chemical oxygen demand (COD), total ammonium nitrogen (TAN), and total phosphates (TP) in the supernatant after 30 min of settlement.

  5. Effects of Hot Water Treatment and Temperature on Seedling ...

    African Journals Online (AJOL)

    An experiment was conducted at the Faculty of Agriculture, University of Maiduguri, to study the effect of hot water treatment and temperature on the morphological characteristics of Arabic gum. The experiment was laid out in a Randomized Complete Block Design in a factorial arrangement. The treatments included a ...

  6. Effectiveness of Acupuncture in the Treatment of Gulf War Illness

    Science.gov (United States)

    2013-01-01

    diagnosis and treatment is the type of acupuncture we offered the veterans and we found good results. 11 We will mail a public version of these...325. 7 Wigers SH, Stiles TC, Vogael PA. Effects of aerobic exercise versus stress management treatment in fibromyalgia : a 4.5 year prospective study

  7. Comparative Study of Pre-Germination Treatments and their Effects ...

    African Journals Online (AJOL)

    FIRST LADY

    of leaves (10.05) respectively. Pre-germination treatments of seeds soaked in running water (SRW) for 24 hours were found to be more effective in seedlings growth and biomass production. Keywords: Tectona grandis, pre-germination treatment, seed dormancy, seedling growth. Introduction. Tectona grandis is one of the ...

  8. Predicting the effect of psychoeducational group treatment for hypochondriasis.

    NARCIS (Netherlands)

    Buwalda, F.M.; Bouman, T.K.

    2008-01-01

    Both individual cognitive-behavioural therapy and short-term psychoeducational courses have shown to be effective in reducing hypochondriacal complaints. However, it is unknown which patients benefit from treatment. The aim of the present study is to explore which variables predict treatment outcome

  9. Effect of heat treatment on structure and magnetic properties

    Indian Academy of Sciences (India)

    Fe46Co35Ni19/CNTs nanocomposites have been prepared by an easy two-step route including adsorption and heat treatment processes. We investigated the effect of heat treatment conditions on structure, morphology, nanoparticle sizes and magnetic properties of the Fe46Co35Ni19 alloy nanoparticles attached on the ...

  10. Effects of thermal treatments and germination on physico-chemical ...

    African Journals Online (AJOL)

    Certain physico-chemical properties including viscoelasticity, crystallinity and maltose content of corn depends on the gelatinization of starch under different treatments. Three different treatments were performed; boiling in water, steam heating, and germination. The effects of gelatinization on viscoelastic property of corn ...

  11. Effect of time on dyeing wastewater treatment

    Science.gov (United States)

    Ye, Tingjin; Chen, Xin; Xu, Zizhen; Chen, Xiaogang; Shi, Liang; He, Lingfeng; Zhang, Yongli

    2018-03-01

    The preparation of carboxymethylchitosan wrapping fly-ash adsorbent using high temperature activated fly ash and sodium carboxymethyl chitosan (CWF), as with the iron-carbon micro-electrolysis process simulation and actual printing and dyeing wastewater. The effects of mixing time and static time on decolorization ratio, COD removing rate and turbidness removing rate were investigated. The experimental results show that the wastewater stirring times on the decolorization rate and COD removal rate and turbidity removal rate influence, with increasing of the stirring time, three showed a downward trend, and reached the peak at 10 min time; wastewater time on the decolorization ratio and COD removing efficiency and turbidness removing rate influence, along with standing time increase, three who declined and reached the maximum in 30min time.

  12. Preliminary observations on the effectiveness of levetiracetam in the open adjunctive treatment of refractory bipolar disorder

    NARCIS (Netherlands)

    Post, RM; Altshuler, LL; Frye, MA; Suppes, T; McElroy, SL; Keck, PE; Leverich, GS; Kupka, R; Nolen, WA; Luckenbaugh, DA; Walden, J; Grunze, H

    Objective: Levetiracetam is a recently approved, well-tolerated anticonvulsant with a unique mechanism of action yielding efficacy in treatment-refractory seizure disorders and positive effects in an animal model of mania. Given the effectiveness of a range of other anticonvulsants in bipolar

  13. Requirements for effective modelling strategies.

    NARCIS (Netherlands)

    Gaunt, J.L.; Riley, J.; Stein, A.; Penning de Vries, F.W.T.

    1997-01-01

    As the result of a recent BBSRC-funded workshop between soil scientists, modellers, statisticians and others to discuss issues relating to the derivation of complex environmental models, a set of modelling guidelines is presented and the required associated research areas are discussed.

  14. Neuroimaging in aphasia treatment research: Standards for establishing the effects of treatment

    Science.gov (United States)

    Kiran, Swathi; Ansaldo, Ana; Bastiaanse, Roelien; Cherney, Leora R.; Howard, David; Faroqi-Shah, Yasmeen; Meinzer, Marcus; Thompson, Cynthia K

    2012-01-01

    The goal of this paper is to discuss experimental design options available for establishing the effects of treatment in studies that aim to examine the neural mechanisms associated with treatment-induced language recovery in aphasia, using functional magnetic resonance imaging (fMRI). We present both group and single-subject experimental or case-series design options for doing this and address advantages and disadvantages of each. We also discuss general components of and requirements for treatment research studies, including operational definitions of variables, criteria for defining behavioral change and treatment efficacy, and reliability of measurement. Important considerations that are unique to neuroimaging-based treatment research are addressed, pertaining to the relation between the selected treatment approach and anticipated changes in language processes/functions and how such changes are hypothesized to map onto the brain. PMID:23063559

  15. Prolotherapy: An Effective Treatment for Low Back Pain?

    Science.gov (United States)

    ... pain? Is prolotherapy an effective treatment for chronic low back pain? Answers from Brent A. Bauer, M.D. Prolotherapy is ... reduced pain. Studies of prolotherapy in people with low back pain have had mixed results. A combination of prolotherapy ...

  16. Cancer treatment: fertility and sexual side effects in women

    Science.gov (United States)

    ... cancer Colorectal cancer Uterine cancer Vaginal cancer Breast cancer Bladder cancer Types of Sexual Side Effects For women, the ... used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed ...

  17. Steroid-associated osteonecrosis: Epidemiology, pathophysiology, animal model, prevention, and potential treatments (an overview

    Directory of Open Access Journals (Sweden)

    Xin-Hui Xie

    2015-04-01

    Full Text Available Steroid-associated osteonecrosis (SAON is a common orthopaedic problem caused by administration of corticosteroids prescribed for many nonorthopaedic medical conditions. We summarised different pathophysiologies of SAON which have adverse effects on multiple systems such as bone marrow stem cells (BMSCs pool, bone matrix, cell apoptosis, lipid metabolism, and angiogenesis. Different animal models were introduced to mimic the pathophysiology of SAON and for testing the efficacy of both prevention and treatment effects of various chemical drugs, biological, and physical therapies. According to the classification of SAON, several prevention and treatment methods are applied at the